Neurodevelopmental Outcomes In Children Research Articles

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.

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.

Maternal preconception and prenatal stressful life events in association with child neurodevelopmental outcome in MARBLES: A high familial likelihood cohort

BackgroundPrenatal stressful life events (SLEs) have been inconsistently associated with autism spectrum disorder (ASD). Mothers who are already raising a child with ASD could experience compounding effects of prenatal SLEs. This study prospectively examined prenatal SLEs in association with child neurodevelopmental outcomes in a high familial likelihood cohort. MethodsParticipants were 317 mother-child pairs from the Markers of Autism Risk in Babies: Learning Early Signs (MARBLES) Study, where pregnant women have previously had at least one other child with ASD. Mothers were interviewed during and at the end of pregnancy about whether they had experienced any of 7 SLE categories relating to finance, marriage, death, and more.Child neurodevelopment at three years old was classified as typically developing (TD), Non-TD, or ASD using an algorithm applied to Autism Diagnostic Observation Schedule (ADOS) and the Mullen Scales of Early Learning (MSEL) scores. Relative risk ratios (RRR) with TD as the reference outcome were estimated using multinomial logistic regression. ResultsExperiencing legal problems was significantly associated with an increased relative risk of child Non-TD (RRR 3.75; 95% CI: 1.15, 12.22). However, this finding was based on a small sample size (n = 6) and should be interpreted with caution. All other associations with Non-TD and ASD were non-significant. ConclusionsFindings agree with previous literature suggesting prenatal SLEs might not increase likelihood for ASD and most were not associated with Non-TD. Future studies measuring perceived stress or stress biomarkers are warranted to further understand the true association of prenatal stress and likelihood of ASD.

Programming the next generation of prenatal programming of stress research: A review and suggestions for the future of the field.

In this article, I highlight core ideas, empirical findings, and advances in the study of how stress during pregnancy may prenatally program child neurodevelopmental, psychopathological, and health outcomes, emphasizing reviews, metanalyses, and recent contributions of conceptual and empirical work. The article offers a perspective on the history of this area of science, the underrecognized contributions of influential scholars from diverse fields of study, what we know from the evidence to date, the persistent challenges in sorting through what is left to learn, and suggestions for future research. I include sections focused on promoting resilience, pregnancy interventions that demonstrate positive effects across two generations, and the translational implications of the accruing data for practice and policy, highlighting opportunities for integrating across a range of fields and sectors. In the concluding sections, I discuss lessons learned from conducting this work and provide a closing summary of progress and future directions. The goal of this writing was to provide a viewpoint on some ways that emerging intergenerational transmission scholars might responsibly contribute to the future of the field of developmental psychopathology.

Understanding the multidimensional neurodevelopmental outcomes in children after congenital Zika virus exposure.

Since 2016, international research groups have focused on assessing outcomes of children with in utero Zika virus (ZIKV) exposure. While the more severe outcomes of congenital Zika syndrome (CZS) occur in up to 10% of children with antenatal exposure, early findings among ZIKV-exposed children without CZS ages 0-5 years suggest that they may also have differences in multiple domains of neurodevelopment. Thus, longitudinal follow-up of all children with antenatal ZIKV exposure has been recommended. This review presents a summary of neurodevelopmental phenotypes of infants and children following antenatal ZIKV exposure. We present a multidimensional framework to understand child neurodevelopment from an interdisciplinary and whole-child perspective (International Classification of Functioning, Disability and Health model) and multi-domain ZIKV Outcome Toolboxes. The toolboxes are for clinicians, researchers, child educators, and others to implement longitudinal multi-domain neurodevelopmental assessments between ages 0-12 years. Recent innovations in telehealth and neuroimaging can help evaluate outcomes in ZIKV exposed children. The objective is to describe the multiple facets of neurodevelopmental focused care that can support the health, function, and well-being of children with antenatal ZIKV exposure. The research and clinical follow-up strategies are applicable to ZIKV and other congenital infectious or environmental exposures that can impact child neurodevelopment. IMPACT: International longitudinal cohort studies have revealed a range of differences in neurodevelopment among children with antenatal Zika virus (ZIKV) exposure. A multidimensional and whole-child framework is necessary to understand the neurodevelopment of children with antenatal ZIKV exposure in relation to family life, community participation, and environment. Multi-domain toolboxes that utilize parent questionnaires and child evaluations are presented. These toolboxes can be used internationally alongside telehealth, brain imaging, and other innovations to improve understanding of child outcomes.

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.

Comparing Neurodevelopmental Outcomes in Infants With Patent Ductus Arteriosus Stenting Versus Blalock-Taussig-Thomas Shunt: A Pilot Study

BackgroundPatent ductus arteriosus stenting (PDAS) is a nonsurgical alternative to Blalock-Taussig-Thomas shunt (BTTS) for infants with ductal-dependent congenital heart disease. In this single-center study, we aimed to compare neurodevelopmental outcomes in children who underwent BTTS as initial palliation versus PDAS. MethodsBayley Scales of Infant and Toddler Development Screening Test (Bayley-III) reports and mode of feeding data were collected for any patient who underwent PDAS or BTTS at Rady Children’s Hospital from 2013 to 2021. We also prospectively administered the Parents’ Evaluation of Development Status questionnaire (PEDS) to parents of children aged 2-8 years in this patient population. ResultsOf the 99 patients, 64 received a Bayley-III assessment and/or PEDS screen. Of the 35 who had a Bayley-III, there was a higher proportion of patients with PDAS who scored as developmentally appropriate compared with BTTS. PEDS screen showed that a higher proportion of patients with PDAS had no parental concern for delay than that of patients with BTTS (63% vs 30%). Patients with BTTS were more likely to undergo gastrostomy tube placement than patients with PDAS. ConclusionsOur study suggests that neurodevelopmental measures are feasible, clinically relevant, and should be included in comparative effectiveness studies of infant congenital interventions. Whether PDAS offers neurodevelopmental benefit over BTTS should be confirmed in a prospective powered randomized controlled clinical trial.

Neurodevelopmental Outcomes for Individuals With Congenital Heart Disease: Updates in Neuroprotection, Risk-Stratification, Evaluation, and Management: A Scientific Statement From the American Heart Association.

Over the past decade, new research has advanced scientific knowledge of neurodevelopmental trajectories, factors that increase neurodevelopmental risk, and neuroprotective strategies for individuals with congenital heart disease. In addition, best practices for evaluation and management of developmental delays and disorders in this high-risk patient population have been formulated based on literature review and expert consensus. This American Heart Association scientific statement serves as an update to the 2012 statement on the evaluation and management of neurodevelopmental outcomes in children with congenital heart disease. It includes revised risk categories for developmental delay or disorder and an updated list of factors that increase neurodevelopmental risk in individuals with congenital heart disease according to current evidence, including genetic predisposition, fetal and perinatal factors, surgical and perioperative factors, socioeconomic disadvantage, and parental psychological distress. It also includes an updated algorithm for referral, evaluation, and management of individuals at high risk. Risk stratification of individuals with congenital heart disease with the updated categories and risk factors will identify a large and growing population of survivors at high risk for developmental delay or disorder and associated impacts across the life span. Critical next steps must include efforts to prevent and mitigate developmental delays and disorders. The goal of this scientific statement is to inform health care professionals caring for patients with congenital heart disease and other key stakeholders about the current state of knowledge of neurodevelopmental outcomes for individuals with congenital heart disease and best practices for neuroprotection, risk stratification, evaluation, and management.

Identifying critical windows of prenatal phenol, paraben, and pesticide exposure and child neurodevelopment: Findings from a prospective cohort study

BackgroundThis study aimed to investigate how exposure to a mixture of endocrine disrupting chemicals (EDCs) during two points in pregnancy affects early childhood neurodevelopment. MethodsWe analyzed publicly-available data from a high-risk cohort of mothers and their children (2007–2014) that measured six EDCs including methyl-, ethyl- and propyl parabens (MEPB, ETPB, PRPB), Bisphenol-A (BPA), 3,5,6-trichloro-2-pyridinol (TCPy), 3-phenoxybenzoic acid (3-PBA) in prenatal urine samples during the second and third trimesters. Neurodevelopmental scores were assessed using Mullen Scales of Early Learning (MSEL) at age 3. We used mean field variational Bayes for lagged kernel machine regression (MFVB-LKMR) to investigate the association between trimester-specific co-exposure to the six EDCs and MSEL scores at age 3, stratified by sex. ResultsThe analysis included 130 children. For females, the relationship between BPA and 3PBA with MSEL score varied between the two trimesters. In the second trimester, effect estimates for BPA were null but inversely correlated with MSEL score in the third trimester. 3PBA had a negative relationship with MSEL in the second trimester and positive correlation in the third trimester. For males, effect estimates for all EDCs were in opposing directions across trimesters. MFVB-LKMR analysis identified significant two-way interaction between EDCs for MSEL scores in both trimesters. For example, in females, the MSEL scores associated with increased exposure to TCPy were 1.75 units (95%credible interval −0.04, −3.47) lower in the 2nd trimester and 4.61 (95%CI −3.39, −5.84) lower in the third trimester when PRPB was fixed at the 75th percentile compared to when PRPB was fixed at the 25th percentile. ConclusionOur study provides evidence that timing of EDC exposure within the prenatal period may impact neurodevelopmental outcomes in children. More of these varying effects were identified among females. Future research is needed to explore EDC mixtures and the timing of exposure during pregnancy to enhance our understanding of how these chemicals impact child health.

Neurodevelopmental outcomes of preterm and growth-restricted neonate with congenital heart defect: a systematic review and meta-analysis.

Based on a low level of evidence, prematurity and/or growth retardation appear to accentuate specific neurodevelopmental outcomes in certain CHD subgroups. Further evidence is needed to confirm these findings. PROSPERO [CRD42020201414]. • Children born with CHD, preterm birth, or growth restriction at birth are independently at higher risk for neurodevelopmental impairment. • The additional effect of preterm birth and/or growth restriction on neurodevelopmental outcomes in children with CHD remains unclear. • Prematurity and/or growth retardation appear to accentuate specific neurodevelopmental outcomes in certain CHD subgroups. • Children with CHD, particularly those born preterm or with growth restriction, should undergo lifelong systematic comprehensive neurodevelopmental assessment.

Neurodevelopmental outcomes after prenatal exposure to lamotrigine monotherapy in women with epilepsy: a systematic review and meta-analysis

BackgroundLamotrigine has become one of the most commonly prescribed antiseizure medications (ASM) in epileptic women during pregnancy and therefore requires regular updates regarding its safety. The aim of this study was to estimate the association between in utero exposure to lamotrigine monotherapy and the occurrence of neurodevelopmental outcomes.MethodsAll comparative studies assessing the occurrence of neurodevelopmental outcomes after epilepsy-indicated lamotrigine monotherapy exposure during pregnancy were searched. First, references were identified through a snowballing approach, then, through electronic databases (Medline and Embase) from 2015 to June 2022. One investigator evaluated study eligibility and extracted data and a second independent investigator reviewed the meta-analysis (MA). A systematic review and random-effects model approach were performed using a collaborative WEB-based meta-analysis platform (metaPreg.org) with a registered protocol (osf.io/u4gva).ResultsOverall, 18 studies were included. For outcomes reported by at least 4 studies, the pooled odds ratios and 95% confidence interval obtained with the number of exposed (N1) and unexposed children (N0) included were: neurodevelopmental disorders as a whole 0.84 [0.66;1.06] (N1 = 5,271; N0 = 22,230); language disorders or delay 1.16 [0.67;2.00] (N1 = 313; N0 = 506); diagnosis or risk of ASD 0.97 [0.61;1.53] (N1 = at least 5,262; N0 = 33,313); diagnosis or risk of ADHD 1.14 [0.75;1.72] (N1 = at least 113; N0 = 11,530) and psychomotor developmental disorders or delay 2.68 [1.29–5.56] (N1 = 163; N0 = 220). The MA of cognitive outcomes included less than 4 studies and retrieved a significant association for infants exposed to lamotrigine younger than 3 years old but not in the older age groups.ConclusionPrenatal exposure to lamotrigine monotherapy is not found to be statistically associated with neurodevelopmental disorders as a whole, language disorders or delay, diagnosis or risk of ASD and diagnosis or risk of ADHD. However, the MA found an increased risk of psychomotor developmental disorders or delay and cognitive developmental delay in less than 3 years old children. Nevertheless, these findings were based exclusively on observational studies presenting biases and on a limited number of included children. More studies should assess neurodevelopmental outcomes in children prenatally exposed to lamotrigine.

Short-term neonatal and long-term neurodevelopmental outcome of children born term low birth weight

This study aimed to examine the impact of term LBW on short-term neonatal and long-term neurodevelopmental outcomes in children 5–7 years of age. This is a population-based cohort study that merged national data from the Korea National Health Insurance claims and National Health Screening Program for Infants and Children. The participants were women who gave birth at a gestational age of ≥ 37 weeks between 2013 and 2015 in the Republic of Korea, and were tracked during 2020 for the neurodevelopmental surveillance of their children. Among 830,806 women who gave birth during the study period, 31,700 (3.8%) of their babies weighed less than 2500 g. By Cox proportional hazard analysis, children aged 5–7 years who had LBW were associated with any developmental, motor developmental delay, cognitive developmental delay, autism spectrum, attention deficit hyperactivity disorders, and epileptic and febrile seizures.Children born with term LBW were more vulnerable to neurodevelopmental disorders at 5–7 years of age than those with normal and large birth weights. This study further substantiates counseling parents regarding the long-term outcomes of children being born underweight.

Antenatal diagnosis, neonatal brain volumes, and neurodevelopment in transposition of the great arteries.

To examine whether antenatal diagnosis modifies relationships between neonatal brain volumes and 18-month neurodevelopmental outcomes in children with transposition of the great arteries (TGA). In a retrospective cohort of 139 children with TGA (77 antenatally diagnosed), we obtained total brain volumes (TBVs) on pre- (n = 102) and postoperative (n = 112) magnetic resonance imaging. Eighteen-month neurodevelopmental outcomes were assessed using the Bayley Scales of Infant and Toddler Development, Third Edition. Generalized estimating equations with interaction terms were used to determine whether antenatal diagnosis modified associations between TBVs and neurodevelopmental outcomes accounting for postmenstrual age at scan, brain injury, and ventricular septal defect. Infants with postnatal diagnosis had more preoperative hypotension (35% vs 14%, p = 0.004). The interactions between antenatal diagnosis and TBVs were significantly related to cognitive (p = 0.003) outcomes. Specifically, smaller TBVs were associated with lower cognitive scores in infants diagnosed postnatally; this association was attenuated in those diagnosed antenatally. Antenatal diagnosis modifies associations between neonatal brain volume and 18-month cognitive outcome in infants with TGA. These findings suggest that antenatal diagnosis may be neuroprotective, possibly through improved preoperative clinical status. These data highlight the need to improve antenatal diagnosis rates.

648 Indications for antenatal late preterm steroids and childhood neurodevelopmental outcomes

648 Indications for antenatal late preterm steroids and childhood neurodevelopmental outcomes

19 Neonatal Hypoglycemia in Pregnancies at Risk for Late Preterm Birth: Childhood Neurodevelopmental Outcomes

19 Neonatal Hypoglycemia in Pregnancies at Risk for Late Preterm Birth: Childhood Neurodevelopmental Outcomes

Assessment of the Prognostic Factors for Abnormal Neurodevelopmental Outcomes in Children with Acute Bacterial Meningitis by Using RNDA Tool

This observational follow up study was carried in the Department of Paediatrics, Institute of Child and Mother Health (ICMH), Matuail, Dhaka, during November 2016 to December 2017, to determine the prognostic factors for assessment of the prognostic factors for abnormal neurodevelopmental outcomes in children with acute bacterial meningitis by using RNDA tool. A total of 56 children with acute bacterial meningitis of age &gt; 1month - 15 years admitted in the inpatient department were enrolled in this study. Most 34 (60.7%) of the children belonged to age &lt;12 months and male to female ratio was almost 2:1. More than half (58.9%) children admitted &gt;48hrs after onset of illness, 11(19.6%) children received previous treatment with antibiotics and most (85.7%) of the children had occurrence of seizures prior to admission. More than one third (39.3%) children had &gt;100 cell count in their CSF. CSF glucose/ serum glucose ratio was found &lt;0.2 in case of 8(14.3%) children. More than three fourth (78.6%) children had high protein in their CSF. Abnormal developmental outcome assessed by RNDA on follow ups. It was observed that gross motor development was mildly impaired in 6(12.0%), 8(16.3%) and 5 (11.6%) cases on 1st, 2nd and 3rd follow up respectively. Gross motor was moderately impaired in 4 (8.0%), 3 (6.1%) and 3 (7.0%) cases on 1st, 2nd and 3rd follow up respectively. Accordingly, fine motor was mild impaired in 5 (10.0%), 4 (8.2%) and 5 (11.6%) cases and moderately impaired in 2 (4.0%), 3 (6.1%) and 2 (4.7%) cases on 1st, 2nd and 3rd follow up respectively. Cognition was mild impaired in 11 (22.0%), 12 (24.5%) and 11 (25.6%) cases and moderately impaired in 4 (8.0%), 4 (8.2%) and 3 (7.0%) cases on 1st, 2nd and 3rd follow up respectively. Children found with any selective neurological complication or abnormal developmental outcome in at least one follow up was considered to be abnormal. Hypertonic muscle tone and exaggerated jerk was found in 2(3.8%) children. 5(9.6%) children had developmental regression on follow up. 3(5.8%) children had squint, 2 (3.8%) children had subdural effusion, 2 (3.8%) children had visual deficit, 6 (11.5%) children had hearing deficit and 4 (7.7%) children had afebrile seizures on follow up. One (11.1%) child with focal seizure and 6 (60.0%) children with hazy CSF colour had significantly (p&lt;0.05) developed abnormal developmental outcome. Children under 12 months of age, children who received previous treatment with antibiotics, seizures prior to admission, high WBC count, hazy CSF colour and CSF glucose/ serum glucose ratio below 0.2 were significantly (p&lt;0.05) associated with acute complications during hospital stay. Children with focal seizure and children with hazy CSF colour were significantly (p&lt;0.05) associated to abnormal developmental outcome. Multivariate regression analysis showed no significant (p&gt;0.05) association between acute complications and prognostic factors. Age under 12 months in adjusted OR 0.970 with 95.0% C.I 0.943 to 0.997, CSF leukocytosis in adjusted OR 0.99 with 95.0% C.I. 0.99 to 1.00) and CSF glucose/serum glucose ratio&lt;0.2 in adjusted OR 15.23 with 95.0% C.I. 1.28 to 100.0 were significantly associated with abnormal developmental outcome in multivariate regression analysis.

Examining the relationship of acetaminophen use during pregnancy with early language development in children.

Acetaminophen is the only analgesic considered safe for use throughout pregnancy. Recent studies suggest that use during pregnancy may be associated with poorer neurodevelopmental outcomes in children, but few have examined language development. The Illinois Kids Development Study is a prospective birth cohort in east-central Illinois. Between December 2013 and March 2020, 532 newborns were enrolled and had exposure data available. Participants reported the number of times they took acetaminophen six times across pregnancy. Language data were collected at 26.5-28.5 months using the MacArthur-Bates Communicative Development Inventories (CDI; n = 298), and 36-38 months using the Speech and Language Assessment Scale (SLAS; n = 254). Taking more acetaminophen during the second or third trimester was associated with marginally smaller vocabularies and shorter utterance length (M3L) at 26.5-28.5 months. More acetaminophen use during the third trimester was also associated with increased odds of M3L scores ≤25th percentile in male children. More use during the second or third trimester was associated with lower SLAS scores at 36-38 months. Third trimester use was specifically related to lower SLAS scores in male children. Higher prenatal acetaminophen use during pregnancy may be associated with poorer early language development. Taking more acetaminophen during pregnancy, particularly during the second and third trimesters, was associated with poorer scores on measures of language development when children were 26.5-28.5 and 36-38 months of age. Only male children had lower scores in analyses stratified by child sex. To our knowledge, this is the first study that has used a standardized measure of language development to assess the potential impact of prenatal exposure to acetaminophen on language development. This study adds to the growing body of literature suggesting that the potential impact of acetaminophen use during pregnancy on fetal neurodevelopment should be carefully evaluated.

Neurodevelopmental assessment of normocephalic children born to Zika virus exposed and unexposed pregnant people.

Studies examining the association between in utero Zika virus (ZIKV) exposure and child neurodevelopmental outcomes have produced varied results. We aimed to assess neurodevelopmental outcomes among normocephalic children born from pregnant people enrolled in the Zika in Pregnancy in Honduras (ZIPH) cohort study, July-December 2016. Enrollment occurred during the first prenatal visit. Exposure was defined as prenatal ZIKV IgM and/or ZIKV RNA result at enrollment. Normocephalic children, >6 months old, were selected for longitudinal follow-up using the Bayley Scales of Infant and Toddler Development (BSID-III) and the Ages & Stages Questionnaires: Social-Emotional (ASQ:SE-2). One hundred fifty-two children were assessed; after exclusion, 60 were exposed and 72 were unexposed to ZIKV during pregnancy. Twenty children in the exposed group and 21 children in the unexposed group had a composite score <85 in any of the BSID-III domains. Although exposed children had lower cognitive and language scores, differences were not statistically significant. For ASQ:SE-2 assessment, there were not statistically significant differences between groups. This study found no statistically significant differences in the neurodevelopment of normocephalic children between in utero ZIKV exposed and unexposed. Nevertheless, long-term monitoring of children with in utero ZIKV exposure is warranted. This study found no statistically significant differences in the neurodevelopment in normocephalic children with in utero Zika virus exposure compared to unexposed children, although the exposed group showed lower cognitive and language scores that persisted after adjustment by maternal age and education and after excluding children born preterm and low birth weight from the analysis. Children with prenatal Zika virus exposure, including those normocephalic and have no evidence of abnormalities at birth, should be monitored for neurodevelopmental delays. Follow-up is important to be able to detect developmental abnormalities that might not be detected earlier in life.

Brain injury and neurodevelopmental outcomes in children undergoing surgery for congenital heart disease

ObjectivesBrain injury is commonly seen on magnetic resonance imaging in infants with complex congenital heart disease. The impact of perioperative brain injury on neurodevelopmental outcomes is not well understood. We evaluate the association of brain injury and other markers on neurodevelopmental outcomes in patients undergoing surgery for congenital heart surgery during infancy. MethodsTerm newborns with infant cardiac surgery performed between 2008 and 2019 at a single tertiary center, and both preoperative and postoperative brain magnetic resonance imaging were included. Those with underlying genetic conditions were excluded. Brain injury was characterized using an magnetic resonance imaging scoring system. Neurodevelopmental outcomes were assigned using the Pediatric Stroke Outcome Measure and Glasgow Outcome Scale Extended. Independent risk factors for poor neurodevelopmental outcomes were determined by multivariable Cox regression. ResultsA total of 122 patients were included. New or progressive postoperative brain injury was noted in 69 patients (57%). A total of 101 patients (83%) had at least 1 neurodevelopmental assessment (median age 36 months) with an early assessment (5-24 months) performed in 95 children. Multivariable Cox regression analysis of early neurodevelopmental outcomes identified new stroke on postoperative magnetic resonance imaging to be an independent predictor of poor neurodevelopmental outcome. Postoperative peak lactate was an independent predictor of poor outcome assessed by the Pediatric Stroke Outcome Measure and Glasgow Outcome Scale Extended. ConclusionsOur study reveals that evidence of new stroke on magnetic resonance imaging after infant congenital heart surgery is a predictor of poor neurodevelopmental outcomes in early childhood. Postoperative lactic acidosis is associated with poor neurodevelopmental outcome and may be a surrogate biomarker for ischemic brain injury.