Autism spectrum disorder in a rural community in Bangladesh: A mid-childhood assessment.

Population-based studies employing standardized diagnostics are needed to determine the burden of autism spectrum disorder (ASD) in low-resource settings. A community-based study was conducted among 8-11 year old children in rural, northwestern Bangladesh to establish the prevalence of ASD. A standardized screening and diagnosis protocol was adapted and deployed comprising the social communication questionnaire (SCQ), and the autism diagnostic observation schedule 2, (ADOS-2), and the autism diagnostic interview, revised (ADI-R), respectively. A year-long research training was conducted for a clinical psychologist to be certified to administer ADOS-2 and ADI-R. Over 8000 children were visited at home and administered the SCQ leading to some, based on their score, being further evaluated using the ADOS-2 and ADI-R by the clinical psychologist. Based on ADOS-2 applying the diagnoses of autism or autism spectrum, the prevalence was 40 (95% CI: 27, 54) per 10,000. Autistic disorder using ADI-R was found at 12 (95% CI: 5, 20) per 10,000. Boys were at a higher risk than girls with the rates among boys being 46 (95% CI: 25, 67) using ADOS-2 and 19 (95% CI:6, 33) using ADI-R. Among girls the rates were 34 (95% CI:16, 52) and 5 (95% CI:0, 12) per 10,000, respectively. Challenges to undertaking ASD research in a rural South Asian context are discussed. There was a low-to-moderate prevalence of ASD in a rural, child population in Bangladesh. Future research is needed to estimate rates of ASD and its causes and socioeconomic consequences in rural and urban settings of South Asia. LAY SUMMARY: In a study of over 8000, 8-11 year old children in a rural area of Bangladesh, two to four out of 1000 had ASD. Boys more than girls had ASD. Conducting ASD assessment in this setting was difficult, but more such research is needed to understand what causes ASD and its consequences for the individual, families and the society in rural and urban areas of low-income countries.

Impact of emollient therapy for preterm infants in the neonatal period on child neurodevelopment in Bangladesh: an observational cohort study.

BACKGROUND: Topical treatment with sunflower seed oil (SSO) or Aquaphor® reduced sepsis and neonatal mortality in hospitalized preterm infants <33 weeks' gestational age in Bangladesh. We sought to determine whether the emollient treatments improved neurodevelopmental outcomes during early childhood. METHODS: 497 infants were randomized to receive SSO, Aquaphor®, or neither through the neonatal period or hospital discharge. 159 infant survivors were enrolled in the longitudinal follow-up study using a validated Rapid Neurodevelopmental Assessment tool and the Bayley Scales of Infant Development II (BSID II) administered at three-monthly intervals for the first year and thereafter at six-monthly intervals. Lowess smoothing was used to display neurodevelopmental status across multiple domains by age and treatment group, and Generalized Estimating Equations (GEE) were used to compare treatment groups across age points. RESULTS: 123 children completed at least one follow-up visit. Lowess graphs suggest that lower proportions of children who received massage with either SSO or Aquaphor® had neurodevelopmental delays than control infants in a composite outcome of disabilities. In GEE analysis, infants receiving SSO showed a significant protective effect on the development of fine motor skills [odds ratio (OR) 0.92, 95% confidence interval (CI) 0.86-0.98, p=0.006]. The Psychomotor Development Index (PDI) in the BSID II showed significantly lower disability rates in the Aquaphor group (23.6%) compared to the control (55.2%) (OR 0.21, 95% CI 0.06-0.72, p=0.004). CONCLUSIONS: Emollient massage of very preterm, hospitalized newborn infants improved some child neurodevelopmental outcomes over the first 2 years of follow-up. Findings warrant further confirmatory research. TRIAL REGISTRATION: ClinicalTrials.gov (98-04-21-03-2) under weblink https://clinicaltrials.gov/ct2/show/NCT00162747.

Detecting Developmental Delay and Autism Through Machine Learning Models Using Home Videos of Bangladeshi Children: Development and Validation Study.

BACKGROUND: Autism spectrum disorder (ASD) is currently diagnosed using qualitative methods that measure between 20-100 behaviors, can span multiple appointments with trained clinicians, and take several hours to complete. In our previous work, we demonstrated the efficacy of machine learning classifiers to accelerate the process by collecting home videos of US-based children, identifying a reduced subset of behavioral features that are scored by untrained raters using a machine learning classifier to determine children's "risk scores" for autism. We achieved an accuracy of 92% (95% CI 88%-97%) on US videos using a classifier built on five features. OBJECTIVE: Using videos of Bangladeshi children collected from Dhaka Shishu Children's Hospital, we aim to scale our pipeline to another culture and other developmental delays, including speech and language conditions. METHODS: Although our previously published and validated pipeline and set of classifiers perform reasonably well on Bangladeshi videos (75% accuracy, 95% CI 71%-78%), this work improves on that accuracy through the development and application of a powerful new technique for adaptive aggregation of crowdsourced labels. We enhance both the utility and performance of our model by building two classification layers: The first layer distinguishes between typical and atypical behavior, and the second layer distinguishes between ASD and non-ASD. In each of the layers, we use a unique rater weighting scheme to aggregate classification scores from different raters based on their expertise. We also determine Shapley values for the most important features in the classifier to understand how the classifiers' process aligns with clinical intuition. RESULTS: Using these techniques, we achieved an accuracy (area under the curve [AUC]) of 76% (SD 3%) and sensitivity of 76% (SD 4%) for identifying atypical children from among developmentally delayed children, and an accuracy (AUC) of 85% (SD 5%) and sensitivity of 76% (SD 6%) for identifying children with ASD from those predicted to have other developmental delays. CONCLUSIONS: These results show promise for using a mobile video-based and machine learning-directed approach for early and remote detection of autism in Bangladeshi children. This strategy could provide important resources for developmental health in developing countries with few clinical resources for diagnosis, helping children get access to care at an early age. Future research aimed at extending the application of this approach to identify a range of other conditions and determine the population-level burden of developmental disabilities and impairments will be of high value.

Displaced Rohingya children at high risk for mental health problems: Findings from refugee camps within Bangladesh.

BACKGROUND: The 2017 political violence against the Rohingya people in the state of Rakhine resulted in a large influx of displaced populations into Bangladesh. Given harsh conditions and experiences in Myanmar, and the harrowing journey to the border, raised levels of child neurodevelopmental disorders (NDDs) and mental health problems were expected. METHODS: A team of child development professionals, physicians, psychologists, and developmental therapists screened 622 children in clinics within the refugee camps using the Developmental Screening Questionnaire (DSQ; 0-<2 years), and the Ten Questions Plus (TQP) for NDDs, and Strengths and Difficulties Questionnaire (SDQ; 2-16 years) for mental health problems. Any child positive on the DSQ or the TQP was assessed for NDDs. RESULTS: Only 4.8% children aged 0-<2 years and 7.3% children aged >2-16 years screened positive for NDDs, comparable with a local Bangladesh population. However, 52% of children were in the abnormal range for emotional symptoms on the SDQ, and 25% abnormal for peer problems. Significant risk factors were being parentless and having lost one or more family members in the recent crisis. CONCLUSIONS: This screening study provides objective evidence of the urgent need for psychosocial support of Rohingya children within camps, with special attention to those without parents, including monitoring of their well-being and counselling of families and other care providers.

Validation of a rapid neurodevelopmental assessment tool for 5 to 9 year-old children in Bangladesh.

OBJECTIVE: To validate a rapid neurodevelopmental assessment tool for use by child care professionals to determine neurodevelopmental impairments (NDIs) in children ages 5-9 years (61-108 months) in Bangladesh. STUDY DESIGN: In a convenience sample of community children (n = 18), interrater reliability was determined between 6 testers. Validity was determined in 121 children by simultaneous administration of a test of adaptive behavior (AB) (ie, the Independent Behavior Assessment Scale, or Gold Standard I) and IQ tests (Wechsler Preschool and Primary Scales of Intelligence or the Wechsler Intelligence Scales for Children, or Gold Standard II) by child psychologists. RESULTS: Interrater reliability was excellent (kappa = 1.00). Significantly lower scores were obtained on AB and IQ tests in those identified with "any (≥1) NDI" and most specific NDIs. Sensitivity and specificity for "any NDI" with (a) "significant difficulties" (defined as AB z-scores < -2 SD and/or IQ < 70) or (b) "mild difficulties included" (AB z scores < -1 SD and/or IQ < 85) were 84% and 57%; and 83% and 70%, respectively. CONCLUSION: The rapid neurodevelopmental assessment tool shows promise as a tool for use by a range of professionals for identifying NDIs in children of primary school age. Further refinement for identifying specific impairments is needed.

Follow-up of cases of Haemophilus influenzae type b meningitis to determine its long-term sequelae.

OBJECTIVE: To measure physical and neurologic impact of Haemophilus influenzae type b (Hib) meningitis on surviving children through short- and long-term follow-up. STUDY DESIGN: Cases of Hib meningitis, diagnosed at a tertiary level pediatric hospital, were subjected to short- and long-term follow-up and compared with age, sex, and area of residence matched healthy controls. Follow-up assessments included thorough physical and neurodevelopmental assessments using a standardized protocol by a multidisciplinary team. RESULTS: Assessments of short-term follow-up cohort (n = 64) revealed hearing, vision, mental, and psychomotor deficits in 7.8%, 3%, 20%, and 25% of the cases, respectively. Deficits were 10%, 1.4%, 21%, and 25% in long-term follow-up cohort (n = 71), in that order. Mental and psychomotor deficits were found in 2% of the controls, none of whom had vision or hearing deficits. CONCLUSIONS: In addition to risk of death, Hib meningitis in children causes severe disabilities in survivors. These data facilitated a comprehensive understanding of the burden of Hib meningitis, specifically in developing countries where disabled children remain incapacitated because of lack of resources and facilities. The evidence generated from this study is expected to provide a compelling argument in favor of introduction and continuation of Hib conjugate vaccine in the national immunization program for children.

Validation of rapid neurodevelopmental assessment for 2- to 5-year-old children in Bangladesh.

OBJECTIVE: Validate a tool to determine neurodevelopmental impairments (NDIs) in >2- to 5-year-old children in a country with limited child development expertise. METHODS: Rapid Neurodevelopmental Assessment (RNDA) is a tool designed to detect functional status and NDIs across multiple neurodevelopmental domains. Validity was determined in 77 children enrolled by door-to-door sampling in Dhaka and who were administered the RNDA by 1 of 6 testers (4 developmental therapists, 2 special education teachers) and simultaneously administered a test of adaptive behavior (AB; Independent Behavior Assessment Scale) and intelligence quotient (IQ) tests (Bayley Scales of Infant Development II, Stanford Binet Intelligence Scale, Wechsler Preschool and Primary Scales of Intelligence) by psychologists. RESULTS: Interrater reliability ranged from good to excellent. There were significant differences in AB in mean percentile scores on the Independent Behavior Assessment Scale for motor (P = .0001), socialization (P = .001), communication (P = .001), and full-scale (P = .001) scores in children with ≥1 NDI ("any NDI") versus no NDI. Significant differences in those with versus those without "any NDI" were found on IQ scores. Sensitivity and specificity for "significant difficulties" (defined as AB z-scores < -2 SDs and/or IQ <70) and "mild difficulties included" (AB z-scores < -1SD and/or IQ <85) were 90% and 60% and 80% and 76%, respectively. CONCLUSIONS: The RNDA validity results are promising for use by child care professionals in field and clinical settings, but the tool needs further replication and refinement for assessment of specific impairments of vision, hearing, and seizures.

Prediction of seizure outcome in childhood epilepsies in countries with limited resources: a prospective study.

AIM: To identify predictors of seizure control in newly presenting children with epilepsy in countries with limited resources. METHOD: Three hundred and ninety children (273 males, 117 females) aged 2 months to 15 years with newly diagnosed epilepsy were enrolled prospectively at first visit to the multidisciplinary clinic at the children's hospital in Dhaka, Bangladesh. Data about seizures, motor disability, psychomotor development, and electroencephalography were obtained. Regular monitoring of antiepileptic drug treatment was continued at least for one year. Associations between seizure control and potential predictors were determined by multivariate analysis. RESULTS: Three hundred and ninety children were enrolled in 6 months, of whom over 60% were from low-income families, 60% had onset at under 1 year, 74% had more than one seizure per week, 69% a single-seizure type, and 38% a history of delayed onset of breathing at birth. Cognitive deficits (IQ<70; 58%) and/or motor (significant limitation of daily living activities; 47%) deficits were common. After 1 year of regular treatment, seizure control was good (seizure freedom) in 53%, and poor (at least one seizure in the last 3mo of follow-up) in 47%. The predictors of poor seizure control were an IQ<70, associated motor disability, multiple seizure types, and a history of cognitive regression (1.9 times more likely to have poor seizure control). INTERPRETATION: Seizure control can be predicted using three clinical factors (motor disability, cognitive impairment, and multiple seizure types) at the first clinic visit. Such predictors assist the development of referral plans and management guidelines for childhood epilepsies in resource-poor countries.

Neurodevelopmental sequelae in pneumococcal meningitis cases in Bangladesh: a comprehensive follow-up study.

BACKGROUND: Evaluation of the long-term impact of pneumococcal meningitis on surviving children and their families is critical to fully comprehending the burden of pneumococcal disease and to facilitating an evidence-based decision for the introduction of pneumococcal vaccine. This study was an investigation of the short- and long-term impacts of pneumococcal meningitis among Bangladeshi children. METHODS: Case patients with pneumococcal meningitis who were hospitalized between January 2006 and March 2007 were subjected to short-term follow-up within 30-40 days of discharge. Case patients discharged prior to January 2005 were selected for long-term follow-up at 6-24 months after the date of discharge. Both cohorts were enrolled from Dhaka Shishu Hospital, a pediatric hospital in Bangladesh. Healthy children matched for age, sex, socioeconomic status, and area of residence were recruited from the community as control subjects. During follow-up visits, case patients and control subjects were assessed for their physical and neurodevelopmental status by use of a standardized protocol. The impact of pneumococcal meningitis on siblings and the family as a whole was assessed by means of qualitative interviews. RESULTS: Neurodevelopmental assessments of the short-term follow-up cohort (n=51) revealed hearing, vision, mental, and psychomotor deficits in 33%, 8%, 41%, and 49% of the case patients, respectively. These deficits were 18%, 4%, 41%, and 35% in the long-term follow-up cohort (n=51), respectively. Such deficits were seen in only 2% of the control subjects, none of whom had vision or hearing deficits. CONCLUSIONS: In addition to the risk of death, pneumococcal meningitis in children causes severe disabilities among survivors, as well as disruption of the life of other siblings and family members. This study demonstrated that high rates of sequelae are associated with pneumococcal meningitis. Neurodevelopmental assessment during follow-up of patients with meningitis is critical to our understanding of the burden of the adverse consequences of pneumococcal disease. These data, along with the fact of poor access to health care, provide a compelling argument in favor of the introduction of pneumococcal vaccine, specifically in a setting where access to health care is poor and disabled children remain incapacitated because of a lack of resources and facilities.

Behaviour problems in young children in rural Bangladesh.

OBJECTIVE: To determine the prevalence of child behaviour problems reported by parents in rural Bangladesh. METHODS: A total of 4,003 children aged 2-9 years were identified during a population-based survey of 2,231 households. A predetermined sample of 499 was selected, of which health professionals saw 453 (90.8%) for structured physical and neurological examination, standardized testing of cognition and adaptive behaviour and parent report of developmental history and behaviour problems. RESULTS: The prevalence of behaviour impairments was 14.6% (95% CI 11.4, 17.9). The majority involved somatic complaints, including nocturnal enuresis and pica. Problems such as aggression or restlessness were infrequently reported. Behaviour impairments were significantly associated with malnutrition (prevalence ratio 2.1, 95% CI 1.2, 3.6, p < 0.01) and cognitive, motor or seizure disabilities (prevalence ratio 1.8, 95% CI 1.1, 2.9, p < 0.05). CONCLUSIONS: The prevalence and nature of reported behaviour impairments in rural Bangladesh have implications for public health planning and delivery of health services.

Retinopathy of prematurity in Bangladeshi neonates.

BACKGROUND: Retinopathy of prematurity (ROP) is a potentially blinding eye disorder that primarily affects premature infants. Increased survival of extremely low birth weight infants following advances in antenatal and neonatal care has resulted in a population of infants at high risk of developing ROP. Long term morbidity of ROP has a spectrum ranging from myopia to blindness. Screening programs and early intervention can provide enormous economic and social benefits. MATERIALS AND METHODS: Preterm infants of gestational age <33 weeks admitted to the Special Care Nursery of Dhaka Shishu Hospital for a trial of topical emollient therapy during December 1998-July 2003 were followed-up after hospital discharge, including detailed ophthalmologic examination. Detailed history regarding risks during pregnancy, delivery and hospital stay was documented. ROP cases were managed according to the stage of the disease at diagnosis. RESULTS: Five out of the 114 (4.4%) children seen in follow-up were diagnosed with ROP. Low gestational age, low birth weight, administration of oxygen, apneic spells, sepsis and blood transfusions were common factors among cases who developed ROP. CONCLUSION: As survival of preterm infants in low resource settings increases, ROP will become increasingly important as a potential cause of blindness, emphasizing the critical need for ophthalmologic examination in premature infants, with immediate initiation of treatment when ROP is diagnosed.

Side effects of phenobarbital and carbamazepine in childhood epilepsy: randomised controlled trial.

OBJECTIVE: To compare the behavioural side effects associated with two commonly used antiepilepsy drugs-phenobarbital and carbamazepine-in children in Bangladesh. DESIGN: Prospective randomised controlled single centre trial. SETTING: Specialist children's hospital in Dhaka, Bangladesh. PARTICIPANTS: 108 children aged 2-15 with generalised tonic-clonic (n=51) or partial and secondary generalised seizures (n=57). MAIN OUTCOME MEASURES: Seizure control and behavioural side effects. RESULTS: 91 children were followed up for 12 months. Six required a change of antiepilepsy drug. Side effects were compared in 85 children. In the last quarter of the 12 month follow-up, 71 children were seizure free after one year's treatment. Thirty two in the phenobarbital group and 39 in the carbamazepine group had no seizures in 74 and 102 days after randomisation, respectively. Ten children had increased behavioural problems, which were unacceptable in four (one in the phenobarbital group and three in the carbamazepine group). Independent t tests, however, showed no difference between the two trial drugs. CONCLUSION: There was no excess in behavioural side effects with phenobarbital in children with epilepsy in a country with limited resources. Trial registration NCT00381537.

Ciprofloxacin treatment in preterm neonates in Bangladesh: lack of effects on growth and development.

BACKGROUND: Quinolone-induced arthropathic toxicity in weight-bearing joints observed in juvenile animals during preclinical testing has largely restricted the routine use of ciprofloxacin in the pediatric age group. As histopathologic, radiologic and magnetic resonance imaging monitoring evidence has gathered supporting the safety of fluoroquinolones in children, many pediatricians have started to prescribe quinolones to some patients on a compassionate basis. OBJECTIVE: The objective of this study was to ascertain the safety of ciprofloxacin in preterm neonates <33 weeks gestational age treated at Dhaka Shishu (Children) Hospital in Bangladesh. METHODS: Long-term follow up was done to monitor the growth and development of preterm infants who were administered intravenous ciprofloxacin in the neonatal period. Ciprofloxacin was used only as a life-saving therapy in cases of sepsis produced by bacterial agents resistant to other antibiotics. Another group of preterm neonates with septicemia who were not exposed to ciprofloxacin, but effectively treated with other antibiotics and followed up, were matched with cases for gender, gestational age and birth weight and included as a comparison group. Forty-eight patients in the ciprofloxacin group and 66 patients in the comparison group were followed up for a mean of 24.7 +/- 18.5 months and 21.6 +/- 18.8 months, respectively. RESULTS: No osteoarticular problems or joint deformities were observed in the ciprofloxacin group during treatment or follow up. No differences in growth and development between the groups were found. CONCLUSIONS: Ciprofloxacin is a safe therapeutic option for newborns with sepsis produced by multiply resistant organisms.

Neurodevelopmental outcomes of preterm infants in Bangladesh.

OBJECTIVES: The purpose of this work was to determine neurodevelopmental outcomes of preterm infants followed by a multidisciplinary team in a tertiary hospital in Bangladesh. METHODS: Infants <33 weeks' gestational age were serially assessed for neurodevelopment by physicians and developmental psychologists. An estimate of "low," "moderate," or "high" risk for neurodevelopmental impairments was made at the first visit. At later assessments, neurodevelopmental impairments were graded by severity as "none," "mild," or "serious." RESULTS: Of the 159 enrolled children, 65% survived, 16% died, and 19% were lost to follow-up. Family income was lowest among those who died, and maternal and paternal literacy was highest among the survivors. At a mean age of 31 months, developmental status of the 85 children followed-up for > or = 12 months was normal in 32%; 45% had mild and 23% had serious neurodevelopmental impairments. Cognitive impairment was the most common deficit (60%). Final outcome was significantly better than estimated initially. Most serious (85%) but fewer mild (37%) problems were identified independently by both child health physicians and psychologists. CONCLUSIONS: Parental education and family income had significant influence on postdischarge mortality. Two thirds of infants demonstrated neurodevelopmental impairments. Most mild cognitive impairments would have been missed had either physicians or psychologists alone done the assessments. Preterm infants in this low-resource setting are at high risk for neurodevelopmental impairments, which need to be identified early, preferably by a multidisciplinary team of professionals.

Screening methods for childhood hearing impairment in rural Bangladesh.

OBJECTIVE: The purpose of this study was to determine a feasible strategy for screening young children in rural Bangladesh for hearing impairments. METHODS: Trained community health workers (CHWs) screened 4003 children between the ages of 2 and 9 years using conditioned play audiometry (CPA) and a subset of 569 of these children (ages 2-5 years), using physiologic (otoacoustic emissions [OAEs] and tympanometry). Measures of frequency and cross-tabulations are presented to describe results. RESULTS: Hearing screening using CPA was feasible for most children in the 6-9 years age range, but not for the younger children due to shyness and lack of cooperation. More than two thirds of the younger children were untestable on CPA. In response to this limitation, OAEs and tympanometry, requiring less cooperation on the part of the child, was implemented for a sample of younger children. Of the 569 children who received both CPA and OAE/tympanometry, 69% were untestable using CPA and 8.9% were untestable using OAE and tympanometry. CONCLUSIONS: These results suggest that hearing screening using CPA for older (6-9 years) and OAE/tympanometry for younger (2-5 years) children is feasible. Using the physiologic measures of OAE/tympanometry significantly reduced the number of untestable children, resulting in fewer referrals for diagnostic assessments. Thus, if only one methodology could be implemented, physiologic measure would be preferred. This is important because trained audiologists are scarce in Bangladesh. Technology is available and feasible for hearing screening in developing countries. Focus needs now to center on increasing the number of trained audiologists in developing countries to ensure better follow-up and accessibility to audiological services.

Profile of childhood epilepsy in Bangladesh.

Very little is known about childhood epilepsies in Bangladesh. This study was conducted within a national children's hospital in Dhaka city to provide baseline information on diagnosis and clinical outcomes of 151 children (98 males, 53 females, age range between 2 months to 15 years, median age of 3 years). Participants who presented with recurrent unprovoked seizures were followed up in an epilepsy clinic for at least 1 year. Of presenting families, 68.3% were from middle-income and lower-income groups. A history of perinatal asphyxia and neonatal seizures was present in 46.4% and 41.1% of participants respectively. Generalized, partial, and unclassifiable epilepsy were found in 63.6%, 25.2%, and 11.2% respectively. Severe outcome (malignant) epilepsy syndromes were diagnosed in 14.6%. Symptomatic epilepsy was found in 61%. Poor cognitive development was present in 72.8% and poor adaptive behaviour in 57%. Poor seizure remission occurred in 50.3%. Factors most predictive of poor seizure remission were: multiple types of seizures, poor cognition at presentation, high rates of seizures, associated motor disability, and EEG abnormalities. The study suggests that most children presenting at tertiary hospitals for seizure disorders come late and with associated neurodevelopmental morbidities. Specialized services are needed closer to their homes. The process for establishing early referral and comprehensive management of childhood epilepsies in Bangladesh requires further study.