case study in pediatrics

Case Studies

If you are interested in submitting a Puzzler of your own, please see Puzzler guidelines here .

Quiz: Can you diagnose these muscle spasms in a 19-year-old-male?

Take this Contemporary Pediatrics quiz, and see if you can correctly diagnose the patient in this case study. Submit your answer to see if you were correct.

11-year-old boy with testicular pain and rash

An 11-year-old boy presented to the emergency department complaining of left testicular pain for 2 days, described as intermittent and stabbing, which ranged between 5 and 8 of 10 in intensity. Read the full case to see if you can correctly diagnose the patient.

Newborn with midline neck lesion

A 4-day-old boy with a midline neck lesion was born at term by normal vaginal delivery. After birth, mid line lesion had the configuration of a linear cleft with a cephalocaudal orientation, extending from the level below the hyoid bone to the suprasternal notch with a length of 2.5 cm and a width of 0.5 cm. What's the diagnosis?

A 13-year-old girl with well-demarcated rash on back and chest

A healthy 13-year-old girl presented with a 1-month history of an asymptomatic, well-demarcated rash on her back and upper chest. The eruption consisted of discrete, dark brown papules that coalesced into large, flat-topped plaques with mild superficial scale and accentuation of skin markings. What's the diagnosis?

Suspicious facial swelling in a 22-month-old girl

A 22-month-old female patient with sickle cell disease on folic acid and penicillin prophylaxis with a 3-day history of nasal congestion, rhinorrhea, fever and decreased oral intake presents to the emergency department (ED) for acute facial swelling noted when she woke up from a nap. What's the diagnosis?

Friction-induced blistering on a child’s feet

You are called to the hospital nursery to evaluate a healthy full-term newborn boy who developed painful flaccid blisters and erosions on the tops of his feet and ankles shortly after birth. His mother had a history of similar recurrent skin lesions that healed with scarring. She also had oral and gastrointestinal tract involvement. What's the diagnosis?

Hypothermia and abnormal eye movements in a 5-week-old infant

A 5-week-old female infant born at 38 weeks presents to her pediatrician with abnormal eye movements. What’s the diagnosis?

Neonate experiences coffee ground emesis

The infant did not show signs of illness; her mother experienced a routine pregnancy and prenatal lab test results were normal. What is the diagnosis?

Muscle spasms in a 19-year-old male

A 19-year-old male presents to the emergency department (ED) with headache and fever of 4 days’ duration. Six days earlier, his left palm had been punctured by a rusty nail. What's the diagnosis?

Treating an 18-month-old who tested positive for cannabis exposure

As more and more states legalize recreational marijuana, caregivers need to be vigilant about keeping products out of reach of children.

Scalp thickening and folding in a pubertal boy

A 16-year-old boy with developmental delay and intellectual disability developed dramatic chronic wrinkling of his scalp over a year ago. The lesions were persistent but not symptomatic. What's the diagnosis?

Worsening acne after isotretinoin treatment in an adolescent girl

A healthy 17-year-old girl with inflammatory acne had failed to respond to topical tretinoin, benzoyl peroxide, and oral minocycline. What's the diagnosis?

Psychosis in an 18-year-old male

Alex, an 18-year-old male, presented to the emergency department with a 4-day history of paranoia, agitation, and disorganized behavior. He had no psychiatric history or prior mental health contact and no known medical conditions.

Congenital hypopigmented macules on a healthy child

You are asked to evaluate an African American boy aged 4 years with a birthmark on his back and right arm. He is healthy with normal growth and development. What's the diagnosis?

Just a little birthmark?

You are asked to evaluate a healthy 1.5-day-old girl who has a congenital red patch with coarse telangiectasias and a surrounding ring of pallor on the right shoulder. What's your diagnosis?

Can intranasal corticosteroids improve obstructive sleep apnea syndrome in children?

A study featured at CHEST 2022 investigated INCS in children with OSAS to determine if the therapy improved their symptoms, polysomnography findings, behavior, and quality of life.

Case of inflammatory acne or something else?

This case study analyzes variants of majocchi granuloma and potential treatment.

A case of late-onset group B Streptococcus infection in fraternal twins

A 29-year-old White woman presented to the labor and delivery unit due to preterm premature rupture of membranes and delivered twins. The twins were transferred to the neonatal intensive care unit following delivery.

Bilateral blurry vision in a 9-year-old boy

A 9-year-old boy with no significant medical history presented to the emergency department with 2 days of painless blurry vision. What's the diagnosis?

A case of shin guard dermatitis?

A healthy 14-year old boy was evaluated for an intensely pruritic shin rash that developed 2 weeks prior and had been treated with oral antibiotics for 10 days.

A renal anomaly? Look for a Müllerian anomaly as well

A retrospective study found that postmenarchal women with a renal anomaly were also at risk of having a Müllerian anomaly.

A case of progressive joint pain and rash in a 5-year-old

A 5-year-old nonverbal boy with autism spectrum disorder and global developmental delay presented to the emergency department with bilateral lower-extremity bruising and progressive difficulty ambulating. What's the diagnosis?

Fever and facial swelling in a neonate

An 18-day-old girl whose right cheek had become increasingly red and warm over 24 hours was directly admitted to an inpatient unit. She had firmness and pain to the affected area, fussiness, increased sleeping, and poor feeding, preferring the bottle to breastfeeding. What's the diagnosis?

Altered mental state in a 2-year-old boy

A 26-month-old boy presents for mild altered mental status and balance issues following a fall the day before. There was no loss of consciousness or vomiting but he subsequently complained of left-sided head pain. What's the diagnosis?

Painful red lumpy leg

A healthy 4-year-old boy presents with painful deep-seated bumps on the front of his right leg. He also complains of a sore throat for the last 4 days. What's the diagnosis?

Severe hemorrhage from infantile hemangioma

A 5-month-old girl with a large scalp infantile hemangioma (IH), present since 6 weeks of age, is evaluated in the emergency department for lethargy and pallor.

Generalized, eruptive lichen planus in a pediatric patient

A healthy 14-year-old boy presented at our dermatology practice with acute onset of an intensely itchy rash that first appeared 2 months prior.

Annular scars with hyperpigmentation

An 18-month-old girl presents with ringed scars with hyperpigmentation on the right side of her buttocks and back. What's the diagnosis?

Lower-extremity nodules in a 2-year-old girl

A 2-year-old girl presents with an itchy, bilateral leg rash. Additionally, the child had several bruises that felt like "hard welts" and were warm to the touch. What's the diagnosis?

Persistent foot and leg swelling in a 17-year-old female

A 17-year-old girl presents with a 2-year history of unilateral swelling of the left lower extremity as well as a poorly healed ankle sprain of the affected extremity 3 years prior that slowly resolved but left persistent swelling. What's the diagnosis?

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• Case Files®: Pediatrics
• Pediatrics Examination and Board Review
• Neonatal-Perinatal Medicine: Specialty Board Review
• Symptom-Based Diagnosis in Pediatrics

Case Files: Pediatrics, 6e

Author(s): Eugene C. Toy; Mark D. Hormann; Robert J. Yetman; Margaret C. McNeese; Sheela L. Lahoti; Emma A. Omoruyi; Abby M. Geltemeyer

• 2 Infant of a Diabetic Mother
• 3 Neonatal Hyperbilirubinemia
• 4 Sepsis and Group B Streptococcal Infections
• 6 Neonatal Herpes Simplex Virus Infection
• 8 Transient Tachypnea of the Newborn
• 10 Failure to Thrive
• 38 Child Abuse
• 14 Pneumonia
• 17 Pelvic Inflammatory Disease
• 27 Bacterial Meningitis
• 28 Bacterial Enteritis
• 40 Immunodeficiency
• 54 Appendicitis
• 55 Acute Epstein-Barr Virus (Infectious Mononucleosis)
• 29 Subdural Hematoma
• 30 Complex Febrile Seizure
• 48 Migraine Without Aura
• 56 Myasthenia Gravis
• 60 Concussion
• 22 Patent Ductus Arteriosus With Heart Failure
• 23 Truncus Arteriosus
• 18 Cystic Fibrosis
• 20 Asthma Exacerbation
• 61 Electronic Cigarette or Vaping Induced Acute Lung Injury (EVALI) Online Only
• 7 Esophageal Atresia
• 15 Rectal Bleeding
• 34 Intestinal Malrotation
• 53 Inflammatory Bowel Disease
• 35 Posterior Urethral Valves
• 52 Acute Postinfectious Glomerulonephritis
• 11 Anemia in the Pediatric Patient
• 13 Sickle Cell Disease With Vaso-Occlusive Crisis
• 19 Acute Lymphoblastic Leukemia
• 33 Suspected Neuroblastoma
• 42 Diabetic Ketoacidosis
• 44 Growth Hormone Deficiency
• 45 Precocious Puberty
• 41 Trisomy 21
• 50 Turner Syndrome
• 37 Immune Thrombocytopenic Purpura
• 39 Kawasaki Disease
• 51 Systemic Lupus Erythematosus
• 57 Oligoarticular Juvenile Idiopathic Arthritis
• 58 Anaphylactoid Purpura (Henoch-Schönlein Purpura)
• 49 Adolescent Substance Use Disorder
• 62 Alopecia Areata Online Only
• 5 Accidental Ingestion of Opioids
• 25 Lead Ingestion (Microcytic Anemia)
• 59 Attention Deficit Hyperactivity Disorder
• 31 Duchenne Muscular Dystrophy
• 36 Nursemaid’s Elbow (Radial Head Subluxation)
• 47 Slipped Capital Femoral Epiphysis
• 1 Infant Rashes
• 26 Stevens-Johnson Syndrome
• 32 Atopic Dermatitis
• 9 Congenital Cataracts
• 16 Acute Otitis Media
• 43 Obstructive Sleep Apnea Syndrome
• 46 Retropharyngeal Abscess
• 21 Sudden Infant Death Syndrome
• Accidental Ingestion of Opioids
• Acute Epstein-Barr Virus (Infectious Mononucleosis)
• Acute Lymphoblastic Leukemia
• Acute Otitis Media
• Acute Postinfectious Glomerulonephritis
• Adolescent Substance Use Disorder
• Alopecia Areata Online Only
• Anaphylactoid Purpura (Henoch-Schönlein Purpura)
• Anemia in the Pediatric Patient
• Appendicitis
• Asthma Exacerbation
• Atopic Dermatitis
• Attention Deficit Hyperactivity Disorder
• Bacterial Enteritis
• Bacterial Meningitis
• Child Abuse
• Complex Febrile Seizure
• Congenital Cataracts
• Cystic Fibrosis
• Diabetic Ketoacidosis
• Duchenne Muscular Dystrophy
• Electronic Cigarette or Vaping Induced Acute Lung Injury (EVALI) Online Only
• Esophageal Atresia
• Failure to Thrive
• Growth Hormone Deficiency
• Immune Thrombocytopenic Purpura
• Immunodeficiency
• Infant of a Diabetic Mother
• Infant Rashes
• Inflammatory Bowel Disease
• Intestinal Malrotation
• Kawasaki Disease
• Lead Ingestion (Microcytic Anemia)
• Migraine Without Aura
• Myasthenia Gravis
• Neonatal Herpes Simplex Virus Infection
• Neonatal Hyperbilirubinemia
• Nursemaid’s Elbow (Radial Head Subluxation)
• Obstructive Sleep Apnea Syndrome
• Oligoarticular Juvenile Idiopathic Arthritis
• Patent Ductus Arteriosus With Heart Failure
• Pelvic Inflammatory Disease
• Posterior Urethral Valves
• Precocious Puberty
• Rectal Bleeding
• Retropharyngeal Abscess
• Sepsis and Group B Streptococcal Infections
• Sickle Cell Disease With Vaso-Occlusive Crisis
• Slipped Capital Femoral Epiphysis
• Stevens-Johnson Syndrome
• Subdural Hematoma
• Sudden Infant Death Syndrome
• Suspected Neuroblastoma
• Systemic Lupus Erythematosus
• Transient Tachypnea of the Newborn
• Truncus Arteriosus
• Turner Syndrome

DBP Community Systems-Based Cases

Introduction.

Following are case studies of children with typical developmental behavioral issues that may require a host of referrals and recommendations.

Case Studies

Case 1:                    case 2:                      case 3: sophie                     mark                     alejandro.

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• v.31(2); 2020 Jun

Case Report on Paediatric Nephrotic Syndrome

Shireen prince.

1 Department of Pharmacy Practice, Malla Reddy Pharmacy College, Dhullapally, Secunderabad, Telangana, India

Kunta Naresh

2 Department of Paediatrics, Malla Reddy Institute of Medical Sciences, Secunderabad, Telangana, India

Nephrotic syndrome (NS) is a glomerular disorder typically characterized by gross proteinuria, hypoalbuminemia, hyperlipidemia, and peripheral oedema. We report the case of a 2-year-old male toddler weighing 15 kg with a 1-week history of swelling around the eyes and both legs, and generalized body swelling. She had a history of fever, cough and decreased urine output. Examination revealed bilateral pedal oedema (pitting type).

Laboratory investigations showed protein in urine, reduced serum albumin (2.0 g/dL) with elevated lipid levels. Although kidney biopsy could not be performed due to economic problem of the family, a diagnosis of idiopathic nephrotic syndrome (NS) was made based on clinical and laboratory findings.

The patient was mainly treated with furosemide, prednisolone and enalapril. Urine I/O charting (Intake/Output chart for assessing fluid intake and ability to pass urine in adequate amounts) was done daily until optimal results were obtained.

INTRODUCTION

Primary nephrotic syndrome (PNS), also known as idiopathic nephrotic syndrome (INS), is associated with glomerular diseases intrinsic to the kidney and not related to systemic causes. The subcategories of INS are based on histological descriptions, but clinical-pathological correlations have been made ( 1 ). Diagnosis is generally based on clinical features and investigations including blood tests, renal imaging, and biopsy ( 2 ). The incidence of idiopathic nephrotic syndrome (INS) is 1.15–16.9 per 100 000 children, varying by ethnicity and region. The cause remains unknown but the pathogenesis of idiopathic NS is thought to involve immune dysregulation, systemic circulating factors, or inherited structural abnormalities of the podocyte. Genetic risk is more commonly described among children with steroid-resistant disease. The mainstay of therapy is prednisone for the vast majority of patients who are steroid responsive; however, the disease can run a frequently relapsing course, necessitating the need for alternative immunosuppressive agents. Infection and venous thromboembolism are the main complications of NS with also increased risk of acute kidney injury. Prognosis in terms of long-term kidney outcome overall is excellent for steroid-responsive disease, and steroid resistance is an important determinant of future risk of chronic or end-stage kidney disease ( 3 ).

CASE REPORT

Clinical features.

A 2-year-old male toddler weighing 15 kg presented with a history of fever which is high grade continuous type associated with chills and rigors. The patient had cough (wet cough more in amount) whitish colour sputum not foul smelling. Swelling over face was present which initially started around peri-orbital (which is more during morning) and gradually progressed to face which decreases by evening. The toddler had decreased urine output (oligouria). The baby was delivered by C-section and weighed 2.75 kg after birth. On examination pitting type of oedema was present over lower limbs and swelling over face was present. Based on these clinical presentations, nephrotic syndrome was suspected and specific laboratory testing was performed to establish diagnosis.

Laboratory findings

The urine dipstick indicated for proteinuria, no signs of haematuria. Blood testing showed a significantly depressed C3 level of 0.638 g/L (reference interval 0.9-1.8 g/L) and hypoalbuminaemia of 2.0 g/dL (reference interval 3.5-5.5 g/dL) indicating nephrotic syndrome (NS). The urine creatinine level was – 620 mg/L (reference interval 400-3000mg/L) and APTT was prolonged- 47.7 Sec (reference interval 24-30 Sec). Serologic testing for active infections: anti-streptolysin-O titer was positive. The lipid levels were markedly increased as outlined in the Table 1 . LDL was measured and calculated by enzymatic selective protection (Direct). The urine protein/creatinine ratio was found to be high (7.3). Mantoux test was done before administration of steroids which was negative.

Laboratory parameters

Clinical course

After establishing diagnosis, optimal supportive treatment including Enalapril p.o., Prednisolone p.o., intravenous albumin, furosemide, low salt intake, high caloric and protein diet were given along with Ceftriaxone and Ascoril-LS. The urine output and blood pressure was monitored.

Successful control of peripheral oedema with the administration of albumin and diuresis with furosemide was seen. The peri-orbital oedema and leg swelling reduced, and there was a concomitant increase in serum protein levels. The lipid levels also gradually decreased in due course of time without any medication.

The hallmark of INS is massive proteinuria, leading to decreased circulating albumin levels. The initiating event that produces proteinuria remains unknown. However, strong evidence suggests that INS, at least in part, has an immune pathogenesis.

The classical explanation for oedema formation is a decrease in plasma oncotic pressure, as a consequence of low serum albumin levels, causing an extravasation of plasma water into the interstitial space. The resulting contraction in plasma volume (PV) leads to stimulation of the reninangiotensin-aldosterone axis and anti-diuretic hormone secretion. The resultant retention of sodium and water by the renal tubules contributes to the extension and maintenance of oedema.

A more recent theory of oedema formation posits that massive proteinuria leads to tubule-interstitial inflammation, release of local vasoconstrictors and inhibition of vasodilation. This leads to reduction in glomerular filtration rate and sodium and water retention 4 .

INS is accompanied by disordered lipid metabolism. Apolipoprotein (apo)-B–containing lipoproteins are elevated, including very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), low-density lipoproteins (LDL), with resultant increases in total cholesterol and LDL-cholesterol. Elevations in triglyceride levels occur with severe hypoalbuminemia. Also contributing to the dyslipidemia of INS are abnormalities in regulatory enzymes, such as lecithin-cholesterol acyltransferase, lipoprotein lipase , and cholesterol ester transfer protein ( 4 , 5 ).

Nephrotic syndrome is a hypercoagulable state; the increased risk of thrombosis can be attributed to two basic mechanisms:

• urine losses of antithrombotic proteins and
• increased synthesis of prothrombotic factors.

Abnormalities described in INS include decreased antithrombotic factors and increased synthesis of pro-thrombotic factors ( 6 ).

Risk of infection may be increased in INS because of low immunoglobulin IgG levels, which do not appear to be the result of urinary losses. Instead, low IgG levels seem to be the result of impaired synthesis, again pointing to a primary disorder in lymphocyte regulation in INS. The medications used to treat INS, such as corticosteroids and alkylating agents, further suppress the immune system and increase the risk of infection ( 7 ). The ASO test done in this patient had a positive result.

We have presented a case of idiopathic NS successfully managed with corticosteroid, albumin, furosemide and enalapril. We could not perform kidney biopsy but could make a diagnosis based on clinical features and investigations, and fortunately our patient recovered and attends monthly follow-up visits.

TAKE HOME MESSAGES/LEARNING POINTS

• In order to establish the presence of nephrotic syndrome, laboratory tests should confirm nephrotic-range proteinuria, hypoalbuminemia, and hyperlipidemia.
• A 3+ proteinuria on dipstick is highly suggestive of nephrotic syndrome to be confirmed by appropriate laboratory work-up.
• Serologic testing for active infections should be done as the patients with NS are more prone to it.
• Mantoux test [purified protein derivative (PPD)] should be performed prior to steroid treatment to rule out TB infection.

Contribution of authors

Shireen and Dr. Naresh conceived the idea and wrote and edited the manuscript.

Dr. Tulasi was the paediatrician managing the patient and contributed to the manuscript.

• Case report
• Open access
• Published: 05 February 2022

A case report of pediatric acute lymphoblastic leukemia with e8a2 BCR/ABL1 fusion transcript

• Aleksandra Mroczkowska   ORCID: orcid.org/0000-0002-8837-6517 1 ,
• Bożena Jaźwiec 1 , 2 ,
• Justyna Urbańska-Rakus 3 ,
• Sylwia Szymanowska 1 ,
• Anna Tessmann 1 ,
• Sonia Pająk 3 ,
• Katarzyna Machnik 3 ,
• Olga Haus 4 &
• Tomasz Wróbel 2  

BMC Medical Genomics volume  15 , Article number:  20 ( 2022 ) Cite this article

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Metrics details

Acute lymphoblastic leukemia is the most common type of cancer in children. Most often it affects the age group between 2 and 5 years of age. Studies have shown an improvement in general survivability, more than 90% 5-year overall survival (OS). Current treatment protocols for acute lymphoblastic leukemia require verification of the presence of favorable and unfavorable genetic abnormalities, which help qualify patients to the appropriate risk group and select a more suitable treatment. The presence of the BCR/ABL1 fusion gene stratifies the patient into a high-risk group and requires special treatment with tyrosine kinase inhibitors (TKI). The three dominant mRNA transcripts are e1a2, e13a2, and e14a2. Nevertheless, cases of atypical BCR/ABL1 transcripts have also been reported.

Case presentation

This paper presents the case of a pediatric patient with Ph + B-cell precursor acute lymphoblastic leukemia with rare atypical e8a2 BCR/ABL1 fusion transcript. Our patient achieved complete remission after 33 days of treatment. Molecular and cytogenetic studies in TP1 did not reveal the presence of the BCR/ABL1 transcript. The PCR-MRD test in TP1b was negative, the patient did not require hematopoietic stem cell transplantation.

Genetic evaluation of the bone marrow sample is crucial in the initial stage of the diagnosis. Fluorescent in situ hybridization and reverse transcriptase polymerase chain reaction with Sanger sequencing are the appropriate methods used in the detection of rare variants of BCR/ABL1 transcripts.

Peer Review reports

Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy. ALL is a heterogeneous neoplasm derived from the precursors of the lymphoid lineage. About 80–85% of cases are B-cell precursor leukemias, while T-lineage leukemias are about 15–20%. The ALL diagnoses are based on certain criteria including clinical presentation, laboratory tests, a bone marrow biopsy, immunophenotypic analysis and genetic tests. Currently, cytogenetic and molecular tests play a very important role in determining prognosis and stratification for suitable treatment of pediatric ALL [ 1 , 2 ]. The typical recurrent translocations occurring in ALL are t(12;21)(p13;q22) causing ETV6/RUNX1 , t(1;19)(q23;p13) causing TCF3/PBX1 , t(9;22)(q34;q11.2) causing BCR/ABL1 , and the most common rearrangement of KMT2A gene, t(4;11)(q21;q23) causing KMT2A/AFF1 . ETV6/RUNX1 is associated with a favorable prognosis and the last three genetic abnormalities have unfavorable outcomes [ 3 , 4 ].

BCR/ABL1 fusion transcripts occur approximately in 2–5% cases of childhood ALL and the frequency of BCR/ABL1(+)ALL increases with the patient’s age [ 5 ]. ALL cases with this genetic abnormality are associated with poor outcome and are qualified to the high risk group. Due to the introduction of tyrosine kinase inhibitors to the therapy, the prognosis of Ph + patients has improved.

The most common mRNA transcripts of BCR/ABL1: e1a2, e13a2, e14a2, occur in about 99% of Ph + cases. Approximately 70% of Ph + ALL patients have an e1a2 transcript and more than 25% e13a2 or e14a2. 1% of patients with Ph + shows atypical transcripts like e19a2, e6a2, e1a3, e13a3, e14a3 and e8a2 [ 6 ].

We present here a case of a pediatric patient with Ph + BCP-ALL (B cell precursor ALL) with an e8a2 BCR/ABL1 transcript.

An 11-year-old boy was admitted to the Unit of Pediatric Hematology and Oncology, City Hospital, Chorzów, Poland due to a suspicion of acute leukemia. Five days before admission to the hospital, he developed a severe and difficult to stop nosebleed. Since then, the boy was experienced weakness, lethargy, lack of appetite. Additionally he developed abdominal pain, a headache and nausea. Physical examination revealed pale skin with petechiae, inflammation of the gingiva, tooth decay and splenomegaly. Lymphadenopathy, hepatomegaly and the presence of a Central Nervous System (CNS) disease/leukemia were not observed. Family Health History has no indication of any genetic, hematologic or cancerous diseases. Patient was not exposed to any physical (i.e. ionic radiation) or chemical factors (organic solvents, pesticides, herbicides, paints, lacquers) during childhood nor fetal period. He was born out of second pregnancy, first childbirth (first pregnancy ended due to spontaneous miscarriage around eighth week). Weight at birth 2400 g. Mother's age at birth: 19, father: 21. Patient has younger step-sister (same mother, different father), showing no symptoms of ALL or any other hematological disorders.

By the time of diagnosis of ALL, the patient had been sick sporadically and had no routine blood tests—including morphology. The patient has not taken any medications on a permanent basis.

The laboratory results showed: white blood cell 206,900/µl, platelet count 142,000/µl and hemoglobin level 10.2 g/dl. The bone marrow was highly cellular, represented by a homogeneous population of small blasts with lymphoid morphology (88.5%). Flow cytometric analysis showed BCP-ALL phenotype: CD45dim + , CD38 + , CD34(+), CD81(+), CD24(+), CD19(+), CD79a(+), TdT(+), CD10(+), CDdim33(+), CD20dim(+), CD22dim(+), CD15(-), CD117(-). The boy was diagnosed with common B-cell precursor ALL and qualified for treatment according to the AIEOP-BFM ALL 2017 protocol.

The cytogenetic and molecular examinations of the patient's bone marrow were performed by the Laboratory of Molecular Biology and Cytogenetics at the University Clinical Hospital in Wroclaw. Karyotype analysis and fluorescence in situ hybridization (FISH) was performed on the bone marrow sample according to the AIEOP-BFM ALL 2017 protocol. According to the protocol, tests for genetic diagnostics were performed. By day 6, a FISH test was performed to obtain a result for the presence of the Philadelphia chromosome. Up to day 33, the FISH test was performed for the frequent genetic aberrations: ETV6/RUNX1 translocation and rearrangements in the KMT2A and TCF3 genes. At the same time, molecular tests were carried out using the RT-PCR method for the presence of the BCR/ABL1 and KMT2A/AFF1 fusion gene. G-banded chromosome analysis revealed an abnormal male karyotype 46,XY,t(9;22)(q34;q11) [ 11 ]/46,XY [ 9 ] (Fig.  1 A). The FISH study showed no rearrangements in ETV6/RUNX1, TCF3 (MetaSystems Probes, Germany) or KMT2A (Vysis, Abbott Molecular, Illinois, USA). The FISH study performed with the BCR/ABL1 dual color, dual fusion translocation probe (Vysis, Abbott Molecular, Illinois, USA) disclosed a typical translocation pattern 2 green/orange BCR/ABL1 fusion signals, 1 green BCR signal, and one orange ABL1 signal in 90% of the interphase cells (Fig.  1 B). Reverse transcription-polymerase chain reaction (RT-PCR) was performed to detect the presence or absence of the KMT2A /AFF1 and BCR/ABL1 fusion gene using primers as per JJM van Dongen et al. [ 7 ]. The test was negative in both cases. Due to the positive result of the FISH test for BCR/ABL1 , another RT-PCR was performed in order to search for atypical BCR/ABL1 transcripts. New RT-PCR analysis was performed based on primers BCR-6 and ABL-3 published by T. Burmeister and R. Reinhardt [ 6 ]. Electrophoresis showed a band of ~ 489 bp (Fig.  2 A). Sanger sequencing confirmed the direct junction between exon 8 of BCR (NM_004327.4) and exon 2 of ABL1 (NM_005157.6) (Fig.  2 B). The Sanger sequencing was important because this method determined the type of transcript by analyzing the direct junction between exons. Transcript type information is crucial for monitoring the presence of BCR/ABL1 transcript by RT-PCR method.

A —Conventional G-banding karyotype analysis showing typical translocation between chromosome 9 and 22. B —FISH analysis on interphase and metaphase with LSI BCR/ABL1 Dual Color, Dual Fusion Translocation Probe

A —Detection of e8a2 BCR/ABL1 transcript by RT-PCR. Lane 1: size marker; lane 2: patient sample; lane 3: negative control, lane 4: internal reference gene—ABL1. B —Sanger sequencing demonstrating the direct junction between BCR exon e8 and ABL1 exon a2

The patient’s induction therapy started according to the protocol IA-Pred. On the 8th day of treatment, the patient had a poor response to prednisone. Due to the presence of the BCR /ABL1 fusion gene, further treatment was performed according to the EsPhALL 2009 protocol (European intergroup study of post-induction treatment of Philadelphia-chromosome-positive ALL). Imatinib at a dose of 300 mg/m 2 daily was started on day 15 of treatment, but on day 28 was withheld due to hepatotoxicity (WHO grade III). Evolution of peripheral blood cell counts during therapy is presented in Table 1 . In accordance to protocol, the patient's bone marrow was collected on days 15 and 33 of treatment. Examination of the bone marrow sample on day 15 revealed 15.4% blast cells in bone marrow morphology. Flow cytometry (FCM) revealed 23.48% of blasts. On day 33 (TP1), the bone marrow was already aplastic. Nevertheless, a PCR-MRD (Minimal Residual Disease) result was obtained. MRD in TP1 was low-positive (< 10 −4 ). Bone marrow smear revealed a total of 2.6% of blasts. Despite the poor quality of the material in TP1, it was also possible to perform a FISH study (Fig.  3 A) and RT-PCR test (Fig.  3 B). Both molecular and cytogenetic tests were negative. According to the EsPhALL 2009 protocol the boy should have been classified as poor risk Ph(+) ALL group because of PPR (prednisone poor responder) on the 8th day, but due to complete remission on day 33 (LBL 1.2%, PC-MRD < 10 –4 ) he was classified as good risk Ph(+) ALL group. From about day 32 of treatment, the patient reported abdominal pain, constipation, nausea and vomiting. Physical examinations showed hepatomegaly and lazy intestinal peristalsis. The symptoms were most likely caused by paralytic intestinal obstruction after chemotherapy. Additionally, the patient developed a fungal infection of the bladder.

A —FISH study on day 33 of treatment, B —RT-PCR test on day 33 of treatment. Lane 1: size marker; lane 2: positive control; lane 3: patient; lane 4: negative control, lane 5: internal reference gene—ABL1

Due to the general condition of the patient, consolidation treatment was delayed by 25 days. After this time, according to the EsPhALL 2009 protocol the IB protocol was started and Imatinib was resumed. Another PCR-MRD test was performed on day 17 of treatment (TP1b) of the IB protocol. PCR-MRD in TP1b was negative. Therefore the patient continued chemotherapy without qualification for HSCT (Hematopoietic Stem Cell Transplantation). The patient after consolidation therapy was in haematological remission of ALL. The patient remains without a transplant for 8 months after diagnosis.

Discussion and conclusions

The very rare e8a2 transcript (about 8% from 1% of non-typical BCR/ABL1 transcripts) has been reported mainly in cases of chronic myeloid leukemia (CML) [ 8 , 9 , 10 , 11 , 12 , 13 , 18 ]. Two cases have been reported in adult ALL [ 14 , 15 ]. The e8a2 BCR/ABL1 transcript could be associated with worse prognosis than the e13a2 or the e14a2 transcripts in CML patients. However, there were cases of good response to treatment with imatinib with an achievement of a major molecular response [ 8 , 10 , 12 ]. CML cases with this transcript that have been reported so far, additionally had insertions from ABL1 intron 1b or 1a, from BCR intron 8 or another gene such as PRDM12 , MAST2 [ 11 , 16 , 17 ]. Only one patient with CML and e8a2 BCR/ABL1 transcript had no additional insertions and after treatment with imatinib achieved a complete cytogenetic response [ 12 ]. In adult acute lymphoblastic leukemia one case was reported with insertion of 2 nucleotides from ABL1 intron 1a [ 14 ]. One adult ALL woman that had RALGPS1 exon 8 inserted into the fusion, was treated with FLAG-Ida (fludarabine, cytarabine, granulocyte-colony stimulating factor [G-CSF], idarubicin) and dasatinib and after re-induction therapy achieved hematological, cytogenetic and molecular remission [ 15 ]. Unfortunately, the e8a2 variant in adult ALL patients is so rare, that its impact on outcome remains unknown. To the best of our knowledge, our patient is the first pediatric ALL case with e8a2 BCR/ABL1 transcript. Our case sequencing analysis revealed e8a2 BCR/ABL1 transcript without any insertion. Creation of the e8a2 transcript by the exact fusion of BCR exon e8 to ABL1 exon a2 could encode an oncogenic protein, therefore our patient was qualified for treatment with the EsPhALL 2009 protocol. Our patient achieved complete remission after 33 days of treatment. Molecular and cytogenetic studies in TP1 did not reveal the presence of the BCR/ABL1 transcript. The PCR-MRD test in TP1b was negative, the patient did not require hematopoietic stem cell transplantation.

The presence of the BCR/ABL1 fusion gene is considered an unfavorable genetic abnormality and is associated with poor prognosis but survival has improved with the development of TKI. Our case shows that atypical transcripts of BCR/ABL1 also occur in cases other than CML or adult ALL. RT-PCR and sequencing are appropriate methods for identifying these atypical transcripts. Using both conventional cytogenetics and molecular methods, we are able to detect many genetic changes occurring in leukemias. It is important to identify them accurately and use this information to monitor the patient’s treatments. The monitoring of the presence and quantity of the BCR/ABL1 transcript using the RT-qPCR method is a gold standard in monitoring of Ph + patients with chronic myeloid leukemia. This method can also be used in monitoring of Ph + ALL patients to assess treatment efficiency. For proper patient monitoring it is important to evaluate the type of transcript at the time of diagnosis. Detection of a rare atypical transcript may affect the patient's treatment and may be associated with a worse prognosis.

Availability of data and materials

The Sanger Sequencing data generated in the study has been submitted to NCBI GenBank BankIt with the accession number OL672741;  https://www.ncbi.nlm.nih.gov/nuccore/OL672741 . Reference sequences used in this study are available in the following link: https://www.ncbi.nlm.nih.gov/nuccore/NM_004327.4 ; https://www.ncbi.nlm.nih.gov/nuccore/NM_005157.6 . https://www.ncbi.nlm.nih.gov/nuccore/MF925339.1/ .

Abbreviations

Overall survival

Tyrosine kinase inhibitors

B cell precursor Acute Lymphoblastic Leukemia

Central Nervous System

Fluorescence in situ hybridization

Reverse transcription-polymerase chain reaction

Hematopoietic Stem Cell Transplantation

Chronic myeloid leukemia

Granulocyte-colony stimulating factor

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Aleksandra Mroczkowska, Bożena Jaźwiec, Sylwia Szymanowska & Anna Tessmann

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Justyna Urbańska-Rakus, Sonia Pająk & Katarzyna Machnik

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AM wrote the manuscript with support from TW and OH. BJ, AM conducted molecular genetics experiments and interpreted the Sanger sequencing data. SS, AT performed cytogenetical experiments. JU-R, SP, KM contributed to the clinical part of the study, prepared a clinical data and edited a clinical part of manuscript. All authors have read and agreed to the published version of the manuscript.

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Correspondence to Aleksandra Mroczkowska .

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This study was approved by the ethics committee of Wroclaw Medical University, Poland (committee’s reference number: KB 716/2018). Written consent to participate was obtained from patient which served as negative control.

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Mroczkowska, A., Jaźwiec, B., Urbańska-Rakus, J. et al. A case report of pediatric acute lymphoblastic leukemia with e8a2 BCR/ABL1 fusion transcript. BMC Med Genomics 15 , 20 (2022). https://doi.org/10.1186/s12920-022-01169-0

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Evaluating the association between duration of breastfeeding and fine motor development among children aged 20 to 24 months in Butajira, Ethiopia: a case-control study

• Rediate Shiferaw 1 ,
• Robel Yirgu 2 &
• Yalemwork Getnet 2  

BMC Pediatrics volume  24 , Article number:  216 ( 2024 ) Cite this article

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A Suitable environment and proper child nutrition are paramount to a child’s physical and mental development. Different environmental factors contribute to proper child development. Breast milk is an important source of nutrition during the early years of life and contains essential nutrients that are the building blocks for growth and development.

To assess the association between the duration of breastfeeding and fine motor development among children aged 20 to 24 months living in Butajira, southern Ethiopia.

Community-based case-control study design was employed among mother-child dyads of children aged 20 to 24 months in Butajira Southern Ethiopia. Children were screened for fine motor delay using the Denver II developmental screening and identified as cases and controls. A repeated visit was done to gather the rest of the information and 332 samples, 83 cases, and 249 controls were available and assessed. Epi-data version 4.4.2.1 software was used to prepare a data entry template, which was later exported to and analyzed using STATA version 14 statistical software. Finally, a Multivariable logistic regression model was used to adjust for confounders and estimate the independent effect of breastfeeding duration on fine motor development.

We didn’t find a significant association between the duration of breastfeeding from 21 to 24 months and fine motor delay compared to children who were breastfed less than 18 months[AOR: 0.86, 95% CI: (0.36, 2.05)]. Children who have mothers > 35 years of age were 78% less likely than children who had mothers younger than 25 years, Children who had mothers in secondary school and above were 77% less likely than mothers who didn’t have formal education, Females were 1.86 times more likely than males, and Children who scored 20–29 on the Home score were 51% less likely than Children who scored < 20 to have fine motor delay.

Duration of breastfeeding was not significantly associated with fine motor delay for children aged 20 to 24 months old. The age of the mother, the educational status of the mother, being female, and Home score were identified to have a significant association with fine motor delay. Improving the educational status and empowerment of women is essential. Further work should be done on avoiding gender differences starting from a young age and creating a conducive environment for child development is crucial.

Peer Review reports

The first 2 years can predict the quality of life a child can have. Appropriate connections are formed and wired in this window if this stage is passed then it is hard to rewire the brain connections [ 1 ]. Child development is a dynamic process that is a result of the interaction between biological and environmental factors [ 2 ]. Motor development is also seen as an indicator of global child development [ 3 ]. Motor development is the development of the child’s bones, muscles, and ability to move around and manipulate their environment [ 4 ]. Motor development is a critical factor in child behavior, being associated with the foundation of cognitive and social-emotional development[ 3 ]. Fine motor development is very important for the development of gross motor skills and is connected to how a child performs later on other cognitive tasks, reading and solving mathematical problems [ 5 ]. Fine motor skill is the ability to control movement through activities and coordination of the nervous system, fibril, and muscles such as fingers and hands [ 6 ]. Fine motor skills are important to do certain activities such as eating and handwriting. The United Nations has set sustainable developmental Goals to improve early child development by 2030. Goal 4 Target 4.2 supplies all children to get access to quality early childhood development so they are ready for primary education [ 7 ].

Child development is a dynamic process that is a result of the interaction between biological and environmental factors. Although infant development is influenced by several factors, The centrality of good nutrition cannot be ignored by providing the important building blocks for development [ 2 ]. Breastfeeding is the main source of important nutrients for children at this age. Breastfeeding has been identified by the World Health Organization (WHO) as an ideal source that contains important nutrients that can help for the optimal growth and development of children. WHO recommends continuing to breastfeed for up to 2 years with additional complementary foods [ 8 ]. Especially fatty acids Docosahexaenoic acid and Arachidonic acid in breast milk are important for brain growth and development and the formation of important synapses or connections in the brain. When a child is adequately nourished with important nutrients in the foundational period it creates a base for lifetime proper brain function [ 9 ]. Motor skills are also affected by factors such as caregiving practice, and stimulating environments [ 1 ]. Nutritional supplementation and psychosocial stimulation together result in greater improvements in child development than either intervention alone [ 9 ]. Determining the solo influence of breastfeeding on child development is difficult because child development is interrelated and associated with different environmental and biological factors. The complexity of child development makes it difficult to evaluate these effects [ 10 ]. The effects of environmental factors are pronounced in areas with limited access to the requirements for development [ 11 ]. Especially in developing countries, the problem can be worse due to limited resources in the environment that can aggravate the problem [ 12 ]. In resource-limited environments, limited resources such as poor stimulating environments and poor nutrition can limit the developmental potential of the children. Therefore, we need to study the effect of multiple environmental factors and nutrition on child development especially in a developing country context. To our best knowledge there are limited studies regarding developmental delays and also the practice of assessing child development in Ethiopia is low. Therefore, knowing the current status and assessing the impact is helpful for early intervention to prevent different adverse outcomes.

Materials and methods

Study design, area, and period.

Community-based Case-control study was conducted from March to May 2019 among children aged 20 to 24 months living in Butajira Health and demographic surveillance site located in Southern Nations and Nationalities (SNNP), Ethiopia. The area is located 135 km south of Addis Ababa and 50 km to the west of Zeway town in the Rift Valley, 8.2 o north latitude and 38.5 o east longitude. The climate varies from arid dry lowland areas at altitudes around 1,500 m (tropical climate) to cool mountainous areas up to 3,500 m above mean sea level (temperate climate). The livelihood of the residents is based on mixed farming. Khat (Catha edulis Forsk) and chili-peppers are the main cash crops, while maize and “false banana” or Ensete (Ensete ventricosun) are the main staples [ 13 ].

Source population

All children within the age group of 20 to 24 months living in Butajira HDSS are the Source population.

Study population

Children within the age group of 20 to 24 months living in Butajira HDSS have been identified as cases and controls based on the Denver developmental screening test.

Case definition

Cases were children who were identified as being suspect for fine motor delay and controls were children without fine motor delay.

Case (Suspect ): Two or more cautions (Item on which the age line fails or between the 75th and 90th percentile). This means 75% of the children can pass the test below the child’s age, and /or One or more delays (a child fails to perform an activity that fails completely to the left of the age line) using the Denver developmental screening test.

It is considered that a child fails to perform an item that 90% of children can perform at an earlier age.

Control (normal)

No delays and a maximum of one caution using the Denver developmental screening test.

Study variables

The outcome variable was Fine motor delay. The exposure variables were Nutritional factors (Breastfeeding duration, Dietary habits of the infant), Child characteristics (sex of the child, birth order), Socio-demographic variables (age of mother, occupation of mother, education status of mother, socioeconomic status), and Caregiving practice: (Home environment.)

Sample size calculation

The required sample size was calculated using EPI INFO 7 software using an unmatched case-control study using Proportion of Controls among those who breastfeed < 6 months P = 89.97% and Proportion of Cases among those who breastfeed < 6 months P = 76.4% and OR = 0.36 A study done in Taiwan [ 14 ].

At precision level of 5%, 95% confidence interval, and 80% power and using r = 3(ratio of cases to controls) and 10% for non-response compensation the sample size becomes 360 with 271 controls and 90 cases.

Sampling method

A survey (screening) was conducted from March to May 2019 in Butajira HDSS by obtaining a sampling frame from the Butajira HDSS. Participants were all children from 20 to 24 months living in the Butajira HDSS. The total population of children in Butajira HDSS from 20 to 24 months was 453.

After going into each Keble and household 376 children that were available were assessed using the Denver developmental screening test and identified as cases and controls. We found 85 cases and 291 controls. Then after identifying the households with cases and controls a repeated visit on the same household and on the same child was done to gather the rest of the information. After visiting the households 332 samples 332 samples 83 cases and 249 controls were available and were assessed using interviewer-administered questioners.

Operational definition

Caregiver (caretaker).

The people who look after infants and young children [ 15 ].

Breastfeeding less than 18 months

mothers while in the data collection period report that they have breastfed their babies less than 18 months.

Continue to breastfeed 18 to 20 months

mothers while in the data collection period report that they have breastfed their babies from 18 to 20 months and stopped.

Continue to breastfeed 21 to 24 months

mothers while in the data collection period report that they have breastfed their babies from 21 to 24 months.

• Fine motor development

The fine motor section of Denver II contains 33 items. Each test item on Denver II is presented on a chart by a horizontal bar partitioned into 25, 50, 75 and 90 percentile ages of passing the items. After calculating the exact age draw the age line after drawing the age line the child was asked to perform an activity to the left of the age line, this was done until the child was able to pass three or more consecutive items. Also, the child was tested for items above the age line until the child failed three or more consecutive items.

A child can pass-fail or refuse an item on which the age line fails.

By then identifying the child’s outcome using all the scores that the child has and finding the results will be carried out.

The scoring has 4 items.

“P” for pass – the child successfully performs the item or the caregiver reports (when appropriate) that the child does the item.

“F” for fail- the child does not successfully perform the item, or the caregiver reports (when appropriate) that the child does not do the item.

“N.O” for no opportunity- the child has not had the opportunity to perform the item, due to restrictions from the caregiver or other reasons. This score may only be used on “report” items.

“R” for refusal- the child refuses to attempt the item. Refusal can be minimized by telling the child what to do rather than asking. If given instruction in proper administration, the caregiver may administer the item. Report items cannot be scored as refusals.

no delays and a maximum of one caution.

Caution items are interpreted when a child fails or refuses an item on which the age line fails or between the 75th and 90th percentile. This means 75% of the children can pass the test below the child’s age. Delays are considered when a child fails to perform an activity that fails completely to the left of the age line. (Not on the item that the age line passes) It is considered that a child fails to perform an item that 90% of children can perform at an earlier age. This means 75% of the children can pass the test below the child’s age. When a child passes, fails, or refuses an item that is between the 25th and 75th percentile it is considered normal.

Delays suspect

Two or more cautions and /or one or more delays.

Caution items are interpreted when a child fails or refuses an item on which the age line fails or between the 75th and 90th percentile. This means 75% of the children can pass the test below the child’s age [ 16 ].

Adequate dietary diversity

Children who receive foods from 4 or more food groups using 24-hour recall [ 8 ].

Inadequate dietary diversity

Children who received foods less than four groups using 24-hour recall [ 8 ].

Household wealth index —is households’ living status and was constructed by using household asset data on housing conditions like the type of floor, the material of the wall, the material of roof; ownership of assets like radio, TV, telephone, vehicle; the presence of functional latrine, source of drinking water, ownership of domestic animals, ownership of farmland and amount of grain harvested in the last production year among others. After running principal components analysis (PCA) in STATA, the households’ wealth index was grouped into quintiles (lowest quintile, second quintile, middle quintile, fourth quintile, and highest quintile).

Data collection instrument and procedure

Development was assessed by the Denver developmental screening test which is designed to test the development of the child. The data collection started by Screening for a suspect for fine motor development. The fine motor was assessed using the Denver II developmental screening test. The tool contains different materials that help to examine the development of the child and a test form that contains all the developmental domains in sections. The Denver II tool was adapted in Jimma into a developing country context and was validated in Butajira Ethiopia [ 17 , 18 ]. The Denver II was assessed by a BSC nurse trained and certified for assessing children using the Denver developmental screening test.

The test was done in a natural and comfortable environment where the child could play with minimal disturbance in the presence of the caretaker. The test was started by informing the mother that the child is not expected to pass all the items.

The test contains a total of 125 items in four developmental domains: personal-social, fine motor, language, and gross motor. The fine motor section of Denver II contains 33 items. Each test item on Denver II is presented on a chart by a horizontal bar partitioned into 25, 50, 75 and 90 percentile ages of passing the items.

Draw the exact age without rounding off days, weeks, or months. Age scales are placed at the top and bottom of the page. Spaces between the age marks represent 1 month until 24 months. After carefully identifying the child’s age draw the age line using the age scales draw an age line from the top to the bottom of the form. After drawing the age line the child was asked to perform an activity to the left of the age line, this was done until the child was able to pass three or more consecutive items. Also, the child was tested for items above the age line until the child failed three or more consecutive items.

For each item, there are 25th, 50th, 75th and 90th percentile.

The age line, pass through the following tasks.

16. Dump coffee bean demonstrated.

Show the child 2 or 3 times how to dump the coffee bean out of the bottle. Then ask the child to get it out. (Do not use the word “dump.”)

Pass if the child dumps the coffee bean out of the bottle or rakes the coffee bean close to the opening and then dumps it out. Do not pass if the child removes the coffee bean with a finger.

17. Tower of cubes – 2, 4, 6, 8.

With the child sitting high enough at the table so that elbows are level with table top and hands are on the table, place the blocks on the table in front of the child. Encourage the child to stack them by demonstration and words. It may be helpful to hand the blocks to the child, one at a time. Three trials may be given.

Pass Tower of 2 cubes if the child puts one block on top of another so that it does not fall when he/she removes his/her hand.

Pass Tower of 4, 6, 8 cubes , depending upon the greatest number of blocks the child stacks in three trials.

A pass of 4, 6, or 8 cubes also passes the lower tower items (for example, passing Tower of 6 cubes also passes Tower of 2 and 4 cubes ).

“N.O” for no opportunity- the child has not had the opportunity to perform the item, due to restrictions from the caregiver or other reasons. This score may only be used on “report” items. “R” for refusal- the child refuses to attempt the item. Refusal can be minimized by telling the child what to do rather than asking. If given instruction in proper administration, the caregiver may administer the item. Report items cannot be scored as refusals.

By then identifying the child’s outcome using all the scores that the child has and finding the results were carried out.

no delays (the child successfully performs the action) and a maximum of one caution (between the 75th or 90th percentile).

two or more cautions and/or one or more delays (the child fails to perform an activity that fails completely to the left of the age line.)

refusal scores on one or more items completely to the left of the age line or on more than one item intersected by the age line in the 75-90% area.

Praise the child even for items that are failed. This will build the confidence of the child to attempt more difficult items.

Data on socio-demographic, breastfeeding, and nutritional histories were collected using interviewer-administered questions.

Total Breastfeeding duration was assessed from a study that assessed breastfeeding duration since birth [ 19 ]. It was taken by asking the mother to recall the total duration she breastfed her child. Whether she is still breastfeeding or to recall the time she stopped breastfeeding her child.

Complimentary food was assessed using WHO dietary diversity [ 8 ]. Dietary diversity was collected using dietary diversity scores adapted from the WHO standardized questionnaire for infant and young child feeding (IYCF). Mothers or caregivers were asked to recall all the food items that the child consumed during the past 24 h [ 8 ]. The home environment was assessed using the Home inventory used in different studies [ 20 ]. The Home score was assessed by interview-administered questionnaires. It was done by giving the mother a picture book and the mother will show the picture book to the child. Observation will be made on the interaction and the response the mother has towards her child. The interview was conducted in a free and friendly environment. The observation was made on the maternal and child interaction and maternal responses towards the child while asking other questions from the Home inventory.

The training was given to data collectors and supervisors regarding the objective and method of data collection and discussions were made for unclear questions in the questionnaire.

Data processing and analysis

Data were checked manually for completeness and entered into Epi-data version 4.2.2.1 statistical software and exported into STATA version 14 for data cleaning and analysis. Frequencies and summary statistics (median, interquartile range, percentage, and range) were used to describe the study population in relation to relevant variables.

Nutrition-related variables such as duration of breastfeeding were categorized based on the duration of breastfeeding in months and were grouped as breastfed less than 18 months, 18 to 20, and 21 to 24 months. Dietary diversity was also assessed using a Minimum dietary diversity score comparing children who had consumed four or more food groups and children who scored less than four groups using 24-hour recall. Socioeconomic status was analyzed based on the wealth index by using Principal component analysis (PCA). Childcare practices, maternal-child interaction were checked using the Home score.

Binary logistic regression was used to check for the association between the dependent, fine motor delay, and independent variables. Variables with P- value < 0.2 and which had clinical importance or subject matter were included in the multiple logistic regression. In the multiple logistic regressions, Variables with 95% CI of AOR which did not include 1 were considered to have significant association with the outcome variables. The goodness of fit test indicated (P = 0.0518) that the model was good enough to fit the data well.

Ethical consideration

Before data collection ethical clearance was obtained from Addis Ababa University School of Public Health Institutional Review Board (AAU-IRB). Written Informed consent was obtained from parents (legal guardians) before participating in the study. All study participants were informed about the purpose of the study, their right to deny participation, anonymity, and confidentiality of the information. All methods were carried out in accordance with relevant guidelines and regulations. The Denver II developmental screening test used in this study to measure the developmental milestone was assessed by a well-trained and certified data collector to ensure the safety of the children. It was conducted in a free and friendly environment. It was explained to the parents that the scale determines the child’s current developmental status and that it’s not an IQ test and the child is not expected to pass all the tests administered. The beneficence of the participants was assured by providing education to the participants about the benefits of breastfeeding, growth, and development. For Children identified with developmental delay, further education was given on methods of improving the motor skills of the Children. The confidentiality of the information of the participants was not disclosed.

Socio-demographic characteristics of the study participants

Mothers in the age group from 25 to 29 years were 35(42.17%) in the cases while 101(40.56%) were in the controls. The median age of the mothers was 28, IQR (25 33%). About 48(57.83%) of mothers in the cases and 93(37.65%) of mothers in the controls didn’t have any formal education. About 58(69.88%) of the cases and 185(74.60%) of mothers from the controls were Housewives. About 39(46.99%) fathers in the cases and 67(26.91%) in the controls didn’t have any formal education. About 23(27.71%) of the cases and 52(20.88%) in the controls were from the lowest quintile. About 69(83.13%) of the cases and 179(71.89%) of the controls were Rural residents (Table  1 ).

Child-related characteristics

The study included 168 male and 164 female children from the age group of 20–24 months. About 36(43.37%) males were cases while 132(53.01%) were in the controls (Table  2 ).

Delivery and nutritional characteristics of the study participants

Health facility delivery among the cases was 67(80.72%) and 213(85.54%) among the controls. Breastfeeding at least once was 81(97.59%) among the cases and 248(99.60%) among the controls. About 49(59.04%) mothers in the cases and 139(55.82%) in the controls reported that they are currently breastfeeding.

About 66(79.52%) children in the cases and 177(71.08%) children in the controls continued to be breastfed from 21 to 24 months. There was no significant variation among cases and controls by the duration of breastfeeding 95% CI (p = 0.234) (Table  3 ).

Dietary practices and nutritional characteristics of the children

About 46(55.42%) of children in the cases and 179(71.89%) in the controls started solid or semi-solid food within 6 to 8 months. There was a difference among cases and controls on children at the time of starting solids and semisolid foods (Table  4 ).

Caregiving practice

About 41(49.40%) of children in the cases and 172(69.08%) in the controls had a score between 20 and 29 on the Home score. The Home score had a minimum score of 13 and a maximum score of 32 (Table  5 ).

Association of different characteristics of children with suspect of fine motor delay

In the binary logistic regression variables with p-value < 0.2 or factors that had clinical importance were identified (Table  6 ).

After adjusting for these variables age of the mother, the educational status of the mother, the sex of the child, and the Home score were identified to have a significant association with fine motor delay.

We didn’t find a significant association between duration of breastfeeding and fine motor delay for children who were breastfed from 18 to 20 months [AOR: 0.45, 95% CI: (0.13, 1.56)] and for children who were breastfed from 21 to 24 months [AOR: 0.86, 95% CI: (0.36, 2.05)] compared to children who were breastfed less than 18 months. Children who have mothers > 35 years of age were 78% less likely to have fine motor delay than mothers who were < 25 years old [AOR: 0.22, 95% CI: (0.05, 0.87)]. Children who had mothers in primary school were 66% less likely [AOR: 0.34, 95% CI: (0.14, 0.81)] and children who had mothers in secondary school and above were 77% less likely [AOR 0. 23, 95% CI: (0.06, 0.80)] to have fine motor delay than mothers who didn’t have any formal education. Females were 1.86 times more likely to have fine motor delay than males [AOR: 1.86, 95% CI: (1.05, 3.28)]. Children who scored 20–29 on the Home score were 51% less likely to have fine motor delay than Children who scored < 20 [AOR: 0.49, 95% CI: (0.27, 0.88)] (Table  6 ).

Child development is an important aspect of human life. Development can be affected by different factors. Environmental factors and nutritional factors together play a significant role in child development. Nutritional factors have a great role in development but due to the adverse environmental and social factors, the outcome could be influenced by different factors, especially in developing countries [ 1 ].

Breastfeeding is known to have a significant effect on child growth and development [ 11 ] but in our study, We didn’t find a significant association between the duration of breastfeeding and fine motor delay for children who were breastfed from 18 to 20 and for children who were breastfed from 21 to 24 months compared to children who were breastfed less than 18 months.

Our findings are consistent with some studies that didn’t find a significant association between duration of breastfeeding and fine motor development [ 21 , 22 , 23 ]. All the studies acknowledged that breastfeeding is important for development but they suggested that other factors also have a role in influencing fine motor development. Similar to our study, A study in Singapore didn’t find a significant association between breastfeeding and fine motor development at 24 months [ 21 ]. Another study done in rural Brazil didn’t find a significant association between breastfeeding and fine motor development at 12 months and suggested home stimulation, maternal education, and income were influencing the outcome [ 22 ].

The study in Singapore suggested they have used specific research tools and have controlled for a large number of potential confounders and they didn’t find any relationship between breastfeeding on fine motor development [ 21 ]. The study in Brazil investigates the association between breastfeeding and mental and motor development, controlling for comprehensive measures of the child’s socioeconomic maternal, and environmental background, and nutritional status. They didn’t find a significant association between breastfeeding and motor development. They explained that the reason most studies have found an association between breastfeeding and development is that the studies have been done in relatively affluent populations where, in general, mothers who succeed in breastfeeding have higher socio-economic status, better educated with higher educational attainment. While In their study mothers who were breastfeeding longer had lower socioeconomic status, poorer education, and provided less stimulating home environments. They explained the reason that most studies found the association was due to incomplete adjustment for covariates, differences in methodological robustness, and types of tests used are likely to be contributory, which will result in an apparent breastfeeding benefit. To prevent this bias they controlled for different covariates. They suggested that no subgroup is differentially protected by breastfeeding, but rather that all groups benefit. The benefit of breastfeeding was an important factor that benefited all the comparison groups, while it has a beneficial effect, breastfeeding didn’t have a protective effect on fine motor development. The difference in the outcome was appreciated by other potential determinants. They found home stimulation and family income to be more important factors [ 22 ].

This is similar to our study finding that mothers who were breastfeeding longer had lower socio-economic status and poorer education. We also have found other environmental factors to be significantly associated. Similar to these studies environmental factors were playing a significant role in fine motor development.

All the studies acknowledged that breastfeeding is important for development but they suggested that other factors were influencing fine motor delay and we need to take into consideration other factors that could also affect or contribute to child development.

A systematic review also suggested that development is influenced by different environmental and psychological factors. Different factors need to be put into consideration that can affect the developmental potential of the children. Their analysis reveals that there are studies that have shown an apparent decrease in effect after multivariate analysis. Given that tight control of confounders resulted in a greater likelihood of the disappearance of the breastfeeding effect. Studies completed in middle-income and low-income countries were nearly twice as likely to find no association compared with studies set in developed countries. The fact that this relationship is less apparent in developing countries suggests that much of the observed relationship may be due to parental social advantage, confounding the choice to breastfeed [ 23 ].

In conclusion, the systematic review suggests that much of the reported effect of breastfeeding on child developmental abilities is due to maternal and socioeconomic effects. They suggested additional, future studies in this field are needed to rigorously control for all important confounders [ 23 ]. Development is not the solo effect of breastfeeding alone but a combination of different factors working together.

All these studies have used different developmental screening tools so the comparison should be done cautiously.

Contrary to our study A study in Malawi among children who breastfeed from 9 to 10 months found a small but significant protective effect on fine motor development at 12 to 18 months [ 24 ]. Studies in Western countries, a study done in Taiwan and Greece assessed the effect of duration of breastfeeding more than 6 months and fine motor assessed at 18 months. They found that any increase in the duration of breastfeeding was associated in decreasing in the odds of fine delay which persisted after controlling for different factors [ 25 , 26 ]. The Taiwan study has shown that mothers who breastfeed longer were older, had a university education, and were from a better socioeconomic class and suggested that the positive result could be due to the presence of these factors [ 25 ]. These factors were different in our setting, the majority of the mothers in this study who breastfeed for longer durations were less educated. Studies have shown that mothers who are more educated create a more favorable and stimulating environment and when breastfeeding is added to these factors there could be better results that can be helpful for child development [ 27 , 28 ]. This might be one of the reasons why we couldn’t find a significant association.

We have also found the age of the mother to have a significant association with the development of the child. We have found older mothers had more favorable outcomes than young mothers. Similar findings have suggested that older mothers tend to create a more favorable environment for child development and would also breastfeed for longer durations [ 29 – 31 ].

Also, we have found the education level of the mother to be significantly associated with fine motor delay. Children who had mothers in primary and secondary school were less likely to have fine motor delay than mothers who didn’t have formal education. Studies have shown that a mother’s education is important because as the educational level of the mother increases the level of stimuli the mother gives to her child also increases [ 27 ]. In addition to that, as the education level of the parents increases the socioeconomic status also could increase and will create a more favorable environment for the children [ 32 ].

Another factor that we found significant was the sex of the child. We have found females have greater odds of being affected by fine motor delay than males. Contrary to our study different studies have suggested females have a better score on fine motor and boys have a higher risk of having developmental delay [ 33 , 34 ]. While we cannot give a general conclusion other factors in the environment could affect the development of females. A study in India has shown that Girls are breastfed for shorter durations than boys due to the gender preferences of the mothers. Mothers will start early weaning for girls than boys to have another pregnancy and not to delay another pregnancy [ 35 ]. The gender preferences of the mother could affect the duration of breastfeeding and the care the child will have [ 36 ]. This gender preference could lead to a developmental delay in the female population.

We have found the Home score to have a significant association with fine motor development. Similarly, studies found the Home environment to have a significant association with fine motor development [ 37 , 38 ]. Motor development can be regulated critically by the home environment and maternal and child interaction [ 39 ]. The role of the mother or the caregiver has a protective role even for children growing up in limited environments such as low socioeconomic status, low levels of education, chronic illness, conflict, and mental health problems of caregivers. Mothers’ sensitivity is important because it creates a conducive environment for the development of the child [ 40 ]. A study done in Iran did not find a significant positive association between home motor affordances and motor development in their sample. They suggested that this could be due to the tool that they used was not sensitive enough to detect differences [ 3 ]. Home environment is a very important factor for childhood development a study has shown in nutrition-related interventions certain amount of stimulation from the environment was necessary and nutritional intervention alone was insufficient to bring brain development [ 40 ].

The Strengths of this study are the study was a community-based case-control study which is helpful to asses multiple exposure or risk factors. We have also used new cases that were identified at the time of collection which could prevent misclassification bias. We have used tools that are validated in our setting which can measure the case of interest in a better way.

The following limitation needs to be taken into account when interpreting the results. Most of the mothers in our study group had the practice of long-term breastfeeding durations and conducting the study where different information or different study groups are available would help to further strengthen the study finding. Our study was conducted in a rural setting but including the figure of urban mothers would further enrich the information that can be found. Even though birth weight is an important factor for development we didn’t have information on the birth weight of the children.

Conclusions

This study still supports that breastfeeding is important for child development. However, in our study, we didn’t find a significant association between the duration of breastfeeding from 18 to 20 months and for duration of breastfeeding from 21 to 24 months compared to children who were breastfed less than 18 months on fine motor development. Children from older mothers were less likely to be affected than young mothers. Children who had mothers in primary and secondary school were less likely to have fine motor delay than mothers who didn’t have formal education. Females have higher odds of being suspect of fine motor delay than males. Children who had better maternal care practices or Home scores were less likely to be affected than Children who had lower maternal care practices or lower Home scores.

Based on our findings we forward the following recommendations: Health care providers should be the first-line source of information to provide appropriate information to the mothers and the community during delivery or during any visit the mother makes to the health facility. They should educate the mothers and the community about the importance of child feeding and childcare and creating a conducive environment for child development. Older mothers tend to create more conducive environments for child development. Delaying early pregnancies is helpful to have physically and psychologically mature mothers. Since mothers are the primary caretakers improving maternal education and empowerment to improve developmental outcomes is helpful for child development. Therefore policymakers should work on improving the educational status and empowerment of women and work on avoiding gender differences starting from a young age. Assessment of Developmental delay in children should also be done routinely by Health care providers to catch delays during the early years and to have early interventions. Further studies should be done in a different setup to appreciate the difference and the effect of other environmental factors. Further follow-up studies should be done to prevent recall bias in a better way. Thus, overall, child development can be influenced by different factors in the environment, and having a holistic approach is mandatory to tackle the problem.

Data Availability

The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.

Abbreviations

Infant and Young Child Feeding

Arachidonic acid

Docosahexaenoic acid

Ethiopian Demographic and Health Survey

Health and Demographic Surveillance site

Nationalities and Peoples Regional State

World Health Organization

Adjusted Odds Ratio

Confidence Interval

Crude Odds Ratio

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Acknowledgements

We acknowledge the data collectors, study participants, and all those who were involved in the study. We would like to extend our gratitude to Professor Frances Abound for his comment, support, and advice. We would also like to thank Dr. Teklu Gemechu for his help and guidance and Miss. Mashresa Harisgo for her help and dedication during the data collection.

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Shiferaw, R., Yirgu, R. & Getnet, Y. Evaluating the association between duration of breastfeeding and fine motor development among children aged 20 to 24 months in Butajira, Ethiopia: a case-control study. BMC Pediatr 24 , 216 (2024). https://doi.org/10.1186/s12887-023-04391-6

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DOI : https://doi.org/10.1186/s12887-023-04391-6

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