Neurodevelopmental Domains Research Articles

Neurodevelopmental Deficits in 16p11.2 Microdeletion Syndrome Would Risperidone Make A Difference? A 2- year- old male toddler Case Study

Deletion in chromosome 16 at location 11p.2 has been associated with multiple neurodevelopmental disorders including intellectual disability; autism spectrum disorder (ASD) and impaired social communication and interaction; behavioural dysfunctions including oppositional defiant disorder (ODD) and other disruptive behavioural disorders such as aggression, irritability, and noncompliance; and impaired/ delayed development of speech and language. To the best of our knowledge, there is no known pharmacological approach to address early stage of the neurobiological pathogenesis of this neurodevelopmental disorder. Methods: Two-year-old boy, with established diagnosis of 16p11.2 microdeletion syndrome, has been referred to Child and Adolescent Mental Health community service, the Northern of the Netherlands due to intolerable disruptive behaviour. Besides, this toddler demonstrated absence of expressive language, social impairment, headbanging and other motor stereotypies. Treatment with risperidone was started and the effect of treatment has been evaluated during a follow up period of 16 weeks using clinical interview with the parents, inspection of toddler’s behaviour and by using Child Aberrant Behaviour Checklist. Results: Clinically meaningful improvement has been observed in the 3 main affected neurodevelopmental domains, expressive language, behavioural disorder and social communication could be observed during the follow up period. Conclusion: Risperidone - induced improvement in the 16p11.2 microdeletion associated neurodevelopmental deficits calls for further investigations to explore the potential therapeutic role of antipsychotics in the early phases of this syndrome and other conditions sharing the same neurobiological pathogenesis including autism spectrum disorder.

Discovering structure in multiple outcomes models for tests of childhood neurodevelopment.

Bayesian model-based clustering provides a powerful and flexible tool that can be incorporated into regression models to better understand the grouping of observations. Using data from the Seychelles Child Development Study, we explore the effect of prenatal methylmercury exposure on 20 neurodevelopmental outcomes measured in 9-year-old children. Rather than cluster individual subjects, we cluster the outcomes within a multiple outcomes model. By using information in the data to nest the outcomes into groups called domains, the model more accurately reflects the shared characteristics of neurodevelopmental domains and improves estimation of the overall and outcome-specific exposure effects by shrinking effects within and between domains selected by the data. The Bayesian paradigm allows for sampling from the posterior distribution of the grouping parameters; thus, inference can be made about group membership and their defining characteristics. We avoid the often difficult and highly subjective requirement of a priori identification of the total number of groups by incorporating a Dirichlet process prior to form a fully Bayesian multiple outcomesmodel.

Screening for neurodevelopmental disorders in children with congenital heart disease

Neurodevelopmental disorders (NDD) are the most common, and potentially the most damaging sequelae in children with congenital heart disease (CHD) [1] . All areas could be affected impacting social adaptation, academic achievements, and quality of personal and family life even in adulthood. In our region, there is currently no specific additional follow-up for children with CHD. The objective was to assess the frequency of NDD in children with « significant » CHD (mild and moderate operated CHD, severe CHD), associated factors and frequency of follow-up in developmental therapies. This is a prospective observational study on children with significant CHD aged from 6 to 66 months conducted over a period of 6 months. Ages & Stages Questionnaire in French, Third Edition (ASQ-3) was used to screen neurodevelopmental domains. NDD were defined as cut-off scoring ≤ 1 SD below the normative mean. – 1 SD corresponding to «Monitor» range: children with minor or emerging disorders; – 2 SD corresponding to «Refer» range: children exhibiting neurodevelopemental delays. Socio-medico-surgical data were collected to assess associated factors and follow-up in developmental care services. Among the 210 included children, the rate of NDD was 60,0% ( n = 126, 95%CI(53.4 - 66.6)). 40 children were in «Monitor» range, and 86 in «Refer» range. There was no difference regarding the severity of CHD ( P = 0.99). Only presence of comorbidities (OR = 2.1; 95%CI(1.1 - 4.2); P = 0.02) was a significant associated factor of NDD in multivariate backward logistic regression analysis. 46 children with NDD had no follow-up in developmental services (among them 21 were in «Refer» range) despite provision of pathway of care for children with NDD. Children with CHD are at risk for NDD regardless of the severity of the CHD. Systematic and early monitoring in a specific program of care is necessary for all children with CHD for a better long-term prognosis.

Neurodevelopmental Trajectory During Infancy and Diagnosis of Autism Spectrum Disorder as an Outcome at 32 Months of Age.

Little is known about the extent to which neurodevelopmental trajectories in infancy predict a later diagnosis of autism spectrum disorder (ASD). We investigated the association between the neurodevelopmental trajectory classes identified using a latent class growth analysis and the distal clinical outcome. Participants included 952 infants from the Hamamatsu Birth Cohort for Mothers and Children (HBC study). Neurodevelopment was measured using the Mullen Scales of Early Learning, which contains five subscales (gross motor, fine motor, visual reception, receptive language, and expressive language), at seven time points from 1 to 24 months of age. ASD was diagnosed in 3.1% of the children at 32 months of age. The clinical outcome was included in our analysis model. Five neurodevelopmental classes were identified: high normal (11.5%), normal (49.2%), low normal (21.2%), delayed (14.1%), and markedly delayed (4.0%). The probability of a diagnosis of ASD in the markedly delayed class was highest (32.6%) when compared with the other classes. The probabilities of receiving a diagnosis of ASD in the delayed and low normal classes were 6.4% and 4.0%, respectively, whereas the probabilities in the normal and high normal classes were both 0%. A diagnosis of ASD may be predicted by the neurodevelopmental trajectories during infancy, which can be evaluated both routinely and objectively in clinical settings. In this representative population, children diagnosed with ASD showed early signs in neurodevelopmental domains during the first 2 years of life.

Adult mood problems in children with neurodevelopmental problems: evidence from a prospective birth cohort followed to age 50

PurposeSpecific child neurodevelopmental (ND) disorders such as ADHD and learning problems are associated with concurrent and future (up to early adulthood) mood problems. However, it is unclear whether findings generalise to population traits as well as diagnoses, to general as well as specific neurodevelopmental domains, and whether risk associations extend to later adulthood or diminish with age.MethodsWe used data from a UK cohort of children born in 1958, the National Child Development Study (NCDS). ND problems were assessed at ages 7 and 11 years with parent- and teacher ratings of restlessness, hyperactivity and motor co-ordination difficulties, and by individual tests of reading, arithmetic and general cognitive ability. Mood (depression/anxiety) problems were assessed using the Malaise symptom screen at 23, 33, 42, and 50 years. Factor analyses were conducted to assess whether the specific neurodevelopmental domains could be aggregated into a general “ND” latent factor as well as specific factors. Associations with mood outcomes were then tested.ResultsA bi-factor model with a general “ND” latent factor and specific “motor” and “cognition” factors fits the data well. The specific cognition and motor factor scores were associated with mood problems in early adulthood only. The “ND” factor demonstrated associations with mood problems at each adult follow-up (men - age 23 years: β = 0.17; age 33: β = 0.16; age 42: β = 0.14; age 50: β = 0.16; women - 23 years: β = 0.25; 33 years: β = 0.26; 42 years: β = 0.14; 50 years: β = 0.16; all ps < 0.01). Interactions by sex indicated that the association between this general factor and mood problems was more pronounced for women than men at ages 23 years (β = 0.09, p = 0.005) and 33 years (β = 0.10, p = 0.003), but not at 42 or 50 years (ps > 0.8).ConclusionsOur results suggest that, in a population-based cohort, a general, childhood neurodevelopmental difficulty factor is stably associated with mood problems in adult life.

Deep clinical and biological phenotyping of the preterm birth and small for gestational age syndromes: The INTERBIO-21st Newborn Case-Control Study protocol

Background: INTERBIO-21 st is Phase II of the INTERGROWTH-21 st Project, the population-based, research initiative involving nearly 70,000 mothers and babies worldwide coordinated by Oxford University and performed by a multidisciplinary network of more than 400 healthcare professionals and scientists from 35 institutions in 21 countries worldwide. Phase I, conducted 2008-2015, consisted of nine complementary studies designed to describe optimal human growth and neurodevelopment, based conceptually on the WHO prescriptive approach. The studies generated a set of international standards for monitoring growth and neurodevelopment, which complement the existing WHO Child Growth Standards. Phase II aims to improve the functional classification of the highly heterogenous preterm birth and fetal growth restriction syndromes through a better understanding of how environmental exposures, clinical conditions and nutrition influence patterns of human growth from conception to childhood, as well as specific neurodevelopmental domains and associated behaviors at 2 years of age. Methods: In the INTERBIO-21 st Newborn Case-Control Study, a major component of Phase II, our objective is to investigate the mechanisms potentially responsible for preterm birth and small for gestational age and their interactions, using deep phenotyping of clinical, growth and epidemiological data and associated nutritional, biochemical, omic and histological profiles. Here we describe the study sites, population characteristics, study design, methodology and standardization procedures for the collection of longitudinal clinical data and biological samples (maternal blood, umbilical cord blood, placental tissue, maternal feces and infant buccal swabs) for the study that was conducted between 2012 and 2018 in Brazil, Kenya, Pakistan, South Africa, Thailand and the UK. Discussion: Our study provides a unique resource for the planned analyses given the range of potentially disadvantageous exposures (including poor nutrition, pregnancy complications and infections) in geographically diverse populations worldwide. The study should enhance current medical knowledge and provide new insights into environmental influences on human growth and neurodevelopment.

Associations Between Genetic Risk For Psychiatric Disorders and Childhood Neurodevelopment: Investigating Polygenic Risk Scores For Psychiatric Disorders and Traits In General Population Samples

Most psychiatric disorders are thought to have their origins at least in part in childhood, even if early manifestations of liability are quite different from the later full-blown clinical picture. This work aims to identify traits relevant to risk for psychiatric disorders early in development by investigating which "neurodevelopmental domains" are associated with psychiatric disorder risk alleles during childhood. Findings will be presented testing the hypothesis that psychiatric disorder risk alleles, as measured by polygenic risk scores, affect normative, dimensional childhood characteristics in the general population. Specifically, this work investigates associations between polygenic risk scores for schizophrenia, bipolar disorder, major depressive disorder and Attention Deficit Hyperactivity Disorder and primarily pre-pubertal neurodevelopmental traits using longitudinal general population samples.

Deep clinical and biological phenotyping of the preterm birth and small for gestational age syndromes: The INTERBIO-21 st Newborn Case-Control Study protocol

Background: INTERBIO-21 st is Phase II of the INTERGROWTH-21 st Project, the population-based, research initiative involving nearly 70,000 mothers and babies worldwide coordinated by Oxford University and performed by a multidisciplinary network of more than 400 healthcare professionals and scientists from 35 institutions in 21 countries worldwide. Phase I, conducted 2008-2015, consisted of nine complementary studies designed to describe optimal human growth and neurodevelopment, based conceptually on the WHO prescriptive approach. The studies generated a set of international standards for monitoring growth and neurodevelopment, which complement the existing WHO Child Growth Standards. Phase II aims to improve the functional classification of the highly heterogenous preterm birth and fetal growth restriction syndromes through a better understanding of how environmental exposures, clinical conditions and nutrition influence patterns of human growth from conception to childhood, as well as specific neurodevelopmental domains and associated behaviors at 2 years of age. Methods: In the INTERBIO-21 st Newborn Case-Control Study, a major component of Phase II, our objective is to investigate the mechanisms potentially responsible for preterm birth and small for gestational age and their interactions, using deep phenotyping of clinical, growth and epidemiological data and associated nutritional, biochemical, omic and histological profiles. Here we describe the study sites, population characteristics, study design, methodology and standardization procedures for the collection of longitudinal clinical data and biological samples (maternal blood, umbilical cord blood, placental tissue, maternal feces and infant buccal swabs) for the study that was conducted between 2012 and 2018 in Brazil, Kenya, Pakistan, South Africa, Thailand and the UK. Discussion: Our study provides a unique resource for the planned analyses given the range of potentially disadvantageous exposures (including poor nutrition, pregnancy complications and infections) in geographically diverse populations worldwide. The study should enhance current medical knowledge and provide new insights into environmental influences on human growth and neurodevelopment.

Deep clinical and biological phenotyping of the preterm birth and small for gestational age syndromes: The INTERBIO-21st Newborn Case-Control Study protocol

Background: INTERBIO-21st is Phase II of the INTERGROWTH-21st Project, the population-based, research initiative involving nearly 70,000 mothers and babies worldwide coordinated by Oxford University and performed by a multidisciplinary network of more than 400 healthcare professionals and scientists from 35 institutions in 21 countries worldwide. Phase I, conducted 2008-2015, consisted of nine complementary studies designed to describe optimal human growth and neurodevelopment, based conceptually on the WHO prescriptive approach. The studies generated a set of international standards for monitoring growth and neurodevelopment, which complement the existing WHO Child Growth Standards. Phase II aims to improve the functional classification of the highly heterogenous preterm birth and fetal growth restriction syndromes through a better understanding of how environmental exposures, clinical conditions and nutrition influence patterns of human growth from conception to childhood, as well as specific neurodevelopmental domains and associated behaviors at 2 years of age. Methods: In the INTERBIO-21st Newborn Case-Control Study, a major component of Phase II, our objective is to investigate the mechanisms potentially responsible for preterm birth and small for gestational age and their interactions, using deep phenotyping of clinical, growth and epidemiological data and associated nutritional, biochemical, omic and histological profiles. Here we describe the study sites, population characteristics, study design, methodology and standardization procedures for the collection of longitudinal clinical data and biological samples (maternal blood, umbilical cord blood, placental tissue, maternal feces and infant buccal swabs) for the study that was conducted between 2012 and 2018 in Brazil, Kenya, Pakistan, South Africa, Thailand and the UK. Discussion: Our study provides a unique resource for the planned analyses given the range of potentially disadvantageous exposures (including poor nutrition, pregnancy complications and infections) in geographically diverse populations worldwide. The study should enhance current medical knowledge and provide new insights into environmental influences on human growth and neurodevelopment.

Effects of maternal (pre)pregnancy lifestyle interventions in obese women on child neurobehavioral development: Follow-up of two RCT studies

Background Obesity is a major public health problem. The prevalence of obesity in women of reproductive age ranges from 7 to 25% in European countries. Children of women who were obese before or during pregnancy are at increased risk for neurodevelopmental delay and behavioral problems. Improving the lifestyle of obese women before and during pregnancy may have a great potential to optimize child neurobehavioral development, but no previous study has assessed this however. We examined the effects of two maternal lifestyle interventions before and during pregnancy in obese women on child neurobehavioral development. Methods This study concerns the follow-up of two randomized controlled trials that were successful in reducing maternal weight or gestational weight gain: the Finnish RADIEL and the Dutch LIFEstyle trial. Women with a pre-pregnancy BMI ≥ 29 kg/m2 wishing to conceive or who were already pregnant ( Results We had data of 161 (40%) RADIEL and 96 (32%) LIFEstyle children. In both studies, child total neurodevelopmental score (B = −0.17, 95% confidence interval (−0.51 to 0.16) and B = 0.06 (−0.38 to 0.51) respectively) and total behavioral problem score (B = −0.06 (−0.38 to 0.27) and B = 0.01 (−0.47 to 0.48) respectively) did not differ between children of the intervention and the control group. Children of the intervention and the control group also did not differ in neurodevelopmental domain scores and specific behavioral problem scores. Also, when comparing children of the mothers of the intervention group who attained the lifestyle intervention goal with children of mothers of the control group, no differences in neurobehavioral development were found. Conclusion Although previous findings of neurobehavioral problems in children of obese mothers give reason to suggest maternal (pre-) pregnancy lifestyle intervention to be preventive, this follow-up of two randomized controlled trials is the first to show that lifestyle interventions before and during pregnancy in obese women do not affect child neurobehavioral development at age 3–5 years.

Altered resting-state functional connectivity in children and adolescents born very preterm short title.

The formation of resting-state functional networks in infancy has been reported to be strongly impacted by very preterm birth. Studies in childhood and adolescence have largely focused on language processing networks and identified both decreased and increased functional connectivity. It is unclear, however, whether functional connectivity strength is altered globally in children and adolescents born very preterm and whether these alterations are related to the frequently occurring cognitive deficits. Here, resting-state functional MRI was assessed in a group of 32 school-aged children and adolescents born very preterm with normal intellectual and motor abilities and 39 healthy term-born peers. Functional connectivity within and between a comprehensive set of well-established resting-state networks was compared between the groups. IQ and executive function abilities were tested with standardized tasks and potential associations with connectivity strength were explored. Functional connectivity was weaker in the very preterm compared to the term-born group between the sensorimotor network and the visual and dorsal attention network, within the sensorimotor network and within the central executive network. In contrast, functional connectivity was stronger in the very preterm group between the sensorimotor network and parts of the salience and the central executive network. Little evidence was found that these alterations underlie lower IQ or poorer executive function abilities. This study provides evidence for a long-lasting impact of very preterm birth on the organization of resting-state networks. The potential consequence of these alterations for other neurodevelopmental domains than the ones investigated in the current study warrants further investigation.

Neurodevelopmental profile of Fetal Alcohol Spectrum Disorder: A systematic review

BackgroundIn an effort to improve the screening and diagnosis of individuals with Fetal Alcohol Spectrum Disorder (FASD), research has focused on the identification of a unique neurodevelopmental profile characteristic of this population. The objective of this review was to identify any existing neurodevelopmental profiles of FASD and review their classification function in order to identify gaps and limitations of the current literature.MethodsA systematic search for studies published up to the end of December 2016 reporting an identified neurodevelopmental profile of FASD was conducted using multiple electronic bibliographic databases. The search was not limited geographically or by language of publication. Original research published in a peer-reviewed journal that involved the evaluation of the classification function of an identified neurodevelopmental profile of FASD was included.ResultsTwo approaches have been taken to determine the pathognomonic neurodevelopmental features of FASD, namely the utilization of i) behavioral observations/ratings by parents/caregivers and ii) subtest scores from standardized test batteries assessing a variety of neurodevelopmental domains. Both approaches show some promise, with the former approach (which is dominated by research on the Neurobehavioral Screening Tool) having good sensitivity (63% to 98%), but varying specificity (42% to 100%), and the latter approach having good specificity (72% to 96%), but varying sensitivity (60% to 88%).ConclusionsThe current review revealed that research in this area remains limited and a definitive neurodevelopmental profile of FASD has not been established. However, the identification of a neurodevelopmental profile will aid in the accurate identification of individuals with FASD, by adding to the armamentarium of clinicians. The full review protocol is available in PROSPERO (http://www.crd.york.ac.uk/PROSPERO/); registration number CRD42016039326; registered 20 May 2016.

Hotspots of missense mutation identify neurodevelopmental disorder genes and functional domains.

Although de novo missense mutations have been predicted to account for more cases of autism than gene-truncating mutations, most research has focused on the latter. We identified the properties of de novo missense mutations in patients with neurodevelopmental disorders (NDDs) and highlight 35 genes with excess missense mutations. Additionally, 40 amino acid sites were recurrently mutated in 36 genes, and targeted sequencing of 20 sites in 17,689 NDD patients identified 21 new patients with identical missense mutations. One recurrent site (p.Ala636Thr) occurs in a glutamate receptor subunit, GRIA1. This same amino acid substitution in the homologous but distinct mouse glutamate receptor subunit Grid2 is associated with Lurcher ataxia. Phenotypic follow-up in five individuals with GRIA1 mutations shows evidence of specific learning disabilities and autism. Overall, we find significant clustering of de novo mutations in 200 genes, highlighting specific functional domains and synaptic candidate genes important in NDD pathology.

Early postnatal illness severity scores predict neurodevelopmental impairments at 10 years of age in children born extremely preterm.

IntroductionA neonatal illness severity score, The Score for Neonatal Acute Physiology-II (SNAP-II), predicts neurodevelopmental impairments at two years of age among children born extremely preterm. We sought to evaluate to what extent SNAP-II is predictive of cognitive and other neurodevelopmental impairments at 10 years of age.MethodsIn a cohort of 874 children born before 28 weeks of gestation, we prospectively collected clinical, physiologic and laboratory data to calculate SNAP-II for each infant. When the children were 10 years old, examiners who were unaware of the child's medical history assessed neurodevelopmental outcomes, including neurocognitive, gross motor, social, and communication functions, diagnosis and treatment of seizures or attention deficit hyperactivity disorder (ADHD), academic achievement, and quality of life. We used logistic regression to adjust for potential confounders.ResultsAn undesirably high SNAP-II (≥ 30), present in 23% of participants, was associated with an increased risk of cognitive impairment (IQ, executive function, language ability), adverse neurological outcomes (epilepsy, impaired gross motor function), behavioral abnormalities (attention deficit disorder and hyperactivity), social dysfunction (autistic spectrum disorder) and education-related adversities (school achievement and need for educational supports.In analyses that adjusted for potential confounders, Z-scores ≤ -1 on 11 of 18 cognitive outcomes were associated with SNAP-II in the highest category and 6 of 18 were associated with SNAP-II in the intermediate category. Odds ratios and 95% confidence intervals ranged from 1.4 (1.01, 2.1) to 2.1 (1.4, 3.1). Similarly, 2 of the 8 social dysfunctions were associated with SNAP-II in the highest category, and 3 of 8 were associated with SNAP-II in the intermediate category. Odds ratios and 95% confidence intervals were slightly higher for these assessments, ranging from 1.6 (1.1, 2.4) to 2.3 (1.2, 4.6).ConclusionAmong very preterm newborns, physiologic derangements present in the first 12 postnatal hours are associated with dysfunctions in several neurodevelopmental domains at 10 years of age. We are unable to make inferences about causality.

Imaging genetics in attention-deficit/hyperactivity disorder and related neurodevelopmental domains: state of the art.

Joint analysis of genetic and neuroimaging data, known as Imaging Genetics (IG), offers an opportunity to deepen our knowledge of the biological mechanisms of neurodevelopmental domains. There has been exponential growth in the literature on IG studies, which challenges the standardization of analysis methods in this field. In this review we give a complete up-to-date account of IG studies on attention deficit hyperactivity disorder (ADHD) and related neurodevelopmental domains, which serves as a reference catalog for researchers working on this neurological disorder. We searched MEDLINE/Pubmed and identified 37 articles on IG of ADHD that met our eligibility criteria. We carefully cataloged these articles according to imaging technique, genes and brain region, and summarized the main results and characteristics of each study. We found that IG studies on ADHD generally focus on dopaminergic genes and the structure of basal ganglia using structural Magnetic Resonance Imaging (MRI). We found little research involving multiple genetic factors and brain regions because of the scarce use of multivariate strategies in data analysis. IG of ADHD and related neurodevelopmental domains is still in its early stages, and a lack of replicated findings is one of the most pressing challenges in the field.

Characterization of infant mu rhythm immediately before crawling: A high-resolution EEG study

Crawling is an important milestone in infant motor development. However, infants with developmental motor disorders can exhibit delays, or even miss, in the acquisition of crawling skill. And little information is available from the neurodevelopmental domain about the changes in brain function with intervention. The mu rhythm can potentially play a substantial role in understanding human motor development at early ages in infants, as it has in adults. Studies about the mu rhythm in infants were in coarse temporal resolution with longitudinal samples taken months or years apart. Details about the infant mu rhythm at a fine age resolution has not been fully revealed, which leads to contradictory evidence about its formulation and developmental changes of its spectral origins and, therefore, impedes the full understanding of motor brain development before crawling skill acquisition. The present study aims to expand knowledge about the infant mu rhythm and its spatio-spectral pattern shifts along maturation immediately before crawling. With high-density EEG data recorded on a weekly basis and simultaneous characterization of spatio-spectral patterns of the mu rhythm, subtle developmental changes in its spectral peak, frequency range, and scalp topography are revealed. This mu rhythm further indicates a significant correlation to the crawling onset while powers from other frequency bands do not show such correlations. These details of developmental changes about the mu rhythm provide an insight of rapid changes in the human motor cortex in the first year of life. Our results are consistent with previous findings about the peak frequency shifting of the mu rhythm and further depict detailed developmental curves of its frequency ranges and spatial topographies. The infant mu rhythm could potentially be used to assess motor brain deficiencies at early ages and to evaluate intervention effectiveness in children with neuromotor disorders.

Differential Effect of Intrauterine Growth Restriction on Childhood Neurodevelopment: A Systematic Review

(BJOG. 2015;122(8):1062–1072) Intrauterine growth restriction (IUGR) is the second leading cause of perinatal morbidity and mortality worldwide, and is associated with significant neurodevelopmental impairment. Despite this, there have been no systematic reviews that examine the effects of IUGR on various neurodevelopmental domains throughout childhood (up to 12 y), nor has there been an attempt to differentiate the contributions of several insults often are associated with IUGR to childhood neurodevelopmental outcomes.

Differential effect of intrauterine growth restriction on childhood neurodevelopment: a systematic review.

Neurodevelopmental disorders are increasingly believed to originate from intrauterine growth restriction (IUGR). Current reviews exploring the neurodevelopmental effects of IUGR, however, are mostly based on birthweight, an inadequate proxy. We aimed to examine the association between IUGR documented in utero, and neurodevelopmental outcomes during childhood. Medline, CINAHL, PsycInfo and Scopus were searched for relevant studies published after 1970. The analysis included studies that identified IUGR in utero, with follow-up assessments between 1 month and 12 years of age. Data was extracted for cognitive, behavioural, language, motor, hearing, vision or sleep outcomes. Studies were summarised separately for children born at <35 and ≥35 weeks gestation. Of 28 876 titles identified, 38 were suitable for inclusion. IUGR children born ≥35 weeks gestation scored on average 0.5 SD lower than non-IUGR children across all neurodevelopmental assessments. IUGR children born <35 weeks of gestation scored approximately 0.7 SD lower than non-IUGR children across all neurodevelopmental assessments. IUGR children with evidence of fetal circulatory redistribution (preferential perfusion of the brain) had more severe neurodevelopmental impairments than those born IUGR alone. IUGR increases the risk of neurodevelopmental impairment during childhood differentially across domains. IUGR children born preterm or with evidence of fetal circulatory redistribution are more severely affected. IUGR is associated with an overall risk for neurodevelopmental delay in a range of neurodevelopmental domains.

Association of clinical features of acute viral encephalitis with mortality and neurodevelopmental outcomes

Background : Acute viral encephalitis is a world-wide health problem with severe morbidity, significant mortality and a high incidence of residual sequelae in survivors.Objective : To identify the association of clinical features of acute viral encephalitis with mortality and neurodevelopment outcomes.Methodology : It is a hospital based comparative observational prospective study done in Dhaka Shishu Hospital during the period of October 2005 to March 2006. Children with 1 month to 12 years of both sex presenting with specific clinical features and laboratory evidences suggestive of acute viral encephalitis (seizures, altered consciousness, features of raised intracranial pressure, cerebrospinal fluid evidences of viral encephalitis) were included. 44 children were enrolled according to inclusion criteria. Data were collected on clinical and socio demographic status. SPSS 16 version program was used for data analysis.Result : Among the 44 cases, the mean age bellow 2 years was 14 months and above 2 years was 66 months. The incidence of acute viral encephalitis was highest within first 3 years of age. Most of the mortality 8(72.73%) occurred in low income group (P=0.003). 29(66 %) patients had Glasgow Coma Score &lt;8 on admission, low Glasgow Coma Score at presentation had significant association with outcome, 11(100%) patients who died had Glasgow Coma Score &lt;8(P=0.003). 28(68 %) patients stayed in hospital for &gt;7 days, indicating more time taking for improvement from acute illness. There was significant association of duration of hospital stay and outcome (P=0.008). In Neurodevelopmental assessment domains were Gross motor, Fine motor, Vision, Hearing and Cognition and impairments were different in different patients. Impairments persisting in different domain at follow up comparing with admission showed satisfactory improvement. Improvement was significant in case of Gross motor (P=.005), Fine motor (P=.08) and Cognition (P=.09).Conclusion : It was observed from this study that children with acute viral encephalitis are at high risk of mortality and morbidity. Lower age at presentation, low socio-economic status, low Glasgow Coma Score on admission and short duration of hospital stay were associated with high mortality and were at high risk of future neurodevelopmental impairmentsNorthern International Medical College Journal Vol.6(2) 2015: 50-52

Behavioural markers for autism in infancy: Scores on the Autism Observational Scale for Infants in a prospective study of at-risk siblings

We investigated early behavioural markers of autism spectrum disorder (ASD) using the Autism Observational Scale for Infants (AOSI) in a prospective familial high-risk (HR) sample of infant siblings (N=54) and low-risk (LR) controls (N=50). The AOSI was completed at 7 and 14 month infant visits and children were seen again at age 24 and 36 months. Diagnostic outcome of ASD (HR-ASD) versus no ASD (HR-No ASD) was determined for the HR sample at the latter timepoint. The HR group scored higher than the LR group at 7 months and marginally but non-significantly higher than the LR group at 14 months, although these differences did not remain when verbal and nonverbal developmental level were covaried. The HR-ASD outcome group had higher AOSI scores than the LR group at 14 months but not 7 months, even when developmental level was taken into account. The HR-No ASD outcome group had scores intermediate between the HR-ASD and LR groups. At both timepoints a few individual items were higher in the HR-ASD and HR-No ASD outcome groups compared to the LR group and these included both social (e.g. orienting to name) and non-social (e.g. visual tracking) behaviours. AOSI scores at 14 months but not at 7 months were moderately correlated with later scores on the autism diagnostic observation schedule (ADOS) suggesting continuity of autistic-like behavioural atypicality but only from the second and not first year of life. The scores of HR siblings who did not go on to have ASD were intermediate between the HR-ASD outcome and LR groups, consistent with the notion of a broader autism phenotype.