Milk-cereal mix supplementation during infancy and impact on neurodevelopmental outcomes at 12 and 24 months of age: a randomised controlled trial in India.

Inadequate protein intake and lack of micronutrients may affect neurodevelopment in infants. This randomised controlled trial was conducted to measure the effect of two milk-cereal mixes with modest and high amounts of protein and enriched with multiple micronutrients, given between 6 and 12 months, on cognitive, language, motor and behavioural scores at 12 and 24 months of age, compared with no-supplementation. The two supplements were also compared with each other. The study was conducted in urban Delhi, India, and the infants were randomised in a 1:1:1 ratio to the three study groups. At 12 and 24 months of age, 1134 and 1214 children were available, respectively. At 12 months of age, compared with no-supplement group, an increase in the motor scores (mean difference, MD 1·52, 95 % CI: 0·28, 2·75) and a decrease in the infant temperament scores (MD - 2·76, 95 % CI: -4·23, -1·29) in the modest-protein group was observed. Those in the high-protein group had lower socio-emotional scores (MD - 1·40, 95 % CI: -2·43, -0·37) and higher scores on Infant Temperament Scale (MD 2·05, 95 % CI: 0·62, 3·48) when compared with modest-protein group. At 24 months, no significant differences in any of the neurodevelopment scores between the three study groups was found. In conclusion, supplementation with modest amount of protein and multiple micronutrients may lead to short-term small improvements in motor function and infant temperament. There appears no advantage of supplementing with high protein, rather negative effects on infant behaviour were observed.

Developmental trends in early childhood and their predictors from an Indian birth cohort.

BACKGROUND: Early childhood developmental pattern analyses not only project future cognition potential, but also identify potential risks for possible intervention. The current study evaluates developmental trends in the first 3 years of life and their predictors in a low and middle income country setting. METHODS: Trends of early childhood development at 6, 15, 24 and 36 months of age and their predictors were explored in a longitudinal community-based birth cohort study in an urban slum in Vellore, South India. Development was assessed using the Bayley Scales of Infant and Toddler Development-III (BSID-III). RESULTS: The birth cohort enrolled 251 children with 94, 91, 91 and 87% follow-up at 6, 15, 24 and 36 months respectively. Child development domains of cognition, language, motor and social skills showed a significant decline in scores between 6 and 36 months of age. Higher socioeconomic position (SEP) and nurturing home environment contributed to increase in cognition scores by 1.9 and 0.9 units respectively. However, stunting caused a decline in cognition scores by 1.7 units. Higher maternal cognition, higher SEP, and caregiver responsivity positively contributed to language change over time, while higher maternal depression contributed negatively. An enriching home environment, growth parameters and blood iron status had positive association with change in motor skills. CONCLUSIONS: A triple intervention plan to enhance home environment and nurturance, early childhood nutrient supplementation, and maternal education and well-being might prevent child developmental decline in high risk settings.

Association between head circumference at two years and second and fifth year cognition.

BACKGROUND: Head circumference (HC) measurement is routinely not performed in early childhood and there is conflicting information about its utility in literature. The current study analyses the association between HC at two years of age and cognition at two and five years of age. METHODS: A community based birth-cohort recruited between 2010 and 2012 was followed up till five years of age in an urban slum in Vellore, India. Children were recruited at birth after informed parental consent by consecutive sampling using eligibility criteria of healthy new-born, singleton pregnancy and family's availability in the study area during follow-up. HC measured at two years of age was used as the exposure variable to calculate association with cognition at both two and five years of age. Cognitive domain of Bayley scale of infant development was used at two years of age and Wechsler Preschool Primary Scales of Intelligence at five years. RESULTS: Of the 251 enrolled children, 138 (55%) were girls and 71 (30%) belonged to lower socioeconomic status. At 2 years, 8.81% of children had HC < - 3SD. Compared to children with HC z-scores ≥ - 2 SD, those with measurements < - 3 SD had a lower cognition scores by - 2.21 [95% CI: - 3.87 - -0.56] at 2 years. Also, children with HC < - 3 SD at two years scored significantly lower scores in cognitive domains of verbal, - 7.35 [95% CI: - 11.78 - -2.92] and performance, - 7.07 [95% CI: - 11.77 - -2.36] intelligence at five years. CONCLUSIONS: This study showed that smaller HC at 2 years of age was negatively associated with cognition at both 2 and 5 years of age. Early childhood HC measurements can be utilised as a cheaper screening tool to identify children at risk in LMIC settings. Further studies can confirm these findings in diverse settings.

Home environment: Short-term trends and predictors in early childhood from an Indian community birth cohort.

BACKGROUND: Early childhood home environment is intricately linked to child development and later cognitive and academic skills. There is limited literature evaluating home environmental trends and predictors in the low- and middle-income country settings. AIMS: Determine the trends of early childhood home environment changes between 6 and 36 months of age, and the factors associated with these changes. STUDY DESIGN: Longitudinal community-based birth cohort follow-up study in a semi-urban slum in Vellore, South India. SUBJECTS: Consecutive sampling of a birth cohort between March 2010 and February 2012. OUTCOME MEASURES: Home environment was objectively assessed using the 'Home Observation for the Measurement of the Environment' (HOME) scale. Predictors of change in the home environment over time also were analyzed. Multivariable linear regression models and linear mixed effect models were used to identify the factors associated with HOME score at individual time points and over-a-time period, respectively. RESULTS: The birth cohort enrolled 251 children with a follow-up of 235, 228 and 218 children at 6, 24 and 36 months, respectively. The socio-economic status (SES) was the single biggest predictor for the HOME score at each time point, with increasing strength over time. Maternal education predicted home environment at 24 months, while maternal depression was negatively associated at 6 and 24 months of age. SES and maternal factors contributed to the overall change in the HOME score. Maternal factors predicted relational home environmental change over time. CONCLUSION: SES and maternal factors consistently predicted early childhood home environment at 6, 24 and 36 months of age and its change over time. It is important to support maternal education and wellbeing along with socio-economic measures to optimize early childhood environment.

Body iron and lead status in early childhood and its effects on development and cognition: a longitudinal study from urban Vellore.

OBJECTIVE: Early childhood factors can have persisting effects on development and cognition in children. We propose to explore the trends of Fe deficiency and Pb toxicity in early childhood and their association with child development at 2 years of age and cognition at 5 years. DESIGN: Longitudinal birth cohort study. SETTING: Urban slum, Vellore, India. PARTICIPANTS: Children enrolled at birth were followed up regularly in the first 2 years with developmental and cognitive assessments at 2 and 5 years of age, respectively. RESULTS: The birth cohort enrolled 251 children with 228 children followed up at 2 years and 212 at 5 years of age. Fe deficiency (ID) was highest at 15 months of age and improved subsequently at 24 months. Blood Pb levels (BLL) remained high at all age groups with an increasing trend with age; 97 % at 36 months having high BLL. Persistent high mean BLL at 15 and 24 months had negative association with both cognition and expressive language raw scores of 24 months, while high mean BLL at 15, 24 and 36 months had no significant association with any of the domains of cognition at 5 years of age. Early childhood cumulative body Fe status at 7, 15 and 24 months did not show any association with child development at 2 years, but was associated with verbal, performance and processing speed components of cognition at 5 years. CONCLUSIONS: Optimising body Fe status and limiting Pb exposure in early childhood can augment child development and school entry cognition.

Early Life Child Micronutrient Status, Maternal Reasoning, and a Nurturing Household Environment have Persistent Influences on Child Cognitive Development at Age 5 years: Results from MAL-ED.

BACKGROUND: Child cognitive development is influenced by early-life insults and protective factors. To what extent these factors have a long-term legacy on child development and hence fulfillment of cognitive potential is unknown. OBJECTIVE: The aim of this study was to examine the relation between early-life factors (birth to 2 y) and cognitive development at 5 y. METHODS: Observational follow-up visits were made of children at 5 y, previously enrolled in the community-based MAL-ED longitudinal cohort. The burden of enteropathogens, prevalence of illness, complementary diet intake, micronutrient status, and household and maternal factors from birth to 2 y were extensively measured and their relation with the Wechsler Preschool Primary Scales of Intelligence at 5 y was examined through use of linear regression. RESULTS: Cognitive T-scores from 813 of 1198 (68%) children were examined and 5 variables had significant associations in multivariable models: mean child plasma transferrin receptor concentration (ß: -1.81, 95% CI: -2.75, -0.86), number of years of maternal education (ß: 0.27, 95% CI: 0.08, 0.45), maternal cognitive reasoning score (ß: 0.09, 95% CI: 0.03, 0.15), household assets score (ß: 0.64, 95% CI: 0.24, 1.04), and HOME child cleanliness factor (ß: 0.60, 95% CI: 0.05, 1.15). In multivariable models, the mean rate of enteropathogen detections, burden of illness, and complementary food intakes between birth and 2 y were not significantly related to 5-y cognition. CONCLUSIONS: A nurturing home context in terms of a healthy/clean environment and household wealth, provision of adequate micronutrients, maternal education, and cognitive reasoning have a strong and persistent influence on child cognitive development. Efforts addressing aspects of poverty around micronutrient status, nurturing caregiving, and enabling home environments are likely to have lasting positive impacts on child cognitive development.

Low head circumference during early childhood and its predictors in a semi-urban settlement of Vellore, Southern India.

BACKGROUND: Stunting in developing countries continues to be a major public health problem. Measuring head circumference (HC) during clinical anthropometric assessment can help predict stunting. The aim of this study was to assess burden and determine the predictors of low HC (<- 2 SD) at birth and during first 2 years of life in a semi- urban settlement of Vellore. METHODS: The study uses baseline data and serial HC measurements from the birth cohort of MAL-ED study, where 228 children from Vellore completed follow-up between March 2010 to February 2014. Analysis of baseline, maternal and paternal characteristics, micro-nutrient status and cognition with HC measurements was performed using STATA version 13.0 software. RESULTS: The mean HC (±SD) at 1st, 12th and 24th month were 33.37 (1.29) cm, 42.76 (1.23) cm and 44.9 (1.22) cm respectively. A third of the infants (75/228) had HC less than - 2 SD at first month of life, and on follow-up, 50% of the cohort had HC ≤ -2 SD both at 12th and 24th month. Low HC measurements at all three time-points were observed for 21.6% (46/222) infants. Low HC was significantly associated with stunting in 37.3% (OR = 10.8), 57.3% (OR = 3.1) and 44.4% (OR = 2.6) children at 1st, 12th and 24th month respectively. Bivariate analysis of low HC (<- 2 SD) at 12th month showed a statistically significant association with lower socioeconomic status, low paternal and maternal HC and low maternal IQ. Multivariable logistic regression analysis showed maternal (AOR = 0.759, 95% CI = 0.604 to 0.954) and paternal (AOR = 0.734, 95% CI = 0.581 to 0.930) HC to be significantly associated with HC attained by the infant at the end of 12 months. CONCLUSIONS: One-third of the children in our cohort had low head circumference (HC) at birth, with one-fifth recording low HC at all time-points until 2 years of age. Low HC was significantly associated with stunting. Paternal and maternal HC predicted HC in children. HC measurement, often less used, can be a simple tool that can be additionally used by clinicians as well as parents/caregivers to monitor child growth.

Early childhood growth and cognitive outcomes: Findings from the MAL-ED study.

Although many studies around the world hope to measure or improve developmental progress in children to promote community flourishing and productivity, growth is sometimes used as a surrogate because cognitive skills are more difficult to measure. Our objective was to assess how childhood measures of anthropometry correlate with measures of child development in low-income settings with high prevalence of poor nutrition and enteric disease, to inform studies considering growth outcomes in the absence of direct child developmental skill assessment. Children from the MAL-ED study were followed from birth to 24 months of age in field sites in 8 low- and middle-income countries across 3 continents. Monthly weight, length, and head circumference measurements were performed. At 24 months, the Bayley Scales of Infant and Toddler Development was administered. We correlated cognitive measures at 24 months with anthropometric measurements from birth to 2 years comparing 3 constructs: absolute attained monthly measures, summative difference in measures from the mean growth curve, and rate of change in measures. Growth faltering at multiple time periods is related to Bayley cognitive outcomes at 24 months. Birthweight, overall growth by 18-24 months, and rate of growth in the 6- to 18-month period were most associated with 24-month developmental scores. In this study, head circumference measurements, compared with length, was more closely linked to cognitive scores at 24 months. Notably, all studies between growth and cognitive outcomes exhibited low r2 values (0.001-0.049). Anthropometric measures, particularly head circumference, were related to cognitive development, although explaining a low percent of variance. When feasible, direct measures of child development may be more useful.

Establishment of the MAL-ED birth cohort study site in Vellore, Southern India.

The Indian Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) site is in Vellore, Tamil Nadu, in south India and is coordinated by the Christian Medical College, Vellore, which has many years of experience in establishing and following cohorts. India is a diverse country, and no single area can be representative with regard to many health and socioeconomic indicators. The site in Vellore is an urban semiorganized settlement or slum. In the study site, the average family size is 5.7, adults who are gainfully employed are mostly unskilled laborers, and 51% of the population uses the field as their toilet facility. Previous studies from Vellore slums have reported stunting in well over a third of children, comparable to national estimates. The infant mortality rate is 38 per 1000 live births, with deaths due mainly to perinatal and infectious causes. Rigorous staff training, monitoring, supervision and refinement of tools have been essential to maintaining the quality of the significantly large quantity of data collected. Establishing a field clinic within the site has minimized inconvenience to participants and researchers and enabled better rapport with the community and better follow-up. These factors contribute to the wealth of information that will be generated from the MAL-ED multisite cohort, which will improve our understanding of enteric infections and its interactions with malnutrition and development of young children.

The MAL-ED cohort study: methods and lessons learned when assessing early child development and caregiving mediators in infants and young children in 8 low- and middle-income countries.

More epidemiological data are needed on risk and protective factors for child development. In The Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) cohort study, we assessed child development in a harmonious manner across 8 sites in Bangladesh, Brazil, India, Nepal, Pakistan, Peru, South Africa, and Tanzania. From birth to 24 months, development and language acquisition were assessed via the Bayley Scales of Infant and Toddler Development and a modified MacArthur Communicative Development Inventory. Other measures were infant temperament, the child's environment, maternal psychological adjustment, and maternal reasoning abilities. We developed standard operating procedures and used multiple techniques to ensure appropriate adaptation and quality assurance across the sites. Test adaptation required significant time and human resources but is essential for data quality; funders should support this step in future studies. At the end of this study, we will have a portfolio of culturally adapted instruments for child development studies with examination of psychometric properties of each tool used.

Structured early childhood education exposure and childhood cognition - Evidence from an Indian birth cohort.

Experiences in early childhood form the bedrock of future human potential. In impoverished settings, structured early childhood education (ECE) in preschool years can augment overall childhood and later human abilities. The current study evaluates preschool learning exposure and childhood cognition, using longitudinal follow-up of a community-based birth cohort in Vellore, south India. The birth cohort study site in Vellore recruited 251 newborns between 2010 and 2012 from dense urban settlements and further followed up into childhood. Preschool enrolment details were obtained from parents. Childhood cognition was assessed by Weschler's preschool primary scale of intelligence (WPPSI) and Malin's intelligence scale for Indian Children (MISIC) at 5 and 9 years of age respectively. Bivariate and multivariate regression analyses were performed with adjustments for socio-economic status (SES), maternal education, stunting status and home environment. Out of 251 new-borns recruited into the MAL-ED birth cohort, 212 (84.46%) and 205 (81.7%) children were available for the 5 year and 9 year follow-up respectively. At 5 years, structured ECE of 18 to 24 months duration was significantly associated with higher cognition scores, with the highest increase in processing speed [ß: 19.55 (11.26-27.77)], followed by full-scale intelligence [ß: 6.75 (2.96-10.550)], even after adjustments for SES, maternal cognition, home factors and early childhood stunting status. Similarly adjusted analysis at 9 years showed that children who attended 1.5-2 years of structured ECE persisted to have higher cognition, especially in the performance domain [ß: 8.82 (2.60-15.03)], followed by the full-scale intelligence [ß: 7.24 (2.52-11.90)]. Follow-up of an Indian birth cohort showed that structured ECE exposure was associated with better school entry cognition as well as mid-childhood cognition. Strengthening ECE through a multi-pronged approach could facilitate to maximize cognitive potential of human capital.

Prevalence of functional difficulty among school-aged children and effect on school enrolment in rural southern India: A cross-sectional analysis.

Despite the large number of children in India, there is little information on the impact of children's disability on school enrolment, and how this differs by population. We estimated the prevalence of childhood disability in two sites in Tamil Nadu, southern India, and the effect of functional difficulty on school enrolment. We used a parent-reported survey containing the UNICEF-Washington Group questions to identify children aged 5 to 17 years with functional difficulty during a census conducted for an ongoing trial. We estimated pooled- and gender-specific prevalence of functional difficulty among 29,044 children. We fitted regression models to identify subgroups with higher rates of functional difficulty and the effect of functional difficulty on reported school enrolment. We estimated the modification of the effect of functional difficulty by age, gender, socioeconomic status, household education, and sub-site, on additive and multiplicative scales. We found of 29,044 children, 299 (1.0%) had any functional difficulty, equal among boys and girls. Being understood (0.5%) and walking (0.4%) were the most common difficulties. Functional difficulty was strongly associated with non-enrolment in school (Prevalence ratio [PR] 4.59, 95% CI: 3.87, 5.43) after adjusting for age, gender, and site. We show scale-dependent differences between age and socioeconomic groups in the effect of functional difficulty on enrolment. This study shows that at least one in a hundred children in this region have severe functional difficulties and nearly half of these children are not enrolled in school, highlighting the need for further efforts and evidence-based interventions to increase school enrolment among these groups.

Consensus Statement of the IAP - Neurodevelopmental Chapter On Neurodevelopmental Disorders Habilitation Process: Strategic Plan for Prevention, Early Detection and Early Intervention.

JUSTIFICATION: Neurodevelopmental disorders, as per DSM-V, are described as a group of conditions with onset in the development period of childhood. There is a need to distinguish the process of habilitation and rehabilitation, especially in a developing country like India, and define the roles of all stakeholders to reduce the burden of neurodevelopmental disorders. PROCESS: Subject experts and members of Indian Academy of Pediatrics (IAP) Chapter of Neurodevelopmental Pediatrics, who reviewed the literature on the topic, developed key questions and prepared the first draft on guidelines. The guidelines were then discussed by the whole group through online meetings, and the contentious issues were discussed until a general consensus was arrived at. Following this, the final guidelines were drafted by the writing group and approved by all contributors. OBJECTIVES: These guidelines aim to provide practical clinical guidelines for pediatricians on the prevention, early diagnosis and management of neurodevelopmental disorders (NDDs) in the Indian settings. It also defines the roles of developmental pediatricians and development nurse counselor. STATEMENT: There is a need for nationwide studies with representative sampling on epidemiology of babies with early NDD in the first 1000 days in India. Specific learning disability (SLD) has been documented as the most common NDD after 6 years in India, and special efforts should be made to establish the epidemiology of infants and toddlers at risk for SLD, where ever measures are available. Preconception counseling as part of focusing on first 1000 days; Promoting efforts to organize systematic training programs in Newborn Resuscitation Program (NRP); Lactation management; Developmental follow-up and Early stimulation for SNCU/ NICU graduates; Risk stratification of NICU graduates, Newborn Screening; Counseling parents; Screening for developmental delay by trained professionals using simple validated Indian screening tools at 4, 8, 12, 18 and 24 months; Holistic assessment of 10 NDDs at child developmental clinics (CDCs) / district early intervention centre (DEICs) by multidisciplinary team members; Confirmation of diagnosis by developmental pediatrician/developmental neurologist/child psychiatrist using clinical/diagnostic tools; Providing parent guided low intensity multimodal therapies before 3 years age as a center-based or home-based or community-based rehabilitation; Developmental pediatrician to seek guidance of pediatric neurologist, geneticist, child psychiatrist, physiatrist, and other specialists, when necessary; and Need to promote ongoing academic programs in clinical child development for capacity building of community based therapies, are the chief recommendations.

Genetic analysis of asthma exacerbations.

BACKGROUND: Identifying genetic markers of susceptibility to exacerbations may improve patient management, decrease morbidity, and lead to drug development. OBJECTIVES: To assess whether genetic markers associated with severe asthma exacerbations in previous reports are associated with less severe events that do not require intensive care and intubation and to identify additional markers in candidate genes and throughout the genome. METHODS: A total of 199 patients and 502 controls (individuals without an exacerbation) were identified from 4 clinical trials. We genotyped 51 markers from 17 genes previously reported to be associated with exacerbations; a whole genome scan was used to identify additional markers. Admixture analysis was conducted to characterize the presence of ancestral groups. The genetic marker effects were assessed by logistic regression for each study followed by a meta-analysis. RESULTS: Several coding variants in the IL4R gene had a genetic effect across 3 studies, including rs1805011 in IL4R (P < .0006). In addition, 3 markers in the IFNB1 gene showed evidence of association (P < .002) but only in the study with African Americans. Because these markers did not meet the prespecified multiplicity-adjusted significance level of P = .0002, we were unable to confirm previously published results for less severe events. The whole genome scan identified genes related to mast cell mediator release. The admixture analysis suggests that ancestry was best characterized by the presence of 3 ancestral groups. CONCLUSION: We were unable to confirm previously reported associations of genetic markers with asthma exacerbations. Although, in general, the patients studied had less severe asthma than patients in earlier reports, these results suggest involvement of similar pathways. TRIAL REGISTRATION: clinicaltrials.gov Identifiers: NTC00452699, NCT00452348, NTC00102765, NCT00843193.

Mosaic double aneuploidy: Down syndrome and XYY.

Chromosomal abnormalities are seen in nearly 1% of live born infants. We report a 5-year-old boy with the clinical features of Down syndrome, which is the most common human aneuploidy. Cytogenetic analysis showed a mosaicism for a double aneuploidy, Down syndrome and XYY. The karyotype was 47, XY,+21[19]/48, XYY,+21[6]. ish XYY (DXZ1 × 1, DYZ1 × 2). Mosaic double aneuploidies are very rare and features of only one of the aneuploidies may predominate in childhood. Cytogenetic analysis is recommended even if the typical features of a recognized aneuploidy are present so that any associated abnormality may be detected. This will enable early intervention to provide the adequate supportive care and management.

Self-Care Behaviour of Patients With Breast Cancer in the Management of Side Effects of Chemotherapy.

Aim The breast is the leading site of cancer among females. Chemotherapy is the standard treatment of breast cancer and it results in multiple side effects. Apart from pharmacological management, self-care behaviors may significantly influence the management of these side effects. The study aimed to assess the self-care behavior of patients with breast cancer in the management of side effects of chemotherapy. Methods A longitudinal descriptive study was conducted at the Daycare chemotherapy unit of the Radio Therapy Department, Government Medical College Hospital Thiruvananthapuram, Kerala, India. In total, 170 female patients with breast cancer receiving their first cycle of chemotherapy participated in the study. Self-care behavior was the primary outcome variable of the study. Sociodemographic and clinical data were measured by using a structured questionnaire. The severity of side effects and self-care behaviors for their management were measured by a Self Care Diary (SCD). Result A total of 170 with breast cancer receiving chemotherapy participated in the study. The severity of side effects and self-care behaviors for their management were measured at two separate time intervals, T1 and T2. Severe fatigue was found in 80.0% of participants at T1 and 61.2% at T2. Vomiting (47.7%), mucositis (48.2%), and nausea (49.1%) were also found to be severe at T1, but these side effects were moderate (53.8%, 58.8%, and 51.8% respectively) at T2. Despite the high number of self-care behaviors used to prevent infection, nausea/vomiting, bleeding, decreased appetite, sleeping difficulty, and constipation, overall self-care behaviors were found to be poor. A negative correlation was found between self-care behavior and side effects of chemotherapy. Conclusion The study revealed a negative correlation between self-care behaviors and side effects. This indicates that supportive education and training should be given to patients and caregivers to enhance the self-care behaviors of patients to manage the side effects.

Morphometric analysis of Corpus Callosum in autistic and typically developing Indian children.

Corpus callosum (CC) is the largest commissural white matter bundle in the brain, responsible for the integration of information between hemispheres. Reduction in the size of the CC structure has been predominantly reported in children with autism spectrum disorder (ASD) compared to typically developing children (TD). However, most of these studies are based on high-functioning individuals with ASD but not on an inclusive sample of individuals with ASD with varying abilities. Our current study aimed to examine the CC morphometry between children with ASD and TD in the Indian population. We also compared CC morphometry in autistic children with autism severity, verbal IQ (VIQ) and full-scale IQ (FSIQ). T1-weighted structural images were acquired using a 3T MRI scanner to examine the CC measures in 62 ASD and 17 TD children. The length and height of the CC and the width of genu were decreased in children with ASD compared to TD. There was no significant difference in CC measures based on autism severity, VIQ or FSIQ among children with ASD. To our knowledge, this is the first neuroimaging study to include a significant number (n = 56) of low-functioning ASD children. Our findings suggest the atypical interhemispheric connectivity of CC in ASD.

Secular Growth Trends in Early Childhood-Evidence from Two Low-Income Birth Cohorts Recruited over a Decade in Vellore, India.

Stunting and extreme poverty are considered significant risk factors impacting child development in low-and-middle-income countries. We used two birth cohorts recruited 8-9 years apart in urban low-income (slum) settings in Vellore, south India and analyzed secular growth trends and their predictors. In the rotavirus cohort recruited between 2002 and 2003, 373 children completed the 3-year follow-up. "The Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development" (MAL-ED) cohort recruited between 2010 and 2012 had 215 children completing follow-up. The MAL-ED cohort had better socio-economic status (SES) markers and mothers were better educated compared with the previous cohort. Children in the MAL-ED cohort had less stunting at 1, 2, and 3 years of age. The linear mixed effects model evaluating linear growth during the first 3 years of age showed that low birth weight and being a female child were associated with stunting in both cohorts. There was no association between SES and stunting in the rotavirus cohort, whereas SES was associated with linear growth in the MAL-ED cohort. Future studies could incorporate nutritional and nonnutritional interventions in vulnerable populations to evaluate their effect on birth weight as well as early childhood stunting.

Case report of a rare purine synthesis disorder due to 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase (AICAR) deficiency.

BACKGROUND: AICA (5-aminoimidazole-4-carboxamide) ribosiduria is an inborn error in purine biosynthesis caused due to biallelic pathogenic variants in the 5-aminoimidazole-4-carboxamide ribonucleotide-formyltransferase/imp cyclohydrolase (ATIC) gene located on chromosome 2q35. ATIC codes for a bifunctional enzyme, AICAR transformylase and inosine monophosphate (IMP) cyclohydrolase, which catalyse the last two steps of de novo purine synthesis. This disorder has been previously reported in only 4 cases worldwide, and herein, we report the first from India. CASE REPORT: The proband presented with global developmental delay, developmental hip dysplasia (DDH), acyanotic heart disease and nystagmoid eye movements. Whole exome sequencing (WES) identified compound heterozygous pathogenic variants in the ATIC. A novel splice site variant; c.1321-2A > G and a previously reported missense variant; c.1277A > G (p.Lys426Arg) were identified. Segregation analysis of parents showed the father to be a heterozygous carrier for the splice site variant and the mother, a heterozygous carrier for the missense variant. CONCLUSION: This case of a rare genetic disorder of purine biosynthesis of ATIC deficiency is the first case reported from India. Early diagnosis lead to early interventional therapy and genetic counselling.

Are early childhood stunting and catch-up growth associated with school age cognition?-Evidence from an Indian birth cohort.

BACKGROUND: Millions of children worldwide especially in the Asian subcontinent are vulnerable to early childhood stunting. There are contradictory reports of the association between catch-up growth in childhood and school age cognition. METHODS: A community-based birth cohort recruited between 2010 and 2012 from urban slums in Vellore, India was followed up until 9 years of age. From regular anthropometric measurements, stunting status for each individual child was calculated at 2, 5 and 9 years. Cognition was assessed at 9 years of age using the Malin's Intelligence Scale for Indian Children (MISIC). Children were divided into groups based on stunting at each time point as well as catch-up growth, and a regression model was utilised to evaluate their association with cognition at 9 years. RESULTS: Among 203 children included in this analysis, 94/203 (46.31%) children were stunted at 2 years of age, of whom 39.36% had a catch-up growth at 5 years of age, and 38.30% at 9 years. Around 10% of the cohort remained stunted at all time points. In the multivariable analysis, children who were stunted at 2, 5 and 9 years had a significantly lower verbal and total intelligence quotient (IQ) scores by 4.6 points compared to those who were never stunted. Children with catch up growth following stunting at 2 years had higher cognition scores than those who were persistently stunted throughout the childhood. CONCLUSIONS: This study showed persistent stunting in childhood was associated with lowering of 4-5 IQ points in childhood cognition at 9 years of age. Recovery from early life stunting in children with catch up growth prevented further lowering of cognition scores in these children compared to persistently stunted children. Nutritional supplementation during late infancy and early toddlerhood in addition to continuing nutritional supplementation programmes for preschool and school children can improve childhood stunting and cognitive abilities in vulnerable populations.