research paper on fetal alcohol syndrome

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• Published: 23 February 2023

Fetal alcohol spectrum disorders

• Svetlana Popova   ORCID: orcid.org/0000-0002-6308-1157 1 ,
• Michael E. Charness 2 , 3 , 4 , 5 ,
• Larry Burd 6 ,
• Andi Crawford 7 ,
• H. Eugene Hoyme 8 ,
• Raja A. S. Mukherjee 9 ,
• Edward P. Riley   ORCID: orcid.org/0000-0001-8747-891X 10 &
• Elizabeth J. Elliott 11 , 12  

Nature Reviews Disease Primers volume  9 , Article number:  11 ( 2023 ) Cite this article

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• Human behaviour
• Neonatal brain damage

Alcohol readily crosses the placenta and may disrupt fetal development. Harm from prenatal alcohol exposure (PAE) is determined by the dose, pattern, timing and duration of exposure, fetal and maternal genetics, maternal nutrition, concurrent substance use, and epigenetic responses. A safe dose of alcohol use during pregnancy has not been established. PAE can cause fetal alcohol spectrum disorders (FASD), which are characterized by neurodevelopmental impairment with or without facial dysmorphology, congenital anomalies and poor growth. FASD are a leading preventable cause of birth defects and developmental disability. The prevalence of FASD in 76 countries is >1% and is high in individuals living in out-of-home care or engaged in justice and mental health systems. The social and economic effects of FASD are profound, but the diagnosis is often missed or delayed and receives little public recognition. Future research should be informed by people living with FASD and be guided by cultural context, seek consensus on diagnostic criteria and evidence-based treatments, and describe the pathophysiology and lifelong effects of FASD. Imperatives include reducing stigma, equitable access to services, improved quality of life for people with FASD and FASD prevention in future generations.

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Introduction.

Alcohol consumption has occurred for centuries, with harms from prenatal alcohol exposure (PAE) being mentioned in Greek and biblical verses and depicted in the art and literature of the eighteenth and nineteenth centuries 1 , 2 . A French-language publication from 1968, which received little attention at the time, described perinatal death, prematurity, growth retardation, facial features and malformations in the offspring of women who consumed alcohol during pregnancy 3 . Unaware of the French publication, Jones et al. described a similar pattern of altered morphogenesis and function in 11 children of mothers with ‘alcoholism’ in the Lancet in 1973 (ref. 4 ). They reported specific facial features (thin upper lip, smooth philtrum (the vertical groove between the base of the nose and the border of the upper lip) and short palpebral fissures) and coined the term fetal alcohol syndrome (FAS) 5 . By 1977, the US government had issued a warning about the health risks of alcohol use during pregnancy, which was endorsed by professional organizations in the USA 6 , 7 . In 1981, the US Surgeon General issued stronger advice that “women who are pregnant (or considering pregnancy) not drink alcoholic beverages” 8 and other countries subsequently issued similar advice. The teratogenic effects of alcohol were subsequently confirmed in animal studies 9 .

Later studies found that, in addition to FAS, PAE could cause behavioural, cognitive and learning problems, such as attention deficit hyperactivity disorder (ADHD) and speech and language delay, in the absence of facial and other physical features 10 . Recognition of the disconnect between the neurodevelopmental and physical effects (which relate to first-trimester exposure) of PAE and the wide range of outcomes caused by PAE led to the introduction of the term fetal alcohol spectrum disorders (FASD) 11 . Subsequent research identified groups at increased risk of FASD 12 and associations between FASD and metabolic, immunological and cardiovascular diseases in adults 13 , 14 .

FASD occur in all socioeconomic and ethnic groups 15 and are complex, chronic conditions that affect health and family functioning 16 . Individuals with FASD usually require lifelong health care as well as social and vocational support. Some require remedial education and others interact with the justice system. Early diagnosis and a strength-based management approach will optimize health outcomes.

FASD are the most common of the potentially preventable conditions associated with birth anomalies and neurodevelopmental problems 13 , and their global effects, including huge social and economic costs, are substantial 17 . For example, in Canada, the annual cost associated with FASD is an estimated ~CAD$ 1.8 billion (CAD$ 1.3 billion to CAD$ 2.3 billion) 17 , which is attributable in part to productivity loss (41%), correction services (29%) and health care (10%). In North America, the lifetime cost of supporting an individual with FASD is estimated at >CAD$ 1 million 18 . Addressing and preventing alcohol use in pregnancy is a public-health imperative.

This Primer presents the epidemiology of FASD and the latest understanding of its pathophysiology as well as approaches to diagnosis, screening and prevention. The Primer also describes outcomes across the lifespan, management and quality of life (QOL) of people living with FASD, and highlights important areas for future research and clinical practice.

Epidemiology

Alcohol use during pregnancy.

No safe level of PAE has been established 19 , and international guidelines advise against any amount or type of alcohol use during pregnancy 20 , 21 , 22 , 23 . Nevertheless, ~10% of pregnant women worldwide consume alcohol 24 , 25 . The highest prevalence of alcohol use during pregnancy is in the WHO European Region (25.2% 24 ; Fig.  1 ), consistent with the prevalence of heavy alcohol use, heavy episodic drinking and alcohol use disorders in this region 26 .

The highest pooled prevalence (%) of alcohol use during pregnancy in the general population is estimated in the WHO European Region (25.2%, 95% CI 21.6–29.6), followed by the Region of the Americas (11.2%, 95% CI 9.4–12.6), the African Region (10.0%, 95% CI 8.5–11.8), the Western Pacific Region (8.6%, 95% CI 4.5–11.6) and the South-East Asia Region (1.8%, 95% CI 0.9–5.1), and the lowest prevalence is estimated in the Eastern Mediterranean Region (0.2%, 95% CI 0.1–0.9), where most of the population is of Muslim faith and the rates of abstinence from alcohol are very high. The pooled global prevalence of alcohol use during pregnancy in the general population is estimated at 9.8% (95% CI 8.9–11.1). Data from ref. 24 .

In 40% of the 162 countries evaluated, >25% of women who consumed any alcohol during pregnancy drank at ‘binge’ levels (defined as ≥4 US standard drinks containing 14 g of pure alcohol per drink on a single occasion). Binge drinking, which increases the risk of FASD, is common in early pregnancy and before pregnancy recognition 25 , 27 . Many fetuses are inadvertently exposed to alcohol because binge drinking is prevalent in young women, millions of women who consume alcohol report having unprotected sex and approximately half of all pregnancies are unplanned 28 , 29 , 30 , 31 . Alcohol use during pregnancy is higher in certain subpopulations, including some Indigenous populations in Australia (55%) 32 , South Africa (37%) 33 and Canada (60%) 34 , often in the context of disadvantage, violence and ongoing traumatic effects of colonization 35 .

Risk factors for maternal alcohol consumption

Various risk factors have been identified for maternal alcohol use in pregnancy, including higher gravidity and parity 36 , delayed pregnancy recognition, inadequate prenatal care or reluctance of health professionals to address alcohol use 37 , 38 , a history of FASD in previous children 38 , alcohol use disorder and other substance use (including tobacco) 39 , mental health disorders (such as depression) 39 , a history of physical or sexual abuse, social isolation (including living in a rural area during pregnancy), intimate partner violence 38 , 40 , alcohol and/or drug use during pregnancy by the mother’s partner 38 , 41 or other family members 38 , 41 , and poverty 42 .

Risk factors for alcohol use during pregnancy vary across countries and throughout the course of pregnancy. For example, in Australia, first-trimester alcohol use was associated with unplanned pregnancy 43 , age <18 years at first intoxication 30 , frequent and binge drinking in adolescence 44 , and current drinking and a tolerant attitude to alcohol use in pregnancy 45 . Women who continued to drink alcohol throughout pregnancy were more likely to be older, have higher socioeconomic status, salary and educational levels, smoke, have a partner who consumes alcohol, and have an unintended pregnancy than those who abstained, and were less likely to agree with guidelines that recommend avoiding alcohol use in pregnancy 30 , 31 , 46 , 47 .

FASD prevalence

The estimated global prevalence of FASD among the general population is 7.7 cases per 1,000 individuals 25 , 48 . Consistent with rates of alcohol use during pregnancy, FASD prevalence (Fig.  2 ) is highest in the WHO European Region (19.8 per 1,000) and lowest in the WHO Eastern Mediterranean Region (0.1 per 1,000) 25 , 48 . In terms of individual countries, South Africa (111.1 per 1,000), Croatia (53.3 per 1,000), Ireland (47.5 per 1,000), Italy (45.0 per 1,000) and Belarus (36.6 per 1,000) have the highest FASD prevalence, whereas Bahrain, Kuwait, Oman, Qatar, Saudi Arabia and the United Arab Emirates have no recorded cases of FASD 25 , 48 . Furthermore, 76 countries have a prevalence of FASD of >1% 25 , 48 , which exceeds the prevalence of neurodevelopmental conditions, including Down syndrome (trisomy 21), Edwards syndrome (trisomy 18), spina bifida and anencephaly in the USA 49 , and is similar to the prevalence of autism spectrum disorders (1.1–2.5%) 50 .

In line with the prevalence of alcohol use during pregnancy, the highest pooled prevalence (per 1,000) of fetal alcohol spectrum disorders (FASD) was in the WHO European Region (19.8 per 1,000 population, 95% CI 14.1–28.0), followed by the Region of the Americas (8.8 per 1,000 population, 95% CI 6.4–13.2), the African Region (7.8 per 1,000 population, 95% CI 5.4–10.7), the Western Pacific Region (6.7 per 1,000 population, 95% CI 4.5–11.7) and the South-East Asia Region (1.4 per 1,000 population, 95% CI 0.6–5.3), and the lowest prevalence was estimated in the Eastern Mediterranean Region (0.1 per 1,000 population, 95% CI 0.1–0.5). The pooled global prevalence of FASD was estimated to be 7.7 (95% CI 4.9–11.7) per 1,000 in the general population. Data from refs. 25 , 48 .

Based on global epidemiological data, an estimated 1 in 13 women who consume alcohol while pregnant will deliver a child with FASD, resulting in the birth of ~630,000 children with FASD globally every year 48 . FASD confers lifelong disability, and an estimated >11 million individuals aged 0–18 years and 25 million aged 0–40 years have FASD 51 .

A systematic review and meta-analysis revealed that FASD prevalence is 10–40 times higher in some subpopulations than in the general population, including in children in out-of-home care and correctional, special education, and specialized clinical settings 12 (Fig.  3 ). The pooled prevalence of FASD among children in out-of-home or foster care is 25.2% in the USA and 31.2% in Chile (32-fold and 40-fold higher than the global prevalence, respectively) 12 . FASD prevalence among adults in the Canadian correctional system (14.7%) is 19-fold higher than in the general population, and the prevalence among special education populations in Chile (8.4%) is over 10-fold higher than in the general population 12 . Moreover, the prevalence of FASD is 62% among children with intellectual disabilities in care in Chile 52 , >50% in adoptees from Eastern Europe 53 , 54 and ~40% among children in Lithuanian orphanages 55 . The prevalence of FASD is 36% in one Australian youth correctional service 56 , >23% in Canadian youth correctional services 57 , >14% among USA populations in psychiatric care 58 and 19% in some remote Australian Indigenous communities 59 . The highest prevalence estimates for FAS (46–68%) are in children with developmental abnormalities in Russian orphanages 60 . The high prevalence of FASD in some subpopulations has prompted calls for targeted screening in these groups.

The pooled prevalence (per 1,000) of fetal alcohol spectrum disorders (FASD) is markedly higher in some subpopulations than in the general global population. Subpopulations with a high prevalence of FASD include children in out-of-home care, individuals involved with correctional services and those receiving special education. FAS, fetal alcohol syndrome.

Mechanisms/pathophysiology

Alcohol rapidly equilibrates between the maternal and fetal compartments and is eliminated primarily through maternal metabolism 61 . As previously mentioned, no safe level of PAE has been established 19 . Several developmentally important molecular targets of alcohol, including the L1 neural cell adhesion molecule and GABA A receptors, are disrupted at blood alcohol concentrations attained after one or two US standard drinks 62 , 63 , 64 , 65 , 66 . Hence, repeated exposure to low levels of alcohol or a single exposure at critical periods in gestation could affect development. Indeed, drinking ≤20 g of alcohol per occasion (≤1.5 US standard drinks) or ≤70 g alcohol per week (≤5 US standard drinks) was associated with mild facial dysmorphology (determined via 3D facial imaging) 67 , microstructural brain abnormalities, and externalizing behaviours such as aggression and violation of social norms 68 . The Adolescent Brain Cognitive Development (ABCD) Study, a large, prospective, longitudinal study of child and adolescent development, reported a dose-dependent association between low-level drinking during pregnancy, increased cerebral volume and regional cortical surface area, and a range of adverse cognitive, psychiatric and behavioural outcomes in children aged 9–10 years 69 . There was no inflexion point in the dose–response curves to suggest a cut-off for PAE effects, and significant effects were observed with as little as 1.1 US standard drinks per week throughout pregnancy. Increased brain volume was attributed to impairment of synaptic pruning in the preadolescent brain, consistent with research demonstrating the effect of PAE on trajectories of brain development 70 , 71 .

Genes associated with PAE

Several gene variants confer heightened risk or resilience to PAE 72 , 73 , 74 , and there is higher concordance for FAS among monozygotic than among dizygotic twins 74 . Genetic effects may be exerted through the mother and/or the fetus 72 . ADH1 (encoding alcohol dehydrogenase 1) polymorphisms, such as ADH1B*2 and ADH1B*3 , which increase alcohol metabolism and decrease blood alcohol levels, are associated with reduced risk of FASD 72 . Moreover, zebrafish with pdgfra (encoding platelet-derived growth factor receptor-α) haploinsufficiency have increased susceptibility to craniofacial malformations caused by PAE, which is mirrored in individuals with PDGFRA polymorphisms 75 . Similarly, haploinsufficiency of either Shh or Gli2 (a downstream effector of Shh ) is clinically silent in mice; however, PAE in these mice results in midline craniofacial malformations 76 . Interestingly, hypermethylation of GLI2 (which decreases GLI2 expression) was identified in genome-wide DNA methylation profiling of children with FASD 77 . Prenatal or postnatal choline supplementation improves cognition in animal models and clinical studies 78 and the effect of choline supplementation is modified by polymorphisms in SLC44A1 (encoding choline transporter-like protein 1) 79 .

Timing and quantity of PAE during gestation

The effects of PAE vary according to the quantity, frequency, duration, pattern and timing of exposure 80 . Periconceptional alcohol exposure can adversely affect fetal development and predispose to disease in later life 81 , 82 . PAE at different stages of organogenesis has distinct developmental consequences. PAE during first-trimester organogenesis may cause brain, craniofacial, skeletal and internal organ dysmorphology 80 . In mice, PAE during gastrulation (equivalent to the third week post-fertilization in humans, when an embryo transforms from a bilaminar disc to a multilayered structure comprising the three primary germ layers: ectoderm, mesoderm and endoderm) reproduces the sentinel craniofacial abnormalities of FAS: thin upper lip, smooth philtrum and short palpebral fissures 9 (Fig.  4 ). By contrast, alcohol exposure during neurulation (starting in gestational week three in humans, resulting in the folding of the neural plate to form the neural tube) produces a facial phenotype that resembles DiGeorge syndrome, a chromosomal disorder (22q11.2 deletion) associated with facial anomalies, immune dysfunction, cardiac defects and neurodevelopmental abnormalities 83 .

a , b , The facial phenotype of fetal alcohol spectrum disorders can be reproduced in a preclinical model. Comparable to the facial features of the child with fetal alcohol syndrome (FAS) (part a ), the mouse fetus exposed prenatally to alcohol shows a thin upper lip with a smooth philtrum, short palpebral fissures and a small midface (part b ). c , The normal features in a control mouse fetus (not prenatally exposed to alcohol). Part a courtesy of Sterling Clarren. Parts b and c adapted with permission from ref. 9 , AAAS.

The brain is vulnerable to PAE throughout pregnancy 84 , 85 . PAE after 8 weeks of gestation affects neurogenesis, differentiation of neural precursor cells, neuronal migration, pathfinding, synaptogenesis and axon myelination 72 , 85 , 86 but does not cause sentinel craniofacial dysmorphology or major organ defects. Thus, PAE after major organogenesis may result in a FASD phenotype with neurodevelopmental disorder but without physical alterations, making diagnosis difficult 80 . Nutritional deficiency during pregnancy may potentiate the effects of PAE on developmental outcomes, and maternal alcohol intake may further reduce the availability of developmentally important nutrients 87 .

Effects of PAE on the embryo and fetus

Brain development.

As previously mentioned, PAE can affect brain development 88 , 89 . Retrospective examination of 149 brains from individuals with PAE who died between birth and adulthood identified gross abnormalities in brain development causing microcephaly (a smaller than normal head for age and sex using population-based normative data, often associated with a smaller than normal brain (micrencephaly)) in 20.8%. This study found isolated hydrocephalus in 4.0% of individuals with PAE, corpus callosum defects in 4.0%, prenatal ischaemic lesions in 3.4%, minor subarachnoid heterotopias (the presence of normal tissue at an abnormal location, such as an ectopic cluster of neurons within the white matter, often due to abnormal neuronal migration during early brain development) in 2.7%, holoprosencephaly (whereby the embryonic forebrain fails to develop into two discrete hemispheres, often affecting midline brain and craniofacial structures) in 0.7% and lissencephaly (smoothness of the brain surface due to impaired development of cerebral gyri) in 0.7% 88 . Hence, because macroscopic neuropathology is not present in most individuals with FASD, microscopic neuropathology likely underlies many of the associated cognitive and behavioural abnormalities of this disorder. Studies in non-human primates show that first-trimester-equivalent alcohol exposure reduces brainstem and cerebellar volume and disrupts various white matter tracts, including one connecting the putamen and primary sensory cortex 90 . Third-trimester-equivalent alcohol exposure reduced hippocampal neuronal numbers in infant and juvenile Vervet monkeys 86 .

Brain structure

Relatively few macroscopic brain lesions have been identified in clinical neuroimaging studies of children with FASD 80 , 91 . Blind evaluation of clinical MRI studies by neuroradiologists identified clinically significant abnormalities in 3% of individuals with PAE or FASD and in 1% of typically developing controls 91 . Four of 61 patients with FAS had heterotopias 92 . By contrast, quantitative research imaging studies in groups of children with PAE and FASD have revealed region-specific increases or decreases in grey matter thickness, microstructural white matter abnormalities, and neuronal and glial migration defects 69 , 93 , 94 . Volume reduction is disproportionate in the cerebrum, cerebellum, caudate, putamen, basal ganglia, thalamus and hippocampus after accounting for overall reductions in brain volume 94 . Age-dependent decreases in cortical gyrification are also observed 94 , 95 , 96 and the corpus callosum can be hypoplastic, posteriorly displaced or, in rare cases, absent 94 , 97 , 98 , 99 , 100 . Moreover, studies using diffusion tensor imaging reveal reduced integrity of large white matter tracts, including in the corpus callosum, cerebellar peduncles, cingulum and longitudinal fasciculi 101 . Hypoplasia of the corpus callosum in children with FASD is associated with impaired interhemispheric transfer of information 102 .

Imaging studies have also demonstrated the effect of PAE on postnatal grey matter development 99 , 103 . Typical brain development is associated with a large increase in cortical grey matter during early childhood followed by loss of cortical grey matter during late childhood and adolescence via synaptic pruning, a process that reflects cortical plasticity 70 . By contrast, children with FASD show region-specific loss of grey matter and decreased gyrification from early childhood through adolescence 70 , 99 , 102 . This change may partly explain contradictory findings of increased or decreased grey matter volume in various studies, which sampled different brain regions during distinct developmental periods or evaluated populations with different levels of PAE 69 . A relatively small sample size is another source of variation in results among brain imaging studies 104 .

One frequently observed effect of PAE is the disruption of brain plasticity 105 . Animal models and human studies have demonstrated enduring deficits in learning and memory following PAE, associated with abnormal plasticity in hippocampal, thalamic, cortical and cerebellar circuits 105 , 106 , 107 . These deficits are associated with changes in alpha oscillations on magnetoencephalography, fractional anisotropy (a measure of white matter integrity) on diffusion tensor imaging, and functional and resting-state MRI in children with PAE 68 , 94 , 108 , 109 .

Craniofacial development

Brain and craniofacial development are mechanistically linked; therefore, brain and craniofacial abnormalities frequently co-occur 98 , 110 . For example, abnormalities of midline brain structures, such as the corpus callosum, diencephalon and septum, are associated with midline craniofacial abnormalities 98 , 103 , 110 . Craniofacial development relies on the highly choreographed migration of cranial neural crest cells and is most sensitive to PAE during the third week of gestation. Alcohol induces apoptosis of neural crest cells through oxidative injury and disruption of Sonic hedgehog (Shh) signalling 111 . Shh regulates embryonic morphogenesis and organogenesis, including the organization of cells of the central nervous system (CNS), limbs and other body parts. In animal models, diverse antioxidants and inhibitors of apoptosis mitigate the effects of alcohol on neural crest cells 112 , 113 .

Mechanisms of alcohol teratogenesis

Multiple mechanisms of alcohol-induced teratogenesis have been elucidated 9 , 80 , 114 , 115 (Fig.  5 ). Alcohol has protean effects on brain and craniofacial development in part because it is a weak drug that requires millimolar concentrations to produce even mild euphoria 116 . For example, in the USA, legal intoxication is defined as 17.4 mM or 0.08 g/dl; at these high concentrations, alcohol interacts with diverse molecules and signalling pathways that regulate development 117 .

Alcohol (ethanol) metabolism to acetaldehyde and acetic acid generates reactive oxygen species (ROS) that induce programmed cell death. During gastrulation, acetaldehyde competes with retinaldehyde for metabolism by retinaldehyde dehydrogenase 2 (RALDH2), reducing the biosynthesis of retinoic acid, a critical morphogen. Acetyl-CoA, a metabolite of acetic acid, acetylates histones and, therefore, modifies gene expression. Alcohol also alters epigenetic gene regulation through changes in DNA methylation. Moreover, alcohol disrupts neuronal–glial interactions, induces inflammatory changes in the developing brain and causes microencephaly partly by depletion of neural stem cells. Other effects of alcohol include the disruption of Shh signalling (an effect that is potentiated by cannabinoids) and disrupted neuronal migration. The effects of alcohol on the placenta contribute to intrauterine growth retardation and adverse neurodevelopmental outcomes. Modification of gut microbiota by alcohol may influence brain development through the action of circulating microbial by-products. Collectively, these actions of alcohol result in altered neural circuits and decreased neuronal plasticity. ADH, alcohol dehydrogenase; ALDH2, aldehyde dehydrogenase.

Epigenetic changes and disrupted development

Epigenetic changes are chemical modifications (methylation or acetylation) to DNA and surrounding histones that influence gene expression and often occur in response to environmental exposures 118 , 119 . Normal development depends on numerous epigenetic changes in embryonic stem cells that facilitate their transition to fully differentiated and functional cell lineages such as neurons, muscle and fat cells 120 . Alcohol can disrupt development by inducing DNA methylation and histone acetylation in gene clusters and altering gene expression 121 . Epigenetic alterations resulting from PAE have been observed in animal models and humans, and these changes may be lifelong and inherited by future generations 118 , 122 , 123 , 124 . A pattern of DNA methylation in buccal epithelial cells was reasonably accurate (positive predictive value 90%; negative predictive value 78.6%) in discriminating children with FASD from typically developing controls or children with autism spectrum disorders 125 . Large replication studies in different populations are required before this approach might be considered for diagnostic purposes.

Brain injury

Exposure of astrocytes to alcohol and metabolism of alcohol by cytochrome P450 2E1 result in the production of damaging reactive oxygen species 84 , 126 . Alcohol is metabolized to acetaldehyde, a toxin that causes DNA damage, epigenetic gene regulation, mitochondrial and proteosome dysfunction, and altered cellular metabolism 127 , 128 , 129 . Metabolism of acetaldehyde to acetate and then to acetyl-CoA modifies gene expression in the brain via increased histone acetylation 121 (Fig.  5 ).

Disruption of morphogens and growth factors

Retinoic acid is a critical morphogen (a signalling molecule that alters cellular responses to modulate patterns of tissue development), and its deficiency causes craniofacial defects similar to those of FASD 127 , 130 . Retinol is oxidized to retinaldehyde, which is subsequently oxidized by retinaldehyde dehydrogenase 2 (RALDH2) to retinoic acid (Fig.  5 ). During gastrulation, RALDH2 is the predominant enzyme for acetaldehyde metabolism. Therefore, acetaldehyde and retinaldehyde compete for RALDH2, reducing the synthesis of retinoic acid and inducing a state of retinoic acid deficiency, thereby promoting craniofacial defects associated with PAE 127 , 130 .

Another critical morphogen, Shh, is a downstream target of retinoic acid 72 , 130 . Genetic abnormalities of the Shh pathway cause holoprosencephaly syndrome, which is associated with abnormal midline craniofacial and brain development similar to that of FASD 72 , 76 . Alcohol exposure in chick embryos decreases Shh expression and induces craniofacial dysmorphology and cranial neural crest cell death; viral vector-mediated expression of Shh rescues these effects 111 . Alcohol exposure during neurulation of the mouse rostroventral neural tube disrupts the function of cilia, which transduce Shh signals by modulating the expression of genes that regulate ciliogenesis, protein trafficking and stabilization of primary cilia 131 , 132 . The associated dysmorphology in zebrafish can be mitigated by activating downstream elements in the Shh signalling pathway 133 . Alcohol also decreases cellular stores of cholesterol, thereby reducing the covalent binding of cholesterol to Shh (which is necessary for Shh secretion and function) 72 , 134 . These findings suggest that alcohol causes a transient ciliopathy, secondarily disrupting Shh signalling within cilia and producing craniofacial and brain dysmorphology 131 .

Disruption of neuronal and glial migration

PAE is associated with macroscopic and microscopic evidence of impaired neuronal and glial migration, including heterotopias (collections of aberrantly migrated neurons). Heterotopias are associated with seizures, and seizures or abnormal EEG results are reported in up to 25% of individuals with FASD 135 . The L1 neural cell adhesion molecule regulates neuronal migration, axon fasciculation and pathfinding in the developing brain 136 . Mutations in L1CAM (which encodes L1) cause neurodevelopmental abnormalities such as those observed in FASD, including hydrocephalus, hypoplasia or agenesis of the corpus callosum, and dysplasia of the anterior cerebellar vermis 64 . Alcohol inhibits L1-mediated cell adhesion by binding to specific amino acids at a functionally important domain in the extracellular portion of L1 (ref. 137 ). The sensitivity of L1 to alcohol is regulated by phosphorylation, which promotes L1 association with the cytoskeleton 62 , 138 . Importantly, molecules that block alcohol inhibition of L1 adhesion prevent the teratogenic effects of alcohol in mouse embryos 62 , 139 .

GABAergic interneurons comprise the principal inhibitory network of the brain. Alcohol enhances GABA A receptor-mediated depolarization of migrating GABAergic interneurons through activation of L-type voltage-gated calcium channels, thereby accelerating tangential migration 63 . Dysfunction of GABAergic interneurons may impair inhibitory control of brain networks. In mice, PAE during corticogenesis also disrupts radial migration and pyramidal cell development in the somatosensory cortex, which could be linked to decreased tactile sensitivity during adolescence 140 .

Effects on neural stem cells

Effects of PAE on neural stem cells (NSCs) may contribute to reduced brain volume in individuals with FASD. Alcohol causes cell death in differentiated neural cells but not in NSCs; rather, PAE depletes NSCs by blocking their self-renewal and accelerating their transition into more mature neural progenitors and differentiation into astroglial lineages 141 . PAE also selectively upregulates gene expression for the calcium-activated potassium channel Kcnn2 in neural progenitor cells from the motor cortex, and Kcnn2 blockers in adult mice reduced motor learning deficits 142 . Alcohol may trigger the maturation of NSCs by increasing the release of selected microRNAs (miRNAs) from extracellular vesicles in NSCs and activating certain pseudogenes that encode non-protein-coding RNAs 141 , 143 . Proteomic analysis revealed selective enrichment of extracellular vesicles for RNA-binding and chaperone proteins in alcohol-exposed NSCs 144 .

Disruption of neuronal–glial interactions

Brain growth and development are dependent on neuronal–glial interactions 84 , 85 . PAE decreases the proliferation of radial glial cells partly by decreasing Notch1 and fibroblast growth factor 2 receptor signalling 145 . This altered signalling reduces the density and fasciculation of radial glial fibres, which serve as a scaffold for migrating neurons 85 , 145 . PAE perturbs the maturation of oligodendroglia in human fetal brains, increasing the expression of markers of early oligodendroglia progenitors (Oct4 and Nanog) and decreasing the expression of markers of mature oligodendroglia (Olig1, Olig2 and myelin basic protein) 146 . Alcohol also increases apoptosis to a greater extent in oligodendroglia than in neurons 146 , 147 . As myelination is mediated by oligodendroglia, apoptosis of these cells might partly account for the effects of PAE on white matter integrity. The associated upregulation of oligodendroglia-derived chemokines (CXCL1/GRO, IL-8, GCP2/CXCL6, ENA78 and MCP1) could also affect neuronal survival 146 . Astroglial apoptosis is mediated by acetaldehyde toxicity, reactive oxygen species, reductions in the antioxidant glutathione and inflammatory signalling 85 .

Neuroinflammation

PAE activates an inflammatory response in the developing nervous system. Alcohol stimulates the production of reactive oxygen species in microglia and astrocytes, leading to neuronal apoptosis 84 . Moreover, alcohol stimulates the production of pro-inflammatory cytokines (such as IL-1β and TNF) and chemokines (such as CCL2 and CXCL1) through enduring epigenetic modifications that sustain a chronic neuroinflammatory response 119 (Fig.  5 ). Unique networks of pro-inflammatory cytokines in serum from women in the second trimester of pregnancy are markers of PAE and adverse neurodevelopmental outcomes 148 . The persistence of pro-inflammatory cytokines in childhood could predispose to autoimmune and inflammatory conditions later in life 149 . Similarly, PAE may hypersensitize microglia to increased inflammatory signalling, leading to an enduring, heightened neuroinflammatory response 84 .

Gut microbiota alterations

PAE may cause enduring changes in the gut microbiota 150 , and there is increasing recognition of the interplay between gut microbes and nervous system development and function. In a mouse model of PAE, gut microbial metabolites were detected in maternal plasma, fetal liver and fetal brain 151 . Further research is required to determine how effects of PAE on the gut microbiota influence development and later health.

Placental effects

Not all developmental effects of PAE result from the direct actions of alcohol on the developing nervous system. A retrospective autopsy study reported placental abnormalities in 68% of individuals with PAE or FASD 88 . PAE in humans decreases placental weight, epigenetic marks, vasculature and metabolism 81 . PAE during the first 60 of 168 days of gestation in rhesus macaques caused diminished placental perfusion and ischaemic placental injury from middle to late gestation 152 . RNA sequencing analysis revealed activation of inflammatory and extracellular matrix responses. Rats with PAE demonstrate reduced nitric oxide-mediated uterine artery relaxation, potentially contributing to dysregulation of uterine blood flow and intrauterine growth retardation 153 . miRNA act by silencing RNA and modifying post-transcriptional regulation of gene expression. A cluster of 11 extracellular miRNA from serum of women in the second trimester of pregnancy was a marker of PAE and predicted adverse neurodevelopmental outcomes in Ukrainian and South African populations 154 , 155 . Injection of the same 11 miRNAs into pregnant mice decreased placental and fetal growth, suggesting that they mediate the adverse outcomes of PAE 156 .

Synergistic effects of alcohol and other substances

PAE is often associated with prenatal exposure to other drugs. Among 174 individuals with PAE, almost all had prenatal nicotine exposure 88 . Nicotine and alcohol synergistically decrease birthweight and increase the risk of sudden infant death syndrome 157 . The legalization of cannabis has led to increases in the combined use of cannabinoids and alcohol during pregnancy 158 . Alcohol and cannabinoids synergistically increase the frequency of ocular defects in mice by disrupting separate elements in the Shh signalling pathway 132 . PAE and opioids each affect neurodevelopment, raising the possibility of additive or synergistic effects 159 . Alcohol also disrupts the developing blood–brain barrier, exposing the developing CNS to drugs and toxins that are normally excluded 160 .

Diagnosis, screening and prevention

Diagnosis of fasd, principles of diagnosis.

Diagnosis of FASD requires assessment of PAE, neurodevelopmental function and physical features, including facial features (Fig.  6 ). Timely, accurate diagnosis of FASD is crucial to enable early intervention and improve outcomes 161 , but there is no diagnostic test, biomarker or specific neurodevelopmental phenotype for FASD. Ideally, assessment and diagnosis should be conducted by a multidisciplinary team (MDT) comprising paediatricians, neuropsychologists, speech pathologists, occupational therapists, physiotherapists and social workers, with access to psychiatrists and geneticists/dysmorphologists. However, this approach is expensive, time consuming and unavailable to many children worldwide. Often, children present first to family physicians, paediatricians and psychologists who lack sufficient expertise to confidently diagnose FASD. Thus, education and training are urgently needed to increase the capacity for recognition of FASD outside specialist FASD assessment services 51 , 162 and to address its underdiagnosis and misdiagnosis 163 , 164 .

Fetal alcohol syndrome has three characteristic (sentinel) facial features: thin upper lip (with absent cupid bow), smooth philtrum (with absence of the normal midline vertical groove and lateral ridges extending from the base of the nose to the vermilion border of the upper lip) and short palpebral fissures (the space between the medial and lateral canthus of the open eye). Image created by Ria Chockalingam using an image from Generated Photos and modified with Adobe Photoshop.

Approaches to the diagnosis of FASD

The most commonly used diagnostic systems for FASD are the Collaboration on FASD Prevalence (CoFASP) Clinical Diagnostic Guidelines 10 , the University of Washington 4-Digit Diagnostic Code 165 , 166 and the Canadian Guidelines 167 (Table  1 ). The Canadian Guidelines have been adapted for use in Australia 168 and the UK 169 and are also used in New Zealand 170 . Guidelines have also been recommended by the US Centers for Disease Control and Prevention 171 , the State Agency for Prevention of Alcohol-Related Problems (PARPA) in Poland 172 , and The German Federal Ministry of Health 173 .

All diagnostic systems recommend evaluating PAE, facial and non-facial dysmorphology, and CNS structure and function using an MDT approach. Although all these systems recommend assessing otherwise unexplained prenatal and postnatal growth restriction, the Canadian and derivative guidelines exclude growth as a diagnostic criterion. The diagnostic systems differ in their definitions of PAE, thresholds for individual diagnostic elements, required combination of elements to confirm an FASD diagnosis and diagnostic classifications.

Diagnosis of FASD can be challenging. Confirmation of PAE by biological mothers during a diagnostic assessment of children with suspected FASD is often difficult: the topic is sensitive and recall bias is possible 174 . Additionally, many children live in foster or adoptive care, and obstetric records often lack details about PAE 80 . In these situations, clinicians should seek firsthand witness reports and child protection, justice and medical records. A standardized tool 175 , 176 , 177 should be used, when possible, to record the pattern of alcohol intake, either at an interview with the biological mother or using witness reports or records. A challenge in evaluating facial dysmorphology is the unavailability of suitable lip-philtrum guides and standards for palpebral fissure length (PFL) for many racial and ethnic groups, including Indigenous Australians 178 . PFL is the distance between the endocanthion and exocanthion of the eye (the inner (nasal) and outer points, respectively, where the upper and lower eyelids meet) and may be shortened following PAE. Because some domains of cognitive function cannot be evaluated in infants and young children, confirmation of brain dysfunction in this population may be based on global developmental delay, established using a validated tool 10 , 167 . FASD are diagnosed with increasing confidence in children aged 6 years and older, who are more cooperative in physical examinations, and in whom facial dysmorphology and neurocognitive function can be assessed with greater reliability using digital photography and standardized psychometric tests.

In the absence of a ‘gold standard’ for diagnosis of FASD, no diagnostic system may be considered superior. Each system has advantages and disadvantages, including its use in clinical and community settings and the sensitivity and specificity of diagnostic criteria. Diagnosis using these systems shows incomplete agreement 179 , 180 , 181 , confirming the need for a unified approach internationally (Table  1 and Supplementary Boxes  1 and 2 ).

A clinical diagnosis of FASD requires recognition of neurodevelopmental disabilities and a reproducible pattern of minor malformations (dysmorphic features), none of which are pathognomonic, and many of which overlap with other teratogenic or genetic disorders (phenocopies). Thus, a diagnosis of FASD is a diagnosis of exclusion that is made after considering and excluding other causes for the phenotype 10 , 167 . For example, prenatal exposure to teratogens, such as toluene, anticonvulsants or phenylalanine (when the mother has phenylketonuria), can result in dysmorphic features also observed in FASD 10 , 182 , 183 . Additionally, postnatal exposures (such as adverse childhood experiences (ACE)) can contribute to neurodevelopmental impairment, comorbidities (Box  1 ) and adverse ‘secondary’ outcomes (Box  2 ). Genetic conditions with dysmorphic features similar to FASD include Aarskog syndrome, blepharophimosis, ptosis, epicanthus inversus syndrome, CHARGE syndrome, de Lange syndrome, 22q11.2 deletion, Dubowitz syndrome, inverted duplication 15q, Noonan syndrome, Smith–Lemli–Opitz syndrome and Williams syndrome. Patients with intellectual disability without a recognizable pattern of anomalies may also share some dysmorphic features with FASD 10 , 182 . Thus, before establishing a diagnosis of FASD, it is important to ask whether the family history suggests a genetic disorder, whether other teratogenic exposures occurred during pregnancy and whether the patient has features not previously described in FASD. If so, referral to a clinical geneticist/dysmorphologist for evaluation is recommended. When indicated, genetic testing should include chromosome microarray analysis 184 , 185 and exclusion of Fragile X syndrome 186 as a minimum, and whole-exome sequencing should be performed if other genetic pathologies due to point mutations are suspected 10 , 187 . When PAE is confirmed and/or the physical and neurodevelopmental examinations are supportive, the diagnosis can be made by a paediatrician or other health professional familiar with FASD.

Neurobehavioural impairment accounts for the major functional disabilities associated with FASD. Although the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-5) 188 criteria for intellectual disability are not always met in patients with FASD, cognitive impairment is often identified and can affect multiple domains, including executive function, memory, mathematical and other academic skills, attention and visuospatial processing 80 , 189 . Poor social skills, inattention and impaired impulse control can adversely affect school and work performance and independent living.

Although no specific constellation of neurobehavioural deficits have been identified in FASD, some groups have attempted to characterize clusters of impairment associated with PAE 190 , 191 . One set of criteria, Neurodevelopmental Disorder associated with PAE, has been proposed as a condition for further study in the DSM-5 (ref. 188 ); it requires deficits in cognition, behaviour and social adaptation. The ICD-11, published in 2022, lists several ‘toxic or drug-related embryofetopathies’ (code LD2F.0) including ‘fetal alcohol syndrome’ (code LD2F.00) 192 . The confounding or potentiating influence of ACE presents a major challenge in identifying a specific neurobehavioural profile 193 .

Box 1 Common comorbidities in patients with fetal alcohol spectrum disorders

More than 400 comorbid conditions have been identified in individuals with fetal alcohol spectrum disorders, which span 18 of the 22 chapters of the ICD-10 (ref. 13 ), the most prevalent coming from the groups of:

Congenital malformations, deformations and chromosomal abnormalities (Chapter XVII) and Mental and behavioural disorders (Chapter V). Shown below are selected comorbid conditions (with codes) from Chapters V and XVII and diseases of the eye (Chapter VII) and ear (Chapter VIII). For more detailed information, see ref. 13 .

Chapter XVII. Congenital malformations, deformations and chromosomal abnormalities

Q02 Microcephaly

Q03 Congenital hydrocephalus

Q04.0 Congenital malformations of corpus callosum

Q04.3 Other reduction deformities of brain

Q04.6 Congenital cerebral cysts

Q04.8 Other specified congenital malformations of brain

Q04.9 Congenital malformation of brain, unspecified

Q05 Spina bifida

Q06.8 Other specified congenital malformations of spinal cord

Chapter V. Mental and behavioural disorders

F10.2 Mental and behavioural disorders due to use of alcohol, dependence syndrome

F19.2 Mental and behavioural disorders due to the use of multiple drugs and use of other psychoactive substances, dependence syndrome

F41.1/F33.8 Anxiety/depression

F80.1 Expressive language disorder

F80.2 Receptive language disorder

F81.9 Developmental disorder of scholastic skills, unspecified

F89 Unspecified disorder of psychological development

F90.0 Disturbance of activity and attention

F91 Conduct disorder

G40 Epilepsy/seizure disorder

Chapter VII. Diseases of the eye

H47.0 Disorders of optic nerve

H52.6 Refractive errors

H54 Visual impairment

Q10.0 Congenital ptosis

Q10.3 Other congenital malformations of eyelid

Q10.6 Other congenital malformations of lacrimal apparatus

Q11.2 Microphthalmos

Q12.0 Congenital cataract

Chapter VIII. Diseases of the ear

H65.0 Acute serous otitis media

H65.2 Chronic serous otitis media

H90.8 Mixed conductive and sensorineural hearing loss, unspecified

Box 2 Challenges for adolescents and adults with fetal alcohol spectrum disorders

Involvement in child welfare services (75%) 309

Disrupted school experiences due to learning and/or behavioural problems (61%) 267

Interaction with the justice system (30% 309 to 60% 267 )

Confinement (detention, prison, or psychiatric or alcohol/drug inpatient setting; 50%) 267

Substance use disorder: alcohol and other drugs (50%) 309

Inappropriate sexual behaviour (49%) 236 , 310

Increased risk of metabolic abnormalities (includes type 2 diabetes, low high-density lipoprotein, high triglycerides, and female-specific overweight and obesity) 311

Difficulties with independent living and trouble gaining and retaining employment (80%) 267

Mean life expectancy (34 years; 95% CI 31–37 years) is considerably lower than in the general population 275 ; leading causes of death are ‘external causes’ (44%), including suicide (15%), accidents (14%), poisoning by illegal drugs or alcohol (7%) and other external causes (7%)

Screening for alcohol use in pregnancy

Early detection of alcohol use during pregnancy can lead to decreased consumption, abstinence or decreased risk of alcohol use in subsequent pregnancies 22 , 194 . The early identification of alcohol use facilitates education about the harms of PAE, delivery of timely, office-based brief interventions, and referral to substance use treatment services if required. Reducing the high prevalence of FASD requires large-scale, population-based screening programmes to ensure that every pregnant woman is asked about alcohol use, with special attention to populations at high risk 22 , 195 , 196 (Table  2 ).

Screening for alcohol use during pregnancy is underused globally 197 , 198 . Barriers to screening include lack of public-health guidelines 199 or screening mandates, insufficient clinician training 200 , 201 , 202 , 203 , competing demands on clinician time, the cost of completing validated alcohol use screening questionnaires 204 , 205 , 206 , and the unavailability of clinically reliable biological markers for PAE. Even a single, clinician-directed question about alcohol use may reduce PAE 207 , 208 ; however, successful screening requires that practitioners understand the importance of preventing PAE and providing non-judgmental screening and brief interventions 196 . Preliminary evidence suggests that web-based or app-based mobile health interventions may mitigate patient stigma and reluctance to report alcohol use and might circumvent barriers related to clinician time constraints, training and motivation 209 . Similarly, mobile health approaches may reduce alcohol and substance use in the preconception, prenatal, and postnatal periods 209 and improve access to interventions for families in rural and remote settings. Empathic, compassionate support of abstinence during pregnancy may improve opportunities for treatment of substance use disorders 22 , 47 , 196 , 202 . Screening for alcohol and substance use should be repeated throughout pregnancy and equally across populations to avoid stigmatizing marginalized populations with selective screening 22 , 196 , 210 , 211 . People who screen positive should be directed to a well-developed management pathway for clinical care.

Prevention (Fig.  7 ) and treatment of alcohol and substance use disorders in pregnancy are central to the 2015 United Nations Sustainable Development Goals (SDG 3.5) 212 . The WHO recommends universal screening and intervention for alcohol use in pregnancy as a primary prevention strategy for FASD 22 , 213 . Prevention programmes should be evidence based and evaluated following implementation. A wide range of approaches has been deployed, including public awareness strategies, preconception interventions (such as preconception clinics and school-based FASD education), holistic support of women with substance use disorders, and postpartum support for new mothers and babies 214 , 215 . These approaches show promise in increasing awareness of FASD and decreasing alcohol use during pregnancy 216 ; however, the quality of supporting evidence is highly variable. Any primary prevention strategy must be underpinned by evidence-based policy and legislation intended to minimize harms from alcohol, including increased alcohol pricing and taxation, restrictions on advertising and promotion of alcohol, and restricted access to alcohol such as by limiting opening hours and the density of liquor outlets 217 . Public-health authorities agree that the alcohol industry should have no involvement in the development of public-health policies owing to their inherent conflict of interest 218 , 219 . The framework in Fig.  7 illustrates one approach that could be linked to national policy to address diverse aspects of population-based prevention of FASD.

A hierarchy of strategies can be used to prevent fetal alcohol spectrum disorder (FASD), ranging from awareness campaigns for the whole population to health, educational and social support for women and children. The strategies are placed in the context of cultural, political and environmental factors that influence access to, use of and attitudes towards alcohol use in pregnant women. SES, socioeconomic status.

Level 1: raising public awareness through campaigns and other broad strategies

Public-health initiatives that promote and support women’s health, in general, may raise awareness about PAE/FASD. More specific measures include warning signs on alcohol products, pamphlets and public education programmes that encourage healthy, alcohol-free pregnancies 220 , 221 . However, evidence in support of these campaigns is preliminary 216 . Moreover, campaigns that use triggering imagery or blaming/shaming language (such as ‘FASD is 100% preventable’) can stigmatize and isolate pregnant women who use alcohol, particularly when paired with judgmental interventions 196 . Reframing alcohol use in pregnancy as a shared responsibility of women, partners, prenatal health-care providers, treatment programmes for substance use disorder, families, community and government may be helpful 222 .

Level 2: brief counselling with women and girls of reproductive age

Discussing alcohol use and its associated risks with women of childbearing age during preconception conversations about reproductive health is effective in preventing PAE and FASD 215 , primarily by improving contraception use 207 . Screening, Brief Intervention and Referral to Treatment (S-BIRT) for non-pregnant adolescent and adult women reduces the risk of PAE 207 , particularly following multi-session interventions 223 . Preliminary studies suggest that such interventions are also beneficial for Indigenous communities 224 , 225 .

Level 3: specialized prenatal support

Treatment for alcohol use during pregnancy may prevent ongoing PAE and decrease adverse infant outcomes 226 . The combination of case management by a social worker or nurse (including problem identification and preparation, implementation and monitoring of a health-care plan) and motivational interviewing (an evidence-based approach to facilitating behaviour change) reduce drinking by pregnant women at high risk 194 . Moreover, specialized, intensive home-visiting interventions for pregnant women at high risk improve maternal and child outcomes and are cost-effective in preventing new cases of FASD 227 , 228 . Improving maternal nutrition and reducing smoking and family violence may also improve child outcomes in current and future pregnancies 227 , 229 , 230 .

Level 4: specialized postnatal support

In the postpartum period, home-visiting of women at high risk by health professionals or lay supporters improves child outcomes and reduces the risk of PAE in future pregnancies 227 , 231 , 232 . Application of a FASD prevention framework requires consideration of local policy and practices. Best practice programmes support the needs of both the mother and child, recognizing the connections between women’s alcohol use, parenting, family influences and child development. Central to the effective implementation of prevention strategies is the establishment of strong cross-cultural and community partnerships and the embrace of cultural knowledge systems and leadership 233 . Mitigating stigma is vital while addressing the structural and systemic factors that promote prenatal alcohol consumption 35 .

Principles of management of FASD

The complex pathophysiology of FASD (Boxes  1 and  2 ) emphasizes the need for thorough, individualized assessment and treatment. Treatment plans should be culturally appropriate, consider the family and community context, and be developed in partnership with families and individuals with lived experience of FASD 234 , 235 .

Therapeutic approaches must be tailored to individual strengths and needs. For example, an individual who has experienced trauma but has normal intelligence and social and emotional skills requires a trauma-informed, emotion-focused approach. By contrast, an individual with cognitive deficits and poor social and emotional skills may require a more directed, psycho-educational approach or environmental modifications to support and prevent secondary outcomes of FASD such as poor academic performance or inability to obtain/maintain employment 236 .

Management involves multiple service providers and changing interventions across the lifespan. Treatment comprises interventions to anticipate the delivery of a newborn with PAE, prevention of exposure to ACE, home-visiting by a public-health nurse, referral to infant developmental services, vision and hearing screening, preschool speech and language therapy, school-based support for learning disorders, occupational and physical therapy, behavioural and psychological interventions, pharmacotherapy, vocational support, and support for independent living in adolescence and adulthood. Specialized medical or surgical interventions may be required for congenital anomalies and accompanying comorbidities. There remains limited evidence from high-quality trials to support specific interventions for FASD 237 , 238 .

Behaviour support

Several large-scale randomized controlled trials (RCTs) support specific developmental and psychological interventions for FASD in children but few high-quality studies have been conducted in adolescents and adults 237 .

Positive behaviour support 239 is supported by positive results from RCTs and underpins three interventions for FASD: GoFAR 240 , the Math Interactive Learning Experience (MILE) 241 and the Families Moving Forward programme 242 . Positive behaviour support strengthens skills that enhance success and satisfaction in social, academic, work and community settings while proactively preventing problem behaviours; maintaining family involvement is an important element 16 . Where available, these specialized programmes oblige therapists to prioritize treatment for individuals most likely to benefit. The GoFAR intervention (FAR is an acronym for Focus and plan, Act, and Reflect) promotes self-regulation and adaptive function using direct instruction, practice and feedback, and strategies for emotional and behavioural self-regulation 243 . Interventions such as GoFAR, which involve the child and parents in the context of real-life adaptive behavioural problems, improve daily living skills and attention 243 . The MILE intervention provides individualized mathematical instruction through interactive learning and environmental modifications and improves math knowledge and parent report of child behaviour problems 241 , 244 , 245 . Families Moving Forward helps parents reframe their child’s behaviour within a neurodevelopmental paradigm. Adaptation of this approach to an app-based platform may reduce barriers to care 242 .

Self-regulation and executive function

Most children with FASD have significant problems with executive function and self-regulation 189 . The ALERT programme, a 12-week manualized approach using sensory integration and cognitive behavioural strategies, aims to help children regulate their behaviour and address sensory challenges 246 in a home environment 247 , 248 but is less effective when delivered in schools 249 . ALERT programme training is available online but requires adaptation to the family and community context 249 .

Social skills

Interventions to improve social connections in children with FASD include the Children’s Friendship Training (CFT) 250 and the Families on Track programme 251 . CFT involves 12 weeks of social and friendship skill training for children with FASD and their parents; it improves social skills and decreases problem behaviours in children with FASD 250 . Similarly, the Families on Track programme increases emotional regulation and self-esteem and decreases anxiety and disruptive behaviour 251 . However, interventions such as CFT and Families on Track are not widely available, and barriers to their use include the need to adapt to cultural context 252 . International partnerships and sharing of expertise may increase accessibility to these interventions 252 .

Pharmacological interventions

Pharmacological interventions for FASD are widely used and include medications, such as cognitive enhancers, to treat core impairments and medications to treat comorbidities, including ADHD, anxiety, and arousal or sleep disorders 253 . Large RCTs evaluating their effectiveness in FASD are urgently needed.

Children with FASD and ADHD have a different pattern of neurocognitive and behavioural abnormalities than children with ADHD alone 254 , suggesting the need for a tailored therapeutic approach. Expert consensus approaches for the management of ADHD in FASD have been developed. Recommendations in the UK suggest the use of a dexamphetamine-based medication (rather than a methylphenidate-based medicine) for first-line treatment of ADHD in children and adults with FASD; however, research is needed to understand the basis of treatment responses 255 . Guanfacine XL or similar medications can be used in individuals with comorbidities such as autism spectrum disorders 255 . Algorithms have also been developed in Canada for the use of psychotropic medications in FASD 256 . Although based on clinical consensus, these strategies form the basis for future research 256 .

Preclinical trials suggest that choline supplements improve cognitive deficits following PAE but clinical data are limited 257 . A small, placebo-controlled RCT demonstrated that children who received choline supplementation had higher non-verbal intelligence and visual-spatial skills, better working memory and verbal memory, and fewer behavioural symptoms of ADHD at 4-year follow-up than children who received placebo 258 . Despite these positive results, choline supplementation is not routinely recommended for children with FASD due to a lack of strong evidence for its effectiveness.

The role of exposure to adversity

A relationship between PAE and ACE is well established, and both may influence the life course in FASD 193 . Comprehensive neuropsychological assessment and MRI show that PAE accounts for the largest proportion of the variance in regional brain size and brain function in children with both exposures 259 . Furthermore, PAE imparts more risk for adverse outcomes than ACE in individuals with PAE in adoptive care 260 . However, adversity does affect the developmental trajectory and ACE are associated with maladaptive problems in children with FASD 261 . For example, school-age children with FASD and ACE are particularly vulnerable to language and social communication deficits 262 , which are hypothesized to result from the additive effect of prenatal and postnatal environmental exposures. This emphasizes the need for an individualized approach to treatment for individuals with life trauma and FASD.

Attempts have been made to understand the individual and combined effects of PAE and postnatal events on individual behaviours in FASD 263 . One model of complex trauma (Supplementary Fig.  1 ) displays neurodevelopmental variation as a complex interplay between prenatal and postnatal events and improves understanding of their interactions and association with outcomes. Child maltreatment viewed through a neurodevelopmental lens highlights the benefit of a sequential model of therapeutics rather than a focus on specific therapeutic techniques 264 .

Supplementary Fig.  1 highlights how vulnerabilities may present, whereas Supplementary Fig.  2 identifies methods to manage the same vulnerabilities based on understanding the individual and using anticipatory interventions to support development. Box  3 contains some useful resources on FASD for professionals and parents.

Box 3 Resources on alcohol use in pregnancy and fetal alcohol spectrum disorders

Australian guidelines to reduce health risks from drinking alcohol

Canada No. 245 — Alcohol Use and Pregnancy Consensus Clinical Guidelines 312

Centers for Disease Control and Prevention

Collaborative Initiative on Fetal Alcohol Spectrum Disorders (CIFASD)

Fetal Alcohol Spectrum Disorders (FASD) — American Academy of Pediatrics

FASD Hub Australia

FASD United

FASD — Care Action Network

Learning with FASD

National Organization for FASD Australia (NOFASD)

National Institute for Health and Care Excellence UK. Quality Standard QS204. FASD

National Institute on Alcohol Abuse and Alcoholism. Fetal Alcohol Exposure

Pan American Health Organization. Assessment of Fetal Alcohol Spectrum Disorders (2020) 313

The European FASD Alliance

WHO. Guidelines for identification and management of substance use and substance use disorders in pregnancy (2014) 22

Quality of life

Few published studies address QOL in individuals with FASD. One systematic review and meta-analysis identified more than 400 comorbid conditions among individuals with FASD, spanning 18 of 22 chapters of the ICD-10 (ref. 13 ). The most prevalent conditions were within the chapters of “Congenital malformations, deformations, and chromosomal abnormalities” (Chapters Q00–Q99; 43%) and “Mental and behavioural disorders” (Chapters F00–F99; 18%). Comorbid conditions with the highest pooled prevalence (50–91%) included abnormal functional studies of the peripheral nervous system and special senses, conduct disorder, receptive and expressive language disorders, and chronic serous otitis media 13 . Other studies report a high prevalence of vision and hearing problems among people with FASD 265 , 266 . All of these comorbid conditions affect the function and QOL of individuals with FASD and their families (Box  1 ).

Neurodevelopmental impairments may lead to lifelong ‘secondary’ disabilities, including academic failure, substance abuse, mental health problems, contact with law enforcement and inability to live independently or obtain/maintain employment 267 (Box  2 ). These conditions adversely affect QOL and require health, remedial education and correctional, mental health, social, child protection, developmental, vocational and disability services across the lifespan 17 , 268 , 269 . Lack of societal understanding of FASD is a barrier to addressing these secondary disabilities 16 , 270 .

A shift from a deficit-based to a strength-based management approach emphasizes the need to harness the abilities of individuals with FASD to improve their QOL and well-being. A review of 19 studies exploring the lived experience of people with FASD highlighted their strengths, including self-awareness, receptiveness to support, capacity for human connection, perseverance and hope for the future 271 . The lack of accessible, FASD-informed services perpetuates a deficit-based model.

Longitudinal cohort studies of FASD consistently show that adverse outcomes are more likely where support services are lacking. These studies are limited by selection bias and are based on cohorts with severe deficits rather than population-based cohorts receiving adequate support 267 , 270 . Nevertheless, they suggest the potential to modify developmental trajectories by addressing postnatal environmental exposures and opportunities. To address QOL, future studies should better articulate outcomes of interest for individuals and families living with FASD 272 .

FASD is associated with an increased risk of premature death of affected individuals, their siblings and mothers 273 , 274 . One study reported a mean age at death of 34 years for individuals with FASD 275 . Individuals with FASD have nearly fivefold higher mortality risk than people of the same age and year of death, and nearly half of all deaths occur in young adults 276 . In childhood, the leading causes of death in FASD are congenital malformations of the CNS, heart or kidney, sepsis, cancer, and sudden infant death syndrome, and more than half of deaths (54%) occur in the first year of life 277 . In the USA, >29% of adolescent males with FASD reported a serious suicide attempt, which is >19-fold higher than the national average 236 , 278 .

Among children and adolescents with FASD, the mortality rate of siblings with and without FASD is 114 per 1,000, which is approximately sixfold higher than among age-matched controls 273 . Furthermore, mothers of children with FASD have a 44.8-fold increased mortality risk compared with mothers of children without FASD 274 .

Caregiver burden

The complexity of parenting a child with FASD increases across adolescence and young adulthood. Caregivers of children with FASD experience increased burden, levels of stress and feelings of isolation 279 , 280 . The lifelong challenges and unmet needs of caregivers negatively affect family functioning and QOL 281 .

Early recognition of FASD and early emphasis on the prevention of secondary disabilities may decrease demands on families. Moreover, a diagnosis of FASD may indicate the need for specific interventions and parenting supports such as respite care, peer-support groups, treatment for parental alcohol misuse and education of other professionals who care for people with FASD.

FASD are the most common preventable cause of neurodevelopmental impairment and congenital anomalies 164 . These disorders are the legacy of readily available alcohol and societal tolerance to its widespread use, including during pregnancy. FASD affect all strata of society, with enormous personal, social and economic effects across the lifespan.

Diagnostic challenges

The greatest global challenges in the clinical management of FASD are the paucity of resources for diagnosis and treatment and the large number of affected individuals 163 . A substantial increase in resources is required, both for centres of expertise with MDTs and to build diagnostic capacity among non-specialist health services. However, this alone will not bridge the gap in services for children and adults, and a paradigm shift is needed. This might include recognition of the important role of primary care providers and use of new technologies such as app-based screening, diagnostic and treatment tools. Telehealth services will reduce the need for face-to-face care 282 and tele-education could build clinician awareness and skills, especially in rural and remote areas 283 . However, in many low-income and middle-income countries, this technology is not widely available.

Without a definitive diagnostic test, a clinical diagnosis of FASD must be made. Diagnosis is facilitated by identification of PAE in association with neurodevelopmental impairment, with or without specific craniofacial dysmorphology, and exclusion of alternative diagnoses. Many clinicians fail to document alcohol use in pregnancy or PAE in children, highlighting the need for enhanced training, standardized tools to document PAE and, especially, routine screening for alcohol use before and during pregnancy. Biomarkers for PAE are urgently needed because many children with FASD live in out-of-home care and reliable PAE histories are frequently unavailable. Although biomarkers for PAE (such as fatty acid ethyl esters, ethyl glucuronide and phosphatidylethanol) are identifiable in maternal hair, blood and meconium, their clinical use is limited, and testing may be costly or unavailable 284 . Identification of miRNAs from women in the second trimester and epigenetic signatures in placental and infant tissue hold promise as biomarkers for PAE and hence for risk of abnormal neurodevelopment 154 , 155 , 156 , 187 ; however, further research is required before their use becomes routine in clinical practice 81 , 125 .

Accessible e-health technologies to facilitate the diagnosis of FASD are under development. For example, 3D facial imaging may facilitate diagnosis by automatically quantifying the three sentinel facial features of FASD and identifying more subtle facial dysmorphology that reflects PAE after gastrulation 67 , 285 . The use and availability of 3D imaging will increase as more sophisticated and cheaper 3D cameras evolve and image capture on smartphones combined with cloud-based image analysis become available. Similarly, web-based tools are in development for identification of neurocognitive impairments associated with FASD. BRAIN-online enables screening for cognitive and behavioural features of PAE or FASD 286 . Decision trees simplify neurocognitive testing by including only tests that contribute most to the diagnosis of FASD 287 . Porting this software to tablets or online websites will broaden access to relevant neurocognitive testing. For example, the FASD-Tree 288 provides a dichotomous indication and a risk score for FASD, considering both neurobehaviour and dysmorphology, and successfully discriminates between children with and without PAE with a high predictive value 289 .

The lack of internationally agreed diagnostic criteria for FASD is challenging and hinders the comparison of prevalence and clinical outcomes between studies. In response, the National Institute on Alcohol Abuse and Alcoholism (NIAAA) has convened an international consensus committee to analyse data derived from existing diagnostic systems and develop a consensus research classification for FASD 290 . The field would also benefit from improved, population-based, normative data for growth and PFL as well as internationally accepted definitions of a standard drink and of the ‘low, moderate and high’ levels of risk of PAE. Additionally, the range and aetiology of adult outcomes require clarification to inform assessment and prognosis in FASD 291 . A research initiative for elderly people with FASD is urgently needed as there is virtually no information about the diagnostic criteria or neuropsychological outcomes of FASD in this age group.

Understanding pathophysiology

Functional MRI can be used to elucidate brain growth trajectories and disruptions to neuronal pathways after PAE (including low-level PAE), thereby assisting our understanding of CNS dysfunction in FASD 68 . Advances in our understanding of the genetics of rare neurodevelopmental disorders may identify genes that govern susceptibility or resilience to PAE and provide additional insights into the pathogenesis of FASD 187 . Advances in neuroscience research, including novel preclinical studies, may help elucidate the relationship between PAE-induced brain dysfunction and the FASD phenotype and inform therapeutics and prevention 292 .

Prevention and management

Preclinical studies suggest that epigenetic changes induced by PAE underpin metabolic, immunological, renal and cardiac disorders in FASD 13 , but further studies in patients are required to confirm this. The paucity of high-quality evidence to inform the treatment of neurodevelopmental impairments and comorbidities associated with FASD across the lifespan requires urgent redress 237 , 238 . Behavioural, family-based, school-based and pharmacological treatments require evaluation through multicentre RCTs. Moreover, little attention has been paid to preventing and managing the secondary outcomes of FASD in adults: substance use, mental health disorders, contact with the justice system, and issues with sleep, sexuality and violence. These must be prioritized to improve the QOL of individuals and reduce the societal and economic effects of FASD.

The COVID-19 pandemic demonstrated the use of telemedicine for virtual neuropsychiatric assessment and delivery of therapy 282 . Telemedicine approaches may also partly fill the need to increase health professionals’ capacity for FASD-informed care and to help education, child protection and justice professionals to recognize and understand FASD 283 .

Improving the primary prevention of alcohol use in pregnancy and hence FASD is also warranted 237 , 238 . Alcohol consumption and binge drinking are increasing among women of childbearing age in many countries, particularly in the most populous countries such as China and India 26 . This rise reflects increased availability of alcohol, societal acceptance of drinking among women, shifting gender roles, increasing income of women, and targeted marketing of alcohol to women and predicts a future global increase in FASD prevalence. Alcohol use in adolescence predicts subsequent use during pregnancy, and family physicians can play a role in identifying young women at risk 293 .

Another concern is that a large proportion of pregnancies globally are unplanned 29 , which can result in unintentional exposure of the embryo to PAE in the earliest stages of pregnancy. Accordingly, effective and cost-effective population-based preventive strategies should be adapted such as those promoted by the WHO in their Global Action Plan for the Prevention and Control of NCDs 294 and their Global Strategy to Reduce the Harmful Use of Alcohol 295 .

Although the role of national guidelines, community education and family support is important, these efforts must be underpinned by strategies proven to drive behavioural change and reduce alcohol harm, including legislated restrictions on the advertising and promotion of alcohol, appropriate taxation and pricing, and limited access to alcohol through restricted liquor outlets and opening hours and community-initiated alcohol restrictions 26 , 295 .

In pregnant women with ongoing alcohol consumption, food supplementation with folic acid, selenium, DHA, L-glutamine, boric acid or choline may reduce the effects of PAE 87 , 296 . However, research is required to define optimal levels of nutritional supplementation for pregnancy. Women who consume large amounts of alcohol often have iron deficiency, which increases the risk of FASD, and iron supplementation may be valuable 297 . Although novel in utero therapies with potential to prevent harm from PAE have been explored in preclinical models, none have been proven safe or effective in human RCTs 298 , 299 , 300 , 301 , 302 , 303 , 304 , 305 , 306 , 307 . Candidate therapies include agents that reduce ethanol-induced oxidative stress, cerebral neuronal apoptosis, growth deficits and structural anomalies caused by PAE 308 .

Future research should be collaborative and informed by people living with FASD and their families. FASD is a lifelong condition and information must be sought about adult patients, including the elderly. Further understanding of the pathophysiology underpinning the teratogenic and neurotoxic effects of PAE is required to inform prevention and management. Moreover, novel diagnostic tools and treatments must be rigorously tested, and new approaches are needed to reduce stigma, improve the QOL of people with FASD and prevent FASD in future generations.

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Acknowledgements

M.E.C. and E.P.R.: part of the work on mechanisms of alcohol harm was done in conjunction with the Collaborative Initiative on Fetal Alcohol Spectrum Disorders (CIFASD), which is funded by grants from the National Institute on Alcohol Abuse and Alcoholism (NIAAA). Support was provided by U24 AA014811 (E.P.R. and M.E.C.). Additional information about CIFASD, including information on how to request data, can be found at www.cifasd.org . H.E.H.: the section on diagnostic guidelines was partially supported by the National Institute on Alcohol Abuse and Alcoholism grants R01 AA11685, R01/U01 AA01115134, and U01 AA019879-01/NIH-NIAAA (Collaboration on Fetal Alcohol Spectrum Disorders Prevalence (CoFASP)), and by the Oxnard Foundation, Newport Beach, CA, USA. E.J.E. is supported by an Australian Medical Research Futures Fund Next Generation Fellowship (#MRF1135959) and National Health and Medical Research Council of Australia funding for a Centre of Research Excellence in FASD (#GNT1110341).

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Svetlana Popova

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Michael E. Charness

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PERSPECTIVE article

Responding to the unique complexities of fetal alcohol spectrum disorder.

• 1 Canada Fetal Alcohol Spectrum Disorder Research Network, Vancouver, BC, Canada
• 2 Department of Educational Psychology, University of Alberta, Edmonton, AB, Canada
• 3 Department of Psychology, University of Guelph, Guelph, ON, Canada
• 4 Department of Psychology, Laurentian University, Sudbury, ON, Canada
• 5 Department of Psychiatry, University of Saskatchewan, Saskatoon, SK, Canada
• 6 Society of Obstetricians and Gynaecologists of Canada, Ottawa, ON, Canada
• 7 Department of Obstetrics and Gynecology, University of Ottawa, Ottawa, ON, Canada
• 8 Faculty of Social Work, University of Calgary, Calgary, AB, Canada

Fetal alcohol spectrum disorder (FASD) is a multifaceted disability, characterized not only by brain- and body-based challenges, but also high rates of environmental adversity, lifelong difficulties with daily living, and distinct sociocultural considerations. FASD is one of the most common neurodevelopmental disabilities in the Western world and associated with significant social and economic costs. It is important to understand the complexities of FASD and the ways in which FASD requires unique consideration in research, practice, and policy. In this article, we discuss our perspectives on factors that distinguish FASD from other disabilities in terms of complexity, co-occurrence, and magnitude. We provide an overview of select literature related to FASD as a socially rooted disability with intergenerational impacts and multiple layers of stigma. These social issues are intertwined with notable experiences of adversity across the lifespan and high rates of co-occurring health concerns for individuals with FASD, all of which present unique challenges for individuals, caregivers, families, service providers, and policy makers. Understanding these factors is the first step in developing and implementing specialized initiatives in support of positive outcomes for individuals with FASD and their families. Future directions are proposed for advancing research, practice, and policy, and responding to the unique complexities of FASD.

Introduction

At least 4–5% of individuals in Canada and the United States are estimated to have fetal alcohol spectrum disorder [Fetal alcohol spectrum disorder (FASD); May et al., 2018 ; Popova et al., 2019 ]. Although it is one of the most common neurodevelopmental disabilities (NDDs) in the Western world, knowledge and awareness of FASD within the public and among service providers continues to lag compared with other disabilities ( Johnson et al., 2010 ; Mukherjee et al., 2015b ; Choate et al., 2019 ). FASD stems from prenatal alcohol exposure (PAE) and is characterized by cognitive, behavioral, emotional, social, and adaptive difficulties ( Cook et al., 2016 ) along with many co-occurring physical and mental health concerns ( Popova et al., 2016 ; Himmelreich et al., 2020 ). Without adequate support, individuals with FASD can experience a range of negative outcomes, but positive trajectories may be encouraged through early diagnosis, intervention, and high-quality caregiving environments ( Streissguth et al., 2004 ).

Complexities of Fetal Alcohol Spectrum Disorder

Fetal alcohol spectrum disorder is a unique NDD ( Di Pietro and Illes, 2016 ), distinct from other disabilities through a combination of several inter-related and compounding factors (see Figure 1 ). Although these factors may be relevant across disability groups, FASD is distinct in terms of the complexity, co-occurrence, and magnitude with which they occur. It is critical for researchers, service providers, and policy makers to understand factors that contribute to the complexity of FASD. With increased awareness and understanding comes the potential to improve resources, strengthen advocacy efforts, and ultimately promote wellbeing and positive outcomes for individuals with FASD, their families, and communities. Here, we present our perspectives on the unique complexities of FASD, informed by our collective experience and expertise in clinical psychology, psychiatry, women’s health, disability, child welfare, and social policy, situated within the context of the current evidence base.

Figure 1. Factors contributing to the unique complexity of FASD. FASD, fetal alcohol spectrum disorder; PAE, prenatal alcohol exposure.

Prenatal Alcohol Exposure and Social Determinants of Health

There are myriad factors that both directly and indirectly influence why a pregnant woman may consume alcohol, many of which parallel the social determinants of health (SDHs; Government of Canada, 2020 ). Experiences of trauma ( Bhengu et al., 2019 ); stressful life events ( Edwards et al., 2019 ); intimate partner violence ( Deutsch, 2019 ); having a partner who uses substances ( Ortega-García et al., 2020 ); lower levels of education ( May et al., 2020 ); less or later access of prenatal health care ( May et al., 2020 ; Popova et al., 2021 ); and mental health challenges ( Hyer et al., 2020 ; Popova et al., 2021 ) have all been associated with an increased risk of alcohol use during pregnancy. Many pregnancies are unplanned, and not all women recognize their pregnancy during the early stages. People may also have limited awareness about the harms associated with alcohol use during pregnancy ( Bitew et al., 2020 ), or may have received conflicting information from the media or health care professionals ( Elek et al., 2013 ). Although other disabilities have been associated with SDHs in that SDHs can be influenced by disability status ( Frier et al., 2018 ), or may impact caregiver beliefs ( Zuckerman et al., 2015 ) and wellbeing ( Spencer et al., 2021 ), with FASD, compromised SDHs are uniquely associated as potentially causal factors.

Given the association between prenatal alcohol exposure (PAE) and SDHs ( Abadir and Ickowicz, 2016 ), comprehensive initiatives are needed to reduce the complex risk factors linked to alcohol use during pregnancy and promote health and wellness in a way that is respectful and responsive to high levels of vulnerability ( Poole et al., 2016 ; Hubberstey et al., 2019 ).

Intergenerational Impacts

Researchers have recently begun to explore the multi-generational contributors to FASD. Although the specific mechanisms underlying the intergenerational aspects of FASD are not fully understood, possible genetic and epigenetic contributors have been examined ( Govorko et al., 2012 ; Harper et al., 2014 ; Mead and Sarkar, 2014 ; Popoola et al., 2017 ). PAE is an early life stressor that can damage the developing brain and cause neurological alterations leading to a heightened vulnerability to stress, mental health problems, and substance use ( Weinberg et al., 2008 ; Hellemans et al., 2010 ; Ciafrè et al., 2020 ). In animal models of PAE, researchers have found that the brain’s altered stress response system and resulting epigenetic impacts can be carried on for at least three generations ( Nizhnikov et al., 2016 ). Environmental stressors and experiences of trauma may further exacerbate these risk factors. In one study, grandmothers of children with FASD were more likely to have experienced trauma, injuries, and difficulties related to alcohol use compared to grandmothers of children without FASD ( Kvigne et al., 2008 ). Other researchers have reported that individuals with FASD experience high rates of intergenerational trauma ( Samaroden, 2018 ), alcohol and substance use ( Dodge et al., 2019 ; Goldschmidt et al., 2019 ), as well as risky sexual behavior ( De Genna et al., 2015 ). When these behaviors and experiences are combined, in the absence of adequate services and supports, individuals with FASD may themselves be at increased risk of having future alcohol-exposed pregnancies.

The causal pathways of FASD are multi-faceted and complex ( McQuire et al., 2020 ), involving genetic and biological, behavioral, interpersonal, sociocultural, and historical factors. Together, these pathways can increase the risk of trauma, health and economic disparity, substance use, and other risk factors that perpetuate the intergenerational cycle of FASD ( Meurk et al., 2014 ; Cloete and Ramugondo, 2015 ; Gonzales et al., 2021 ).

Compounding Stigma

Research on stigma and NDDs is relatively scarce; however, there is some evidence that FASD is stigmatized in numerous compounding ways. Like other disabilities, stigma affects individuals with FASD and their care providers through experiences of marginalization, negative stereotypes, lower self-esteem, and misperceptions about the individual’s abilities ( Bell et al., 2015 ). Negative attitudes about life trajectories are prevalent, with the positive potential of individuals with FASD overshadowed by a public perception that negative outcomes are inevitable ( Bell et al., 2015 ; Olson and Sparrow, 2021 ). This stigma can create significant barriers to service access for individuals with FASD and their caregivers by undermining their willingness to seek supports ( Bell et al., 2015 ). Moreover, these barriers may be compounded by a misunderstanding of FASD among professionals, and the disqualification of individuals with FASD from mainstream services ( Anderson et al., 2019 ). Even service providers who are knowledgeable about the disability may hesitate to diagnose an individual with FASD because of concerns about how stigma will impact the individual and their family ( Payne et al., 2005 ; Elliott et al., 2006 ; Mukherjee et al., 2015a ; Howlett et al., 2019 ).

In addition to the general stigmatization that impacts people across disabilities groups, FASD is uniquely seen through a “criminalized” public lens ( Bell et al., 2015 ; Aspler et al., 2018 ). In the media, individuals with FASD are often portrayed as people who commit crimes, which perpetuates harmful generalizations about criminality and further stigmatizes individuals with FASD ( Aspler et al., 2018 ). Another layer of stigma that is unique to FASD is the shame and blame that is targeted toward women and mothers ( Corrigan et al., 2017 ). FASD has been inextricably linked to women’s behavior and mothers are often held responsible for “victimizing” ( Aspler et al., 2019 ) or “causing” harm to their child ( Bell et al., 2015 ). This stigma can be particularly harmful as it impedes women from seeking support or discussing alcohol consumption with care providers out of fear of judgment, child removal, or incarceration ( Poole et al., 2016 ). Because the direct cause of FASD is PAE, it may be seen as preventable, in principle. However, this oversimplification can be misleading and harmful, further stigmatizing and marginalizing women who consume alcohol during pregnancy, as well as individuals with FASD and their families ( Roozen et al., 2020 ).

Another unique layer of stigma in FASD exists at the sociocultural level, whereby it is commonly, and incorrectly, misperceived to be an “Indigenous issue” ( McKenzie et al., 2016 ; Aspler et al., 2019 ). In fact, there are no recent or rigorous prevalence studies to support this misconception ( Flannigan et al., 2018 ). Although cultural factors are relevant to FASD insofar as they can help to guide prevention, diagnosis, and intervention efforts ( Samaroden, 2018 ; Pei et al., 2019 ; Gibson et al., 2020 ; Hamilton et al., 2020 ; Gonzales et al., 2021 ), cultural stigma can cause substantial harm. By disproportionately focusing on FASD in Indigenous communities, not only are negative stereotypes perpetuated, but individuals with other NDDs may be misdiagnosed or overlooked, which can impact resource allocation and lead to a lack of appropriate supports ( Di Pietro and Illes, 2014 , 2016 ). There is a critical need to address the harms of cultural stigma and support FASD work in Indigenous communities through community-led approaches with consideration of contextual factors, historical and contemporary trauma, and the ongoing marginalization of Indigenous peoples and communities ( Gonzales et al., 2021 ).

Multi-layered and targeted efforts are needed to reduce the stigma associated with FASD at the individual, familial, community, and societal levels to better understand, respect, and provide services for individuals with FASD and their families.

Environmental Adversity

Individuals with FASD experience disproportionately high rates of prenatal and postnatal adversity, which has profound impacts on their developmental trajectories ( Price et al., 2017 ; Lebel et al., 2019 ). Beginning early in life, exposure to adverse experiences such as caregiving disruption, death of a parent, abuse and neglect, and exposure to familial substance use, violence, mental health problems, and criminal justice system involvement, are well-documented in this population ( Coggins et al., 2007 ; Koponen et al., 2009 ; McLachlan et al., 2015 , 2016 ; Kambeitz et al., 2019 ). Adverse experiences continue throughout the lifespan for individuals with FASD, with high rates of problems with school, employment, housing, independence, victimization, and legal involvement ( Streissguth et al., 2004 ; Rangmar et al., 2015 ; McLachlan et al., 2020 ). Although environmental adversity is common for individuals across disability groups ( Austin et al., 2016 ), including those with developmental disabilities ( Emerson, 2014 ; Reichman et al., 2018 ), it is especially pervasive, chronic, and complex among those with FASD ( McLachlan et al., 2015 , 2020 ; Kambeitz et al., 2019 ; Flannigan et al., 2021a ).

Exposure to adversity, particularly in the early years, can have a profoundly damaging and cumulative effect on an individual’s long-term health and wellbeing ( Felitti et al., 1998 ; Chartier et al., 2010 ). Environmental adversity can exacerbate the brain-based vulnerability resulting from PAE and further increase the risk of negative outcomes ( Price et al., 2017 ).

Considering the increased biopsychosocial vulnerability of individuals with FASD, supports and services should be delivered early, and incorporate a holistic, family-focused, and long-term approach to promoting safety, stability, and wellbeing.

Co-occurring Conditions

Although co-occurring mental health issues are common for individuals with various developmental disabilities ( Cooper et al., 2007 ; Simonoff et al., 2008 ), the rates of comorbidity tend to be higher among those with FASD. It is estimated that 90% or more of individuals with FASD experience co-occurring neurodevelopmental and mental health diagnoses ( Streissguth et al., 2004 ; Pei et al., 2011 ; Weyrauch et al., 2017 ; Temple et al., 2019 ). Compared to the general population, individuals with FASD are reported to be 10 times more likely to have ADHD, 20 times more likely to have substance use problems, and 25 times more likely to be diagnosed with a psychotic disorder ( Popova et al., 2016 ; Weyrauch et al., 2017 ). Challenges with substance use ( Dodge et al., 2019 ; Goldschmidt et al., 2019 ) and suicidality ( Dirks et al., 2019 ; O’Connor et al., 2019 ; Flannigan et al., 2021b ) are also common in this population.

Mental health challenges among individuals with FASD occur alongside complex biopsychosocial vulnerabilities, which may obstruct a clear understanding of the underlying needs of the individual. FASD is a heterogeneous disability and the varying ways in which FASD and comorbid conditions can manifest and are interpreted have serious implications for diagnosis and treatment ( Grant et al., 2013 ). The presence of multiple health conditions can make it difficult for service providers to identify the root cause of symptoms or behaviors, assign an accurate diagnosis, and apply effective interventions. Moreover, most individuals with FASD show no obvious physical signs of impairment ( Andrew, 2011 ), and the “hidden” nature of the disability can further compound the challenges of accurate identification. There is a critical lack of mental health and substance use interventions for individuals with FASD ( Flannigan et al., 2020 ). Furthermore, a lack of recognition of the potential for wellness and resilience among individuals with FASD may create barriers to service access where mental health and substance use treatments are denied because of service providers’ misperceptions about the disability ( Anderson et al., 2019 ).

The clinical complexities of FASD underscore the multifaceted needs of individuals with this disability and highlight the importance of effective communication, professional education strategies, as well as comprehensive and needs-driven services and supports ( Pei et al., 2021 ).

Caregiver and Family Experiences

The complex needs associated with FASD present significant challenges for caregivers, and can result in distress, isolation, grief, and loss ( Paley et al., 2006 ; Sanders and Buck, 2010 ; Kautz et al., 2020 ; Skorka et al., 2020 ). Caregivers often report feeling under-supported, misunderstood, and at times, blamed by service providers for the challenges of their family member with FASD ( Mukherjee et al., 2013 ; Coons et al., 2018 ; Domeij et al., 2018 ). Although these concerns may be a reality for families of individuals with any disability ( Heifetz et al., 2019 ; Miranda et al., 2019 ; Marquis et al., 2020 ; Masefield et al., 2020 ), caregivers of those with FASD experience stressors that are unique, and in some cases more severe, relative to other disability populations. For instance, there is emerging evidence suggesting that parents of children with FASD experience significantly higher levels of pessimism, poor parent-child interactions, difficult child characteristics, and less hope for the future, compared to parents of children with autism ( Watson et al., 2013a , b ). Importantly, because of limited service availability for individuals with FASD as they transition to adulthood ( Burnside and Fuchs, 2013 ), many caregivers will play a long-standing role in assisting and advocating for their family member in navigating support systems. Notably, caregivers also demonstrate remarkable adaptability in raising individuals with FASD ( Coons et al., 2016 ).

Caregiver challenges become more complicated when situated in the broader context of stigmatization, intergenerational impacts, and chronic adversity associated with FASD. As such, evidence-based interventions to support caregivers of individuals with FASD are essential ( Mohamed et al., 2020 ). Comprehensive networks of support that leverage caregiver strengths and community resources should be prioritized.

Discussion and Future Directions

A growing body of evidence highlights the unique complexity of FASD and informs our understanding of the diverse factors that must be addressed to support wellbeing and positive trajectories for this population. This research lays a foundation for the advancement of FASD research, practice, and policy.

There is an ongoing need to address the individual and biopsychosocial factors that contribute to alcohol use during pregnancy through targeted supports for people who experience these risk factors. Initiatives are needed to improve public awareness of FASD and to reduce the stigma, shame, and blame experienced by individuals with FASD, their parents, families, and the broader community. Resources are needed to better support women’s overall health and wellbeing in order to reduce the likelihood of PAE, and ultimately improve outcomes for women, children, and families ( Hubberstey et al., 2019 ). Given the intergenerational impacts of FASD, practice and policy initiatives should address the broader social and systemic inequities that place multiple generations of families at risk for FASD. To be as comprehensive and effective as possible, FASD interventions should contextualize the needs and challenges of the individual within their larger family system.

Supports for caregivers and families are urgently needed ( Bobbitt et al., 2016 ), especially those caring for transition-aged youth and adults with FASD who experience needs that are highly complex ( McLachlan et al., 2020 ). Caregiver supports should emphasize self-care, provide support for grief and loss, offer respite, promote social connection, enhance advocacy, and consider the multi-generational impacts of FASD. The responsibility of supporting an individual with FASD across the lifespan should not fall solely on caregivers, and community-based supports should be enhanced to include natural networks that meaningfully foster interdependence for individuals with FASD and their families.

Targeted efforts are needed to increase knowledge of FASD among service providers, improve access for individuals with FASD to needed programming, and ensure that services account for the unique brain-based differences associated with PAE. Service providers should receive specific training on the complexities of FASD to effectively identify and support clients with FASD. Training should involve a prevention component and emphasize compassionate approaches to facilitating safe discussions about alcohol use. Improved knowledge and sensitivity to alcohol use during pregnancy will help to ensure that women and families are adequately supported in seeking services. FASD curricula at the postsecondary level would be especially useful to ensure that professionals are equipped at the outset of their careers with knowledge and strategies specific to FASD.

Funding and resources are needed to develop and implement FASD-specific supports for individuals across the lifespan. FASD services should be individualized, interdisciplinary, trauma-informed, culturally appropriate, family-centered, and lifelong to ensure comprehensive systems of support. Moreover, services should be integrated across systems to address the diverse needs of this population ( Pei et al., 2021 ). More work is needed to explore the ways in which FASD is distinct from other disabilities, as well as shared needs between groups to inform the development of specialized supports. FASD-specific research, practice, and policy must draw upon the lived experiences of individuals with FASD and their families to ensure that their perspectives and realities are meaningfully considered.

Finally, much of the current literature is focused on the challenges associated with FASD, with a critical gap in terms of strengths and successful outcomes ( Olson and Sparrow, 2021 ). Strengths-based work is critical for reducing the stigma associated with FASD, and for identifying and leveraging the positive potential of individuals with FASD and their care providers. Despite the complexities of the disability, individuals with FASD can thrive, and there is an urgent need to provide opportunities for them to do so.

Fetal alcohol spectrum disorder represents the intersection of complicated biological, family, community, and societal circumstances that increase risk for social inequity, intergenerational trauma, and health disparity. To fully understand FASD and its associated challenges, and to effectively identify and support individuals with FASD and their families, it is necessary to contextualize the disability within this complex web of risk and vulnerability. Working with individuals with FASD and their families requires empathy, flexibility, creativity, resourcefulness, and cross-disciplinary collaboration. FASD is a significant social and health issue, and targeted work is needed to better address the unique challenges associated with the disability, recognize and build strengths and resilience, and promote the long-term wellbeing of individuals with FASD, their families, and their communities.

Data Availability Statement

The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.

Author Contributions

KF wrote the first draft. JP, KM, KH, and MM contributed writing to sections of the manuscript. All authors contributed to the conception of this manuscript and read, revised, and approved the submitted version.

Funding for the open access publishing of this article is provided by the Canada FASD Research Network.

Conflict of Interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

Acknowledgments

An earlier version of this manuscript was previously published as a Canada FASD Research Network issue paper, available at: https://canfasd.ca/wp-content/uploads/publications/FASD-as-a-Unique-Disability-Issue-Paper-FINAL.pdf . We would like to acknowledge Kathy Unsworth, Dorothy Reid, Marsha Wilson, Simon Laplante, Lindsay Wolfson, Gail Andrew, and Sabrina Eliason for their support in preparing this work.

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Keywords : fetal alcohol spectrum disorder (FASD), neurodevelopmental disability, complex needs, research advances, practice and policy issues

Citation: Flannigan K, Pei J, McLachlan K, Harding K, Mela M, Cook J, Badry D and McFarlane A (2022) Responding to the Unique Complexities of Fetal Alcohol Spectrum Disorder. Front. Psychol. 12:778471. doi: 10.3389/fpsyg.2021.778471

Received: 16 September 2021; Accepted: 31 December 2021; Published: 25 January 2022.

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Copyright © 2022 Flannigan, Pei, McLachlan, Harding, Mela, Cook, Badry and McFarlane. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: Katherine Flannigan, [email protected]

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Janet F. Williams , Vincent C. Smith , the COMMITTEE ON SUBSTANCE ABUSE; Fetal Alcohol Spectrum Disorders. Pediatrics November 2015; 136 (5): e20153113. 10.1542/peds.2015-3113

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Alcohol-related birth defects and developmental disabilities are completely preventable when pregnant women abstain from alcohol use.

Neurocognitive and behavioral problems resulting from prenatal alcohol exposure are lifelong.

Early recognition, diagnosis, and therapy for any condition along the FASD continuum can result in improved outcomes.

○ no amount of alcohol intake should be considered safe;

○ there is no safe trimester to drink alcohol;

○ all forms of alcohol, such as beer, wine, and liquor, pose similar risk; and

○ binge drinking poses dose-related risk to the developing fetus.

This clinical report has been reaffirmed with reference and data updates. New or updated references or datapoints are indicated in bold typeface. No other changes have been made to the text or content.

The AAP would like to acknowledge Carol Cohen Weitzman, MD, FAAP, for these updates.

Fetal alcohol spectrum disorders (FASDs) is an overarching phrase that encompasses a range of possible diagnoses, including fetal alcohol syndrome (FAS), partial fetal alcohol syndrome, alcohol-related birth defects (ARBD), alcohol-related neurodevelopmental disorder (ARND), and neurobehavioral disorder associated with prenatal alcohol exposure (ND-PAE). FAS refers to a clinical diagnosis based on a specific constellation of physical, behavioral, and cognitive abnormalities resulting from prenatal alcohol exposure (PAE). 1 By 1973, sufficient research evidence had accrued to devise basic diagnostic criteria such that FAS became established as a diagnostic entity. 1 The US Surgeon General issued the first public health advisory in 1981 (reissued in 2005) that alcohol during pregnancy was a cause of birth defects. 2 , 3 In 1989, Congress mandated that alcohol product labels include a warning about potential birth defects. Nineteen states and the District of Columbia have now enacted laws requiring these warnings at the point of sale, including bars and restaurants. 4  

As it became evident that PAE resulted in a spectrum of lifelong manifestations, varying from mild to severe and encompassing a broad variety of physical defects and cognitive, behavioral, emotional, and adaptive functioning deficits, the term “fetal alcohol effects” was adopted to describe children who had PAE manifestations yet did not meet the FAS diagnostic criteria, primarily by lacking physical abnormalities associated with FAS. Because the term was too broad and vague for practical clinical or epidemiologic use, it was retired from use in 1996 and replaced with 2 pathophysiologically based diagnostic categories: ARBD and ARND. 5 , – 7  

Despite greater public awareness, improved terminology, and an accruing body of research, the lack of uniformly accepted diagnostic criteria for FAS and other related disorders has critically limited efforts to determine accurate prevalence figures, expand awareness and prevention campaigns, actuate early identification and intervention programs, and delineate the full continuum of alcohol-related conditions. As part of the fiscal year 2002 appropriations legislation, Congress mandated that the Centers for Disease Control and Prevention (CDC) develop diagnostic guidelines for FAS and related disorders and integrate them broadly across medical and allied health professions’ training curricula. Under the auspices of the CDC, acting through the National Center on Birth Defects and Developmental Disabilities FAS Prevention Team, in conjunction with the National Task Force on Fetal Alcohol Syndrome and Fetal Alcohol Effects, a multidisciplinary scientific working group of key national experts engaged in an intensive collaborative effort to draw conclusions about PAE effects. This collaborative conducted a comprehensive review of scientific and clinical evidence and extensively consulted with clinicians, experts, and families to delineate clear diagnostic criteria for FAS on the basis of a combination of 3 cardinal facial features, growth problems, and central nervous system abnormalities qualified by confirmed or unknown PAE ( Fig 1 ). 8 Through this effort, practical clinical approaches were endorsed so that those children with PAE could be more readily identified, the condition could be diagnosed with greater accuracy, and children could be referred for appropriate services. 9 , 10  

Child presenting with the 3 diagnostic facial features of FAS: (1) short palpebral fissure lengths, (2) smooth philtrum (Rank 4 or 5 on the Lip-Philtrum Guide), and (3) thin upper lip (Rank 4 or 5 on the Lip-Philtrum Guide). Legend written by Susan Astley, PhD. © 2015, Susan Astley PhD, University of Washington.

In April 2004, the National Institutes of Health, CDC, and the Substance Abuse and Mental Health Services Administration, along with additional experts in the field, were convened by the National Organization on Fetal Alcohol Syndrome to develop the following consensus definition of FASD: “FASD is an umbrella term describing the range of effects that can occur in an individual whose mother drank alcohol during pregnancy. These effects include physical, mental, behavioral, and/or learning disabilities with possible lifelong implications. The term FASD encompasses all other diagnostic terms, such as FAS, and is not intended for use as a clinical diagnosis.” 11  

Research continued to accrue about ARND, that is, individuals with PAE-associated neurodevelopmental and behavioral abnormalities yet without the FAS facial phenotype, so that in late 2011, the Interagency Coordinating Committee on Fetal Alcohol Spectrum Disorders organized a consensus conference to define ARND diagnostic criteria and related screening and referral needs. 7 As an outgrowth of this conference, a subcommittee collaborated with the American Psychiatric Association in preparing the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition , reorganized on a neurologic disorders framework. The manual includes FASD under the term “FAS (ND-PAE).” 12 , 13 FASD terminology continues to evolve, and research evidence suggests that ARBD may be declining in use while ARND/ND-PAE terminology remains incompletely defined. ND-PAE may become the accepted diagnostic term for moderate PAE findings, and “static encephalopathy” associated with PAE is a suggested diagnostic term for severe PAE effects. 14  

FASDs remain among the most commonly identifiable causes of developmental delay and intellectual disability yet are generally accepted to be vastly underrecognized. FAS, ARBD, and ARND prevalence rates and occurrence patterns have been the subject of many studies since the late 1970s. The wide variance in reported rates reflects the specific diagnoses studied and the different research methodologies used, the 3 most common methodologies being clinic-based studies, passive surveillance of existing records often limited to a geographic area, and active case ascertainment studies. 15 , 16 Although the prevalence of FAS in the United States during the 1980s and 1990s was reported as 0.5 to 2 cases per 1000 live births, recent studies aggressively diagnosing FASD have reported FAS rates and FASD estimates of 6 to 9 cases and 24 to 48 cases per 1000 children (or up to 5%), respectively, while continuing to consider these rates underestimates. 15 , – 18 Rates as high as 9 cases per 1000 live births have long been documented among vulnerable populations, usually related to isolation and socioeconomic impoverishment, such as can be more often found among certain American Indian and other racial/ethnic minority populations. 19 , – 21 An FAS prevalence of 1.0% to 1.5% has been reported among children in foster care. 22 A recent study among a population of foster and adopted youth referred to a children’s mental health center reported a FASD misdiagnosis rate of 6.4% and a missed diagnoses rate of 80.1%. 23 FAS is the FASD with the most explicit diagnostic criteria, so it only represents a fraction of individuals affected by PAE. FASDs other than FAS are more challenging to diagnose, so the true FASD prevalence remains unknown and the actual impact underappreciated. 15 , – 18  

Approximately half of all US women of childbearing age have reported past month alcohol consumption, and use ranged from sporadic intake to 15% reporting binge drinking. 24 Binge drinking is a pattern of drinking that raises a person’s blood alcohol concentration to 0.08% or greater and was originally defined as 5 or more standard drinks per occasion (generally within 2 hours). 25 A “standard drink” contains approximately 0.5 fluid oz of pure ethanol, which is the amount found in a 1.5-oz shot of distilled spirits, 5 oz of wine, or 12 oz of beer. In 2004, the National Institute on Alcohol Abuse and Alcoholism changed the binge drinking definition for women to “the ingestion of 4 or more drinks per occasion” to account for known physiologic gender-related differences affecting alcohol absorption. 26 Setting this lower threshold for binge drinking among women also served to increase prevalence. 27 Binge drinking in the preconception period is associated with unintended pregnancy and a higher likelihood of risky behaviors, including drinking during pregnancy. 28 Often, PAE is unintentional, occurring before the woman knows that she is pregnant. Women continue to drink alcohol and binge drink during pregnancy despite the US Surgeon General’s warnings and their awareness that risk for potential harm exists. 29 , – 31 Although most women report cutting down or abstaining from alcohol use during pregnancy, 7.6% of pregnant women report continued alcohol use, and 1.4% report binge drinking. 24  

FASD as such is not heritable, and having an FASD does not increase a woman’s risk of having a child with FASD. No genetic factors are known to be predictive of which particular children with PAE will have FASDs or the extent of effects. Multiple studies and meta-analyses have focused on how various patterns of drinking during pregnancy might affect fetal and child development. 32 , – 43 Mills et al prospectively studied approximately 31 000 pregnancies to determine how much alcohol pregnant women could safely consume and found increased risk of infant growth retardation even when consumption was limited to 1 standard drink daily. 32 Although a consensus is still lacking about the effects of low levels of PAE, harmful effects are well documented related to moderate or greater PAE and to binge drinking. 34 , – 42 The potential for fetal harm increases as maternal alcohol consumption rises. 34 , 42 Despite methodologic differences, potentially confounding factors, and variable sensitivity among the detection methods applied, these studies support advising that the healthiest choice regarding alcohol use during pregnancy is to abstain.

Ongoing work seeks to define specific diagnostic criteria for each of the FASD conditions along the continuum, such as has been possible for FAS. The FAS diagnosis is made only when an individual meets all 3 diagnostic criteria: prenatal and/or postnatal growth deficiency, the 3 cardinal facial features (reduced palpebral fissure length, smooth philtrum, and thin upper vermillion lip border [ Figs 2 , 3 , 4A , 4B and 5 ]), and any of a range of recognized structural, neurologic, and/or functional central nervous system deficits. 8 , – 10 , 44 Confirmed PAE strengthens the evidence, but FAS can be diagnosed without this history when all of the specific FAS diagnostic criteria have been met. Diagnosing FAS also means a comprehensive history has documented any other in utero substance exposures, including tobacco, medications, or illicit substances of abuse, and that other possible genetic and environmental etiologies have been excluded, specifically Williams, Noonan, 22q deletion syndromes, trisomy 21, and fetal toluene embryopathy, because some dysmorphological features are shared with FAS. 45  

The palpebral fissure length is defined by the distance between the endocanthion (en) and exocanthion (ex) landmarks. Legend written by Susan Astley, PhD. © 2015, Susan Astley PhD, University of Washington.

The palpebral fissure length (the distance from the inner corner to outer corner of the eye) being measured with a small plastic ruler. Legend written by Susan Astley, PhD. © 2015, Susan Astley PhD, University of Washington.

Lip-Philtrum Guide 1 is one of two Guides (see Fig 4B ) used to rank upper lip thinness and philtrum smoothness. The philtrum is the vertical groove between the nose and upper lip. The guide reflects the full range of lip thickness and philtrum depth observed among Caucasians with Rank 3 representing the population mean. Ranks 4 and 5 reflect the thin lip and smooth philtrum that characterize the FAS facial phenotype. Guide 1 is used for Caucasians and all other races with lips like Caucasians. This guide is available from fasdpn.org as a free digital image for use on smartphones. © 2015 Susan Astley, PhD, University of Washington. Legend written by Susan Astley, PhD.

Lip-Philtrum Guide 2 is one of two Guides (see Fig 4A ) used to rank upper lip thinness and philtrum smoothness. The philtrum is the vertical groove between the nose and upper lip. The guide reflects the full range of lip thickness and philtrum depth observed among African Americans with Rank 3 representing the population mean. Ranks 4 and 5 reflect the thin lip and smooth philtrum that characterize the FAS facial phenotype. Guide 2 is used for African Americans and all other races with thicker lips like African Americans. This guide is available from fasdpn.org as a free digital image for use on smartphones. © 2015 Susan Astley, PhD, University of Washington. Legend written by Susan Astley, PhD.

All other FASD conditions have a range of PAE-associated findings that meet only some of the FAS diagnostic criteria. A computer-based 3-dimensional facial image analysis is showing promise in identifying PAE-affected children who have cognitive impairments but lack the FAS diagnostic facial features. 46 ARBD refers to children with confirmed PAE and certain physical findings related to congenital structural malformations and dysplasias affecting organ systems and/or specific minor anomalies but normal neurodevelopment. 10 , 14 , 33 A confirmed history of PAE should also prompt careful developmental screening and assessment for ARND/ND-PAE, which is among the possible diagnoses when there are no physical stigmata of FAS, yet evidence of brain abnormalities, and either structural or functional neurocognitive disabilities manifest as problems with neurodevelopment, behavior, adaptive skills, and/or self-regulation. 7 , 9 , 10 Other individuals whose features meet most but not all of the diagnostic criteria for FAS are described as having partial fetal alcohol syndrome. Fetal exposure to alcohol and to one or more additional substances complicates the causal explanation of clinical findings because the potential teratogenic, fetal growth, and neurobehavioral effects might be attributable to exposure to the other drug(s) alone, to multiple different exposures, or to drug combinations, including alcohol.

Although a classic FAS diagnostic triad has long been identified, other findings, including microcephaly, behavioral abnormalities, and “noncardinal” abnormal facial features, such as maxillary hypoplasia, cleft palate, or micrognathia, are also well recognized to co-occur with PAE. 1 , 45 , 47 A wide range of developmental and/or medical problems can accompany FAS as a result of alcohol’s structural and/or functional effects on the brain and various other organs or systems, particularly the cardiovascular, renal, musculoskeletal, ocular, and auditory systems. 1 , 45 , 48 A growing body of FASD research has focused on delineating how various brain volume deficits are related to neurocognitive function and facial dysmorphology, and close correlations with alcohol use in the first trimester of pregnancy have been found. 49 , 50 Fetal death is the most extreme PAE outcome, and PAE is also associated with sudden infant death syndrome ( Fig 5 ). 35 , 51  

Young man presenting with the 3 facial features of FAS (small eyes, smooth philtrum, and thin upperlip) at 2 years of age and 20 years of age. Legend written by Susan Astley, PhD. © 2015, Susan Astley PhD, University of Washington.

Children and adolescents with known PAE experience a variety of behavioral and cognitive difficulties, ranging from subtle learning and/or behavioral problems to significant intellectual disability. 10 , 49 , 52 , – 56 PAE is associated with a higher incidence of attention-deficit/hyperactivity disorder (ADHD) and specific learning disabilities, such as mathematics difficulties. 52 , 54 , – 58 The neurocognitive profile associated with FASDs results from deficits in visual-spatial and executive functioning, including impaired impulse control, memory skills, and problem-solving, but also difficulties with abstract reasoning, auditory comprehension, and pragmatic language use. 49 , 58 PAE-associated executive dysfunction is evident as slow information processing and integration, and children with FASD show deficits in cognitive planning, concept formation, set shifting, verbal and nonverbal fluency, social interaction skills, and peer relationships. 49 , 58 Because attention deficits are considered a common characteristic of people with FASD, these skills have been extensively investigated. Children with FASD have demonstrated attention deficiencies with their capacity to hold information temporarily in memory while coding it or performing a mental operation on it and with the ability to shift attention flexibly compared with those with ADHD, who display greater difficulty with focus, concentration, and staying on task. 57 , – 59 Children and adolescents with PAE have difficulty rapidly processing relatively complex information and perform worse on visual than on auditory sustained attention tasks. 60 Although a few case reports have associated extreme PAE with autism spectrum disorders, most reports have delineated qualitative differences in the social difficulties experienced by those with FAS compared with individuals with autism spectrum disorders. 61 , 62  

Compared with the general population, although similar to those with other intellectual disability, individuals with FASD have a higher incidence of concurrent psychiatric, emotional, and behavioral problems. 13 , 49 , 54 , 56 , 63 , – 65 Children and adolescents with FASD have a 95% lifetime likelihood to experience mental health issues, and among the most prevalent are anxiety and mood disorders, particularly depression, as well as ADHD, substance use, addiction, and suicide. Individuals with PAE have greater rates of school disruptions, trouble with the law, and under- or unemployment. 54 , 64 , 65 Failure to achieve age-appropriate socialization and communication skills results in maladaptive and impaired social functioning. Substance use; inappropriate sexual behaviors, such as inappropriate exposure, improper touching, and promiscuity; and consequent legal problems have been reported in adults diagnosed with FAS. 54 , 65 , 66 Delayed diagnosis and misdiagnosis contribute to the higher risk for secondary and co-occurring conditions.

An integrated multifactorial FASD model that includes genetic, PAE, and environmental factors, among others, provides an approach to understanding and assisting this complex and diverse high-risk population. FASDs have no cure, but affected individuals experience improved medical, psychological, and vocational outcomes through longitudinal intervention and treatment that maximize protective factors and build capacity in identified strengths. 67 , – 71 Multimodal symptom treatments that improve long-term outcomes include optimizing environmental modifications, parenting strategies, social support, and developmental and educational interventions that address the neurologically based problems related to FASDs. 67 , – 72 Children with FASDs prescribed neuroleptic medication have shown improved outcomes, but stimulant medication either failed to improve or worsened ADHD symptoms. 73 The heterogeneity of FASD manifestations calls for tailoring treatments to meet individual needs and addressing these constellations of lifelong disabilities across the life span.

Washington State continues to be a national and international leader in FASD diagnostic, prevention, and intervention practices through a long-standing coordinated effort of diverse programs focused on their collective FASD-associated needs and building a strong FASD research and evidence basis. The 2014 recommendations from the Washington State Fetal Alcohol Spectrum Disorders Interagency Work Group highlight evidence-based practices that include identifying risk and protective factors, engaging early intervention, addressing the high FASD risk for substance abuse problems, and applying screening-informed treatment planning, including neuropsychological assessment-guided treatment plans. 74  

Children with FASD are not explicitly designated to receive special education services in the Individuals with Disabilities Education Act; however, some school districts serve affected children through the “Other Health Impaired” category. PAE is not specifically listed in this category but does qualify a child as “at risk” and eligible for early intervention services (Part C). The developmental and behavior difficulties in young children with FASDs qualify for special education services (Part C and Part B). Various school-based educational accommodations have been effective in helping children with FASDs reach their developmental and educational potential, but the transition to the posteducational setting and adulthood poses additional challenges where support services such as vocational training and life skills development are needed. 54 , 69 , 71 , 72 , 74  

The constellation of medical, surgical, behavioral, educational, custodial, judicial, and other services required to care for an individual with FASD results in a large economic burden to the individual, the family, and society. 75 In the 1980s, the estimated annual FAS-related expenses for the United States increased from $75 million to $4 billion, with the lifetime cost of care approaching $1.4 million. 54 , 75 , 76 Cost estimates are similarly high in Canada but also vary widely depending on the methodologies used. 77 During 2005, children with FAS incurred average medical expenditures 9 times higher than those without FAS. 78 When FAS with intellectual disability was considered in making these calculations, average expenditures increased an additional 2.8 times the costs for FAS alone. 79 Because FAS is only 1 subset of FASD, the true economic effect of FASD is much larger. It has been documented in Canada that an FASD evaluation requires 32 to 47 hours for 1 individual to be screened, referred, evaluated, and given the diagnosis of an FASD, resulting in a total cost of $3110 to $4570 per person. 79 On the basis of the cost of a comprehensive multidisciplinary FASD assessment in Canada, the total cost estimate of all FASD screening and diagnosis ranges from $3.6 to $7.3 million per year, excluding treatment costs. 79 The estimated lifetime cost of care, including social and health care services, for each child born with FASD is up to $2.44 million. 75 , 80 The calculated expense of raising a child with FASD is 30 times the cost of preventing the FASD. 81 In 2005, the annual Medicaid cost to care for a child with FASD was 9 times that of a child without FASD. 78  

The main role of a pediatrician and the medical home regarding FASD is to be knowledgeable about the disorder to guide prevention, to suspect and screen for FASD, and to recognize, manage, and refer patients. Pediatricians, medical home team members, and other health professionals are in prime position to provide both primary and secondary FASD prevention education and counseling because young women of childbearing age are among their patient population. 82 Pediatricians build trusted relationships with their adolescent and young adult patients and the parents of these patients, and a routine and expected part of medical home care is to discuss personal health responsibilities, including preventing pregnancy, alcohol, and other substance use and abstaining from sexual activity. Many women have misconceptions about the “safety” of alcohol use and as a result continue to consume alcohol during pregnancy despite the Surgeon General’s warnings. 24 Refraining from alcohol use during pregnancy is an important message to be delivered by health care providers as a part of prenatal care and other health visits during pregnancy. Clear guidance to correct misunderstandings about the risks of alcohol use during pregnancy and educate people about the importance of abstaining from alcohol during pregnancy may prevent further PAE and related outcomes. Earlier termination of alcohol use in pregnancy is associated with fewer alcohol-related complications for the mother and her baby. Specifically, first trimester drinking (vs no drinking) produces 12 times the odds of giving birth to a child with FASD, first and second trimester drinking increases FASD odds 61 times, and drinking in all trimesters increases FASD odds 65 times. 83  

Adolescent patient care standards include providing consistent patient and family education and anticipatory guidance about alcohol use risks, screening for alcohol use and addiction, and intervention to address use and refer patients to treatment. Because adolescents who drink alcohol while pregnant could have a child with a FASD, policies from the American Academy of Pediatrics (AAP) and public domain tools are available to promote pediatrician skills and practices related to alcohol and other drug use screening, brief intervention, and referral to treatment. 84 , – 86  

Given the prevalence in the United States of alcohol use by women who are sexually active or pregnant, pediatricians, through the medical home, should maintain a high level of suspicion for FASD, become familiar with FASD features, and conduct screening to detect PAE and FASD patients as early as possible. Maternal markers that increase the likelihood of a child having had PAE include the mother’s past history of alcohol or drug use problems, such as addiction, multiple drug use, a previous alcohol-exposed pregnancy, little or no prenatal care, unemployment, a transient lifestyle, incarceration, and/or a heavily drinking partner or family member. 66 Primary care providers should consider the possibility for FASD whenever a child has suggestive physical stigmata and/or is being assessed for poor growth, developmental delays, or behavioral concerns, including attention deficit or school failure. Any history of adoption, especially from an environment of socioeconomic impoverishment, whether domestic or international, and any history of involvement with a US child social services system can indicate a higher likelihood of having had PAE and a need for careful screening for FASD. 23 , 53 , 87 A history of involvement with child protective services related to parental substance use or to child neglect, abuse, or abandonment is a strong marker for risk, as is a history of any out-of-home or foster care placement, including kinship care. 87 Many people are not aware of the requirement for health care providers to report FASD to child protective service systems. 88 The 2010 reauthorization of the federal Child Abuse Prevention and Treatment Act legislation included specific policy revisions and mandates about FASD, including “a requirement that health care providers involved in the delivery or care of such infants notify the child protective service system,” make appropriate referrals to this system and other services, and develop a plan of safe care. 88  

Medical home care relevant to FASD patients includes documenting a PAE and other substance exposure history and other historical details as well as physical examination findings, diagnosing FAS in patients when possible, and/or referring for comprehensive FASD assessment and diagnostic evaluation for intervention. 10 , 13 , 72 Effective medical home practices include optimizing the electronic health record use to facilitate documentation of PAE screening as a practice routine and integrating checklists or other tools to facilitate coordinated collaborative care, follow-up connections, and care transitions. Similar to other patients with complex conditions, those with FASDs are best served through periodic well-child care surveillance and coordinated collaborative patient management through referral to medical subspecialists and other health professionals to diagnose and/or manage comorbidities, facilitating access to and enrollment in developmental and educational services, consultation with social work risk assessment services, and coordination with legal and other community resources for the child and family. Partnering with the patient and family helps medical home physicians understand this lifelong diagnosis and how to manage any stigma and emotional responses, such as anger, shame, or blame that may arise from many sources, including themselves. 62 , 89 Working closely with families to engage their child in appropriate developmental and educational services is an ongoing role, and it is important to anticipate and coordinate the eventual transition of individuals with an FASD from pediatric to adult care services. Pediatricians may also refer FASD-diagnosed patients to the Supplemental Security Income (SSI) system so they can obtain income assistance and medical insurance. Many infants and children with FASD may be eligible for SSI. Furthermore, SSI can help adolescents and young adults with income support and medical insurance beyond 26 years of age, if not available through their parents. Early referral to the SSI system is important.

Assessment of physician training needs has shown that although pediatricians are knowledgeable about FASD and PAE risks, they inconsistently provide anticipatory guidance for FASD prevention with adolescent patients and lack confidence about integrating into routine practice the care management and treatment coordination needed by patients affected by FASDs. 90 , 91 To address these gaps, the CDC-funded FASD Regional Training Centers have published a curriculum development guide to create trainings for medical and allied health students and providers. 92 Other educational modalities and practice tools to enhance practitioner confidence with providing FASD care have been cooperatively developed by the CDC and the AAP. 92 Available through the AAP Web site, the FASD Toolkit and clinical algorithm are among the modalities developed to guide FASD screening, diagnosis, and management in the medical home.

There is no known absolutely safe quantity, frequency, type, or timing of alcohol consumption during pregnancy, but having no PAE translates into no FASD. Despite research evidence clearly documenting the spectrum of detrimental consequences of PAE, too many women continue to drink alcohol during pregnancy. Progress continues to be made in understanding the mechanisms of alcohol’s deleterious effects and identifying the most efficacious intervention strategies for preventing and ameliorating deficits associated with FASDs, but each discovery also reveals new challenges. From an economic, societal, educational, family, or health or medical home perspective, FASDs represent a major public health burden. 93 The pediatrician and the medical home as well as cooperative care with practitioners such as obstetricians and family medicine providers play important roles in the success of FASD prevention, intervention and treatment modalities but also in the research progress needed to discover additional means to address the lifelong consequences of FASDs.

AAP FASD Toolkit. www.aap.org/fasd

Astley SJ, Grant T. Recommendations From the Washington State Fetal Alcohol Spectrum Disorders Interagency Work Group, December 2014. Seattle, WA: Washington State Fetal Alcohol Spectrum Disorders Interagency Work Group. http://depts.washington.edu/fasdpn/pdfs/FASD-IAWG-Dec2014-Report.pdf

American College of Obstetricians and Gynecologists. At-Risk Drinking and Alcohol Dependence: Obstetric and Gynecological Implications. www.acog.org/Resources-And- Publications/Committee-Opinions/ Committee-on-Health-Care-for- Underserved-Women/At-Risk- Drinking-and-Alcohol-Dependence- Obstetric-and-Gynecologic- Implications

Centers for Disease Control and Prevention. www.cdc.gov/fasd

FAS Diagnostic and Prevention Network. FAS Facial Photography and Measurement Instruction (using images and animations to teach accurate measurement of FAS facial features). http://depts.washington.edu/fasdpn/htmls/photo-face.htm

National Dissemination Center for Children with Disabilities. www.parentcenterhub.org/nichcy- resources (All About the IEP— Individualized Educational Program: www.parentcenterhub.org/repository/iep/ )

NIAAA Collaborative Initiative on Fetal Alcohol Spectrum Disorders: www.cifasd.org

NOFAS National and State Resource Directory: www.nofas.org/resource-directory

Substance Abuse and Mental Health Services Administration (SAMHSA), Fetal Alcohol Spectrum Disorders (FASD) Center for Excellence: www.fascenter.samhsa.gov

Substance Abuse and Mental Health Services Administration. Addressing Fetal Alcohol Spectrum Disorders (FASD). Treatment Improvement Protocol (TIP) Series 58. HHS Publication No. (SMA) 13-4803. Rockville, MD: Substance Abuse and Mental Health Services Administration, 2014. http://store.samhsa.gov/product/TIP-58- Addressing-Fetal-Alcohol-Spectrum- Disorders-FASD-/SMA13-4803

SAMHSA Treatment Locator: www.samhsa.gov/treatment/index.aspx

Janet F. Williams, MD, FAAP Vincent C. Smith, MD, MPH, FAAP

Sharon Levy, MD, MPH, FAAP, Chairperson Seth D. Ammerman, MD, FAAP Pamela K. Gonzalez, MD, FAAP Sheryl A. Ryan, MD, FAAP Lorena M. Siqueira, MD, MSPH, FAAP Vincent C. Smith, MD, MPH, FAAP

Janet F. Williams, MD, FAAP

Vivian B. Faden, PhD – National Institute of Alcohol Abuse and Alcoholism Gregory Tau, MD, PhD – American Academy of Child and Adolescent Psychiatry

Renee Jarrett, MPH

Sandra L. Friedman, MD, MPH, FAAP

Philip John Matthias, MD, FAAP Paul Seale, MD Yasmin Suzanne Nable Senturias, MD, FAAP Vincent C. Smith, MD, MPH, FAAP Renee M. Turchi, MD, MPH, FAAP David Wargowski, MD Janet F. Williams, MD, FAAP

Jacquelyn Bertrand, PhD – Centers for Disease Control and Prevention Elizabeth Parra Dang, MPH – Centers for Disease Control and Prevention Jeanne Mahoney – American College of Obstetricians and Gynecologists

Rachel Daskalov, MHA Faiza Khan, MPH

Carol Cohen Weitzman, MD, FAAP

American Academy of Pediatrics

attention-deficit/hyperactivity disorder

alcohol-related birth defect

alcohol-related neurodevelopmental disorder

Centers for Disease Control and Prevention

fetal alcohol syndrome

fetal alcohol spectrum disorder

neurobehavioral disorder associated with prenatal alcohol exposure

prenatal alcohol exposure

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• Volume 106, Issue 7
• Fetal alcohol spectrum disorders: an overview of current evidence and activities in the UK
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This article has a correction. Please see:

• Correction: Fetal alcohol spectrum disorders: an overview of current evidence and activities in the UK - November 01, 2021

• http://orcid.org/0000-0002-1348-672X Lisa Schölin 1 ,
• http://orcid.org/0000-0002-2171-928X Raja A S Mukherjee 2 ,
• Neil Aiton 3 ,
• Carolyn Blackburn 4 ,
• Sarah Brown 5 ,
• Kate M Flemming 6 , 7 ,
• Paul R Gard 8 ,
• Helen Howlett 9 ,
• Moira Plant 10 ,
• Alan D Price 11 ,
• Jennifer Shields 5 ,
• Lesley A Smith 12 ,
• Michael Suttie 13 ,
• David C Zammitt 5 ,
• Penny A Cook 14
• The UK FASD Research Collaboration
• 1 School of Health in Social Science , The University of Edinburgh , Edinburgh , UK
• 2 Fetal Alcohol Syndrome Specialist Behaviour Clinic , Surrey and Borders Partnership NHS Foundation Trust , Surrey , UK
• 3 One Stop Clinic , Royal Sussex County Hospital , Brighton , Brighton and Hove , UK
• 4 Centre for the Study of Practice and Culture in Education , Birmingham City University , Birmingham , West Midlands , UK
• 5 Fetal Alcohol Advisory and Support Team , NHS Ayrshire and Arran , Ayr , South Ayrshire , UK
• 6 Department of Public Health, Policy and Systems, Institute of Population Health , University of Liverpool , Liverpool , Merseyside , UK
• 7 Liverpool Centre for Alcohol Research , Liverpool , UK
• 8 School of Pharmacy and Biomolecular Science , University of Brighton , Brighton , East Sussex , UK
• 9 Faculty of Health and Life Science , Northumbria University , Newcastle upon Tyne , Tyne and Wear , UK
• 10 Faculty of Health and Applied Sciences , University of the West of England Bristol , Bristol , UK
• 11 School of Health and Society , University of Salford , Salford , Greater Manchester , UK
• 12 Institute of Clinical and Applied Health Research , University of Hull , Hull , Kingston upon Hull , UK
• 13 Nuffield Department of Women's and Reproductive Health , Oxford University , Oxford , Oxfordshire , UK
• 14 School of Health Sciences , University of Salford , Salford , UK
• Correspondence to Dr Raja A S Mukherjee, Fetal Alcohol Syndrome Specialist Behaviour Clinic, Surrey and Borders Partnership NHS Foundation Trust, Surrey, UK; raja.mukherjee{at}sabp.nhs.uk

Estimates for the UK suggest that alcohol consumption during pregnancy and prevalence of fetal alcohol spectrum disorder (FASD)—the most common neurodevelopmental condition—are high. Considering the significant health and social impacts of FASD, there is a public health imperative to prioritise prevention, interventions and support. In this article, we outline the current state of play regarding FASD knowledge and research in the UK, which is characterised by a lack of evidence, a lack of dedicated funding and services, and consequently little policy formulation and strategic direction. We highlight progress made to date, as well as current knowledge and service gaps to propose a way forward for UK research.

• adolescent health
• neonatology

Data availability statement

No data are available. Not applicable.

https://doi.org/10.1136/archdischild-2020-320435

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What is already known?

Fetal alcohol spectrum disorder (FASD) is a diagnostic term used to describe the physical and neurological deficits caused by prenatal alcohol exposure.

Alcohol use during pregnancy in the UK is estimated to be high, but recognition of FASD is low.

What this study adds?

An overview of current evidence and activities in the UK relating to FASD.

A recognition of the current gap in identification, management, service provision, data and intelligence and prevention in the UK.

Suggestions for next steps in creating better recognition for the condition to ensure support for children and their families.

Introduction

Fetal alcohol spectrum disorder (FASD) is a diagnostic term used to describe the physical and neurological deficits caused by prenatal alcohol exposure (PAE). Individuals affected by FASD have atypical neurodevelopment, 1 although only 5%–10% have physical features such as dysmorphology and prenatal or postnatal growth impact. 2 3 FASD is often referred to as a hidden disability, as the vulnerabilities in understanding, social skills and decision-making can be masked by an age-appropriate physical demeanour, reading level and expressive language skills. 4 Undiagnosed and unsupported individuals struggle to meet the expectations of society. Individuals with FASD are more likely to require access to healthcare services, require additional educational support and may disproportionally appear in the criminal justice system. 4 Early identification and support are associated with improved educational attainment and a reduction in behavioural and physical problems, social exclusion and mental illnesses. 2 The scale of FASD and its impact on the UK population are grossly under-recognised. This has a devastating impact on individuals, families and society as a whole. The cost of FASD for the UK is estimated at £2 billion per annum, 5 based on US data that primarily include healthcare costs and are a likely underestimate of wider costs, such as social care and education.

Current human and animal evidence does not indicate a safe level of alcohol consumption in pregnancy. 6 A complex interplay of maternal genetics, nutritional and environmental exposures are likely to impact on whether alcohol exposure will result in harm at an individual level. 7 While consuming higher levels of alcohol is acknowledged as a risk, individual harm associated with low to moderate levels of alcohol consumption is less well characterised. 8 Animal models show clear dose–response relationships with gestational day, 9 with even chronic low-dose exposure showing effects in older offspring. 10 The uncertainty of risk of consuming alcohol at lower levels during pregnancy has been acknowledged in drinking guidelines in the UK and internationally.

Developments in the last decade

It was only in 2016 that the four Chief Medical Officers of the UK harmonised their recommendations to advise abstinence in their revised guidelines. 6 This development came alongside international guidelines on identification and management of substance use in pregnancy from the WHO, 11 and across the world, a focus on training midwives and other professionals has been key. While there have been initiatives focused on increasing support for women who use alcohol or other substances during pregnancy, attempts at punitive measures have also been evident. In 2015, the Court of Appeal in England dismissed a case where compensation was sought on behalf of a child with fetal alcohol syndrome (FAS).

In the UK, the establishment of the All Parliamentary Party Group on FASD 5 is an important step towards increased political engagement in the topic. A significant gap, however, remains in parent support, which is limited and primarily delivered by the voluntary sector.

In terms of wider awareness raising, warning labels on alcoholic beverages have been proposed as a potentially beneficial public health intervention, 12 but few countries have mandated pregnancy warning labels and progression through international trade agreement forum has been limited. 13 In 2020, Australia progressed to make pregnancy warning labels mandatory after two decades of advocacy and opposition from the alcohol industry.

This remainder of this paper provides an overview of the current FASD evidence base from a UK perspective.

There are no reliable estimates of the prevalence of FASD in the UK, leading to a lack of awareness, which is a barrier for implementing successful prevention programmes and developing services. Prevalence of FASD can be estimated by quantifying the number of women who consume alcohol during pregnancy and modelling the likely outcome in terms of FASD. This relies on self-report, which can be problematic because of reporting bias. 14 15 Estimates of alcohol consumption during pregnancy using Global Burden of Disease models suggest 41.3% of pregnant women in the UK consume alcohol at some point during pregnancy, which can be extrapolated to a modelled estimate of FASD prevalence of 3.2%. 16 Direct estimates of alcohol consumption in pregnancy in the UK were produced from the Screening for Pregnancy Endpoints study, which suggested 75% of women in the UK consumed some alcohol during pregnancy, with 33% reporting binge drinking at least once. 17 The Infant Feeding Survey (IFS), last conducted in 2010 (now discontinued), found that 49% of women who drank alcohol before pregnancy stopped and a further 46% reduced their consumption. 18 These figures conceal significant age and demographic differences in consumption; for example, the IFS found a higher prevalence among women aged over 35 years and in those in managerial and professional occupations, compared with those who had never worked.

The second method of estimating FASD prevalence is through active case ascertainment studies, which are considered gold standard 19 but are yet to be completed in the UK. Passive surveillance screening studies in Scotland and reports from hospital episodes statistics in England demonstrate lower levels of FASD than would be expected based on the prevalence of alcohol exposure in pregnancy. 20 21 Underdiagnosis may occur for a variety of reasons, including lack of knowledge and specialist training among health professionals, and late emergence of behavioural difficulties by which time evidence of PAE may be lacking. A screening algorithm applied to cohort data for one region of the UK suggests 6%–17% of children met criteria for FASD. 3 Given the high FASD prevalence, it is unlikely that highly specialised services for diagnosis and support of affected individuals would meet the demand.

Assessment and diagnosis

FAS was first described over 40 years ago, yet the first UK diagnostic guidelines for individuals with PAE were published in 2019. 22 As the UK evidence base on FASD is limited, this guideline was largely based on best practice from international sources. 23 A pilot study of FASD assessment in NHS Ayrshire and Arran, Scotland, compared specialist versus mainstream models, the latter using Child & Adolescent Mental Health & Community Paediatric Services. The study found disorder-specific pathways less favourable compared with mainstream neurodevelopmental pathways. Mainstream pathways facilitate assessment of other conditions, such as attention deficit hyperactivity disorder (ADHD), developmental coordination disorder and autism spectrum disorder (ASD), alongside FASD. 24 The complexity of overlaps and relatively high prevalence of these conditions, and overlap in methods, makes mainstream pathways a sensible and cost-effective solution to provide diagnostic services. Optimum pathways comprise input from a multidisciplinary team, ideally with access to clinical psychologists, paediatricians, psychiatrists, speech and language therapists, and occupational therapists, alongside carers and education professionals. Individuals with FASD require mental health and/or risk assessment as part of their assessment.

Feedback from individuals with FASD highlight the importance of diagnosis and a holistic understanding of strengths and difficulties, all of which can be described as interventions in themselves. 24 These can be addressed through a comprehensive neurodevelopmental approach. To determine FASD, evidence of PAE alongside significant differences across three brain domains and/or brain anatomy is required. 22 Although best practice advocates for a neuropsychological profile of strengths and weaknesses, further research is required to identify the most sensitive and specific tests, 25 alongside feasibility studies for NHS implementation. To date, however, there are very few places in the UK that offer such approaches. Two services exist in southern England, and one of these FASD services has existed for over a decade. Following national training and ongoing government support, FASD assessments are becoming more accessible in Scotland. Other areas are yet lacking.

In Scotland, direct government support has led to significant progress over recent years by improving the awareness and recognition of FASD. In 2019, the Scottish SIGN Guideline 156—Children and Young People Exposed Prenatally to Alcohol was published. 22 The guidelines provide recommendations based on best available evidence and consensus for the assessment and diagnosis of children and young people affected by PAE to aid service development and delivery. These developments are key to improving the lives of people living with FASD.

FASD is occasionally diagnosed elsewhere: very obvious cases (eg, those with a clear history of PAE and physical stigmata) may be diagnosed in generic paediatrics and genetics services. There is little, if any, assessment in high-risk settings such as child protection and criminal justice.

Interventions following identification

Internationally, the quality of research into interventions for people affected by FASD remains limited. 26 Reviews of the literature over the last decade have shown development of ideas, but limited progress towards gold standard randomised controlled trials (RCTs). 26 27 Two areas can be used to highlight this: parenting and medication. Several parenting interventions have been developed in different areas of the world, ranging from methods of psychoeducation to direct intervention, of which few have been tested in an RCT. 26 One promising pilot RCT is the ‘GoFAR approach’, 28 which targets adaptive function and self-regulation, cited within the Diagnostic and Statistical Manual of Mental Disorders as central difficulties in FASD. However, a larger-scale trial is still awaited. While no medications appear to improve FASD-specific outcomes, the effectiveness of medication for comorbid conditions such as ADHD has been explored. While a small-scale trial has been conducted, it was underpowered to draw firm conclusions. Instead, a consensus of practice-based evidence currently guides the treatment of comorbid FASD and ADHD. 29 These areas highlight that, while globally much work has been done to improve the quality of life and understanding of FASD, there is a need to systematically and robustly evaluate interventions. This needs to be appropriately funded to develop gold standard evidence that can inform guidance development groups, such as the UK National Institute for Health and Care Excellence (NICE).

Prevention of alcohol-exposed pregnancies (AEPs)

Preventing unplanned pregnancies may be a key step in preventing an alcohol-exposed pregnancy (AEP). The CHOICES intervention focuses on women who may become pregnant and has been tested in RCTs primarily in the USA. 30 These interventions have shown effectiveness in reducing risky alcohol use but also in increasing contraceptive use, in student populations as well as in women recruited from wider community settings (eg, see Ingersoll et al 31 ). To date, trials of this intervention have not been undertaken in the UK. International research has also explored trajectory of drinking behaviours in women of childbearing age and how these change or may transfer into, and after, pregnancy. 32 Replication of such research in a UK context, along with exploration of causal factors and attitudes surrounding prenatal alcohol use, is needed.

Providing appropriate antenatal and postnatal care for women who drink alcohol is only possible if those at risk can be identified. Self-reports are influenced by factors such as recall bias, the patient–clinician relationship, expected social norms, fear of perceived judgement 14 and time point when women are asked about their alcohol use. 33 There is a lack of evidence for the accuracy of self-report alcohol screening instruments in antenatal settings in the UK. 34 However, a bespoke screening tool has been developed and implemented in the North East of England and awaits evaluation. To provide further understanding of the prevalence of PAE, studies have evaluated blood biomarkers, alone or a combination with self-report. A UK study found that these biomarkers are efficacious in obtaining measures of alcohol use during pregnancy higher than that of self-report. 35 While a systematic review of a range of biomarkers concluded that the published evidence was not sufficient for supporting routine use in antenatal care, 36 a review of blood biomarkers, along with self-report measures 37 and recent international work, has shown promising results, indicating that further investigation is warranted. 38

Despite the known issues with identifying alcohol use through self-report, results from self-reported screening assessments can inform the delivery of a brief intervention. 39 The efficacy of brief interventions in antenatal care is uncertain primarily due to heterogeneity and varying quality of trials assessing their use for pregnant women. 40 Qualitative research from Scotland, where a national alcohol brief intervention (ABI) programme was introduced in 2009, shows that implementation of ABIs in antenatal care varied between different health boards in relation to screening tools used. A key aspect of improving low rates was to focus on a culturally appropriate conversation, and such local adaptations were necessary to successfully implement ABIs in practice. 41 Doi et al 42 similarly found that Scottish midwives were positive about delivering ABIs, though the midwife–woman relationship may not be well established at the initial appointment, making it harder to discuss the topic. More recent work, including midwives from across the UK, indicated that approaches to assessing women’s alcohol use varies nationally and even at regional level, with no uniform approach. 43 While there is some evidence that preventive approaches vary across the UK, further evaluation of different approaches and their effectiveness is needed.

Training of professionals

FASD training is needed across different professional groups. The relatively low levels of training in the UK are reflected in significant knowledge gaps, and low levels of awareness and confidence. 44 Survey data of UK midwives showed that 19% had not received any training on alcohol screening or management during their prequalification training and 33% had not received any training after qualifying. 43 A survey of paediatricians showed only half were diagnosed with FASD and over a third expressed concerns around stigmatisation of diagnosis. 45 These factors could explain the considerable underdiagnosis in the UK. Screening for alcohol use and FASD and the onward referral processes are acknowledged learning requirements for healthcare professionals. Even so, current practices and services are diverse, haphazard and lack national guidance. 45 Given the high prevalence of FASD, comprehensive multiagency training is required, targeting health professionals, social services, child protection agencies, criminal justice officials and teachers. The majority of early childhood educators in the UK report knowing little or nothing at all about FASD and feel ill-equipped to support children with FASD. 46 This concurs with anecdotal evidence and reports from teachers in primary and secondary education who also received inadequate or no initial teacher training or continued professional development on this topic. 47

Ongoing activities

Funded studies into FASD in the UK remain limited, in contrast with, for example, the USA, where the National Institute on Alcohol Abuse and Alcoholism (NIAAA) has recently issued a US$30 million call specifically for FASD research. Researchers at the University of Salford are undertaking the first active case ascertainment study of FASD in the UK, in a project funded by Greater Manchester Combined Authority (GMCA). The Salford team is also developing a training programme for parents of children with FASD, designed to reduce stress at home and improve life outcomes, in a project funded by the Medical Research Council. A multipronged campaign is under way to reduce AEPs in the Greater Manchester region. This includes FASD-specific training for professionals, and addiction and contraception support for women at risk of an AEP based on the CHOICES intervention, 30 routine alcohol screening at antenatal care, and an online public health campaign to increase understanding of FASD. The impact of these interventions will be evaluated by further research funded by GMCA. Another prevention-focused study, led by University of Hull, involving midwives in the North East of England, has been funded by the National Institute for Health Research and supported by the regional antenatal care network.

Funding from the USA’s NIAAA continues to support the development in Oxford and Brighton of three-dimensional facial analysis of individuals with FASD. Birmingham City University has committed funding to a 4-year doctoral post to explore the lived experiences of adults with FASD in recognition of the paucity of research in this area. Other unfunded research and data continue to be presented from careful evaluation of clinical cohorts. These datasets come with inherent biases, yet provide insights into future hypothesis testing and allow evaluation of ‘natural experiments’, that is, situations that arise by chance but allow an experimental approach which cannot be replicated in research samples for ethical reasons. 48 Without a strategic approach and a coordinated research strategy in the UK to produce specific calls for research in the area, it is likely to remain an understudied area.

Conclusions

The health and social impacts of FASD in the UK are significant and is a public health issue in need of further attention. There is a lack of evidence and prioritisation of FASD, leading to gaps in support services, research funding and acknowledgement of the condition within policy documents, professional education programmes, and clinical practice. However, the Scottish Government has made a clear commitment to FASD and supporting those affected. 49 The Scottish Alcohol Framework includes approaches to prevention, diagnosis, research commissioning and data collection for the years to come.

Estimates indicate that FASD is more common than, for example, ASD, 50 yet in contrast to services for ASD, there is no coordinated investment in diagnosis or support. Only a few places in the UK have dedicated services that provide the important information families need to put appropriate support in place. Most of the evidence currently available for the UK is based on estimates from international work, a small number of UK-based research studies or evidence syntheses. We propose that in order to address this important public health issue, FASD needs to be appropriately recognised in health and social policy, prioritised through research and service provision, and adequately addressed in education of professionals likely to come into contact with pregnant women and individuals with FASD.

Specifically, we recommend that there is investment in

Accurate data collection of alcohol exposure periconception and during pregnancy.

Sustained follow-up of women and children.

Active case ascertainment studies in the general population, and specific populations, for example, care-experienced children and young people.

The mental health impact of individuals with FASD when seen together with comorbid traumatic experiences and prison populations.

Service design and professional education to ensure coordinated diagnosis and support can be provided to affected individuals and their families.

This will provide accurate prevalence figures and allow robust estimates of the (likely great) cost of this condition to UK society. The recent policy and clinical guidelines development in Scotland are positive steps. NICE has announced quality standards to be developed based on these guidelines. We hope these form the first steps for continued progress in this potentially common but under-recognised and often neglected disorder.

Ethics statements

Patient consent for publication.

Not required.

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Twitter @lesaangelica, @rajamukherjee10, @blackbu5, @mykiesutt

Correction notice This article has been corrected since it first published. The provenance and peer review statement has been included.

Contributors RM and PC convened the first meeting of the UK FASD Research Collaboration, where the authors of this paper met to establish research priorities and create an outline of this paper, led by LS. All authors contributed writing sections of the paper, which was edited and coordinated by LS. All authors reviewed the final manuscript before submission.

Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

Competing interests RM is an unpaid voluntary Medical advisor to various UK and international FASD charities and has received occasional honoraria for academic talks related to FASD. JS, SB and DZ have funding from a Scottish Government grant to expand training, research and clinical knowledge of FASD. Remaining authors have no conflict of interest to report.

Provenance and peer review Not commissioned; externally peer reviewed.

Linked Articles

• Original research Genetic testing in patients with possible foetal alcohol spectrum disorder Zena Lam Kathryn Johnson Rosalyn Jewell Archives of Disease in Childhood 2020; 106 653-655 Published Online First: 23 Nov 2020. doi: 10.1136/archdischild-2020-319572
• Atoms Highlights from this issue Nick Brown Archives of Disease in Childhood 2021; 106 i-i Published Online First: 18 Jun 2021. doi: 10.1136/archdischild-2021-322579
• Miscellaneous Correction: Fetal alcohol spectrum disorders: an overview of current evidence and activities in the UK BMJ Publishing Group Ltd and Royal College of Paediatrics and Child Health Archives of Disease in Childhood 2021; 106 e46-e46 Published Online First: 20 Oct 2021. doi: 10.1136/archdischild-2020-320435corr1

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• Volume 8, Issue 12
• Systematic literature review on which maternal alcohol behaviours are related to fetal alcohol spectrum disorders (FASD)
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• Sylvia Roozen 1 , 2 ,
• Gjalt-Jorn Ygram Peters 2 , 3 ,
• Gerjo Kok 1 , 2 ,
• David Townend 1 , 4 ,
• Jan Nijhuis 1 , 5 ,
• Ger Koek 1 , 6 ,
• Leopold Curfs 1
• 1 Governor Kremers Centre , Maastricht University Medical Centre , Maastricht , The Netherlands
• 2 Department of Work and Social Psychology , Maastricht University , Maastricht , The Netherlands
• 3 Faculty of Psychology and Education Science , Open University of The Netherlands , Heerlen , The Netherlands
• 4 Department of Health, Ethics & Society , Maastricht University , Maastricht , The Netherlands
• 5 Department of Obstretrics and Gynaecology , Maastricht University Medical Centre , Maastricht , The Netherlands
• 6 Division of Gastroenterology and Hepatology, Department of Internal Medicine , Maastricht University Medical Centre , Maastricht , The Netherlands
• Correspondence to Sylvia Roozen; sylvia.roozen{at}maastrichtuniversity.nl

Objectives Fetal alcohol spectrum disorders (FASD) is a worldwide problem. Maternal alcohol consumption is an important risk factor for FASD. It remains unknown which alcohol consumption patterns most strongly predict FASD. The objective of this study was to identify these.

Design Systematic literature review.

Methods We searched in PubMed, PsychINFO, PsycARTICLES, ERIC, CINAHL, Embase and MEDLINE up to August 2018. The query consisted of keywords and their synonyms related to FASD, pregnancy and behaviour. Studies were excluded when not published in English, were reviews or involved non-human subjects. Substantial heterogeneity precluded aggregation or meta-analysis of the data. Instead, data were qualitatively inspected.

Results In total, 21 studies were eligible for further data analysis. All studies that measured both maternal alcohol drinking behaviours and FASD reported retrospective data on maternal drinking patterns, employing both continuous and categorical measures and exhibiting substantial heterogeneity in measures of alcohol consumption (eg, timing of exposure, quantification of alcohol measure and definition of a standard drink). Study quality improved over time and appeared higher for studies based on active case ascertainment, especially when conducted in schools and when behaviour was assessed through interviews.

Conclusions We aimed to identify specific maternal drinking behaviour(s) related to FASD. The state of the literature precludes such conclusions. Evidence-based preventive measures necessitate identifying which prenatal alcohol drinking behaviour(s) are most in need of intervention. Therefore, we formulate three recommendations for future research. First, future studies can optimise the value of the collected dataset through specifying measurements and reporting of maternal drinking behaviours and avoiding categorised measures (nominal or ordinal) whenever possible. Second, samples should not be selected based on FASD status, but instead, FASD status as well as maternal alcohol consumption should both be measured in a general population sample. Finally, we provide 10 reporting guidelines for FASD research.

• prenatal diagnosis
• substance misuse
• preventive medicine

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/ .

https://doi.org/10.1136/bmjopen-2018-022578

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Strengths and limitations of this study

This systematic literature review uses a comprehensive search strategy to cover the published literature.

We did not consult grey literature.

Consultation about data aggregation took place with three independent alcohol experts.

Substantial heterogeneity prevented synthesis but yielded a rich set of recommendations as to reporting guidelines and measurement principles.

Introduction 

Prenatal alcohol exposure is one of the leading causes of mental retardation resulting in irreversible lifelong consequences for the unborn child (eg, neurocognitive deficits, growth deficiencies and facial dysmorphology). 1 These adverse outcomes are also known as fetal alcohol spectrum disorders (FASD). The spectrum encompasses various diagnostic subtypes: fetal alcohol syndrome (FAS), partial fetal alcohol syndrome (pFAS), alcohol-related neurodevelopmental disorder (ARND), alcohol-related birth defects (ARBD) and neurobehavioural disorder with prenatal alcohol exposure (ND-PAE). 1 2 Epidemiological research implies that FASD is a worldwide problem. Initial FAS prevalence estimates ranged from 0.5 to 7 per 1000 live births. 3 4 Recent systematic literature reviews 5 6 including multiple meta-analyses reported estimates ranging from 0.11 to 55.42 per 1000 (FAS), from 0.8 to 43.01 per 1000 (pFAS), from 0.12 to 20.25 per 1000 (ARND), from 1.03 to 10.82 per 1000 (ARBD) and from 1.06 to 113.22 per 1000 (FASD).

FASD, as its name implies, is caused by alcohol use. Several reviews have aimed to further elucidate the relationship between alcohol use and filial FASD. 7 8 Specifically, mothers of children diagnosed in the FASD spectrum reported drinking levels ranging from mild to excessive (‘binge drinking’) alcohol use. 7–13 The severity of FASD may be dependent on the level, pattern and timing of prenatal alcohol exposure before and during pregnancy, 13 14 along with other confounding factors such as nutritional status of the mother (eg, vitamin or mineral intake), environmental factors (eg, social relationships, stress), maternal age and genetic makeup. 14–16 As yet, there is no known safe amount of alcohol to drink while pregnant. 1 13 17 18

Two systematic literature reviews reported associations between level of alcohol exposure and negative effects on child development. 7 11 Both reviews show the negative effects of higher amounts of alcohol intake (daily alcohol consumption up to four or more drinks per occasion before and during pregnancy) related to various neuropsychological outcomes (including but not specific for a FASD diagnosis). However, these reviews are inconclusive about behaviours related to the outcome of FASD specifically, 5 7 11 or the effects of consumption of lower amounts of alcohol.

Planning evidence-based health-promoting programmes requires an adequate understanding of which maternal behaviour(s) are associated with FASD. Note that maternal alcohol consumption is not the only factor for filial FASD. Paternal and even grandparental consumption patterns have also been implicated, 19 20 but as yet it remains undecided whether paternal and grandparental consumption should also be included in the FASD definition (effects of paternal and grandparental consumption are considered necessarily either genetic or through influencing maternal alcohol consumption, whereas maternal alcohol consumption has a direct teratogenic effect). However, for the sake of this review, we limited ourselves to maternal alcohol consumption. Specifically, a first step for designing prevention programmes requires defining specific target behaviour(s) of the target population related to FASD. 6 21 However, the literature remains inconclusive about which maternal drinking behaviours are related to alterations of the fetal development. Despite this conflicting and inconclusive evidence of the negative effects on the developing fetus, public health recommendations are made nonetheless. These recommendations share one common principle, namely that complete abstinence of alcohol use during pregnancy is the safest approach to prevent any possible risks to the unborn child. 1 13 17 18 However, despite this common thread, there are also many differences between the recommendations. For example, the British Medical Association lists four different recommendations that are currently made in the UK alone. 13 This heterogeneity is problematic because communicating multiple contrasting recommendations is confusing for the target audiences. At the same time, there are good arguments to tailor the recommendations. For example, it is likely that although any alcohol consumption may entail risks, binge drinking (BAC to 0.08 g per cent or above; four or more drinks in about 2 hours) is one of the serious risk factors and associated with severe forms of FASD. 22 Therefore, it appears that special attention for specific risk groups such as heavily drinking pregnant women is warranted.

Yet, implementing such a tailored approach is currently hindered by the lack of knowledge regarding the dose–response relationship and potential moderators. On the one hand, insufficient evidence is available about the association of different alcohol-related behaviours to FASD-related risk, especially low doses of alcohol, to adequately delineate target groups to enable tailored communication. This would seem to justify foregoing the heterogeneous recommendations and instead converging on an abstinence recommendation. However, in some target populations, such a total abstinence recommendation does not seem feasible. Especially high-risk populations, for example, heavily drinking women, may not be able to completely eliminate their alcohol intake, for example, because of personal factors as self-regulation skills, or environmental factors such as social pressures. Given that a total abstinence recommendation may be unrealistic for some of the highest risk populations, such a recommendation can be ethically problematic.

To illustrate this, consider figure 1 . This figure shows two potential dose–response relationships between weekly maternal alcohol consumption and risk of filial FASD for a given individual (note that individual vulnerabilities can vary). The left panel shows a sigmoid relationship, where risk remains low if less than five units are consumed weekly, whereas in the linear dose–response relationship depicted in the right panel, risk is already considerable at five consumptions weekly. For those subpopulations where abstinence recommendations may be unrealistic, if the dose–response relationship is similar to that shown in the left panel, a harm reduction message such as ‘consume at most five units’ (the yellow areas in figure 1 ) may be easier to defend than if the dose–response relationship is linear. Not only may such a message be easier to defend, it may be more effective at decreasing FASD prevalence. Setting unachievable goals has little behaviour change potential, 23 and if a more achievable goal can stimulate the target population to moderate their alcohol intake enough to decrease the risk of FASD, while an abstinence message, being unrealistic, has no effect, the ethics of an abstinence message become questionable. If, however, the risk increases very rapidly even with light alcohol consumption, deviating from an abstinence message may be damaging.

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Two examples of possible dose–response relationships between maternal alcohol consumption and probability of filial FASD. FASD, fetal alcohol spectrum disorders.

Animal models have provided some evidence as to potential dose–response relationships. However, such models are not fully translatable to humans, 16 and especially given that the present research question concerns not simply whether a dose–response relationship exists, but what the nature of this relationship is, relying on animal models does not seem appropriate.

Further research is warranted to identify behaviours for health promotion programmes to target on. Developing health promoting programmes aiming at reducing alcohol consumption during pregnancy first requires identifying which prenatal alcohol drinking behaviour(s) are most in need of intervention. The purpose of the present study is to conduct a systematic literature review and meta-analysis to identify those maternal alcohol drinking behaviours most strongly related to FASD.

Materials and methods

Protocol and data repository.

Data will be reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline. 24 All materials and supporting documents are publicly available at the Open Science Framework repository at https://osf.io/whq45/. In this repository, we have numbered the directories that organise the materials. Hereafter, we will refer to materials in this repository as ‘resource 1’ through ‘resource 8’, which correspond to these directories.

Ethics statement and patient and public involvement

The current study extracted data from online databases and did not involve participation of participants; therefore, it was not necessary to obtain ethical permission.

Search strategy

A search was conducted in PubMed, PsychINFO, PsychARTICLES, ERIC, CINAHL, Embase and MEDLINE databases up to August 2015 using an extensive query consisting of keywords related to FASD, pregnancy and behaviour (eg, FAS, pregnancy, alcohol use and risk factor). We reran the query just before submitting the manuscript in August 2018 and performed a cursory inspection to scan for newly added papers. Moreover, we applied the ascendancy approach by inspecting the reference lists of included articles (the complete queries are included in resource 1).

Study selection

Resulting hits from the query were exported and screened by two independent screeners in three rounds. The first screening round was based on titles only; the second, on titles and abstracts; and the third, on the full-text articles. Records were included if they were written in English and reported maternal alcohol-related behaviours associated with a FASD diagnosis. Records that were duplicates, concerned reviews or meta-analysis, or concerned studies that involved non-human subjects were excluded. An extensive list of inclusion and exclusion criteria is located in the screening instructions (resource 2).

Data extraction

Data were transferred onto extraction forms, which were templated source code files for R, 25 using Notepad++. Researcher SR completed all extraction forms including the following variables: sampling method (retrospective vs prospective), sampling selection (select vs aselect), variables on which controls were matched (eg, age mother and study year of the child), recruitment setting (eg, school and clinic), descent (native vs non-native population), geography, year of data collection, sample size, subsamples, method of diagnosis (eg, Institute of Medicine (IOM) and 4-digit), syndrome category (eg, FAS and ARND), datatype (eg, aggregate and question), datatype levels (eg, nominal and logical), confirmed maternal alcohol exposure, method of case ascertainment (active vs passive) and data collection method (self-report vs interview). Moreover, variables related to drinking behaviours were extracted. Specifically, period of alcohol consumption (eg, first trimester and before pregnancy), timeframe (concurrent vs retrospective), intensity specification (eg, any day and weekend day), specification of units (eg, oz and mg), specification of timeframe (eg, per year and per month), bingeing and alcoholism. Also, when no indication of one standard drink was provided, the units in grams were granted depending on country and their national alcohol guidelines (eg, one standard drink in the USA=14 g, Australia=10 g; see resource 5). These extraction forms were then read into R and processed by an R script.

Quality assessment

A slightly adapted version of the Newcastle–Ottawa Scale (NOS) was used for assessing the quality of non-randomised studies for further meta-analysis with a maximum of 10 stars 26 (see resource 4 for the complete assessment and comparison with the original version). The quality of each publication was assessed by two independent reviewers (inter-rater reliability=80%) who settled differences by discussion. No studies were excluded based on this quality assessment.

Data synthesis and statistical analysis

In case of sufficient homogeneity, meta-analyses and meta-regressions were to be conducted using metafor, a free package in R. 27

The systematic literature review resulted in 3404 identified hits (see figure 2 ). Twenty-one hits qualified for further screening and analysis. Hits were excluded because they were duplicates, not written in English or did not report associations between prenatal alcohol and FASD. The assessment of the included studies using the NOS revealed a wide range of quality scores with an average score of 6.57 out of 10 (for more details, see resource 5).

Flow chart of publications measuring maternal drinking behaviour(s) related to FASD included in the review. Details regarding the screening procedure and number of exclusions per exclusion criterion can be inspected at resource 2. FASD, fetal alcohol spectrum disorders.

Sample characteristics

Sample characteristics can be inspected in table 1 . First, inspection of the data shows that the included studies were reported from five different countries, including Australia (n=2), Croatia (n=1), Italy (n=2), South Africa (n=12) and USA (n=4). All studies were conducted after the year 1992. Almost all studies relied on interviews (n=17), followed by self-reports (n=3) and medical records (n=1). Moreover, all studies were based on a retrospective sampling method. Behaviour was described in terms of maternal alcohol drinking related to a FASD diagnosis. Behaviours were reported before and during pregnancy where the period during pregnancy was specified per trimester (eg, first, second and third).

• View inline

Overview of characteristics of included studies in this review

Further inspection shows that alcohol consumption was operationalised differently in each study (eg, dichotomous measures; a complete table can be found in table 1 ); in fact, no two studies used the same measure. Some studies reported units, whereas other studies reported subjective estimates (eg, many and less than). Others used dichotomous measures (eg, yes or no), a mixture of ordinal measures (eg, none, mild, moderate and heavy) or interval variables (eg, percentage). The original author’s conclusions on maternal drinking behaviours and FASD can be inspected in table 2 .

Conclusions made by authors of included studies on maternal drinking behaviours and FASD

Dichotomous measures

Dichotomous measures (eg, yes vs no) were available for 12 studies representing 44 measures (see table 1 ). These included questions concerning alcohol consumption before pregnancy. 7 10 11 20 Questions concerning alcohol consumption during pregnancy 2 8 14 included the following variables: binge drinking without specifying how this was defined, 2 8 alcoholism, 1 binge drinking (three or more drinks per occasion; five or more drinks per occasion), 9 10 12–14 alcohol consumption in general, 7 9 11 17 19 smoking as well as binge drinking (three or more drinks per occasion; five or more drinks per occasion. 13 Moreover, questions were measured if pregnant women drank alcohol during the first trimester of pregnancy, 7 9 11 13 14 17 21 second trimester, 7 9 11 13 14 17 21 and/or third trimester. 7 9 11 13 14 17 21 For more detailed information, see resource 5.

Nominal measures

Although alcohol consumption is in fact a continuous variable, it was still operationalised at the nominal level in six nominal measures used in two studies. 4 17 For more detailed information, see resource 5.

Ordinal measures

In total, 24 ordinal measures were used in eight studies (see also the numbered studies in table 1 ). These incorporated questions concerning alcohol consumption before pregnancy, 3 sometimes specified in categories of units, for example, grams a week, stopped during drinking or drank less than current use, 3 5 6 8 20 and alcohol consumption during pregnancy, 1 including variables measuring the categories of alcohol intake in units of, for example, grams a week. 3 15 Moreover, questions were measured for each trimester of pregnancy: alcohol consumption during first trimester of pregnancy 5 8 20 whereby variables were specified with categories, for example, drank less or drank more than current use, 5 8 20 alcohol consumption during second trimester 5 6 8 20 using the categories, for example, drank less or drank more than current use 5 6 8 20 and alcohol consumption during the third trimester 5 6 8 20 whereby variables were specified with categories, for example, drank less or drank more than current use. 5 6 8 20 For more detailed information, see resource 5.

Continuous measures

Surprisingly, continuous measures were only available for six studies. In total, these studies employed 29 measures (see table 1 ). These included questions concerning alcohol consumption before pregnancy 2 8 10 12 18 where variables were sometimes specified in number of drinks, for example, a day or week, 8 10 14 and during pregnancy, 10 14 where variables were sometimes specified in number of drinks, for example, during a drinking day, week and weekend. 2 11 12 14 18 Moreover, number of alcoholic drinks or drinking days were measured during the first trimester of pregnancy, 2 10 12 14 sometimes specified in numbers a day or estimated BAC 8 ; number of drinks or drinking days during second trimester, 2 10 12 14 sometimes specified in numbers a day or estimated BAC 8 ; and/or number of drinks or drinking days during third trimester, 2 10 12 14 sometimes specified in numbers a day or estimated BAC. 8

Integration

Categorical variables were based on different answer options and cut-off values, which precluded further aggregation or integration. Operationalisations on a continuous level of measurement also displayed substantial variation. Where possible, we attempted to transform these continuous measures of alcohol consumption into the same metric (eg, one standard drink defined in grams). However, even this was hindered by heterogeneity in reported standard sizes (sometimes not reported at all), types of alcohol described and other variation across countries. Moreover, few studies reported continuous data. Because of these reasons, conducting meta-analyses of the continuous variables alone was not feasible.

Consultation with three independent alcohol experts (eg, expertise in pharmacology of alcohol and measurements of alcohol drinking behaviours) revealed that aggregation of variables in the current dataset was not feasible. This substantial heterogeneity in operationalisations hindered further meta-analyses, and therefore the data will be described qualitatively below with emphasis on the used operationalisations and timing of exposure.

Because aggregation of the evidence was not possible, we instead sought to explore the heterogeneity exhibited by the included studies (note that all 230 extracted effect sizes are available in file ‘effectsizes.csv’ and an overview of the used operationalisations in ‘Alcohol use variables.csv’, both in resource 6). Given the small number of included studies, we decided to inspect visualisations of the associations between study characteristics. We plotted the quality of the studies (NOS scores), study year, measurement level of the alcohol consumption operationalisation, recruitment setting and data collection methods.

These visualisations revealed interesting patterns. The quality of studies (NOS score) seems to improve over the years. Data derived from clinical records were mainly based on ordinal measures. NOS score appeared higher for studies where maternal alcohol history was based on interviews. Finally, NOS scores appeared higher for samples recruited through active case ascertainment, especially in schools. We have included these visualisations in resource 6.

The wide range of variation in operationalisations provided a unique opportunity to compare them. Continuous measures provide detailed information about specific units (eg, oz, standard drink and BAC). If reported similarly across studies, these could be further meta-analysed. However, this requires reporting all information needed to convert the reported statistics into grams or millilitres of alcohol to enable integration with results from other countries. Other challenges appear to be present for logical, nominal and ordinal measures (eg, cut-off scores). Some studies reported categories, for example, binge drinking including three or more drinks per occasion versus five or more drinks per occasion 28 and less than four drinks a day versus more than four drinks a day. 9 None of the studies reported a description and considerations of why certain cut-off scores were chosen. Cut-off scores likely often followed recommendations by health promotion agencies or suggestions from earlier studies, but without explicit specification, this remains unclear. Perhaps the difficulty of establishing sensible cut-off values partly explains this, as doing so requires evidence syntheses to determine where exactly the effects of the relevant behaviour becomes qualitatively different. Such evidence (eg, meta-analyses of maternal alcohol consumption patterns) is not yet available. However, this should lead researchers to employ continuous operationalisations for now, rather than selecting (more or less arbitrary) cut-off scores.

In this systematic literature review, we aimed to summarise available data of studies that reported maternal alcohol drinking behaviours in relation to FASD. Data were available for 21 studies. The majority of these 21 studies were based on retrospective self-reports or interviews. A substantial heterogeneity in the applied measures for alcohol consumption was observed. Studies were based on continuous and categorical measures (dichotomous, nominal and ordinal). Continuous measures included blood alcohol content, percentages of drinking days, and alcohol consumption in grams or ounces. Categorical measures employed a variety of cut-offs to distinguish the different categories. This heterogeneity was so substantial that it precluded meta-analyses. Therefore, it was not possible to answer the original research question: the extant literature does not enable any conclusions as to the relationship between maternal alcohol consumption and the likelihood of infants developing FASD. Instead, however, a wealth of suggestions for future research was distilled from the literature.

The most striking finding was the variation in measurement instruments that were employed to assess maternal drinking behaviour. Each of the 21 included studies operationalised measures of alcohol consumption differently. The majority of studies used categorical measures. This is not desirable as these impose a discontinuous scale using cut-off scores. Because, as this review evidences, there exists insufficient evidence to derive whether alcohol consumption (as relating to FASD risk) should be considered as a continuous or discontinuous scale, and where the cut-offs should lie in the case of a discontinuous scale, such cut-off scores are necessarily arbitrary to a degree. In addition, categorising continuous data discards variance, thereby potentially obfuscating associations between variables. 29–31 The variation in cut-off scores exhibited in the studies included in this review supports this assumption of arbitrariness and prohibits aggregation of the data collected in those studies. When studies did use continuous measures, studies often did not report how many grams of alcohol were in one standard drink. By making assumptions (eg, based on the standard drink size in the country of data collection), we were able to convert most standard drink-based measures into grams of alcohol, but this was not always feasible.

Strengths and limitations

One of the reasons for this heterogeneity may be that none of the included studies were conducted primarily to investigate the association between maternal drinking behaviour and FASD; although both variables were frequently measured and reported, most studies were designed to determine prevalence or FASD symptoms. It appears that few or no studies have been designed specifically to empirically establish how maternal alcohol consumption in humans is related to the likelihood of FASD. Given the comprehensive set up of this literature review, it is unlikely that such attempts have been overlooked. The search query was very extensive, rendering omission of relevant keywords unlikely. Screening was conducted in three screening rounds by two independent screeners, and all records flagged for inclusion by one screener were retained for closer inspection. In addition, the ascendency approach was applied. Given that reports of studies where these variables were secondary measures preclude conclusions about this relationship, it is as yet not possible to establish which recommendations can be empirically justified. In other words, even though in some target populations a total abstinence recommendation does not seem feasible. Available literature as yet offers no clear guidance that enables exploring a recommendation that could balance feasibility for the target population with dangers to health. Moreover, Mamluk et al 32 underlined the lack of data to make robust conclusions on the harmful effects of prenatal alcohol exposure and the unborn child. However, our inspection of the literature did yield a number of valuable recommendations for future research.

Recommendations

The original aim of this review was to provide a first step on the road to theory-based and evidence-based intervention development. We had hoped that after identifying the risk related to different behavioural patterns, we could provide guidelines for prevention workers working with different target populations (eg, alcohol-dependent pregnant women or teenage mothers). The next step could then be to map the determinants of those behaviours in those populations (ie, why individuals engage in the relevant undesirable and desirable behaviours), 33 so that these can be targeted by behaviour change principles 34 that are then integrated into prevention campaigns. 35 However, it seems that the literature as yet has little guidance to offer. Because designing effective interventions first and foremost requires a thorough understanding of the target behaviour(s), it is therefore important that future research considers the limitations identified in this review so that in the future, a clearer picture may emerge.

The first recommendation is addressed specifically to epidemiological researchers and is based on the observation that the majority of studies assessed maternal drinking as part of a prevalence study. Because these studies form the largest part of the available data regarding associations between maternal alcohol consumption and FASD outcomes, it is important to pay close attention to the measurement of alcohol consumption, even in epidemiological studies with different primary aims.

Second, in general, researchers should anticipate the need to aggregate their measures of alcohol consumption with measures from other studies: in other words, conversion to consumption in metric units, such as grams of alcohol, in a specified time period, such as week or month, should be possible. If such conversion cannot be performed, the study cannot contribute to an accumulation of evidence. For example, many studies did not specify what exactly constituted a unit of alcohol (ie, one standard drink). This means that it was necessary to try and identify the definition of a unit of alcohol in the country where the data were collected in the period where the data were collected, but even then the obtained definition was unreliable as sometimes researchers conduct studies away from their home country yet use their home countries’ unit definitions when reporting the results. Another example is that if timing of exposure was not specified, it is not clear whether the behaviour occurred during the first, second or third trimester (or was an aggregate of those periods).

This recommendation translates into a number of specific suggestions. Most of these are covered by following guidelines for the measurement of alcohol consumption, such as those specified by Dawson 36 and Sobell and Sobell, 37 but specifically, it is recommended that future studies assessing specific maternal drinking behaviours should report at least the following (see below for the recommended approach in each case):

How the sample was selected (eg, retrospective) and which method was used (eg, convenience sampling method).

The maternal characteristics variables (eg, age, descent and educational level).

Which method (or specific questions) was used to assess maternal alcohol consumption (eg, alcohol timeline follow back approach).

The timing of exposure when assessing maternal alcohol consumption (eg, first trimester pregnancy).

The frequency of exposure when assessing maternal alcohol consumption (eg, number of exposure sessions per week or month).

The amount of alcohol consumed per exposure session. 36

The sample size.

What was considered as one standard drink using International System of Units (ie, grams or millilitres of alcohol).

If discontinuous (categorical) measures cannot be avoided, clear justification of the employed cut-offs.

The third recommendation refers to the complexity of exploring the association between maternal alcohol consumption and filial FASD. One cannot recruit children with FASD and then proceed to select children without FASD. This is not helpful because the number of children without FASD but with parents with matched alcohol consumption patterns is the variable of interest. The proportion of children with FASD within each group of parents with a given alcohol consumption pattern is the dependent variable to measure. For example, let us assume that in the left panel of figure 1 (showing the sigmoid relationship), the probability of FASD is 1% if alcohol consumption is lower than five units; 25% if alcohol consumption is between 5 units and 10 units; 75% if alcohol consumption is between 10 units and 15 units; and 99% if alcohol consumption exceeds 15 units. Similarly, let us assume that in the right panel (showing the linear relationship), the probability of FASD is 12.5% is alcohol consumption is lower than 5 units; 37.5% is alcohol consumption is between 5 units and 10 units; 62.5% is alcohol consumption is between 10 units and 15 units; and 87.5% is alcohol consumption exceeds 15 units. This means that for 1000 parents consuming between 0 units and 5 units (the yellow area), in the sigmoid scenario, 10 children will develop FASD and 990 (99 times more) will not, while in the linear scenario, 125 children develop FASD and 875 will not (seven times more). Now, imagine that a researcher visits a school and screens all children for FASD, and 10 children screen positive for FASD. For simplicity’s sake, let us assume that the parents of all these children happened to consume less than 5 units per week during pregnancy. Now, this researcher will not know whether to create a matched control group that is 99 times larger (as would be the case in the sigmoid scenario) or seven times larger (as would be the case in the linear scenario). It is exactly the relative sizes of these groups that is the variable to measure, and the only way to do so is to measure both maternal alcohol consumption patterns and filial FASD in a large sample.

Based on these recommendations, the ideal design would be a large-scale (Note that what constitutes ‘large-scale’ depends on the expected FASD prevalence in a population as well as the target behaviour under investigation, eg, abstinence vs moderated drinking, or abstinence vs regular drinking patterns. These two parameters determine the effect size of the association that is to be estimated, which in turn enables computation of the required sample size for accurate estimation of that effect size using Accuracy in Parameter Estimation methods.) prospective study where maternal and paternal alcohol consumption patterns would be assessed both using self-reports (conform the recommendations made earlier) as well as objective measures such as biomarkers for alcohol consumption. 38 Infants would then be assessed for FASD according to the revised IOM guidelines 1 and other recommendations provided by Roozen et al , 6 and the FASD prevalence would be related to alcohol consumption patterns of both parents separate and in conjunction. This design also enables examination of potential confounders such as social economic status or age. Such an ideal design may not always be feasible. After all, learning about the association of parental drinking patterns to filial FASD requires assessing drinking patterns in all pregnancies: it is not possible to start from identified FASD cases, as we explained earlier. However, even when other designs are used, it is important that researchers anticipate data aggregation over studies and therefore attempt to provide alcohol measures in metric units.

The present review focused on reported data on maternal drinking behaviours. Some of the included studies also reported paternal drinking patterns or grandparental drinking patterns. The role of paternal drinking and transgenerational toxicity on fetal development and FASD is not well understood. A recent review study by Gupta and colleagues 19 reported that paternal alcoholism alters the gene expression for fetal susceptibility to FAS. In another review, Resendiz and colleagues 20 argue that transgenerational toxicity may play a role in FASD aetiology. Moreover, social facilitation by paternal drinking is significantly associated with maternal drinking. 39 The origin of FASD is therefore based on maternal drinking behaviours and by many other factors (eg, genetic and epigenetic predisposition, maternal body makeup and lifestyle). Gupta and colleagues 19 emphasised that FAS aetiology, and also other diagnosis within the FASD spectrum, is based on a complex interaction of different factors whereby cautious interpretation is warranted.

The current knowledge on maternal alcohol drinking behaviours in relation to FASD is limited. Behaviours were measured using various techniques and operationalised differently. For evidence-based preventive measures, it is necessary to identify which prenatal alcohol drinking behaviour(s) are most in need of intervention. Several recommendations have been made that can facilitate accumulation of evidence over studies. Following these recommendations can contribute to establishing the evidence base required for the development of effective preventive health promoting programmes.

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Patient consent for publication Not required.

Contributors SR, G-JYP, GerjK and LC designed the study and directed its implementation, including quality assurance and control. Authors DT, JN and GerK helped supervising the field activities. SR and G-JYP conducted the literature review and analyses and prepared the Materials and Methods and the Discussion sections of the text. All other coauthors contributed to successive drafts. All authors gave significant input in preparation of the article and approved the manuscript and submission.

Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

Competing interests None declared.

Provenance and peer review Not commissioned; externally peer reviewed.

Data sharing statement All data, analysis scripts and other materials are publicly available at the Open Science Framework repository for this study ( https://osf.io/whq45/ ).

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Article Contents

Introduction, social problems, breakdown in public morality, the crusade, moral panic, feverish public concern, exaggerated estimates, biomedical entrepreneurship, distortion of aetiology, democratization, implications.

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FETAL ALCOHOL SYNDROME: THE ORIGINS OF A MORAL PANIC

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ELIZABETH M. ARMSTRONG, ERNEST L. ABEL, FETAL ALCOHOL SYNDROME: THE ORIGINS OF A MORAL PANIC, Alcohol and Alcoholism , Volume 35, Issue 3, May 2000, Pages 276–282, https://doi.org/10.1093/alcalc/35.3.276

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Since its discovery almost 30 years ago, the fetal alcohol syndrome (FAS) has been characterized in the USA, as a major threat to public health. In part because FAS resonated with broader social concerns in the 1970s and 1980s about alcohol's deleterious effect on American society and about a perceived increase in child abuse and neglect, it quickly achieved prominence as a social problem. In this paper, we demonstrate that, as concern about this social problem escalated beyond the level warranted by the existing evidence, FAS took on the status of a moral panic. Through examples taken from both the biomedical literature and the media about drinking during pregnancy, we illustrate the evolution of this development, and we describe its implications, particularly how it has contributed to a vapid public policy response.

Fetal alcohol syndrome (FAS) is a pattern of anomalies occurring in children born to alcoholic women ( Jones and Smith, 1973 ). The main features of this pattern are pre and/or postnatal growth retardation, characteristic facial abnormalities, and central nervous system dysfunction, including mental retardation ( Stratton et al. , 1996 ). Despite the pervasiveness of alcohol and drunkenness in human history ( Abel, 1997 ), FAS went largely unrecognized until 1973, when it was characterized as a ‘tragic disorder’ by Jones and Smith, the Seattle physicians who discovered it ( Jones and Smith, 1973 ). By the 1990s, FAS had been transformed in the United States from an unrecognized condition to a moral panic characterized as a ‘major public health concern’ (e.g. Stratton et al. , 1996) and a ‘national health priority’ ( Egeland et al. , 1998 ). In this paper, we trace this evolution, paying special attention to the ways in which this moral panic has inflated fear and anxiety about the syndrome beyond levels warranted by evidence of its prevalence or impact. To acknowledge that the current level of concern about FAS is exaggerated is not to suggest that the syndrome does not exist. One of us (E.L.A.) has spent his entire professional career researching and writing about FAS and continues to be actively engaged in its prevention.

Any activity people engage in is subject to someone's opprobrium. Activities can rise to the level of ‘social problems' when someone or some group attributes harms or dangers to those activities, calls upon governmental powers to put an end to those harms, and is able to convince others of that view. The likelihood of this occurring increases when the activity that is identified as a problem resonates with underlying societal concerns and anxieties and has endorsement by experts who give legitimacy to such claims ( Blumer, 1971 ; Stone, 1989 ). Such legitimacy has the effect of attracting media attention which in turn can attract further support from the public and policy makers ( Gerbner and Gross, 1976 ; Best, 1990 ).

In the USA alcohol has been a regularly targeted ‘social problem’ since the beginning of the nineteenth century. During the colonial era when per capita alcohol consumption was four times higher than at present and drunkenness was commonplace ( Gusfield, 1963 ; Levine, 1978 , 1983 ), alcohol was hailed by Puritan clerics such as Cotton Mather as ‘the Good Creature of God’ ( Levine, 1983 ). Two centuries later, the ‘Good Creature’ had become symbolic of deep rifts in American society and was rechristened ‘demon rum’. The first anti-drinking reform movement occurred in the 1830s–1850s when the poverty and disease of Irish immigrants was attributed to their liquor consumption. The next occurred in the 1880s– 1910s, when problems of nascent industrialization such as poverty, the disintegration of family life, rising crime, and mental illness, were attributed to the influence of saloons, which were also the gathering places of the second great wave of immigrants. The current anti-alcohol/drug crusade, which attributes rampant crime and the deterioration of inner cities to a breakdown in public morality abetted by alcohol and drug use, began in the 1970s as a reaction to the turbulent 1960s ( Engs, 1997 ) and intensified in the early 1980s, when the ‘war on drugs' was launched. In its wake, grassroots organizations such as Mothers Against Drunk Driving (MADD) emerged, and many states raised their legal drinking age and lowered their blood-alcohol level (BAL) criterion for impaired driving ( Engs, 1997 ). This new wave of morality was heralded in the media as America's ‘new temperance’ ( Newsweek , 12/84; Time , 5/85), the ‘sobering of America’ ( Business Week , 2/85) and ‘America: New Abstinence’ ( Fortune , 3/85) (quoted in Reinarman, 1988 ).

Concurrent with the reinvigoration of the temperance mentality in American life was the emergence of a new social problem: the victimization of children ( Best, 1990 ). The problem of child neglect/abuse, reflected in the ‘battered child syndrome’, was first described in the medical literature in 1962 ( Kempe et al. , 1962 ), and was broadened in the 1970s to encompass not only physical battering, but emotional, sexual and mental mistreatment as well. In the course of this evolution, child abuse and neglect became another symbol of America's moral decay ( Best, 1990 ). It was within this dual context of the new temperance zeitgeist and the concern about the victimization of children prevailing in America that FAS emerged as a social problem in the 1970s, evolved into a moral crusade by the 1980s with its disturbing images of children ‘wounded’ ( Greenfeld, 1989 ) or ‘bruised before birth’ ( Steacy, 1989 ), and became transmogrified into a moral panic characterized as ‘child abuse in the unborn fetus' ( Apolo, 1995 ) in the 1990s.

It is not unreasonable for people to become concerned about an issue which threatens social order, especially if the threat stems from a perceived deterioration in the values which people believe provide guidance for themselves, their children, and their society as a whole. It is probably not a coincidence that FAS entered the arenas of scientific and public awareness in the 1970s and gained such widespread acceptability and attention by the early 1980s, since the issue resonated with the renewed ideology of self control and personal responsibility associated with the conservative political climate that followed the turbulent 1960s ( Reinarman, 1988 ).

The early construction of drinking during pregnancy as a social problem shared many of the same ideologies as those underlying the crusade against drunk-driving, most notably a focus on individual, personal responsibility for ‘lifestyle choices' and a belief in the power of broad-based public education campaigns to change behaviour ( Reinarman, 1988 ). However, in the case of FAS, much of the impetus behind the emerging crusade came from the biomedical community ( Abel, 1984 ). An example of moralizing about the ‘tragic disorder’ of FAS and personal failing was an article in the Journal of Dentistry for Children , which described a despondent mother who consumed alcohol during her pregnancy allegedly lamenting ‘If only I had known’, a regret, the author stated, that occurs ‘all too often’ but need not if pregnant women would only learn, that ‘life is not a beer commercial’ ( Waldman, 1989 , p. 435). Other biomedical experts voiced breast-beating recriminations. A common theme was that the dangers of drinking during pregnancy were well known in Biblical and Greco-Roman times ( Abel, 1984 , 1997 ), implying that if we had only paid attention to the bitter lessons of the past, the modern ‘tragedy' might have been avoided. ‘Physicians, writers and theologians' had written about the effects of alcohol on the fetus ‘since Biblical times' intoned Hill and Tennyson (1980), who then chastized modern society with the inclusive moral lapse of failing ‘to heed the wisdom of our forefathers …' (p. 177). The authors concluded with a statement from a temperance tract dating to the 1860s that said it still ‘holds true today that parents are responsible for their children's infirmities, deafness, blindness and idiocy' (p. 198).

Stirred by such moral rectitude, preventing FAS became an American crusade. The policy response rested on the unproven premise that any amount of drinking in pregnancy posed a threat to the fetus. In 1981, the Surgeon General of the United States advised ‘women who are pregnant (or considering pregnancy) not to drink alcoholic beverages and to be aware of the alcoholic content of foods and drugs' ( Food and Drug Administration, 1981 ). The Surgeon General's warning stands in stark contrast to the official advice offered in other countries. The British Royal College of Obstetricians and Gynaecologists for example, issued guidelines in 1996 stating that ‘no adverse effects on pregnancy outcome have been proven with a consumption of less than 120 grams of alcohol per week’ and recommending that ‘women should be careful about alcohol consumption in pregnancy and limit this to no more than one standard drink per day’ ( Royal College of Obstetricians and Gynaecologists, 1996 ). Although these recommendations have been challenged by some ( Guerri et al. , 1999 ), they are typical of the European stance on prenatal drinking ( EUROMAC, 1992 ).

In the USA in the years following the Surgeon General's warning, several state and local governments mandated ‘point-of-purchase’ warnings about drinking during pregnancy, and federal, state and local governments embarked on public education campaigns to alert all pregnant women to the potential dangers of drinking ( Abel, 1984 ). These campaigns culminated in 1988, when the USA became the first (and still the only) country to adopt legislation requiring an alcohol warning label on every can of beer and bottle of wine and spirits mentioning the potential dangers of drinking during pregnancy (Public Law 100–690, 27 USC 201–211). By the beginning of the following decade, the crusade had turned into a moral panic, when in 1990 Wyoming became the first state to charge a pregnant woman who was drunk with felony child abuse ( Holmgren, 1991 ).

In essence, a moral panic is an exaggerated concern about some ‘social problem’. Among the characteristics of every moral panic are the alleged breakdown in public morality described above, a heightened level of public concern, which is often feverish, exaggerated estimates of the numbers of people allegedly affected by the problem, a distortion of aetiology, and democratization of the condition's occurrence, such that no particular class, race, ethnic group, or any other socially constructed category is singled out as differentially affected ( Goode and Ben-Yehuda, 1994 ; Thompson, 1998 ). The concept of moral panic originated in British sociology in the 1970s and has since been used to describe diverse social phenomena, ranging from Satanic ritual child abuse in the USA to child violence in the UK. Although some observers have critiqued the concept of moral panic and its overuse ( Watney, 1987 ), it has become an established category of explanation in both the professional sociological imagination and in lay thinking. The British media in particular have often resorted to the idea of moral panic to describe social turmoil over pornography, youth culture, mugging, and the AIDS epidemic. In the following sections, we demonstrate how the concept of moral panic is a useful way to understand the American response to FAS and the threat posed by drinking during pregnancy.

Much of the feverish concern over FAS originated and continues to be fanned in Seattle, Washington, where its discoverers first characterized it as a ‘tragic disorder’ ( Jones and Smith, 1973 ) and suggested that doctors urge their pregnant alcoholic patients to consider aborting their pregnancies ( Jones and Smith, 1974 ). Although the abortion recommendation was immediately criticized as unwarranted and alarmist ( Rosett, 1974 ; Sturdevant, 1974 ), Jones and Smith and their colleagues continued recommending that such women ‘be urged to terminate their pregnancies' ( Smith et al. , 1976 ). The fact that no prospective epidemiological study had as yet been conducted warranting such extreme measures did not deter this group, which maintained that such an ‘academic pursuit’ should not get in the way of an ‘important human question’ ( Clarren and Smith, 1978 ). As a result, the abortion recommendation continued to be reiterated until 1980 (e.g. Lindor et al. , 1980), when the first prospective study showed that FAS was a rare outcome of maternal alcoholism during pregnancy ( Sokol et al. , 1980 ), an observation subsequently confirmed by numerous investigators ( Plant, 1985 ; Abel, 1998 a ).

Concern was also fuelled by the Seattle group through a subtle broadening of the problem. The comment that no case of FAS had ever ‘been reported in a human being with a negative maternal history of ethanol use’ ( Clarren and Smith, 1978 ) carried the implication that FAS could occur as a result of any amount of drinking. Although first described in 1973 as a condition related to maternal alcoholism, by 1978, the danger of FAS was now linked to any amount of drinking during pregnancy ( Clarren and Smith, 1978 ), and this in turn carried the implication that the problem was far greater than could be imagined: ‘FAS … resembles an iceberg with the bulk of the problem out of sight and of indeterminate extent’ ( Poskitt, 1984 ). The emotional rhetoric in the biomedical literature was quickly picked up by the American mass media. Articles in newspapers and magazines introduced alleged cases with headlines such as ‘An innocent inherits the anguish of alcohol’ ( Dawson, 1992 ), ‘Pregnancy, alcohol can be a deadly mix’ ( Star-Tribune , 1992 ), ‘Drinking devastating to unborn’ ( King, 1991 ), ‘Kids pay for prenatal drinking’ ( Snider, 1990 ), ‘Children pay the ultimate price for a drink’ ( Wilson, 1998 ), ‘Prescription for tragedy: alcohol and pregnancy stack deck against baby’ ( Seattle Times , 1996 ) and ‘The tragic inheritance’ ( Theroux, 1989 ). The most trenchant description appeared in Michael Dorris's 1989 best-selling book The Broken Cord , an account of his experience raising an adopted son with FAS. The book brought the disorder to national attention and was made into a film for television.

Describing FAS as a ‘tragic disorder’ and a ‘major public health problem’ implies that it claims thousands, if not tens or hundreds of thousands of victims, and is thereby endangering the national health. The estimates of its occurrence, however, rarely supported this notion. The Centers for Disease Control and Prevention (1995 a ) place the incidence of FAS in the general population at less than 1 case/1000 (0.67/1000), similar to that reported in most prospective studies ( Abel, 1998 a ). Predictably, Seattle researchers placed it much higher; their estimate of the combined prevalence of FAS and partial FAS (referring to the presence of only some of the features) is 9.1 cases/1000, or about 1% of all births in the USA ( Sampson et al. , 1997 ). This latter estimate is among the highest in the literature and is based on two carefully selected studies of women, many of whom were at high risk for various kinds of disorders.

Popular media reports of FAS have likewise exaggerated the extent to which the syndrome is increasing in frequency, with claims such as the ‘Rate of alcohol-injured newborns soars' ( Chicago Tribune , 1995 ) and ‘the percentage of babies born with health problems because their mothers drank alcohol during pregnancy [had] increased sixfold from 1979 through 1993’ ( New York Times , 1995 ). However, since in 1979 FAS was still a new condition and most doctors did not recognize it, this ‘sixfold increase’ is more likely to represent an increase in the identification and reporting of cases, and not in incidence. These media stories were based on a report issued by the Centers for Disease Control and Prevention (CDC; 1995 a ) of the US Public Health Service. However, in the original report, the CDC noted that it had included not only diagnosed cases of FAS, but also any indication of excessive drinking, under the rubric of ‘noxious influences’. Not only was the vagueness of this category not mentioned by the media, but neither was an accompanying report the CDC issued on the same day (CDC, 1995 b ) stating that only a small portion of the medical records they examined that were coded for FAS actually met the criteria for a rigorous case definition; that is, there were many false positives for FAS. Three years later, the CDC further invalidated its earlier report when it recognized that ‘not all women who drink heavily will produce children with FAS' (CDC, 1998). In other words, the ‘noxious influences' were not always ‘noxious'. The earlier sixfold increase had in fact lacked validity.

As attention to and anxiety around FAS and drinking during pregnancy grew, the clinical symptoms of FAS multiplied ( Armstrong, 1998 a ). This process of ‘diagnosis expansion’ ( Armstrong, 1998 a ) was closely related to another phenomenon: ‘expertise expansion’ ( Armstrong, 1998 a ), in which physicians and researchers in a wide variety of subspecialties heralded with entrepreneurial zeal this ‘exciting new field’ ( Clarren and Smith, 1978 ) and the ‘new opportunities for research’. Between 1973 and 1984, 1.4% of all the articles in journals listed by Index Medicus dealt with alcohol and pregnancy compared to 0.9% for tobacco and pregnancy and 0.7% for narcotics and pregnancy ( Abel and Welte, 1986 ). Thirty-seven of these journals contained five or more articles specifically related to fetal alcohol research during this period ( Abel, 1990 ). An infusion of federal funding helped to support many new research initiatives. From 1990 to 1994 alone, the National Institute on Alcohol Abuse and Alcoholism (NIAAA) provided about 70 grants totalling between US$9.8 million and US$13.5 million annually ( Stratton et al. , 1996 ).

Subspecialists in virtually every field of medicine responded to the moral fervour and the new funding incentives with a predictable announcement of newly discovered clinical attributes of the syndrome. These new conditions were heralded as ‘a new feature associated with fetal alcohol syndrome’ ( Azouz et al. , 1993 ), a new symptom ‘not previously … described in connection with fetal alcohol syndrome’ ( Adebahr and Erkrath, 1984 ), an ‘underemphasized feature in FAS’ ( Crain et al. , 1983 ), and ‘heretofore unreported symptoms' ( Johnson, 1979 ). Among these ‘new’ symptoms were such isolated and rare anomalies as supernumerary mammillary bodies ( Adebahr and Erkrath, 1984 ), steep corneal curvature ( Garber, 1984 ), bilateral tibial exostoses ( Azouz et al. , 1993 ), tetraectrodactyly ( Herrmann et al. , 1980 ), clitoromegaly, hirsutism, and liver dysfunction (see Abel, 1990 ). Other articles raised the spectre of cancer, with reports of an association between prenatal alcohol exposure and Hodgkin's disease and leukaemia, as well as a formidable litany of tumours in the brain, liver, kidney, and adrenals (see Abel, 1990 ). More often than not, such reports were based on single isolated coincidences. The epidemiological evidence of an association between prenatal alcohol exposure and any of these conditions has never been demonstrated; most of the ‘new features' are so atypical they have only been seen in a single case of FAS and in fact are excluded from the most recent American diagnostic paradigm for FAS ( Stratton et al. , 1996 ).

The amount of alcohol consumed during pregnancy that constitutes a danger to the unborn child was a critical issue in creating the moral panic over FAS, because the lower the amount, the greater the number of potential victims (the proverbial ‘tip of the iceberg’), and consequently the greater the national guilt for condoning such a moral lapse.

The biomedical research community which provided these estimates had a certain pragmatic interest in framing the issue in terms of low thresholds because the greater the national panic, the higher the research budgets to do something to combat this national health problem. It is therefore not surprising that the estimated thresholds were, and continue to be, routinely misrepresented through the obfuscation of citing average consumption over a particular time period, rather than disaggregating the specific kinds of drinking patterns that are associated with FAS. For instance, a woman who has one drink a day every day and a woman who binges once a week, consuming six or more drinks at once, both average seven drinks a week. Yet each of these drinking patterns represents potentially very different levels of alcohol exposure for the woman and her fetus. Since peak blood alcohol levels (BALs) reached per drinking episode are a crucial factor in FAS ( Abel, 1999 ), the ‘average drinks' measure distorts the relationship between alcohol and teratogenesis and muddies our perceptions of risky drinking. Only a handful of researchers, such as Jacobson et al. (1993) and Ernhart (1991) have been forthright enough to clarify this issue. For example, in evaluating children whose mothers drank during pregnancy, Jacobson et al. (1993) placed the threshold for alcohol-related cognitive damage to children at an average of one drink a day during pregnancy, but emphasized that the effects they had observed were due to much higher exposure than indicated by this ‘average’. Since none of the mothers studied drank every day, they acknowledged that the average did not represent a typical drinking day. Instead, ‘the women who drank above this “average” threshold exposed their infants to a median of six drinks per occasion’ (p. 181). Similarly, Ernhart (1991) noted that a woman in her study who consumed an average of one drink a day during the course of her pregnancy, confined her drinking to the first 3 months of her infant's gestation, when she drank a gallon of wine, and a half case of beer, every Friday and Saturday evening. After that she did not drink for 3 months. Nevertheless, because drinking was averaged over the longer period, the woman's drinking appeared to be very low.

This bias in the medical literature has been magnified in the popular press and in lay pregnancy manuals and public health educational materials. Although many researchers recognize the significance of binge drinking as a risk for FAS, the distinction between number of drinks per drinking episode and number of drinks per week or month has been largely glossed over in public discussions of FAS, which tend to present any type of alcohol consumption as dangerous.

The essential criterion for any social problem is its universalization ( Wagner, 1997 ). As long as a problem is orphaned, especially if it is identified as a problem only within a minority race or social class, it has limited impact on society as a whole. Liberal-minded social scientists are especially wary of associating a stigmatized behaviour with race or class, because such associations perpetuate discrimination ( Wagner, 1997 ). By disassociating race or class from a stigmatized behaviour, the problem is more likely to gain public attention, because everyone now feels a vested interest in its elimination. The language of democratization therefore characterizes most social problems, e.g. child abuse, alcoholism, cocaine addiction, teenage pregnancy or domestic violence. Despite the fact that these are not ‘equal opportunity’ disorders ( Abel, 1995 ; Wagner, 1997 ), they are typically scaled up into the middle and affluent classes to draw greater attention to the problem at hand and to overcome any charges of racism, classism, elitism, or any other accusation of discrimination ( Wagner, 1997 ).

FAS has not been immune to democratization. When the disorder was first described in 1973, Jones and Smith and their co-workers took pains to emphasize its universalism by reporting that the eight unrelated children they had observed belonged to ‘three different ethnic groups …’ ( Jones and Smith, 1973 ). However, FAS has never been an ‘equal opportunity birth defect’ ( Abel, 1995 ); its inseparable handmaidens are poverty and smoking ( Bingol et al. , 1987 ; Abel, 1995 ). What Jones and Smith and their colleagues did not emphasize was that the eight children, and virtually all the other children they and others subsequently examined, were seen in hospitals serving a predominantly lower socio-economic status population. Groups whose members suffer disproportionate poverty, such as Native Americans and African Americans, are especially prone to this disorder. In the Yukon and Northwestern areas of Canada, the rate for FAS and partial FAS has been estimated at 46/1000 for Native children compared to 0.4/1000 for non-Native children, a 1000-fold difference ( Asante and Nelms-Matzke, 1985 ). In the USA, the rate of FAS among low income populations is 2.29/1000 compared to 0.26/1000, for middle- and high-income populations ( Abel, 1995 ). Despite the empirical evidence, grass roots organizations, such as the National Organization on Fetal Alcohol Syndrome (NOFAS) continue to espouse the view that FAS is a threat to all pregnancies. When NOFAS was founded, for instance, its executive director stated: ‘I think a lot of middle-class and upper-class women don't know that occasional use of alcohol during pregnancy is dangerous' ( Information Access Company, 1991 ).

While it is true that drinking occurs across all social categories in the USA, FAS is undeniably concentrated among disadvantaged groups. The very large socio-economic differences in FAS rates (Able, 1995) are not due to differences in the number of alcoholic women among the poor compared to the middle classes. In fact, drinking is much more common among the middle and upper classes than among the poor ( Abma and Mott, 1990 ; Caetano, 1994 ; Abel, 1998 a ). Instead, the reason FAS occurs predominantly among poverty stricken women is that they experience, or are characterized by, many more ‘permissive’ factors, such as smoking and poor diet, that exacerbate the effects of alcohol ( Abel and Hannigan, 1995 ). Since FAS cannot be divorced from poverty, insisting that FAS ‘crosses all lines' perpetuates the problem by situating it solely within an alcohol context instead of the wider context of poverty.

Democratization disguises the extent to which moral panic about FAS may in fact spring from much deeper social unease about changing gender roles and about class and particularly race differences ( Armstrong, 1998 a ). Many legal commentators in the USA have noted that the recent rash of prosecutions of pregnant women for substance use and purported fetal harm are concentrated among poor and most often minority women ( Roberts, 1991 ; Gomez, 1997 ). The moral panic over FAS likewise may reflect social divisions typically invisible in American society, particularly rifts over what constitutes a ‘good mother’.

Although a debate exists about the extent to which the USA differs from other countries with regard to the incidence of FAS, there can be little doubt that the American response to drinking during pregnancy is exceptional. The USA remains the only country to legislate warning labels on alcoholic beverage containers; the American Surgeon General's warning about drinking during pregnancy is unique in the strength of its recommendations that women should abstain from alcohol altogether and should, moreover, be vigilant about the miniscule alcoholic content of food and drugs. In this respect, the moral panic over FAS echoes earlier periods of concern about alcohol in American history; to wit, the prolonged struggle over temperance in the nineteenth century and the prohibition of the manufacture, sale and consumption of all alcohol in the USA between 1919 and 1933.

However, the moral panic over FAS in the USA, unlike earlier periods of social preoccupation with alcohol, is driven as much by gender division as by class or socio-economic divisions. Although its sufferers appear to be concentrated among the poor, the public image of the condition as a universal one resonates with issues of social control and gender. As Armstrong (1998 a ) has noted in an earlier analysis, the diagnosis of FAS arose at a period of intense gender agitation in the USA, and thus reflects widespread social unease about the conflict between the traditional maternal role of women and their efforts to embrace more diverse roles in modern society.

Historically, moral entrepreneurs have mobilized moral rhetoric when they have felt social norms threatened by outsiders or newcomers to society; in other words, as response to social deviance. Moral panics may arise when social elites seek to preserve or defend their status in the social hierarchy ( Gusfield, 1963 ); alternatively, moral panics may serve to deflect political attention from intractable social problems, or inequality inherent in the social structure ( Hall et al. , 1978 ). As Plant (1997) has noted in the British context, the moral panic ignited by FAS in the USA served the further purpose of diverting attention from social inequality and displacing blame for poor pregnancy outcomes to individual mothers rather than social circumstances. Women, in their child-bearing and child-rearing roles, have always been held particularly responsible for the ‘future of society’. The case of FAS illustrates that this is still true.

The moral panic ignited by concern over FAS, with its exaggerated claims, especially regarding the dangers of social and moderate drinking, and its universalization, has important implications. Reporting ‘averages' as if they represented a typical drinking day has led to a widespread perception among the American public that even one drink during pregnancy is dangerous. There have been countless reports of visibly pregnant women who were harassed by indignant strangers when seen to be drinking in public; likewise, there are accounts of morally righteous waiters and barstaff who have refused to serve visibly pregnant women alcoholic beverages. Even some American clinicians have fallen prey to this misunderstanding ( Abel and Kruger, 1998 ), which has caused some women to become so anxious that they have considered termination of their non-threatened pregnancies so as to avoid giving birth to a child with FAS ( Armstrong, 1998 b ; Lipson and Webster, 1990 ; Koren, 1991 ).

If we are to reduce the incidence of FAS, we must first accurately comprehend the problem at hand and abandon the rhetoric of moral panic. There is no epidemic of FAS births. Nor is ‘social’ or ‘moderate’ drinking among the almost 4 million pregnant women who give birth annually in the USA a risk factor for FAS. However, the risk is considerably greater for the relatively small number of women who abuse alcohol on a regular basis, and it is even greater for those women who have previously given birth to a child with FAS and continue to drink ( Abel, 1988 ).

While government has a moral duty to alert citizens to potential dangers ( Abel, 1998 b ), public education measures, such as warning labels, have no noticeable effect in reducing drinking during pregnancy ( Hankin, 1996 ), as evidenced by the fact that more, not fewer women, are now drinking during pregnancy than before the appearance of the labels (CDC, 1997). Such broad-based prevention efforts are doomed to fail, because women who give birth to children with FAS are not simply a variant of the general drinking population. A small proportion of women of child-bearing age, especially those who are most disadvantaged by poverty, bear the greatest burden of risk for FAS. If we are going to reduce the incidence of FAS, we need first to know who those women are, as well as what puts them at risk. If we hope to reduce the incidence of this birth defect, we must reconstruct the problem not as a moral panic, but as a moral imperative to find and help those women most at risk of adverse outcomes.

Author to whom correspondence should be addressed at: Mott Center, 275 E. Hancock, Detroit, MI 48201, USA.

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Fetal alcohol syndrome prevention research

Affiliation.

• 1 Department of Sociology, Wayne State University, Detroit, Michigan, USA.
• PMID: 12154653
• PMCID: PMC6683808

Alcohol consumption during pregnancy can have numerous adverse health consequences for the developing fetus, including fetal alcohol syndrome (FAS) and alcohol-related effects, and therefore is a significant public health problem. A variety of programs have been developed to prevent drinking during pregnancy and the resulting health problems. Some of these efforts, such as public service announcements and beverage warning labels, are universal and strive to increase the public's knowledge about FAS. Selective prevention approaches target women of reproductive age who drink alcohol. Such approaches may involve screening all pregnant women for alcohol consumption and counseling those women who do drink. Indicated prevention approaches target high-risk women (e.g., women who have previously abused alcohol or have had a child with FAS or other alcohol-related effects) and typically offer repeated counseling over several years. Both selective and indicated prevention efforts can reduce maternal alcohol consumption and improve the outcome of the offspring.

Publication types

• Alcohol Drinking / adverse effects
• Alcohol Drinking / prevention & control
• Fetal Alcohol Spectrum Disorders / epidemiology
• Fetal Alcohol Spectrum Disorders / prevention & control*
• Mass Media*
• Patient Education as Topic* / methods
• Product Labeling
• Research Design

FASDs: Research

Fetal alcohol spectrum disorders (FASDs) are a group of conditions that can occur in a person who was exposed to alcohol before birth. These effects can include physical problems and problems with behavior and learning. Often, a person with an FASD has a mix of these problems.

CDC works with partners across the country to develop systems to monitor FASD exposures and outcomes, conduct epidemiologic studies and public health research to identify maternal risk factors associated with giving birth to a child with an FASD, and implement and evaluate FASD prevention and intervention programs.

Click on one of the following links to learn more about CDC’s research:

• Monitoring Alcohol Use
• International Research
• CDC Alcohol Portal
• Excessive Alcohol Use
• Binge Drinking
• Drinking & Driving
• Underage Drinking
• Alcohol & Pregnancy

Learn more about the FASD Competency-Based Curriculum Development Guide for Medical and Allied Health Education and Practice

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