Neurodevelopmental Domains Research Articles

Operationalizing Culturally Responsive Research Practices: Documenting the Communication Skills of Children With Confirmed or Possible Exposure to the Zika Virus in Saint Lucia, West Indies

Purpose The purpose of this study is to describe a culturally responsive research investigation of communication and interaction skills in Saint Lucian children impacted by the Zika virus (ZIKV). Method Both quantitative and qualitative data collection strategies that align with positivist and interpretivist strategies were used to gain knowledge about communication and interaction development in a cohort of children impacted by ZIKV in Saint Lucia. Thirty participants received a neurodevelopmental assessment, which included a medical assessment, caregiver interview, participant observation, and data collection using the Bayley Scales of Infant and Toddler Development–Third Edition. Twenty-six participants in the cohort received a communication and interaction assessment, which included a caregiver interview, participant observation, and data collection using the Rossetti Infant–Toddler Language Scale. Results Approximately half of our cohort demonstrated typical neurodevelopment, including typical communication and interaction skills, and half demonstrated delays in neurodevelopmental domains, including communication and interaction. Qualitatively, parents expressed a need for resources about mental health, emotional well-being, financial assistance, and peer support. Conclusions There is a continued need to create knowledge about the impact of ZIKV on communication and interaction development in children worldwide. Moreover, culturally responsive research components should be included in research training programs in communication sciences and disorders.

Developmental outcomes in children exposed to Zika virus in utero from a Brazilian urban slum cohort study.

BackgroundThe prevalence of developmental alterations associated with in-utero Zika virus (ZIKV) exposure in children is not well understood. Furthermore, estimation of the Population Attributable Fraction (PAF) of developmental alterations attributed to ZIKV has not been performed due to lack of population-based cohorts with data on symptomatic and asymptomatic ZIKV exposures and an appropriate control group. The aim of this study was to characterize neurodevelopmental outcomes of children at 11 to 32 months of age with intrauterine ZIKV exposure and estimate the PAF of alterations secondary to ZIKV exposure.Methodology/Principal findingsWe performed a cohort of biannual community-based prospective serosurveys in a slum community in Salvador, Brazil. We recruited women participating in our cohort, with a documented pregnancy from January 2015 to December 2016 and children born to those mothers. Children were classified as ZIKV exposed in utero (born from women with ZIKV seroconversion during pregnancy) or unexposed (born from women without ZIKV seroconversion or that seroconverted before/after pregnancy) by using an IgG monoclonal antibody blockade-of-binding (BoB). We interviewed mothers and performed anthropometric, audiometric, ophthalmological, neurologic, and neurodevelopmental evaluations of their children at 11 to 32 months of age. Among the 655 women participating in the cohort, 66 (10%) were pregnant during the study period. 46 (70%) of them completed follow-up, of whom ZIKV seroconversion occurred before, during, and after pregnancy in 25 (54%), 13 (28%), and 1 (2%), respectively. The rest of women, 7 (21.2%), did not present ZIKV seroconversion. At 11 to 32 months of life, the 13 ZIKV-exposed children had increased risk of mild cognitive delay (RR 5.1; 95%CI 1.1–24.4) compared with the 33 children unexposed, with a PAF of 53.5%. Exposed children also had increased risk of altered auditory behavior (RR 6.0; 95%CI 1.3–26.9), with a PAF of 59.5%.ConclusionsA significant proportion of children exposed in utero to ZIKV developed mild cognitive delay and auditory behavioral abnormalities even in the absence of gross birth defects such as microcephaly and other neurodevelopmental domains. Furthermore, our findings suggest that over half of these abnormalities could be attributed to intrauterine ZIKV exposure.

Associations of prenatal methylmercury exposure and maternal polyunsaturated fatty acid status with neurodevelopmental outcomes at 7 years of age: results from the Seychelles Child Development Study Nutrition Cohort 2

Fish is a primary source of protein and n-3 PUFA but also contains methylmercury (MeHg), a naturally occurring neurotoxicant to which, at sufficient exposure levels, the developing fetal brain is particularly sensitive. To examine the association between prenatal MeHg and maternal status of n-3 and n-6 PUFA with neurodevelopment, and to determine whether PUFA might modify prenatal MeHg associations with neurodevelopment. We examined the Seychelles Child Development Study Nutrition Cohort 2 (NC2) at age 7 y. We used a sophisticated and extensive neurodevelopmental test battery that addressed 17 specific outcomes in multiple neurodevelopmental domains: cognition, executive and psychomotor function, language development, behavior, scholastic achievement, and social communication. Analyses were undertaken on 1237 mother-child pairs with complete covariate data (after exclusions) and a measure of at least 1 outcome. We examined the main and interactive associations of prenatal MeHg exposure (measured as maternal hair mercury) and prenatal PUFA status (measured in maternal serum at 28 weeks' gestation) on child neurodevelopmental outcomes using linear regression models. We applied the Bonferroni correction to account for multiple comparisons and considered P values<0.0029 to be statistically significant. Prenatal MeHg exposure and maternal DHA and arachidonic acid (20:4n-6) (AA) status were not significantly associated with any neurodevelopmental outcomes. Findings for 4 outcomes encompassing executive function, cognition, and linguistic skills suggested better performance with an increasing maternal n-6:n-3 PUFA ratio (P values ranging from 0.004 to 0.05), but none of these associations were significant after adjusting for multiple comparisons. No significant interaction between MeHg exposure and PUFA status was present. Our findings do not support an association between prenatal MeHg exposure or maternal DHA and AA status with neurodevelopmental outcomes at age 7 y. The roles of n-6 and n-3 PUFA in child neurodevelopment need further research.

Lessons learnt from 101 hemispherotomies in children with symptomatic epilepsy. Part I: seizure outcome

To evaluate variables that may predict the outcome after hemispherotomy basing on a retrospective study of a large consecutive pediatric cohort of patients from a single institution.One hundred and one patients with refractory seizures and variable decline in development (n=78) underwent hemispherotomy (med. age - 43 months, med. epilepsy history - 30 months). Developmental pathology was the anatomical substrate of disorder in 42 patients, while the infantile post-stroke scarring and gliosis was its origin in the majority of 43 cases with acquired etiology. The progressive pathology (the Rasmussen encephalitis, Sturge-Weber angiomatosis and tuberous sclerosis) was the etiology in 16 children. Left-sided hemisphere was impaired in 54 cases; some contralateral anatomical and potentially epileptogenic MRI-abnormalities were noted also in «healthy» hemisphere in ¼ of all cases. Eight patients needed second surgery to complete sectioning of undercut commissural fibers. FU is known in 91 patients (med. - 1.5 years) and 73 of them were free of seizures (80.2%), but only 30 of 40 patients with FU > 2 years were still SF (75%). All but one of re-do hemispherotomies were successful. AED-treatment was discontinued in 46 cases and tapered in other 27 patients. Up to 90% of kids demonstrated some improvement in behavior and cognition.Developmental pathology, infantile spasms and younger age onset of seizures are negative predictors for achievement of SF-status (p<0.05). Neither bilateral epileptic EEG-signs, nor MRI-abnormalities in «healthy» hemisphere had any relation to outcome, but focal seizure onset was associated positively with further SF-status (p = 0.03). Kids with multiple lobe unilateral CD do somewhat worse than their counterparts with hemimegalencephaly and acquired etiology. Post-hemispherotomy hemiparesis (either new or worsening of already existed one) has no relation either to the age at surgery, or to the age onset (p = 0.41). Children with left-sided lesions were less successful in every neurodevelopmental domain except maintaining expressive language. Patients with relapse or persisting seizures have good chances to become SF by re-doing hemispherotomy and should be evaluated for the possibly incomplete hemispheric isolation.Проанализировать влияние некоторых клинических факторов (семиология и частота приступов, возраст дебюта эпилепсии и ее длительность, этиология поражения и наличие аномалии в «здоровом» полушарии по данным магнитно-резонансной томографии) и способа дисконнекции пораженного полушария на исходы после гемисферотомии.Оперирован 101 ребенок. Медиана возраста на момент операции 43 мес, длительности эпилепсии 30 мес. У большинства (78) детей имелась задержка в развитии. В 25 наблюдениях на магнитно-резонансных томограммах имелись структурные нарушения и в противоположной, «здоровой», гемисфере. В 55 случаях произведена латеральная периинсулярная деафферентация, в 46 — вертикальная парасагиттальная дисконнекция (в 54 — слева, в 47 — справа). Повторно оперированы 8 пациентов в связи с продолжающимися приступами или их возобновлением (у всех — из-за неполной дисконнекции).Катамнез известен у 91 ребенка, с медианой продолжительности 1,5 года. Приступы прекратились у 73 (80,2%) человек, но только у 30 (75%) из 40 детей с катамнезом 2 года и более. В 80% случаев удалось отменить или упростить лечение антиэпилептическими препаратами (АЭП). Пороки развития мозга, инфантильные спазмы и ранняя манифестация эпилепсии оказались негативными предикторами в отношении вероятности полного прекращения приступов (p<0,05). Фокальное начало в приступах позитивным образом связано с вероятностью их полного прекращения после гемисферотомии (p=0,03). Вероятность появления нового или усугубление уже имевшегося гемипареза, а также его перманентности не связана ни с этиологией эпилепсии, ни с возрастом на момент операции или возрастом дебюта эпилепсии (p=0,41). Сторона поражения сказалась на развитии познавательных способностей и поведении (у детей с левополушарной гемисферотомией сохранились проблемы с их формированием), однако на формирование и развитие экспрессивной речи этот фактор не повлиял.У детей с эпилепсией, обусловленной структурным анатомическим поражением одного из полушарий мозга, гемисферотомия — единственная возможность помощи, если лечение антиэпилептическими препаратами неэффективно.

Prenatal Alcohol Exposure and Autism Spectrum Disorder in 39 Children and Adults: Examination of Behavioural and Cognitive Profiles

ABSTRACT Introduction: There is significant symptom overlap between fetal alcohol spectrum disorder (FASD), which results from prenatal alcohol exposure (PAE), and autism spectrum disorder (ASD). There is also limited research regarding the comorbidity of these disorders. Method: Thirty-nine individuals with ASD and PAE (ASD+PAE) aged 3 to 30 years were matched for age, sex, and IQ to 78 individuals with PAE-only and compared on demographics, comorbid conditions, and 9 domains of neurodevelopmental function. Results: The ASD+PAE group were significantly more likely to have deficits in motor and daily living skills. They also had a greater number of impaired neurodevelopmental domains overall. They were diagnosed with ADHD more often and reported more sensory sensitivities, self-regulation difficulties, and social skills deficits. Conclusions: Overall, the ASD+PAE group had a more complex and severe presentation of symptoms. The relationship between ASD, FASD, and PAE as well as the value of providing an ASD diagnosis in the context of PAE are discussed.

Characterization of an unbalanced translocation causing 3q28qter duplication and 10q26.2qter deletion in a patient with global developmental delay and self-injury.

Chromosomal structural variation can cause severe neurodevelopmental and neuropsychiatric phenotypes. Here we present a nonverbal female adolescent with severe stereotypic movement disorder with severe problem behavior (e.g., self-injurious behavior, aggression, and disruptive and destructive behaviors), autism spectrum disorder, severe intellectual disability, attention deficit hyperactivity disorder, and global developmental delay. Previous cytogenetic analysis revealed balanced translocations present in the patient's apparently normal mother. We hypothesized the presence of unbalanced translocations in the patient due to maternal history of spontaneous abortions. Whole-genome sequencing and whole-genome optical mapping, complementary next-generation genomic technologies capable of the accurate and robust detection of structural variants, identified t(3;10), t(10;14), and t(3;14) three-way balanced translocations in the mother and der(10)t(3;14;10) and der(14)t(3;14;10) translocations in the patient. Instead of a t(3;10), she inherited a normal maternal copy of Chromosome 3, resulting in an unbalanced state of a 3q28qter duplication and 10q26.2qter deletion. Copy-imbalanced genes in one or both of these regions, such as DLG1, DOCK1, and EBF3, may contribute to the patient's phenotype that spans neurodevelopmental, musculoskeletal, and psychiatric domains, with the possible contribution of a maternally inherited 15q13.2q13.3 deletion.

Neurological Findings in Children without Congenital Microcephaly Exposed to Zika Virus in Utero: A Case Series Study.

The Zika virus can induce a disruptive sequence in the fetal brain and is manifested mainly by microcephaly. Knowledge gaps still exist as to whether the virus can cause minor disorders that are perceived later on during the first years of life in children who are exposed but are asymptomatic at birth. In this case series, we describe the outcomes related to neurodevelopment through the neurological assessment of 26 non-microcephalic children who had intrauterine exposure to Zika virus. Children were submitted for neurological examinations and Bayley Scales-III (cognition, language, and motor performance). The majority (65.4%) obtained satisfactory performance in neurodevelopment. The most impaired domain was language, with 30.7% impairment. Severe neurological disorders occurred in five children (19.2%) and these were spastic hemiparesis, epilepsy associated with congenital macrocephaly (Zika and human immunodeficiency virus), two cases of autism (one exposed to Zika and Toxoplasma gondii) and progressive sensorineural hearing loss (GJB2 mutation). We concluded that non-microcephalic children with intrauterine exposure to Zika virus, in their majority, had achieved satisfactory performance in all neurodevelopmental domains. One third of the cases had some impairment, but the predominant group had mild alterations, with low occurrence of moderate to severe disorders, similar to other studies in Brazil.

Abstract 16907: Relationship Between 3 rd Trimester Umbilical Arterial Blood Flow and Neurodevelopmental Outcomes at 2 Years in Major Fetal Heart Disease

Introduction: Congenital heart disease (CHD) requiring surgical intervention in infancy is associated with impaired neurodevelopmental (ND) outcomes which may be due in part to prenatal insults. Supporting this, we recently found an inverse relationship between 3 rd trimester umbilical artery Doppler-based (UA) pulsatility index (PI=systolic velocity-diastolic velocity/mean velocity) and growth and ND outcomes at 2 years in hypoplastic left heart syndrome and d-transposition of great arteries. In the present study we explore associations between 2 nd and 3 rd trimester UA-PI in all major fetal CHD and 2-year ND outcomes. Methods: We identified all patients with major structural CHD and fetal echocardiography who underwent cardiac surgery and 2-year ND and biometric assessments (Western Canadian Complex Pediatric Therapies Follow-up Program) from 2007-2017 in our program. Eligible surgeries were: bypass &lt; 6 weeks, shunts at &lt; 6 months or isomerisms with surgery at &lt; 12 months. Patients with genetic syndromes were excluded. 2 nd and 3 rd trimester UA-PI z scores were examined for relationships with 2 year Bayley III ND scales. Data is presented as mean (SD). Results: Data from 147 children was analysed (see Table). 2 nd and 3 rd trimester fetal echo was performed at 22.4(3.7) and 34.7(2.9) weeks, with UA-PI z scores of 0.18 (0.3), and 0.51(1.4) and respectively. The Bayley III cognitive, language and motor scores were 93(13), 89(15) and 89(14) for the entire group. Multivariable regression analysis of the entire group and specific subgroups showed an inverse relationship between 3 rd trimester UA-PI and ND domains (see Table). No association was found for 2 nd trimester UA-PI and ND for the whole group and subgroups. Conclusions: Increased 3 rd trimester UA-PI, which could reflect an altered late gestation placental circulation, inversely relates to abnormal 2 year ND. These relationships are most notably observed in SVs and in CHD associated with AOTO.

Screening for neurodevelopmental disorders in children with congenital heart disease.

The aim of this study was to evaluate the frequency of neurodevelopmental disorders (NDD) in children with significant congenital heart disease (CHD) and to determine associated factors to NDD and frequency of follow-up in developmental therapies. Two hundred and ten children with significant CHD aged from 6 to 66months were enrolled over a period of sixmonths. The Ages & Stages Questionnaire Third Edition in French (ASQ-3) was used to assess neurodevelopmental domains. NDD were defined if cut-off scores were ≤ - 1SD. -1SD corresponded to "Monitor" range: children with minor or emerging disorders; - 2SD corresponded to "Refer" range: children exhibiting neurodevelopmental delays. Forty children were in "Monitor" range and 86 in "Refer" range. NDD rate was 60.0% (n = 126, 95% CI, 53.4 to 66.6%). There was no difference regarding CHD severity (p = 0.99). Only the presence of non-cardiac disease (OR = 2.14; 95% CI, 1.11 to 4.20) was associated with NDD. Forty-six children with NDD had no developmental follow-up (among them 21 were in "Refer" range (10%)) despite this being available.Conclusion: Children with significant CHD are at risk for NDD regardless of CHD severity. Systematic and early monitoring in a specific care program is required. Barriers that prevent access of care must be identified.Trial registration: Neurodevelopmental Disorders in Children With Congenital Heart Disease. NeuroDis-CHD. NCT03360370. https://clinicaltrials.gov/ct2/show/NCT03360370 What is Known: • Children with CHD are at risk for neurodevelopmental disorders and behavioural problems impacting their social adaptation, academic achievements and quality of personal and family life even in adulthood. What is New: • Children with CHD are at risk for neurodevelopmental disorders regardless of the complexity of the CHD. • Even with the availability of appropriate developmental services, children with CHD are not correctly followed, highlighting the need of a specific program of care for a better outcome. Local barriers that prevent access of care of those children must be identified.

Polygenic risk for autism spectrum disorder associates with anger recognition in a neurodevelopment-focused phenome-wide scan of unaffected youths from a population-based cohort

The polygenic nature and the contribution of common genetic variation to autism spectrum disorder (ASD) allude to a high degree of pleiotropy between ASD and other psychiatric and behavioral traits. In a pleiotropic system, a single genetic variant contributes small effects to several phenotypes or disorders. While analyzed broadly, there is a paucity of research studies investigating the shared genetic information between specific neurodevelopmental domains and ASD. We performed a phenome-wide association study of ASD polygenetic risk score (PRS) against 491 neurodevelopmental subdomains ascertained in 4,309 probands from the Philadelphia Neurodevelopmental Cohort (PNC) who lack an ASD diagnosis. Our main analysis calculated ASD PRS in 4,309 PNC probands using the per-SNP effects reported in a recent genome-wide association study of ASD in a case-control design. In a high-resolution manner, our main analysis regressed ASD PRS against 491 neurodevelopmental phenotypes with age, sex, and ten principal components of ancestry as covariates. Follow-up analyses included in the regression model PRS derived from brain-related traits genetically correlated with ASD. Our main finding demonstrated that 11-17-year old probands with the highest ASD genetic risk were able to identify angry faces (R2 = 1.06%, p = 1.38 × 10-7, pBonferroni-corrected = 1.9 × 10-3). This ability replicated in older probands (>18 years; R2 = 0.55%, p = 0.036) and persisted after covarying with other psychiatric disorders, brain imaging traits, and educational attainment (R2 = 0.2%, p = 0.019). We also detected several suggestive associations between ASD PRS and emotionality and connectedness with others. These data (i) indicate how genetic liability to ASD may influence neurodevelopment in the general population, (ii) reinforce epidemiological findings of heightened ability of ASD cases to predict certain social psychological events based on increased systemizing skills, and (iii) recapitulate theories of imbalance between empathizing and systemizing in ASD etiology.

Child HIV Exposure and CMV Seroprevalence in Botswana: No Associations With 24-Month Growth and Neurodevelopment.

BackgroundWe sought to identify predictors of child cytomegalovirus (CMV) infection overall and by maternal HIV status and to assess associations of child CMV status with growth and neurodevelopmental outcomes at 24 months of age in Botswana.MethodsData and samples were used from the Botswana-based observational Tshipidi study (2010–2014), enrolling pregnant women living with and without HIV and following their infants through 2 years of age. Child plasma samples were tested at 18 months of age for anti-CMV immunoglobulin G (IgG). Associations were assessed between detectable anti-CMV IgG and growth (using the World Health Organization Child Growth Standards) and neurodevelopment (using the Bayley Scales of Infant and Toddler Development III and the Developmental Milestones Checklist) at 24 months of age.ResultsOf 317 children, 215 (68%) had detectable anti-CMV IgG at 18 months of age. Comparatively, 83% (n = 178) of HIV-unexposed uninfected (HUU) children had positive CMV serology vs 47% (n = 139) of HIV-exposed uninfected (HEU) children (P < .01); 100% of HUU vs 10.5% of HEU children breastfed. Child CMV infection was not associated with weight-for-age, weight-for-length, or length-for-age z-scores at 24 months. In HUU children, CMV infection was associated with smaller head circumference (P < .01). No difference was observed by child CMV status in any neurodevelopmental domain at 24 months.ConclusionsWe observed high CMV seropositivity in 18-month-old children in Botswana, with higher seropositivity among breastfed (HUU) children. Positive CMV serostatus was not associated with 24-month child growth or neurodevelopmental outcomes, with the exception of smaller head circumference among HUU CMV-positive children.

Gender gaps in preschool age: A study of behavior, neurodevelopment and pre-academic skills.

Background: Female educational advantage is evident from elementary school and throughout the education system. Understanding the gender differences that precede school entry might provide important insight as to why girls outperform boys later in their educational careers. Aims: The aim of this study was to explore gender differences in early literacy and numeracy skills, as well as a range of neurodevelopmental and behavioral domains between the age of five and six years. Methods: We used questionnaire data from preschool teachers in the Norwegian Mother, Father and Child Cohort Study reported for 7467 children attending the final year in preschool, to explore gender differences and age patterns by fitting flexible regression models predicting pre-academic, behavioral and neurodevelopmental outcomes. Results: We found gender differences favoring girls for all outcomes except internalizing behavior. For neurodevelopment and behavior, differences in adjusted standardized scores ranged from 46% of a standard deviation (95% confidence interval (CI) 0.41, 0.50) in overall school readiness to 31% of a standard deviation difference in externalizing behavior problems (CI 0.21, 0.41). We found gender differences for all literacy skills in favor of girls. The gender gap in naming and adding numbers was small, but in favor of girls. Increasing age was associated with improved pre-academic skills and school readiness, as well as reduction of attention problems and language difficulties, the latter especially for boys. Conclusions: We conclude that gender differences favoring girls exist prior to school entry for a broad range of pre-academic, behavioral and neurodevelopmental skills relevant to school functioning.

Multi-group analysis using generalized additive kernel canonical correlation analysis

Multivariate analysis has been widely used and one of the popular multivariate analysis methods is canonical correlation analysis (CCA). CCA finds the linear combination in each group that maximizes the Pearson correlation. CCA has been extended to a kernel CCA for nonlinear relationships and generalized CCA that can consider more than two groups. We propose an extension of CCA that allows multi-group and nonlinear relationships in an additive fashion for a better interpretation, which we termed as Generalized Additive Kernel Canonical Correlation Analysis (GAKCCA). In addition to exploring multi-group relationship with nonlinear extension, GAKCCA can reveal contribution of variables in each group; which enables in-depth structural analysis. A simulation study shows that GAKCCA can distinguish a relationship between groups and whether they are correlated or not. We applied GAKCCA to real data on neurodevelopmental status, psychosocial factors, clinical problems as well as neurophysiological measures of individuals. As a result, it is shown that the neurophysiological domain has a statistically significant relationship with the neurodevelopmental domain and clinical domain, respectively, which was not revealed in the ordinary CCA.

Anesthetic neurotoxicity in the pediatric population: a systematic review of the clinical evidence

Background: Exposure to general anesthesia (GA) in early life is known to be neurotoxic to animals. Objectives: To evaluate the risk of GA inducing long-term neurodevelopmental deficits in human children. Design: Systematic review. Methods: We included observational and randomized studies that compared the long-term neurodevelopment of postnatal children exposed to GA to the long-term neurodevelopment of children not exposed to GA. We searched MEDLINE, Embase and Web of Science for relevant studies published in the year 2000 or later. We screened all the identified studies on predetermined inclusion and exclusion criteria. A risk of bias assessment was made for each included study. We identified 9 neurodevelopmental domains for which a sub-analysis was made: intelligence; memory; learning; language/speech; motor function; visuospatial skills; development/emotions/behavior; ADHD/attention; autistic disorder. Results: We included 26 studies involving 605.391 participants. Based on AHRQ-standards 11 studies were of poor quality, 7 studies were of fair quality and 8 studies were of good quality. The major causes of potential bias were selection and comparability bias. On 2 neurodevelopmental domains (visuospatial skills and autistic disorder), the available evidence showed no association with exposure to GA. On 7 other neurodevelopmental domains, the available evidence showed mixed results. The 4 studies that used a randomized or sibling-controlled design showed no association between GA and neurodevelopmental deficits in their primary endpoints. Limitations: The absence of a meta-analysis and funnel plot. Conclusions: Based on observational studies, we found an association between GA in childhood and neuro-developmental deficits in later life. Randomized and sibling-matched observational studies failed to show the same association and therefore no evidence of a causal relationship exists at present. Since GA seems to be a marker, but not a cause of worse neurodevelopment, we argue against delaying or avoiding interventional or diagnostic procedures requiring GA in childhood based on the argument of GA-induced neurotoxicity.

Diffusion tensor imaging point to ongoing functional impairment in HIV-infected children at age 5, undetectable using standard neurodevelopmental assessments

BackgroundPerinatal HIV infection negatively impacts cognitive functioning of children, main domains affected are working memory, processing speed and executive function. Early ART, even when interrupted, improves neurodevelopmental outcomes. Diffusion tension imaging (DTI) is a sensitive tool assessing white matter damage. We hypothesised that white matter measures in regions showing HIV-related alterations will be associated with lower neurodevelopmental scores in specific domains related to the functionality of the affected tracts.MethodsDTI was performed on children in a neurodevelopmental sub study from the Children with HIV Early Antiretroviral (CHER) trial. Voxel-based group comparisons to determine regions where fractional anisotropy and mean diffusion differed between HIV+ and uninfected children were done. Locations of clusters showing group differences were identified using the Harvard–Oxford cortical and subcortical and John Hopkins University WM tractography atlases provided in FSL. This is a second review of DTI data in this cohort, which was reported in a previous study. Neurodevelopmental assessments including GMDS and Beery-Buktenica tests were performed and correlated with DTI parameters in abnormal white matter.Results38 HIV+ children (14 male, mean age 64.7 months) and 11 controls (4 male, mean age 67.7 months) were imaged. Two clusters with lower fractional anisotropy and 7 clusters with increased mean diffusion were identified in the HIV+ group. The only neurodevelopmental domain with a trend of difference between the HIV+ children and controls (p = 0.08), was Personal Social Quotient which correlated to improved myelination of the forceps minor in the control group. As a combined group there was a negative correlation between visual perception and radial diffusion in the right superior longitudinal fasciculus and left inferior longitudinal fasciculus, which may be related to the fact that these tracts, forming part of the visual perception pathway, are at a crucial state of development at age 5.ConclusionEven directed neurodevelopmental tests will underestimate the degree of microstructural white matter damage detected by DTI. The visual perception deficit detected in the entire study population should be further examined in a larger study.

The Demographic and Neurocognitive Profile of Clients Diagnosed With Fetal Alcohol Spectrum Disorder in PATCHES Paediatrics Clinics Across Western Australia and the Northern Territory.

Fetal alcohol spectrum disorder (FASD) is a diagnosis relating to neurocognitive impairments associated with prenatal alcohol exposure. A key aspect of improving FASD diagnostic processes and management is understanding the demographic and neurocognitive profile of those living with FASD. The aim of this study was to describe the demographic and neurocognitive profile of the first 199 individuals diagnosed with FASD in PATCHES Paediatrics clinics. A retrospective cross-sectional descriptive study design was conducted with individuals diagnosed with FASD between 2013 and 2018 through a multidisciplinary team according to the Australian FASD Diagnostic Guidelines. Participants were primarily male 133 (66.8%) and Aboriginal Australian 147 (73.9%), aged 2 to 31 (mean 10.5), with 94 (47.3%) from remote or very remote parts of Western Australia. Participants came from low 119 (59.8%), medium 48 (24.1%), and high 32 (16.1%) socioeconomic (SE) backgrounds. Low SE background was found to be a predictor of number of sentinel facial features (Wald χ2 (1)=4.03, p<0.05). Most received a diagnosis of FASD with <3 sentinel features 165 (82.9%). Participants either had 6 or more 46 (23.1%), 5 44 (22.1%), 4 55 (27.6%), or 3 (27.1%) neurodevelopmental domains impaired. Executive functioning was the most commonly impaired neurodevelopmental domain 158 (79.4%), and 31 (61%) reported sleep disturbance. ADHD was the most observed comorbid condition (41.7%). This study improves our current understanding of neurocognitive and demographic profiles in individuals with FASD that have been clinically referred for diagnosis within Western Australia and the Northern Territory, and highlights the importance of prevention and early assessment/diagnosis as well as guidance regarding more targeted interventions. FASD affects individuals from all cultural and SE backgrounds. Individuals from middle to higher SE groups are at risk of FASD with prevention efforts needing to target these sectors of society. Suggestions for future research directions are also provided.

Inattention and hyperactive/impulsive component scores do not differentiate between autism spectrum disorder and attention-deficit/hyperactivity disorder in a clinical sample

BackgroundAlthough there is high co-occurrence between ASD and ADHD, the nature of this co-occurrence remains unclear. Our study aimed to examine the underlying relationship between ASD and ADHD symptoms in a combined sample of children with a primary clinical diagnosis of ASD or ADHD.MethodsParticipants included children and youth (aged 3-20 years) with a clinical diagnosis of ASD (n = 303) or ADHD (n = 319) for a total of 622 participants. Parents of these children completed the social communication questionnaire (SCQ), a measure of autism symptoms, and the strengths and weaknesses of ADHD and normal behavior (SWAN) questionnaire, a measure of ADHD symptoms. A principal component analysis (PCA) was performed on combined SCQ and SWAN items, followed by a profile analysis comparing normalized component scores between diagnostic groups and gender.ResultsPCA revealed a four-component solution (inattention, hyperactivity/impulsivity, social-communication, and restricted, repetitive, behaviors, and interests (RRBI)), with no overlap between SCQ and SWAN items in the components. Children with ASD had higher component scores in social-communication and RRBI than children with ADHD, while there was no difference in inattentive and hyperactive/impulsive scores between diagnostic groups. Males had higher scores than females in social-communication, RRBI, and hyperactivity/impulsivity components in each diagnostic group.LimitationsWe did not formally assess children with ASD for ADHD using our research-criteria for ADHD, and vice versa. High rates of co-occurring ADHD in ASD, for example, may have inflated component scores in inattention and hyperactivity/impulsivity. A disadvantage with using single informant-based reports (i.e., parent-rated questionnaires) is that ASD and ADHD symptoms may be difficult to distinguish by parents, and may be interpreted differently between parents and clinicians.ConclusionsASD and ADHD items loaded on separate components in our sample, suggesting that the measurement structure cannot explain the covariation between the two disorders in clinical samples. High levels of inattention and hyperactivity/impulsivity were seen in both ASD and ADHD in our clinical sample. This supports the need for a dimensional framework that examines neurodevelopmental domains across traditional diagnostic boundaries. Females also had lower component scores across social-communication, RRBI, and hyperactivity/impulsivity than males, suggesting that there may be gender-specific phenotypes related to the two conditions.

Long-term outcomes of survivors of neonatal insults: A systematic review and meta-analysis.

The Millennium Developmental Goals ensured a significant reduction in childhood mortality. However, this reduction simultaneously raised concerns about the long-term outcomes of survivors of early childhood insults. This systematic review focuses on the long-term neurocognitive and mental health outcomes of neonatal insults (NNI) survivors who are six years or older. Two independent reviewers conducted a comprehensive search for empirical literature by combining index and free terms from the inception of the databases until 10th October 2019. We also searched for additional relevant literature from grey literature and using reference tracking. Studies were included if they: were empirical studies conducted in humans; the study participants were followed at six years of age or longer; have an explicit diagnosis of NNI, and explicitly define the outcome and impairment. Medians and interquartile range (IQR) of the proportions of survivors of the different NNI with any impairment were calculated. A random-effect model was used to explore the estimates accounted for by each impairment domain. Fifty-two studies with 94,978 participants who survived NNI were included in this systematic review. The overall prevalence of impairment in the survivors of NNI was 10.0% (95% CI 9.8-10.2). The highest prevalence of impairment was accounted for by congenital rubella (38.8%: 95% CI 18.8-60.9), congenital cytomegalovirus (23.6%: 95% CI 9.5-41.5), and hypoxic-ischemic encephalopathy (23.3%: 95% CI 14.7-33.1) while neonatal jaundice has the lowest proportion (8.6%: 95% CI 2.7-17.3). The most affected domain was the neurodevelopmental domain (16.6%: 95% CI 13.6-19.8). The frequency of impairment was highest for neurodevelopmental impairment [22.0% (IQR = 9.2-24.8)] and least for school problems [0.0% (IQR = 0.0-0.00)] in any of the conditions. The long-term impact of NNI is also experienced in survivors of NNI who are 6 years or older, with impairments mostly experienced in the neurodevelopmental domain. However, there are limited studies on long-term outcomes of NNI in sub-Saharan Africa despite the high burden of NNI in the region. Registration number: CRD42018082119.

Association of Genetic Risks With Autism Spectrum Disorder and Early Neurodevelopmental Delays Among Children Without Intellectual Disability

Autism spectrum disorder (ASD) is highly heritable, and modest contributions of common genetic variants to ASD have been reported. However, the association of genetic risks derived from common risk variants with ASD traits in children from the general population is not clear, and the association of these genetic risks with neurodevelopment in infants has not been well understood. To test whether a polygenic risk score (PRS) for ASD is associated with neurodevelopmental progress at age 18 months and ASD traits at age 6 years among children from the general population. In this cohort study, 876 children in the Hamamatsu Birth Cohort for Mothers and Children in Hamamatsu, Japan, underwent testing for the association of an ASD PRS with neurodevelopmental progress and ASD traits. Data collection began in December 2007 and is ongoing. Data analysis was conducted from April to December 2019. Summary data from the largest genome-wide association study were used to generate ASD PRSs, and significance of thresholds was calculated for each outcome. The Autism Diagnostic Observation Schedule 2 was used to measure ASD traits at age 6 years, and the Mullen Scales of Early Learning was used to measure neurodevelopmental progress at age 18 months. Of 876 participants (mean [SD] gestational age at birth, 38.9 [1.6] weeks; 438 [50.0%] boys; 868 [99.1%] Japanese), 734 were analyzed. The ASD PRS was associated with ASD traits (R2 = 0.024; β, 0.71; SE, 0.24; P = .03). The association of ASD PRS with infant neurodevelopment was most pronounced in gross motor (R2 = 0.015; β, -1.25; SE, 0.39; P = .01) and receptive language (R2 = 0.014; β, -1.19; SE, 0.39; P = .02) scores on the Mullen Scales of Early Learning. Gene set enrichment analyses found that several pathways, such as cell maturation (R2 = 0.057; β, -5.28; SE, 1.40; P < .001) and adenylyl cyclase activity and cyclic adenosine monophosphate concentration (R2 = 0.064; β, -5.30; SE 1.30; P < .001), were associated with ASD traits. Gene sets associated with inflammation were commonly enriched with ASD traits and gross motor skills (eg, chemokine motif ligand 2 production: R2 = 0.051; β, -6.04; SE, 1.75; P = .001; regulation of monocyte differentiation: R2 = 0.052; β, -6.63; SE, 1.90; P = .001; and B-cell differentiation: R2 = 0.051; β, 7.37; SE, 2.15; P = .001); glutamatergic signaling-associated gene sets were commonly enriched with ASD traits and receptive language skills (eg, regulation of glutamate secretion: R2 = 0.052; β, -5.82; SE, 1.68; P = .001; ionotropic glutamate receptor signaling pathway: R2 = 0.047; β, 3.54; SE, 1.09; P = .001; and negative regulation of glutamate secretion: R2 = 0.045; β, -5.38; SE, 1.74; P = .002). In this study, the ASD PRS was associated with ASD traits among children from the general population. Genetic risks for ASD might be associated with delays in some neurodevelopmental domains, such as gross motor and receptive language skills.

Community-based child development service fetal alcohol spectrum disorder assessment: A retrospective clinic audit.

The aims of the current study were to: (i) report on the diagnostic profile of a group of children assessed for fetal alcohol spectrum disorder (FASD) using the Australian Guide to the Diagnosis of FASD; and (ii) to provide information and recommendations for paediatricians and/or multidisciplinary teams conducting FASD assessments, including utilising the Australian Guide to the Diagnosis of FASD, and details of how to do FASD assessment. A retrospective chart review was conducted using relevant demographic and diagnostic data from children assessed for FASD within a community child development service. Results showed the widespread impact of FASD on the brain, with all children showing some level of impairment in at least 5 out of 10 of the neurodevelopmental domains assessed for FASD. Majority of children were diagnosed with co-morbid attention deficit hyperactivity disorder, however, many additional co-morbid diagnoses were evident. The current study detailed the profile of children assessed for FASD and was the first to report the diagnostic profile of children assessed using the Australian Guide to the Diagnosis of FASD within a community child development service. Several recommendations are provided to assist paediatricians and multidisciplinary teams involved in child development assessments.