Neurodevelopmental Outcomes In Children Research Articles

Exposure to endocrine disrupting chemicals including phthalates, phenols, and parabens in infancy: Associations with neurodevelopmental outcomes in the MARBLES study

BackgroundEndocrine disrupting chemicals (EDCs) are widely used compounds with the potential to affect child neurodevelopmental outcomes including autism spectrum disorders (ASD). We aimed to examine the urinary concentrations of biomarkers of EDCs, including phthalates, phenols, and parabens, and investigate whether exposure during early infancy was associated with increased risk of later ASD or other non-typical development (Non-TD) or adverse cognitive development. MethodsThis analysis included infants from the Markers of Autism Risks in Babies—Learning Early Signs (MARBLES) study, a high-risk ASD cohort (n = 148; corresponding to 188 urine samples). Thirty-two EDC biomarkers were quantified in urine among infants 3 and/or 6 months of age. Trends in EDC biomarker concentrations were calculated using least square geometric means. At 36 months of age, children were clinically classified as having ASD (n = 36), nontypical development (Non-TD; n = 18), or typical development (TD; n = 81) through a clinical evaluation. Trinomial logistic regression analysis was used to test the associations between biomarkers with ASD, or Non-TD, as compared to children with TD. In single analyte analysis, generalized estimating equations were used to investigate the association between each EDC biomarkers and longitudinal changes in cognitive development using the Mullen Scales of Early Learning (MSEL) over the four assessment time points (6, 12, 24, and 36 months of age). Additionally, quantile g-computation was used to test for a mixture effect. ResultsEDC biomarker concentrations generally decreased over the study period, except for mono-2-ethyl-5-carboxypentyl terephthalate. Overall, EDC biomarkers at 3 and/or 6 months of age were not associated with an increased risk of ASD or Non-TD, and a few showed significant inverse associations. However, when assessing longitudinal changes in MSEL scores over the four assessment time points, elevated monoethyl phthalate (MEP) was significantly associated with reduced scores in the composite score (β = −0.16, 95% CI: 0.31, −0.02) and subscales of fine motor skills (β = −0.09, 95%CI: 0.17, 0.00), and visual reception (β = −0.11, 95% CI: 0.23, 0.01). Additionally, the sum of metabolites of di (2-ethylhexyl) terephthalate (ƩDEHTP) was associated with poorer visual reception (β = −0.09, 95% CI: 0.16, −0.02), and decreased composite scores (β = −0.11, 95% CI: 0.21, −0.01). Mixtures analyses using quantile g-computation analysis did not show a significant association between mixtures of EDC biomarkers and MSEL subscales or composite scores. ConclusionThese findings highlight the potential importance of infant exposures on cognitive development. Future research can help further investigate whether early infant exposures are associated with longer-term deficits and place special attention on EDCs with increasing temporal trends and whether they may adversely affect neurodevelopment.

Possible associations between prenatal exposure to environmental pollutants and neurodevelopmental outcome in children

This study aimed to evaluate associations between prenatal and childhood exposure to phthalates and prenatal exposure to polychlorinated biphenyls (PCBs) and the development of 4-year-old children. Urinary metabolites of five phthalates were measured in women upon delivery, as well as serum concentrations of four PCB congeners. Postnatal phthalate metabolites were measured from children's urine obtained at the time of developmental assessment. The primary outcome was cognitive function as evaluated by the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III) administered at 4 years. Secondary outcomes were motor function and response to sensory stimuli as evaluated by the Developmental Coordination Disorder Questionnaire (DCDQ) and Short Sensory Profile (SSP) that the mothers filled out, respectively. The study included 57 mother-child pairs. Higher maternal phthalate metabolite concentrations were inversely associated with WPPSI-III scores among boys and not among girls. After using linear regression models and controlling for confounding variables, we found that higher levels of monobenzyl phthalate (MBzP) were the ones associated with lower WPPSI-III scores (p=0.004, 95 %CI [-14.18; −3.16]), lower DCDQ scores (p=0.007, 95 %CI [-6.08; −1.17] and lower SSP scores (p=0.004, 95 %CI [-7.47; −1.79]). No association was found between child urinary phthalate metabolite concentrations or maternal PCB blood concentrations and developmental function. These findings indicate that higher prenatal phthalate metabolite levels may be associated with deficits in neurologic development of young boys.

What are the neurodevelopmental outcomes of children with asymptomatic congenital cytomegalovirus infection at birth? A systematic literature review.

Congenital cytomegalovirus (cCMV) is among the most common congenital infections globally. Of 85%-90% cCMV-infected infants without symptoms at birth, 10%-15% develop sequelae, most commonly sensorineural hearing loss (SNHL); their childhood neurodevelopmental outcomes are less well understood. Embase and MEDLINE were searched for publications from 16th September 2016 to 9th February 2024 to identify studies reporting primary data on neurodevelopmental outcomes in children with asymptomatic cCMV (AcCMV), measured using assessment tools or as evaluated by the study investigators, clinicians, educators, or parents. The Newcastle-Ottawa scale was applied to studies to assess risk of bias. Of 28 studies from 18 mostly high-income countries, there were 5-109 children with AcCMV per study and 6/28 had a mean or median age at last follow-up of ≥5years. Children with AcCMV had better neurodevelopmental outcomes than children with symptomatic cCMV in 16/19 studies. Of 9/28 studies comparing AcCMV with CMV-uninfected children, six reported similar outcomes whilst three reported differences limited to measures of full-scale intelligence and receptive vocabulary among children with AcCMV and SNHL, or more generally in motor impairment. Common limitations of studies for our question were a lack of cCMV-uninfected controls, heterogeneous definitions of AcCMV, lack of focus on neurodevelopment, selection bias and inadequate follow-up. There was little evidence of children with AcCMV having worse neurodevelopmental outcomes than CMV-uninfected children, but this conclusion is limited by study characteristics and quality; findings highlight the need for well-designed and standardised approaches to investigate long-term sequelae.

Minor/Major Congenital Malformations and Neurodevelopmental Outcomes in Children Prenatally Exposed to Levetiracetam, Lamotrigine, and Carbamazepine Monotherapy.

The relationship of older antiseizure drugs with congenital malformations has been known for many years. Studies are mostly limited to major malformations and few studies have investigated minor malformations. In recent years, the long-term cognitive and behavioral effects of these drugs have also come to the fore. The aim of our study was to evaluate the incidence of major and minor congenital malformations and neurodevelopmental outcomes in children prenatally exposed to levetiracetam (LEV), lamotrigine (LTG), and carbamazepine (CBZ) monotherapy. This was a prospective observational study conducted in two university hospital epilepsy centers. It included 32 pregnant women who were continuously treated with LEV, LTG, or CBZ from conception throughout pregnancy. Children were followed up from birth until 18 months. Neurodevelopmental outcomes were evaluated with the Ages and Stages Questionnaire and Denver Developmental Screening Test. Eighteen of the patients were on LEV, 10 were on LTG, and 4 were on CBZ. Diaphragmatic hernia was detected in a child. At least one minor anomaly was observed in 58.1% of the patients. More than 80% of children were normal in the Ages and Stages Questionnaire. The risk of major congenital malformations is lower with newer antiseizure drugs. We found a high incidence of minor ones. However, because the population prevalence of minor malformations is also variable, more studies are needed to confirm the results. Neurodevelopmental outcomes were favorable with LTG and LEV and slightly unfavorable with CBZ. Longer-term follow-up with large groups of children is required to reach more reliable results.

Maternal Uterine Artery Adenoviral Vascular Endothelial Growth Factor (Ad.VEGF-A165) Gene Therapy Normalises Fetal Brain Growth and Microglial Activation in Nutrient Restricted Pregnant Guinea Pigs.

Fetal growth restriction (FGR) is associated with uteroplacental insufficiency, and neurodevelopmental and structural brain deficits in the infant. It is currently untreatable. We hypothesised that treating the maternal uterine artery with vascular endothelial growth factor adenoviral gene therapy (Ad.VEGF-A165) normalises offspring brain weight and prevents brain injury in a guinea pig model of FGR. Pregnant guinea pigs were fed a restricted diet before and after conception and received Ad.VEGF-A165 (1 × 1010 viral particles, n = 18) or vehicle (n = 18), delivered to the external surface of the uterine arteries, in mid-pregnancy. Pregnant, ad libitum-fed controls received vehicle only (n = 10). Offspring brain weight and histological indices of brain injury were assessed at term and 5-months postnatally. At term, maternal nutrient restriction reduced fetal brain weight and increased microglial ramification in all brain regions but did not alter indices of cell death, astrogliosis or myelination. Ad.VEGF-A165 increased brain weight and reduced microglial ramification in fetuses of nutrient restricted dams. In adult offspring, maternal nutrient restriction did not alter brain weight or markers of brain injury, whilst Ad.VEGF-A165 increased microglial ramification and astrogliosis in the hippocampus and thalamus, respectively. Ad.VEGF-A165 did not affect cell death or myelination in the fetal or offspring brain. Ad.VEGF-A165 normalises brain growth and markers of brain injury in guinea pig fetuses exposed to maternal nutrient restriction and may be a potential intervention to improve childhood neurodevelopmental outcomes in pregnancies complicated by FGR.

Choline Supplementation for Infants, Children, and Pregnant People

What Is the Issue? Choline is an essential nutrient produced by humans and animals and is important during pregnancy, fetal growth, and the development of the brain and nervous system. Most people do not get enough choline from their diet. Fetal alcohol spectrum disorders (FASD) are a set of conditions where fetuses have been exposed to alcohol and this affects memory, learning, and development from early childhood to later life. Choline supplements are products used to complement choline-deficient diets. Given the role of choline in fetal development, choline supplements are a potential intervention to support pregnancy or to mitigate the developmental harms in children from prenatal exposure to alcohol if supported by evidence of their effectiveness for these purposes. What Did We Do? To inform decisions about the use and timing of choline supplementation to support health outcomes in infants and children, CADTH sought to identify and summarize the literature about the effectiveness and safety of choline supplementation given to any pregnant people or given to children with either prenatal alcohol exposure or FASD. We also attempted to identify evidence-based recommendations for using choline supplementation in these populations. We searched key resources and conducted a focused internet search for relevant evidence published since 2014. One reviewer screened articles for inclusion based on predefined criteria, critically appraised the included studies, and narratively summarized the findings. What Did We Find? We found few publications investigating this topic, and several studies had low statistical power and imprecise results. The clinical evidence was mixed depending on whether choline was given to the pregnant person or child, which interventional groups were compared, what the clinical exposures or diagnoses were in the study population, the time point and duration of choline supplementation, which outcomes were measured, and how old children were during follow-up. For choline supplementation in healthy pregnant people, evidence was mixed for infant and child neurocognitive and neurodevelopmental outcomes or behavioural symptoms; there were little-to-no differences in safety outcomes. For choline supplementation in pregnant people exposed to alcohol, evidence was mixed for infant and child neurocognitive and neurodevelopmental outcomes, body size, and brain region sizes; some minor side effects were reported overall. For choline supplementation in children with FASD, most evidence showed little-to-no benefits for neurocognitive and neurodevelopmental outcomes, and brain structure; limited evidence showed higher fishy body odour and some other unspecified adverse symptoms for children given choline. Guidelines based mostly on low-quality evidence or expert opinion recommend that all pregnant people, including those with gestational diabetes mellitus or on vegan or vegetarian diets, increase their choline intake through diet or supplements. We did not find clinical effectiveness evidence for choline supplementation in infants with FASD, or guidelines regarding choline supplementation in either infants or children with FASD, that met inclusion criteria for our report. What Does it Mean? Health care professionals and decision-makers can use this evidence to inform decisions around applicability of choline supplementation for pregnant people, or for infants and children with FASD, in their practice. There may be a need to balance the knowledge that choline intake is low at the population level and important for fetal development with the identified clinical effectiveness evidence for choline supplementation, which was limited and mixed for all evaluated patient populations. Careful consideration of the following may also be important to inform decisions about the appropriateness of choline supplementation: the care plan and other intensive and concurrent interventions for children with FASD; stigma and challenges faced by pregnant people and children in the context of prenatal alcohol exposure; cultural dietary practices; and accessibility, cost, and availability of supplements.

Amphetamine use for attention deficit hyperactive disorder during breastfeeding and children's neurodevelopmental outcomes: A pilot study

Attention deficit hyperactive disorder (ADHD) medication use rises among women of childbearing age and during pregnancy. Little is known on the safety of amphetamine stimulants for ADHD treatment during breastfeeding. Most data on the safety of these medications are from recreational abuse of methamphetamine. This study followed children (N = 13) exposed to amphetamine stimulants during breastfeeding. Assessments by Pediatric Quality of Life and Denver Developmental Scale evaluated neurodevelopment and outcomes. Study results showed normal neurodevelopment with no significant adverse effects. Findings suggest amphetamines are likely compatible with breastfeeding; however larger studies are needed.

One-year neurodevelopmental outcome in children with asymptomatic congenital CMV infection

IntroductionInfants with congenital CMV (cCMV) infection may show manifestations at birth and develop symptomatic disease, although the majority have no apparent clinical signs and should be considered asymptomatic (acCMV). Studies about neurodevelopmental and neurological sequelae in acCMV patients during childhood are few and contradictory, thus, the purpose of this study is to evaluate the neurological and neurodevelopmental outcomes in 1-year-old children with acCMV infections. MethodThirty-five infants with acCMV infections were followed-up for 12 months and were compared to healthy children matched for age and gender. The Bayley Scales of Infant Development III (BSID-III) were administered, and neurological examinations were performed. ResultsChildren with acCMV infection showed minimal to mild neurological signs and the score obtained from the Motor Scale was significantly lower than that of the control group. No significant differences between the two groups were found regarding the Cognitive and Language Scales. DiscussionAsymptomatic congenital infection of CMV may be associated with a decrease in motor skills that may become evident during the first year of life. Close monitoring is essential to determine if rehabilitative treatment is required for children with asymptomatic congenital cytomegalovirus (acCMV). Longer follow-up is necessary to provide further details about their neurodevelopmental outcomes.

Teratogenesis, Perinatal, and Neurodevelopmental Outcomes After In Utero Exposure to Antiseizure Medication: Practice Guideline From the AAN, AES, and SMFM.

This practice guideline provides updated evidence-based conclusions and recommendations regarding the effects of antiseizure medications (ASMs) and folic acid supplementation on the prevalence of major congenital malformations (MCMs), adverse perinatal outcomes, and neurodevelopmental outcomes in children born to people with epilepsy of childbearing potential (PWECP). A multidisciplinary panel conducted a systematic review and developed practice recommendations following the process outlined in the 2017 edition of the American Academy of Neurology Clinical Practice Guideline Process Manual. The systematic review includes studies through August 2022. Recommendations are supported by structured rationales that integrate evidence from the systematic review, related evidence, principles of care, and inferences from evidence. The following are some of the major recommendations. When treating PWECP, clinicians should recommend ASMs and doses that optimize both seizure control and fetal outcomes should pregnancy occur, at the earliest possible opportunity preconceptionally. Clinicians must minimize the occurrence of convulsive seizures in PWECP during pregnancy to minimize potential risks to the birth parent and to the fetus. Once a PWECP is already pregnant, clinicians should exercise caution in attempting to remove or replace an ASM that is effective in controlling generalized tonic-clonic or focal-to-bilateral tonic-clonic seizures. Clinicians must consider using lamotrigine, levetiracetam, or oxcarbazepine in PWECP when appropriate based on the patient's epilepsy syndrome, likelihood of achieving seizure control, and comorbidities, to minimize the risk of MCMs. Clinicians must avoid the use of valproic acid in PWECP to minimize the risk of MCMs or neural tube defects (NTDs), if clinically feasible. Clinicians should avoid the use of valproic acid or topiramate in PWECP to minimize the risk of offspring being born small for gestational age, if clinically feasible. To reduce the risk of poor neurodevelopmental outcomes, including autism spectrum disorder and lower IQ, in children born to PWECP, clinicians must avoid the use of valproic acid in PWECP, if clinically feasible. Clinicians should prescribe at least 0.4 mg of folic acid supplementation daily preconceptionally and during pregnancy to any PWECP treated with an ASM to decrease the risk of NTDs and possibly improve neurodevelopmental outcomes in the offspring.

Long-Term Neurodevelopmental Outcomes in Children with Gastroschisis: A Review of the Literature.

This study aimed to investigate and present a review of the literature on long-term neurodevelopmental outcomes in children with gastroschisis. Gastroschisis is the most common abdominal wall defect. Children with gastroschisis are at high risk for premature birth, intestinal failure, sepsis, and repeated anesthesia exposure, which collectively increase the risk for adverse long-term neurodevelopmental outcomes. The existing literature on neurodevelopmental outcomes is limited in number, quality, and generalizability, creating a gap in clinical knowledge and care. Five internet databases were searched by a professional research librarian: Ovid MEDLINE, Scopus, Web of Science, PsycINFO, and Cochrane Library. Included articles were (1) published in English, (2) included postneonatal hospital discharge neurodevelopmental outcomes of children with gastroschisis, and (3) included patients under the age of 18 years. No date parameters were applied. The paucity of literature on long-term neurodevelopmental outcomes in gastroschisis children has left large gaps in the body of knowledge on post-hospital care of such children. In this review, 37 articles were found evaluating neurodevelopmental outcomes in gastroschisis and, while conclusions were contradictory, the literature broadly indicated the potential for neurodevelopmental deficits in the gastroschisis pediatric population. A significant limitation of this review was the heterogeneous samples included in available literature, which confounded the ability to determine cognitive risk of gastroschisis independent of other abdominal wall defects. Findings of this review demonstrate potential risk for neurodevelopmental deficits in the pediatric gastroschisis population exist, yet additional research is needed to definitively predict the significance, type, onset, and trajectory of neurodevelopmental impairment in this population. The significant gaps in long-term outcomes data have elucidated the need for prospective, longitudinal investigation of various cognitive domains in homogenous gastroschisis populations to properly evaluate prevalence of neurodevelopmental deficits and guide recommendations for long-term clinical care. KEY POINTS: · Limited literature exists regarding long-term neurodevelopmental outcomes in gastroschisis.. · There is some evidence to suggest worse cognitive behavioral outcomes in gastroschisis over time.. · Developmental surveillance, screening, and evaluation may be beneficial for gastroschisis patients..

Progesterone for Neurodevelopment in Fetuses With Congenital Heart Defects

Neurodevelopmental outcomes for children with congenital heart defects (CHD) have improved minimally over the past 20 years. To assess the feasibility and tolerability of maternal progesterone therapy as well as the magnitude of the effect on neurodevelopment for fetuses with CHD. This double-blinded individually randomized parallel-group clinical trial of vaginal natural progesterone therapy vs placebo in participants carrying fetuses with CHD was conducted between July 2014 and November 2021 at a quaternary care children's hospital. Participants included maternal-fetal dyads where the fetus had CHD identified before 28 weeks' gestational age and was likely to need surgery with cardiopulmonary bypass in the neonatal period. Exclusion criteria included a major genetic or extracardiac anomaly other than 22q11 deletion syndrome and known contraindication to progesterone. Statistical analysis was performed June 2022 to April 2024. Participants were 1:1 block-randomized to vaginal progesterone or placebo by diagnosis: hypoplastic left heart syndrome (HLHS), transposition of the great arteries (TGA), and other CHD diagnoses. Treatment was administered twice daily between 28 and up to 39 weeks' gestational age. The primary outcome was the motor score of the Bayley Scales of Infant and Toddler Development-III; secondary outcomes included language and cognitive scales. Exploratory prespecified subgroups included cardiac diagnosis, fetal sex, genetic profile, and maternal fetal environment. The 102 enrolled fetuses primarily had HLHS (n = 52 [50.9%]) and TGA (n = 38 [37.3%]), were more frequently male (n = 67 [65.7%]), and without genetic anomalies (n = 61 [59.8%]). The mean motor score differed by 2.5 units (90% CI, -1.9 to 6.9 units; P = .34) for progesterone compared with placebo, a value not statistically different from 0. Exploratory subgroup analyses suggested treatment heterogeneity for the motor score for cardiac diagnosis (P for interaction = .03) and fetal sex (P for interaction = .04), but not genetic profile (P for interaction = .16) or maternal-fetal environment (P for interaction = .70). In this randomized clinical trial of maternal progesterone therapy, the overall effect was not statistically different from 0. Subgroup analyses suggest heterogeneity of the response to progesterone among CHD diagnosis and fetal sex. ClinicalTrials.gov Identifier: NCT02133573.

Intrapartum exposure to synthetic oxytocin, maternal BMI, and neurodevelopmental outcomes in children within the ECHO consortium

BackgroundSynthetic oxytocin (sOT) is frequently administered during parturition. Studies have raised concerns that fetal exposure to sOT may be associated with altered brain development and risk of neurodevelopmental disorders. In a large and diverse sample of children with data about intrapartum sOT exposure and subsequent diagnoses of two prevalent neurodevelopmental disorders, i.e., attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD), we tested the following hypotheses: (1) Intrapartum sOT exposure is associated with increased odds of child ADHD or ASD; (2) associations differ across sex; (3) associations between intrapartum sOT exposure and ADHD or ASD are accentuated in offspring of mothers with pre-pregnancy obesity.MethodsThe study sample comprised 12,503 participants from 44 cohort sites included in the Environmental Influences on Child Health Outcomes (ECHO) consortium. Mixed-effects logistic regression analyses were used to estimate the association between intrapartum sOT exposure and offspring ADHD or ASD (in separate models). Maternal obesity (pre-pregnancy BMI ≥ 30 kg/m2) and child sex were evaluated for effect modification.ResultsIntrapartum sOT exposure was present in 48% of participants. sOT exposure was not associated with increased odds of ASD (adjusted odds ratio [aOR] 0.86; 95% confidence interval [CI], 0.71–1.03) or ADHD (aOR 0.89; 95% CI, 0.76–1.04). Associations did not differ by child sex. Among mothers with pre-pregnancy obesity, sOT exposure was associated with lower odds of offspring ADHD (aOR 0.72; 95% CI, 0.55–0.96). No association was found among mothers without obesity (aOR 0.97; 95% CI, 0.80–1.18).ConclusionsIn a large, diverse sample, we found no evidence of an association between intrapartum exposure to sOT and odds of ADHD or ASD in either male or female offspring. Contrary to our hypothesis, among mothers with pre-pregnancy obesity, sOT exposure was associated with lower odds of child ADHD diagnosis.

Neurodevelopmental delay in children exposed to maternal SARS-CoV-2 in-utero

It is unclear if SARS CoV-2 infection during pregnancy is associated with adverse neurodevelopmental repercussions to infants. We assessed pediatric neurodevelopmental outcomes in children born to mothers with laboratory-confirmed SARS CoV-2 infection during pregnancy. Neurodevelopmental outcomes of in-utero exposed children were compared to that of pre-pandemic control children in Los Angeles (LA), CA, USA and Rio de Janeiro, Brazil. Bayley Scales of Infant and Toddler Development, 3rd edition (Bayley-III), the gold standard tool for evaluating neurodevelopment until 36 months of age and Ages and Stages Questionnaires (ASQ-3), a frequently used screening instrument for evaluating neurodevelopment in this same age group were the assessment tools used. Developmental delay (DD) was defined as having a score < − 2 SD below the norm (< 70) in at least one of three Bayley-III domains, (cognitive, motor or language) or a score below the cut-off (dark zone) in at least one of five ASQ-3 domains (communication, gross motor, fine motor, problem solving, personal-social). Exposed children were born between April 2020 and December 2022 while control children were born between January 2016 to December 2019. Neurodevelopmental testing was performed in 300 children total: 172 COVID-19 exposed children between 5–30 months of age and 128 control children between 6–38 months of age. Bayley-III results demonstrated that 12 of 128 exposed children (9.4%) had DD versus 2 of 128 controls (1.6%), p = 0.0007. Eight of 44 additional exposed children had DD on ASQ-3 testing. Fully, 20 of 172 exposed children (11.6%) and 2 of 128 control children (1.6%), p = 0.0006 had DD. In Rio, 12% of exposed children versus 2.6% of controls, p = 0.02 had DD. In LA, 5.7% of exposed children versus 0 controls, p = 0.12 had DD. Severe/critical maternal COVID-19 predicted below average neurodevelopment in the exposed cohort (OR 2.6, 95% CI 1.1–6.4). Children exposed to antenatal COVID-19 have a tenfold higher frequency of DD as compared to controls and should be offered neurodevelopmental follow-up.

Postnatal Brain Trajectories and Maternal Intelligence Predict Childhood Outcomes in Complex CHD.

Objective: To determine whether early structural brain trajectories predict early childhood neurodevelopmental deficits in complex CHD patients and to assess relative cumulative risk profiles of clinical, genetic, and demographic risk factors across early development. Study Design: Term neonates with complex CHDs were recruited at Texas Children's Hospital from 2005-2011. Ninety-five participants underwent three structural MRI scans and three neurodevelopmental assessments. Brain region volumes and white matter tract fractional anisotropy and radial diffusivity were used to calculate trajectories: perioperative, postsurgical, and overall. Gross cognitive, language, and visuo-motor outcomes were assessed with the Bayley Scales of Infant and Toddler Development and with the Wechsler Preschool and Primary Scale of Intelligence and Beery-Buktenica Developmental Test of Visual-Motor Integration. Multi-variable models incorporated risk factors. Results: Reduced overall period volumetric trajectories predicted poor language outcomes: brainstem ((β, 95% CI) 0.0977, 0.0382-0.1571; p = 0.0022) and white matter (0.0023, 0.0001-0.0046; p = 0.0397) at 5 years; brainstem (0.0711, 0.0157-0.1265; p = 0.0134) and deep grey matter (0.0085, 0.0011-0.0160; p = 0.0258) at 3 years. Maternal IQ was the strongest contributor to language variance, increasing from 37% at 1 year, 62% at 3 years, and 81% at 5 years. Genetic abnormality's contribution to variance decreased from 41% at 1 year to 25% at 3 years and was insignificant at 5 years. Conclusion: Reduced postnatal subcortical-cerebral white matter trajectories predicted poor early childhood neurodevelopmental outcomes, despite high contribution of maternal IQ. Maternal IQ was cumulative over time, exceeding the influence of known cardiac and genetic factors in complex CHD, underscoring the importance of heritable and parent-based environmental factors.

Prenatal Vitamin B12 and Children's Brain Development and Cognitive, Language and Motor Outcomes: A Scoping Review.

Adequate maternal nutrient intake of vitamin B12 is critical to fetal brain development and subsequent neurodevelopmental outcomes. We conducted a scoping review to map the current state of knowledge from human epidemiological studies on the associations between maternal vitamin B12 during pregnancy and children's brain, cognitive, language, and motor development to identify gaps in the literature and suggest directions for future research. PubMed and OVID MEDLINE were searched. Search terms were vitamin B12, prenatal or maternal, neurodevelopment or cognitive development or brain. Animal studies were excluded. In total, 148 publications were identified, of which 19 met our inclusion criteria: (1) maternal vitamin B12 assessed via a measure of status, dietary intake, supplementation, or deficiency; and (2) an outcome related to brain development or cognitive, language, or motor development in children less than 18 years of age was assessed. This scoping review suggests that evidence supporting a relationship between maternal vitamin B12 during pregnancy and children's neurodevelopmental outcomes is inconclusive. Further longitudinal research is needed to clarify the effects of maternal vitamin B12 supplementation, status, and intake on children's brain development and neurodevelopmental outcomes.

Neurodevelopmental Outcomes After Late Preterm Antenatal Corticosteroids

The Antenatal Late Preterm Steroids (ALPS) trial changed clinical practice in the United States by finding that antenatal betamethasone at 34 to 36 weeks decreased short-term neonatal respiratory morbidity. However, the trial also found increased risk of neonatal hypoglycemia after betamethasone. This follow-up study focused on long-term neurodevelopmental outcomes after late preterm steroids. To evaluate whether administration of late preterm (34-36 completed weeks) corticosteroids affected childhood neurodevelopmental outcomes. Prospective follow-up study of children aged 6 years or older whose birthing parent had enrolled in the multicenter randomized clinical trial, conducted at 13 centers that participated in the Maternal-Fetal Medicine Units (MFMU) Network cycle from 2011-2016. Follow-up was from 2017-2022. Twelve milligrams of intramuscular betamethasone administered twice 24 hours apart. The primary outcome of this follow-up study was a General Conceptual Ability score less than 85 (-1 SD) on the Differential Ability Scales, 2nd Edition (DAS-II). Secondary outcomes included the Gross Motor Function Classification System level and Social Responsiveness Scale and Child Behavior Checklist scores. Multivariable analyses adjusted for prespecified variables known to be associated with the primary outcome. Sensitivity analyses used inverse probability weighting and also modeled the outcome for those lost to follow-up. Of 2831 children, 1026 enrolled and 949 (479 betamethasone, 470 placebo) completed the DAS-II at a median age of 7 years (IQR, 6.6-7.6 years). Maternal, neonatal, and childhood characteristics were similar between groups except that neonatal hypoglycemia was more common in the betamethasone group. There were no differences in the primary outcome, a general conceptual ability score less than 85, which occurred in 82 (17.1%) of the betamethasone vs 87 (18.5%) of the placebo group (adjusted relative risk, 0.94; 95% CI, 0.73-1.22). No differences in secondary outcomes were observed. Sensitivity analyses using inverse probability weighting or assigning outcomes to children lost to follow-up also found no differences between groups. In this follow-up study of a randomized clinical trial, administration of antenatal corticosteroids to persons at risk of late preterm delivery, originally shown to improve short-term neonatal respiratory outcomes but with an increased rate of hypoglycemia, was not associated with adverse childhood neurodevelopmental outcomes at age 6 years or older.

Role of one-carbon nutrient intake and diabetes during pregnancy in children's growth and neurodevelopment: A 2-year follow-up study of a prospective cohort

Background & AimsBoth maternal metabolic dysregulation, e.g., gestational diabetes mellitus (GDM), and maternal supply of nutrients that participate in one-carbon (1C) metabolism, e.g., folate, choline, betaine, and vitamin B12, have been demonstrated to influence epigenetic modification such as DNA methylation, thereby exerting long-lasting impacts on growth and development of offspring. This study aimed to determine how maternal 1C nutrient intake was associated with DNA methylation and further, development of children, as well as whether maternal GDM status modified the association in a prospective cohort. MethodsIn this study, women with (n = 18) and without (n = 20) GDM were recruited at 25-33 weeks gestation. Detailed dietary intake data was collected by 3-day 24-hour dietary recall and nutrient levels in maternal blood were also assessed at enrollment. The maternal-child dyads were invited to participate in a 2-year follow-up during which anthropometric measurement and the Bayley Scales of Infant and Toddler Development™ Screening Test (Third Edition) were conducted on children. The association between maternal 1C nutrients and children’s developmental outcomes was analyzed with a generalized linear model controlling for maternal GDM status. ResultsWe found that children born to mothers with GDM had lower scores in the language domain of the Bayley test (p = 0.049). Higher maternal food folate and choline intakes were associated with better language scores in children (p = 0.01 and 0.025, respectively). Higher maternal food folate intakes were also associated with better cognitive scores in children (p = 0.002). Higher 1C nutrient intakes during pregnancy were associated with lower body weight of children at 2 years of age (p < 0.05). However, global DNA methylation of children’s buccal cells was not associated with any maternal 1C nutrients. ConclusionsIn conclusion, higher 1C nutrient intake during pregnancy was associated with lower body weight and better neurodevelopmental outcomes of children. This may help overcome the lower language scores seen in GDM-affected children in this cohort. Studies in larger cohorts and with a longer follow-up duration are needed to further delineate the relationship between prenatal 1C nutrient exposure, especially in GDM-affected pregnancies, and offspring health outcomes.

Neurodevelopmental Outcome of Children with Phenylketonuria after Early Neonatal Screening

Neurodevelopmental Outcome of Children with Phenylketonuria after Early Neonatal Screening

Neurodevelopmental outcomes in children conceived by assisted reproductive treatment

IntroductionImpact of assisted reproductive treatment (ART) techniques on the child’s mental development is the focus of numerous studies. Whereas several studies have found potential negative effects on ART children’s psychosocial health, others recognized that the data on the cognitive and psychosocial development of ART children are comforting.ObjectivesHere, we aim to state the current findings concerning psychological outcomes in children conceived by ART.MethodsUsing as key words “assisted reproductive” and as filter “meta-analysis”, we comprehensively reviewed the scientific literature through new meta-analysis during the five last-years resuming the main conclusions of these studies to define principal through psychological conditions in children conceived by diverse ART techniques and approaches.Results Our review showed that since 1978, the date of the first birth using in vitro fertilization technology (IVF), more than 10 million children are conceived by ART. Our research revealed 441 meta-analysis. After a comprehensive analysis of abstracts, only four meta-analysis were selected. Chronologically from 2019 to 2023, the first studies showed that the risk of intellectual disability and autism spectrum diseases (ASD) were higher in intra-cytoplasmic sperm injection (ICSI) children compared to conventional IVF children. The differences in the risk of neurodevelopmental disorders in children born after frozen and fresh embryo transfers were not significant. Analysis of potential cofounder effects such as multiple and preterm birth having a significant correlation with neurodevelopmental disorders suggested that ART is unlikely to cause negative impacts on children’s neurodevelopment. The findings of the most recent meta-analysis showed that the use of ART did not associate with the risk of ASD,ConclusionsGiven the multitude of factors modulating ART, from the indication and parental background to the type of used technique and approach, the results of the studies that investigated the association between ART and neurodevelopmental outcomes remain yet contradictory.Disclosure of InterestNone Declared

Neurodevelopmental Outcomes in Children After Fetoscopic Endoluminal Tracheal Occlusion for Severe Congenital Diaphragmatic Hernia: Results From a Multidisciplinary Clinic

BackgroundWe compared early neurodevelopmental morbidity in young children with severe CDH who underwent FETO to those without fetal therapy. MethodsWe conducted a prospective study of severe CDH patients undergoing FETO (n = 18) at a single North American center from 2015 to 2021 (NCT02710968). Outpatient survivors (n = 12) were evaluated by a multidisciplinary team and compared to expectantly managed CDH patients. Neurodevelopmental outcomes were assessed using the Capute Scales [Clinical Linguistic and Auditory Milestone Scales (CLAMS) and Cognitive Adaptive Test (CAT)], with a developmental quotient (DQ) < 85 indicative of at-risk for delay. ResultsAt one year, 58% (n = 7) of FETO patients underwent evaluation, with notable concern for language delay (CLAMS median DQ, 80.1 [interquartile range, 67.6–86.7]). FETO scores improved by 24-months, whereas high severity/non-FETO scores declined [CLAMS median DQ (Difference in DQ), 92.3 (+12.2) vs. 77.1 (−13.4), respectively; p = 0.049]. On the initial CAT, FETO patients had concern for visual motor and problem-solving delays, with a median DQ of 81.3 (62.1–89.4). At 24-months, FETO patients had improving scores [Median CAT DQ, 90.8 (+9.5)], whereas high severity/non-FETO [87.5 (−3.0), p = 0.28] had declining scores. ConclusionThese initial data suggest that FETO is associated with favorable neurodevelopmental outcomes at 24-months compared to severe CDH under expectant management. Level of EvidenceIII.