Neurodevelopmental Outcomes In Children Research Articles

Postnatal Zika and Dengue Infection and their Effects on Neurodevelopment Among Children Living in Rural Guatemala.

Prenatal Zika virus (ZIKV) infection leads to microcephaly and adverse neurodevelopment. The effects of postnatal ZIKV infection on the developing brain are unknown. We assessed the neurodevelopmental outcomes of children exposed postnatally during the ZIKV epidemic. A prospective study enrolled infants 0-3 months of age and their mothers, and children 1.5-3.5 years of age in rural Guatemala from 2017 and were followed for 12 months until 2019. Neurodevelopment was evaluated using the Mullen Scales of Early Learning (MSEL). ZIKV and dengue virus (DENV) infections were identified by polymerase chain reaction (PCR) using active surveillance. Serological analyses, stratified by age group flavivirus serostatus at enrollment, were conducted using a focus reduction neutralization test. Of 1371 enrolled participants, 1187 (86.6%) completed the study. No PCR-confirmed ZIKV infections were identified during the study period. One-third of 1.5-3.5-year-old children were ZIKV-seropositive at enrollment (likely postnatal infection). Twenty participants (5.8%) tested positive for DENV by PCR (11 infants, 5 children and 4 mothers); 15 (75%) were DENV-3 infections and 5 were DENV-2. The incidence of DENV infection in infants was 2.6%. No significant differences in MSEL scores were found between infants born seropositive versus seronegative for ZIKV or DENV. DENV seropositivity at enrollment in 1.5-5-year-old children was associated with lower MSEL scores for fine motor, visual reception and language, and microcephaly at 12 months versus seronegative children (all P < 0.05). Postnatal ZIKV infection in children from rural Guatemala was not associated with worse neurodevelopmental outcomes. DENV seropositivity was associated with a higher risk of microcephaly in infants and worse neurodevelopmental outcomes in children.

Being born extremely preterm with low-grade intraventricular haemorrhage had no impact on brain volumes or neurodevelopment in later childhood.

Our aim was to investigate the impact that low-grade intraventricular haemorrhage (IVH) had on neonatal morbidities, brain volumes and neurodevelopmental outcomes in children born extremely preterm (EPT) and compare them with children born EPT without low-grade IVH. This prospective cohort study was carried out in Stockholm, Sweden. It focused on 103 children born EPT from 2004 to 2007, at less than 27 weeks of gestation, without major brain injuries. The group with low-grade IVH, defined as grades I-II, were compared with children born EPT without IVH. Around half (45%) underwent MRI scans at 10 years of age and 55% had neurodevelopmental assessments at 12 years. The low-grade IVH group was sicker during the neonatal period than the children born EPT without IVH. They had lower gestational ages at birth, more days on mechanical ventilation, a higher incidence of necrotising enterocolitis and were more likely to need surgical ligation of patent ductus arteriosus. However, they did not have significantly smaller brain volumes at 10 years of age or worse neurodevelopmental outcomes at 12 years of age. Brain volumes or neurodevelopment were not affected in children born EPT with low-grade IVH, compared to children born EPT without IVH.

Association between prenatal mercury exposure and pediatric neurodevelopment: The Japan environment and children's study

Mercury pollution, including from its use during gold mining and refining, remains an important problem worldwide. In particular, methylmercury, a microbial alteration of mercury released into the environment, is a major environmental neurotoxicant. Although there has been growing concern about the health hazards of exposure to low levels of mercury, the effects of prenatal mercury exposure on neurodevelopmental outcomes in children have remained controversial. In the Japan Environment and Children's Study, a large-scale nationwide birth cohort study, we measured methylmercury and inorganic mercury concentrations in cord blood and conducted developmental scoring tests at ages 2 and 4 years. We then analyzed the associations between mercury levels in cord blood and neurodevelopmental outcomes. Measurements of cord blood obtained from 3822 participants revealed median values of 7.39 ng/ml (5th percentile: 2.95, 95th percentile: 18.1) and 0.25 ng/ml (5th percentile: 0.10, 95th percentile: 0.58) for methylmercury and inorganic mercury, respectively. Analyzing the association with fish consumption, bonito-tuna was most strongly correlated with both methylmercury and inorganic mercury in cord blood. Although the association between cord blood mercury and neurodevelopmental scores was subsequently examined in 3083 individuals, we found no significant association with either methylmercury or inorganic mercury. Further quartile group analysis based on methylmercury concentrations in cord blood revealed no concentration-dependent association between a prenatal mercury exposure and neurodevelopment in children. However, various factors influence neurodevelopment, and long-term observational studies that consider those covariates are necessary for a more definitive conclusion. Although the findings of our study provide important insights into the association between prenatal mercury exposure and neurodevelopment, further research is needed to make recommendations for safe mercury intake thresholds during pregnancy.

Examining Infant and Child Neurodevelopmental Outcomes After Lyme Disease During Pregnancy

Examining Infant and Child Neurodevelopmental Outcomes After Lyme Disease During Pregnancy

Abstract 4135745: Prematurity Predicts Neurodevelopmental Outcomes in Congenital Heart Disease

Background: Neurodevelopmental (ND) impairment is common in both prematurity and congenital heart disease (CHD). Preterm infants with CHD may have a “double hit,” with worse ND impairments than seen in prematurity or CHD alone. We analyzed whether gestational age (GA) at delivery predicted ND outcomes in children with CHD. Methods: We performed a single-institution retrospective study of children who underwent infant heart surgery from 2007-2020 and returned for ND evaluation after discharge. Exclusion criteria were 1) trisomy 21 and 2) PDA ligation alone. The Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) assessed ND between ages 6-40 months. Patients were stratified into 4 GA groups: very/moderately preterm (≤33 weeks), late-preterm (34-36 weeks), early-term (37-38 weeks) or term/post-term (≥39 weeks). Hierarchical linear regression evaluated potential predictors of Bayley-III composite scores including GA category, demographic, medical, and surgical variables. Results: Among 1350 infants, 513 (38%) had a Bayley-III at median age 28 months [IQR 19, 34]. Of these, 448 (87%) were full-term and 65 (13%) preterm. In univariate analyses, children born preterm vs. full term had lower Bayley-III cognitive, language, and motor scores, explaining from 2.4% (language) to 6.2% (motor) of the variance in Bayley composite scores. In the final models, GA remained a strong independent predictor of motor and cognitive scores. Children with GA ≤33 weeks had the worst outcomes, with age-adjusted cognitive and motor composite scores 11 and 15 points lower, respectively, than those of term infants (Figure). Other significant risk factors included lower primary caregiver education, Black race, longer hospital length of stay, and genetic diagnosis. These models ultimately explained 17-26% of the variance in Bayley scores, with the highest explained variance in the motor domain. Conclusions: Adjusting for other patient and medical factors, preterm infants with CHD have worse cognitive and motor outcomes; risk is highest in those born at ≤33 weeks. Further work is needed to identify potentially modifiable factors to tailor prenatal, postnatal and perioperative care of infants with CHD born prematurely.

Neurodevelopment in the First 2 Years of Life Following Prenatal Exposure to Maternal SARS-CoV-2 Infection

The effects of prenatal exposure to SARS-CoV-2 infection on child development throughout the first 2 years of life are unknown. To evaluate whether prenatal exposure to SARS-CoV-2 infection was associated with child neurodevelopmental outcomes during the first 2 years of life. This cohort study used data from the longitudinal, population-based pan-Canadian Pregnancy During the COVID-19 Pandemic cohort, which recruited participants from April 2020 to July 2022. Children were categorized as exposed to prenatal SARS-CoV-2 infection if their birthing parent had a positive polymerase chain reaction test performed by a health authority or as a healthy negative comparison if their birthing parent did not have SARS-CoV-2 antibodies in their postpartum dried blood spot sample. Prenatal SARS-CoV-2 infection. The birthing parent reported on their child's temperament at ages 6 and 24 months, developmental milestones at ages 12 and 24 months, and social-emotional milestones at ages 12 and 24 months. A total of 896 children were included, with 96 children who had been exposed to a prenatal SARS-CoV-2 infection (mean [SD] gestational age at birth, 39.20 [1.50] weeks; 45 [47%] male) and 800 were healthy negative comparisons (mean [SD] gestational age at birth, 39.47 [1.54] weeks; 388 [49%] male). In analyses of covariance adjusted for prepregnancy medical conditions and household socioeconomic status, prenatal exposure to SARS CoV-2 infection was associated with slightly higher regulatory control scores, indicating more regulation, at age 6 months (difference in means, 0.19 [95% CI, 0.02-0.36]; P = .03; ηp2 = 0.01). No significant differences were observed for the other neurodevelopmental outcomes. In mixed models adjusted for the same covariates that aimed to examine change in outcomes over time, prenatal SARS-CoV-2 infection exposure was not associated with developmental change in any neurodevelopmental outcomes between ages 6 and 24 months. In this longitudinal cohort study of multiple aspects of child neurodevelopment between ages 6 and 24 months, negligible associations between prenatal exposure to SARS-CoV-2 infection and child outcomes were observed. Follow-up research is warranted to determine whether these predominantly null effects persist into later childhood.

ADMINISTERING INTRAVITREAL BEVACIZUMAB FOR RETINOPATHY OF PREMATURITY: 8-Year Cognitive Outcomes In A Prospective Cohort.

Determine whether intravitreal injection of bevacizumab exerts long-term effects on neurodevelopmental outcomes in children with retinopathy of prematurity (ROP) when reaching the age of 8 years. In total, 277 children were enrolled. Patients were stratified into full-term, preterm without ROP, ROP without treatment, or ROP with treatment groups, based on gestational age and ROP status. Children under the gestational age of 37 weeks were considered premature. Patients' cognitive outcomes were evaluated using a full-scale intelligence quotient (full score and percentile) generated by the Wechsler Intelligence Scale for Children-Fourth Edition every 1 year to 2 years. At the mean age of 7.8 years, ROP without and with treatment groups demonstrated lower full-scale intelligence quotient scores and percentiles, compared with full-term and premature groups (both P < 0.05). Full-scale intelligence quotient scores and percentiles did not significantly differ between patients who received different treatments for ROP (full score P = 0.19; percentile P = 0.37). After adjusting for gestational age, logMAR best-corrected visual acuity was negatively associated with full-scale intelligence quotient scores ( P = 0.0008) and percentiles ( P = 0.0002). At the mean age of 8 years, patients with ROP undergoing injection of bevacizumab did not exhibit worse cognitive outcomes than those who underwent laser photocoagulation or both treatments. Gestational age and best-corrected visual acuity correlated with cognitive development in children.

Neurodevelopmental outcome in children between one and five years after persistent pulmonary hypertension of term and near-term newborns.

Persistent pulmonary hypertension of the newborn (PPHN) is a serious condition that affects 1-2 per 1,000 newborns. Scientific data report the existence of neurological developmental abnormalities between 10 and 30%, but the description of these disorders linked with this situation of cerebral hypoxia and haemodynamic failure remains poorly documented. The main goal of this study was to describe the prevalence of neuro-psychomotor developmental disorders in children aged between one and five years old who have been hospitalised at birth in a neonatal intensive care unit for the management of PPHN. All of the newborns ≥34 weeks of gestational age (WGA) with PPHN, treated with inhaled nitric oxide in our neonatal intensive care unit between January 2015 and December 2019 were retrospectively enrolled. An ASQ-3 standardised questionnaire, adapted to the appropriate age (12, 24, 36, 48 and 60 months) was performed by the parents. Fifty-five children (81% of answers) with a median age of 36 months (11-68), whose real age was close to the one of the questionnaire (12, 24, 36, 48 and 60 months), have been included in this study. There was 47% of pathological score [borderline: less than 1 standard deviation (SD) or suspect: less than 2SD] in at least one of the five studied domains, mainly in communication (25%) and individual and social skills (22%), despite a high overall score of 250 [220; 285] out of 300 that improved with age. This study showed a significant prevalence of neuro-psychomotor developmental disorders which justifies making more accessible a prolonged and adapted follow-up for early and multidisciplinary screening and management of these children with PPHN history. Larger cohorts are needed to better explore long term outcome of these vulnerable term neonates.

Mode of delivery and behavioral and neuropsychological outcomes in children at 10 years of age.

Previous studies have reported that mode of delivery, particularly cesarean delivery (CD), is associated with neurodevelopmental outcomes in children. This study evaluates behavioral and neuropsychological test scores in children based on mode of delivery. Children enrolled in the Raine Study from Western Australia, born between 1989 and 1992 by instrumental vaginal delivery (IVD), elective CD, and non-elective CD, were compared to those with spontaneous vaginal delivery (SVD). The primary outcome was the Child Behavior Checklist (CBCL) administered at age 10. Secondary outcomes included evaluations of language, motor function, cognition, and autistic traits. Multivariable linear regression was used to evaluate score differences by mode of delivery adjusted for sociodemographic and clinical characteristics, and Poisson regression was used to evaluate for increased risk of clinical deficit. Of 2,855 children, 1770 (62.0 %) were delivered via SVD, 480 (16.8 %) via IVD, 346 (12.1 %) via elective CD, and 259 (9.1 %) via non-elective CD. Non-elective CD was associated with higher (worse) CBCL Internalizing (+2.09; 95 % CI 0.49, 3.96; p=0.01) scores, and elective CD was associated with lower (worse) McCarron Assessment of Neuromuscular Development (MAND) (-3.48; 95 % CI-5.61,-1.35; p=0.001) scores. Differences were not seen in other outcomes, and increased risk of clinical deficit was not observed with either the CBCL Internalizing or MAND scores. Differences in behavior and motor function were observed in children delivered by CD, but given that score differences were not associated with increased incidence of clinical deficit, clinical significance may be limited.

7912 Children's Neurodevelopmental Outcomes at School-Age After Conception with Hysterosalpingography Using Iodinated Contrast Media

Abstract Disclosure: S. Keestra: None. C. Kooper: None. N. van Welie: None. K. Dreyer: Grant Recipient; Self; research grants from Guerbet. Speaker; Self; travel and speaker fees Guerbet. R. van Eekelen: None. T. Roseboom: None. J. Oosterlaan: None. B. Mol: Consulting Fee; Self; Organon Laboratories, Norgine, Merck. Grant Recipient; Self; Merck. Stock Owner; Self; ObsEva. M. Finken: None. V. Mijatovic: Grant Recipient; Self; Guerbet, Merck, Ferring Pharmaceuticals. Speaker; Self; Guerbet, Merck, Ferring Pharmaceuticals. M. Königs: None. Thyroid hormone sufficiency in pregnancy is vital for children's neurodevelopment. Exposure to iodine excess can cause transient disruption of thyroid hormone synthesis through the Wolff-Chaikoff effect. Iodinated contrast media are commonly utilized in hysterosalpingography (HSG) as part of female fertility work-up. When conception occurs shortly after HSG with iodinated contrast, a temporary reduction of maternal and/or foetal thyroid hormone synthesis could jeopardize children's neurodevelopment. We compared the neurodevelopmental outcomes of 6-9-year-old children (n=69) conceived &amp;lt;6 months after HSG with 5-10 ml of oil-based contrast (iodine content: 480mg/ml) or water-based contrasts (iodine content: 250mg/ml) in the follow-up of a nationwide randomised controlled trial (H2Oil trial; Netherlands; 2012-2014; NCT05168228). A community sample of naturally-conceived children (n=44) with similar age, sex and parental education was used as a comparison group (NTR9574). Primary outcomes were intelligence (Wechsler’s Intelligence Scale for Children V), behaviour questionnaires for parents and teachers (Strengths and Difficulties Questionnaire (SDQ); Strengths and Weaknesses of ADHD Symptoms And Normal behaviour (SWAN)), and academic performance. Secondary outcomes were neurocognitive domains assessed in computerized tasks focussing on Processing &amp; Control, Verbal Memory, Visual Memory, Verbal Working Memory, Visual Working Memory, and Visuomotor Integration (Emma Toolbox for Neurocognitive Functioning). We adjusted linear regression models for age, sex, and parental education, applying FDR correction for multiple comparisons. Additional analysis looked at children conceived within 4 weeks, 4-12 weeks, or &amp;gt;12 weeks after HSG. Children conceived &amp;lt;6 months after HSG had lower performance on intelligence tests (-6.81; 95%CI -10.97 to -2.65; p=0.02) and the neurocognitive domain Processing &amp; Control (-0.52; 95%CI-0.84 to -0.19; p=0.02), with processing speed and consistency affected. No differences were found for other neurocognitive domains, behaviour or academic performance. In comparison to naturally-conceived children, children conceived &amp;lt;4 weeks after HSG had lower performance on intelligence tests, but there was no difference for children conceived 4-12 weeks and &amp;gt;12 weeks after HSG. Replication studies with higher power are needed to further evaluate the safety of iodinated contrast media use periconception, including their effects on thyroid function and children's neurodevelopment. Closer monitoring and treatment of thyroid dysfunction in the months following HSG may be warranted. Presentation: 6/1/2024

Routine third-trimester ultrasonography and child neurodevelopmental outcomes: a follow-up of a pragmatic cluster-randomised controlled trial

ABSTRACT Aims/Background Routine third-trimester ultrasonography is increasingly conducted to screen for foetal growth restriction (FGR) and reduce adverse perinatal and child neurodevelopmental outcomes using timely obstetric management. While it did not reduce adverse perinatal outcomes in previous trials, evidence regarding its association with child neurodevelopmental outcome is absent. We examined whether routine third-trimester ultrasonography is positively associated with child developmental and behavioural/emotional outcomes compared to usual care. Design/Methods Dutch mothers with a low-risk pregnancy participating in a subsample (n = 1070) of a nationwide cluster-randomised trial reported infant (age 6 months) and toddler (age 28 months) developmental milestones (Ages and Stages Questionnaire) and toddlers’ internalising and externalising problems (Child Behavior Checklist). Usual care (n = 380) comprised selective ultrasonography. The intervention strategy (n = 690) included two routine third-trimester ultrasounds next to usual care. Both strategies applied the same interdisciplinary protocol for FGR detection and management. Results Adjusted linear mixed-level regressions revealed that routine third-trimester ultrasonography was positively but modestly related to z-standardised infant developmental milestones at 6-month follow-up, B = 0.20, 95%CI [0.07; 0.32], p = 0.003, compared to usual care. At 28-month follow-up, these strategies did not differ in child developmental outcome and internalising and externalising problems. Conclusion Routine third-trimester ultrasonography was positively but modestly associated with infant development. In toddlerhood, routine ultrasonography was not related to child developmental and behavioural/emotional outcomes. Overall, these findings do not support the implementation of routine third-trimester ultrasonography for low-risk pregnant women for reasons concerning children’s early neurodevelopmental outcomes.

Maternal Nutrition during Pregnancy and Offspring Brain Development: Insights from Neuroimaging.

Maternal nutrition during pregnancy is known to be important for offspring growth and health and has also been increasingly recognized for shaping offspring brain development. On the other hand, recent advancements in brain imaging technology have provided unprecedented insights into fetal, neonatal, and pediatric brain morphometry and function. This review synthesizes the current literature regarding the impact of maternal nutrition on offspring brain development, with a specific focus on findings from neuroimaging studies. The diverse effects of maternal nutrients intake or status during pregnancy on neurodevelopmental outcomes in children are discussed. Neuroimaging evidence showed associations between maternal nutrition such as food categories, macronutrients, and micronutrients including vitamins and minerals during pregnancy and child brain imaging features measured using imaging techniques such as ultrasound, magnetic resonance imaging (MRI), electroencephalography (EEG), and magnetoencephalography (MEG). This review demonstrates the capability of neuroimaging in characterizing how maternal nutrition during pregnancy impacts structure and function of the developing brain that may further influence long-term neuropsychological, cognitive, and behavioral outcomes in children. It aims to inspire future research utilizing neuroimaging to deepen our understanding of the critical impacts of maternal nutrition during pregnancy on offspring brain development.

Neurodevelopmental outcomes in children prenatally exposed to opioid maintenance treatment: A population-based study.

Opioid maintenance treatment (OMT), with methadone or buprenorphine, is a key approach for managing opioid use disorder (OUD) during pregnancy. Despite buprenorphine's superior short-term outcomes, its long-term effects remain understudied. This study aims to evaluate the effects of prenatal OMT exposure on the incidence of childhood neurodevelopmental disorders (NDDs) considering timing effect. A retrospective cohort study using Rhode Island Medicaid data linked to vital statistics from 2008 to 2018 was conducted. The study included pregnancies having live birth from 2008 to 2016 with continuous Medicaid insurance and OUD diagnosis within 3 months preceding conception until delivery. At least one buprenorphine dispensing or a claim of methadone was required for exposure definition. Exposure was evaluated during early (0-90 days) or late (>90 days) gestation, or at any pregnancy phase. NDDs, including autism, attention-deficit/hyperactivity disorder (ADHD), learning disabilities, speech/language disorders, developmental coordination disorder, intellectual disability, and behavioral disorders, were identified using validated algorithms. Applying Cox proportional-hazard models with propensity score overlap weighting, adjusted hazard ratios (aHR) were calculated, mitigating potential confounders. Children were followed up from birth until NDD diagnosis, disenrollment, or study end. Of 416 mother-child dyads with OUD, 40% used methadone and 20% had buprenorphine exposure during pregnancy. NDDs were observed in 36% of children with early methadone exposure compared to 17% in the early buprenorphine exposed group (aHR: 2.75; 95% confidence interval [CI]: 1.42-5.35). Further comparison to late buprenorphine exposure, late methadone exposure was associated with higher NDD risk (aHR: 2.05; 95% CI: 1.09-3.86). Compared to unexposed group, children exposed to methadone during early and late periods showed higher NDD incidences (aHR: 2.33; 95% CI: 1.51-3.60 and aHR: 2.42; 95% CI: 1.54-3.80, respectively). The study suggests that buprenorphine is a good treatment option for OUD during pregnancy due to minimal long-term neurodevelopmental impacts on children. However, further extensive research is necessary to rule-out potential confounding.

Implications of Prenatal Cannabis Exposure on Childhood Neurodevelopmental Outcomes: A Summary of the Clinical Evidence.

Cannabis is commonly used by pregnant patients for alleviation of pregnancy-associated symptoms. Multiple national medical associations have recommended against prenatal cannabis use, yet misinformation regarding its safety and efficacy remains prevalent in public discourse. Effective and evidence-based patient counseling on prenatal cannabis use requires a thorough understanding of the existing data on fetal neurodevelopment. The aim of this study was to summarize the existing clinical literature on the impacts of intrauterine cannabis exposure on offspring neurodevelopment. Articles were identified via literature search in PubMed and OVID; relevant articles were reviewed. Limited data have shown associations between intrauterine cannabis exposure and (1) increased startles and difficulty with consolation in the neonatal period, (2) memory challenges, verbal reasoning challenges, and diminished academic performance during early childhood, and (3) inattention, hyperactivity, and aggression during early childhood. Further research with large and diverse samples that use objective measures of cannabis use across multiple time points in pregnancy is required to assess causation, the true extent of impacts, and dose-dependent effects. The existing clinical data regarding the impacts of prenatal cannabis use on fetal neurodevelopment are limited by important confounders like genetic predisposition, concomitant tobacco and other substance use during pregnancy, and low socioeconomic status. However, the theoretical and demonstrated associations between prenatal cannabis use and adverse neurodevelopmental outcomes are compelling enough to warrant complete abstinence during pregnancy, pending further research. Providers can utilize this summary to offer data-driven guidance on prenatal cannabis use for pregnant patients.

Maternal Prenatal Cannabis Use and Child Autism Spectrum Disorder

Despite an increase in maternal prenatal cannabis use and associations with adverse neonatal outcomes, research on child neurodevelopmental outcomes is limited. To evaluate the association between maternal cannabis use in early pregnancy and child autism spectrum disorder (ASD). This population-based retrospective birth cohort study included children born between 2011 and 2019 to pregnant Kaiser Permanente Northern California members screened for prenatal cannabis use during pregnancy. Statistical analysis was conducted February 2023 to March 2024. Maternal prenatal cannabis use was assessed at entrance to prenatal care (approximately 8- to 10-weeks' gestation) via self-report and/or positive urine toxicology test. Use frequency was assessed. Child ASD was defined by International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) diagnosis codes ascertained from the electronic health record. Associations between maternal prenatal cannabis use and child ASD were modeled using Cox proportional hazards regression adjusted for maternal sociodemographic, other substance use and disorders, prenatal care initiation, comorbidities, and clustering among maternal siblings. The study cohort included 178 948 singleton pregnancies among 146 296 unique pregnant individuals, including 48 880 (27.3%) Asian or Pacific Islander, 42 799 (23.9%) Hispanic, 9742 (5.4%) non-Hispanic Black, and 70 733 (39.5%) non-Hispanic White pregnancies. The median (IQR) maternal age at pregnancy onset was 31 (6) years; 8486 (4.7%) screened positive for cannabis use, 7054 (3.9%) via urine toxicology testing and 3662 (2.0%) by self-report. In the total study population, the frequency of self-reported use was monthly or less for 2003 pregnancies (1.1%), weekly for 918 pregnancies (0.5%), daily for 741 pregnancies (0.4%), and unknown for 4824 pregnancies (2.7%). ASD was diagnosed in 3.6% of children. After adjustment for maternal characteristics, maternal prenatal cannabis use was not associated with child ASD (hazard ratio [HR], 1.05; 95% CI, 0.84-1.32). When self-reported frequency of use was assessed, no statistically significant associations were observed after confounder adjustment. No sex-specific associations were documented (males: HR, 1.01; 95% CI, 0.77-1.32; and females: HR, 1.19; 95% CI, 0.77-1.85). In this cohort study, maternal cannabis use assessed in early pregnancy was not associated with child ASD. Additional studies are needed to evaluate different patterns of use throughout pregnancy. Given the known adverse neonatal health effects of maternal prenatal cannabis use, clinicians should follow national guidelines and advise against use.

DNA methylation signatures of prenatal socioeconomic position associated with 36-month language outcomes

BackgroundSocioeconomic position (SEP), which reflects one’s position in society and access to resources, is strongly tied to neurodevelopment and is associated with epigenetic changes. AIM: This study examined whether DNA methylation signatures of prenatal SEP, measured in birth samples, are associated with child neurodevelopmental outcomes at 36 months of age. METHODS: Prenatal SEP DNA methylation scores were derived using 97 placenta and 127 cord blood biospecimens in the Early Autism Risk Longitudinal Investigation cohort. Participants completed the Mullen Scales of Early Learning (MSEL) and Vineland Adaptive Behavior Scales (VABS) at 36 months of age. Generalized regression analyses, adjusting for maternal age and race, were performed to test the association between SEP methylation score, for each birth biospecimen type, and MSEL and VABS scores. RESULTS: Significant associations were observed between placenta SEP methylation score and MSEL Expressive Language outcomes (beta = −2.7, p = 0.046, 95 % CI [- 5.43, −0.05]) and Receptive Language outcomes (beta = −2.5, p = 0.037, 95 % CI [-4.82, −0.16]). In cord blood, methylation-SEP scores were significantly associated with Receptive Language outcomes (beta = −2.0, p = 0.037, 95 % CI [-3.85, −0.12]). No significant associations were observed with VABS scores. CONCLUSION: Our results confirm associations between prenatal SEP and early childhood language development using a novel empiric DNA methylation measure of exposure.

Home-ics: how experiences of the home impact biology and child neurodevelopmental outcomes.

Studies on the -omics of child neurodevelopmental outcomes, e.g. genome, epigenome, microbiome, metabolome, and brain connectome aim to enable data-driven precision health to improve these outcomes, or deliver the right intervention, to the right child, at the right time. However, evidence suggests that neurodevelopmental outcomes are shaped by modifiable socioenvironmental factors. Everyday exposures including family and neighbourhood-level socioeconomic status, housing conditions, and interactions with those living in the home, are strongly associated with child health and have been suggested to alter -omics. Our aim was to review and understand the biological pathways by which home factors contribute to child neurodevelopment outcomes. We review studies suggestive of the home factors contributing to neurodevelopmental outcomes that encompass the hypothalamic-pituitary-adrenal axis, the brain, the gut-brain-axis, and the immune system. We thus conceptualize home-ics as the study of how the multi-faceted living environment can impact neurodevelopmental outcomes through biology and highlight the importance of targeting the modifiable aspects of a child's home to optimize outcomes. We encourage clinicians and health care providers to routinely assess home factors in patient encounters, and counsel families on modifiable aspects of the home. We conclude by discussing clinical and policy implications and future research directions of home-ics. IMPACT: Home-ics can be conceptualized as the study of how home factors may shape child neurodevelopmental outcomes through altering biology. Targeting modifiable aspects of a child's home environment (e.g. parenting style, early intervention, enriched environment) may lead to improved neurodevelopmental outcomes. Clinicians should routinely assess home factors and counsel families on modifiable aspects of the home.

Neonatal Markers of Prematurity as Predictors of Permanent Childhood Hearing Loss and Neurodevelopmental Impairment in Children Admitted to the Neonatal Intensive Care Unit.

Need for admission to the neonatal intensive care unit (NICU) confers an increased risk of hearing loss in the newborn and of later neurodevelopmental impairment. In this retrospective longitudinal case-controlled study, we assess how the degree of prematurity, measured via gestational age, birth weight, and z-scores, in 138 infants admitted to the NICU are associated with permanent childhood hearing loss (PCHI) and 2-year developmental outcomes. Logistic regression analyses, Kruskal-Wallis analysis of variance, and Chi-squared tests were used. Independent of prematurity, PCHI and NICU admission were predictive of poor developmental outcomes. Twenty-one (47%) children with PCHI had a moderate-to-severe developmental delay, compared to three (7%) matched controls. Days in the NICU but not z-scores predicted PCHI. Z-score was not prognostic of moderate or severe developmental impairment in children with PCHI. The odds ratio of moderate-to-severe neurodevelopmental impairment with PCHI was high, at 12.48 [95% CI = 3.37-46.40]. Children with PCHI were significantly more likely to have cerebral palsy than their matched counterparts (30% vs. 2%). These findings challenge the conventional focus on gestational age and birth weight on neurodevelopmental outcomes for children with PCHI and NICU admission. A more nuanced approach to monitoring and intervention is needed.

Neurodevelopmental Outcomes in Children Vertically Exposed to Chikungunya Virus: A Two Years Follow-up Study.

To monitor by the first 24 months of life, children born to mothers with laboratory evidence of chikungunya virus (CHIKV) infection during pregnancy or up to 8 weeks before it, and to describe abnormalities in head circumference (HC), auditory and ophthalmological assessments and neuroimaging tests during the follow-up period. This is a observational, descriptive, longitudinal and prospective study of children born to mothers who had a rash and a positive test for CHIKV during pregnancy or up to 8 weeks before it. They were admitted between November 2015 and May 2019 in the outpatient multidisciplinary clinic to investigate acute exanthematous disease. The exposed children were followed up by a multidisciplinary team and underwent periodic measurements of the HC. The Denver II test was applied, in addition to transfontanellar ultrasound (TU) to evaluate neurodevelopmental outcomes during the study period. Ophthalmological and auditory examinations, echocardiography and laboratory tests were also included. We included in the study 27 children vertically exposed to CHIKV. All children had a negative polymerase chain reaction test for the virus collected at the first outpatient visit (mean age of 16.8 days and standard deviation of 8 days). No clinical condition compatible with congenital infection at birth was reported. A change in HC characterized by macrocephaly and mild global delay development was observed in a 1-year-old child whose mother was infected in the peripartum, but with normal TU. Changes in the TU were observed in 2 other children with nonspecific subependymal cystic malformation that was not evident by the cranial computed tomography. The other children monitored showed normal results in the Denver II test, in the HC and TU. No changes were identified on ocular ophthalmoscopy or auditory brainstem response test. Two children had an increase in serum ferritin levels during the first year of life, with the others' inflammatory disease markers normal. Our study added knowledge about the neurodevelopment of children exposed to CHIKV during pregnancy by a longitudinal and prospective follow-up, throughout their first 24 months of life. We did not observe a negative impact of exposure to the virus on the neurological examination, global developmental test or measurements of the HC of these children.

Parenting stress in infancy was associated with neurodevelopment in 24-month-old children with congenital heart disease.

Having a child with congenital heart disease (CHD) is stressful for parents, but research on the impact this stress can have on child development has been lacking. We investigated the associations between parenting stress when children were infants and neurodevelopmental outcomes in toddlers with CHD. This study was carried out at the Neurocardiac Clinic at the Sainte-Justine University Hospital in Montréal, Canada. Patients born from 2012 to 2019 and followed up to 24 months of age were recruited. Parenting stress levels were measured when the child was 4-6 months and 24 months and the child's neurodevelopment was assessed at 24 months. Multiple linear regressions analyses were carried out. We studied 100 children (56% boys) with CHD. Most of the parenting stress scores were below the clinical threshold. However, they accounted for a significant part of the variance in the children's cognitive (15%-16%), receptive language (14%-15%) and gross motor outcomes (15%-18%). They had no impact on the children's expressive language or fine motor outcomes. Higher parenting stress was associated with poorer neurodevelopmental outcomes in toddlers with CHD. Early screening of parenting stress in CHD clinics is necessary to provide individualised intervention for parents and optimise neurodevelopmental outcomes in children.