Early Childhood Neurodevelopment Research Articles

A Systematic Review of Neurodevelopmental Assessments in Infancy and Early Childhood: Developing a Conceptual Framework, Repository of Measures, and Clinical Recommendations.

The first 6 years of lifeare when 90% of brain development occurs, setting the foundation for lifelong neurodevelopment. The field of infant and early childhood neurodevelopment has made marginal advancements since introduced in 1988. There remains a gap in knowledge around early neurodevelopmental domains and trajectories given that there are few established assessment procedures for infants and young children and controversies around reserving assessments until school age. Throughout this systematic review, we (1) identified neurodevelopmental assessment measures employed in the literature by domain and age of assessment, (2) compiled a repository of 608 domain-specific neurodevelopmental assessment measures, and (3) established a preliminary conceptual framework for cross-domain neurodevelopmental assessments across infancy and early childhood. This review adhered to PRISMA guidelines and spanned three databases (PsycINFO, MEDLINE, PubMed). Articles were reviewed for (1) infancy and early childhood (0-6 years), (2) neurodevelopmental measures, and (3) English language. This systematic review spanned 795 articles from 1978 to 2020 with international representation. Advancements in assessment methods (e.g. measures, domains, frameworks) are essential for the evaluation of early neurodevelopmental profiles to inform early interventions, thus harnessing the neuroplasticity and dynamic development notable during early childhood. We hope this work catalyzes future research and clinical guidelines around early assessments methods.

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.

Neonatal brain dynamic functional connectivity in term and preterm infants and its association with early childhood neurodevelopment

Brain dynamic functional connectivity characterises transient connections between brain regions. Features of brain dynamics have been linked to emotion and cognition in adult individuals, and atypical patterns have been associated with neurodevelopmental conditions such as autism. Although reliable functional brain networks have been consistently identified in neonates, little is known about the early development of dynamic functional connectivity. In this study we characterise dynamic functional connectivity with functional magnetic resonance imaging (fMRI) in the first few weeks of postnatal life in term-born (n = 324) and preterm-born (n = 66) individuals. We show that a dynamic landscape of brain connectivity is already established by the time of birth in the human brain, characterised by six transient states of neonatal functional connectivity with changing dynamics through the neonatal period. The pattern of dynamic connectivity is atypical in preterm-born infants, and associated with atypical social, sensory, and repetitive behaviours measured by the Quantitative Checklist for Autism in Toddlers (Q-CHAT) scores at 18 months of age.

Associations of polymetabolic risk of high maternal pre-pregnancy body mass index with pregnancy complications, birth outcomes, and early childhood neurodevelopment: findings from two pregnancy cohorts

BackgroundA substantial proportion of maternal pregnancy complications, adverse birth outcomes and neurodevelopmental delay in children may be attributable to high maternal pre-pregnancy Body Mass Index (BMI). However, BMI alone is insufficient for the identification of all at-risk mothers and children as many women with non-obesity(< 30 kg/m2) or normal weight(18.5–24.99 kg/m2) and their children may suffer from adversities. Evidence suggests that BMI-related metabolic changes during pregnancy may predict adverse mother–child outcomes better than maternal anthropometric BMI.MethodsIn a cohort of 425 mother–child dyads, we identified maternal BMI-defined metabolome based on associations of 95 metabolic measures measured three times during pregnancy with maternal pre-pregnancy BMI. We then examined whether maternal BMI-defined metabolome performed better than anthropometric BMI in predicting gestational diabetes, hypertensive disorders, gestational weight gain (GWG), Caesarian section delivery, child gestational age and weight at birth, preterm birth, admission to neonatal intensive care unit (NICU), and childhood neurodevelopment. Based on metabolic measures with the highest contributions to BMI-defined metabolome, including inflammatory and glycolysis-related measures, fatty acids, fluid balance, ketone bodies, lipids and amino acids, we created a set of maternal high BMI-related polymetabolic risk scores (PMRSs), and in an independent replication cohort of 489 mother–child dyads tested their performance in predicting the same set of mother–child outcomes in comparison to anthropometric BMI.ResultsBMI-defined metabolome predicted all of the studied mother–child outcomes and improved their prediction over anthropometric BMI, except for gestational hypertension and GWG. BMI-related PMRSs predicted gestational diabetes, preeclampsia, Caesarian section delivery, admission to NICU, lower gestational age at birth, lower cognitive development score of the child, and improved their prediction over anthropometric BMI. BMI-related PMRSs predicted gestational diabetes, preeclampsia, Caesarean section delivery, NICU admission and child’s lower gestational age at birth even at the levels of maternal non-obesity and normal weight.ConclusionsMaternal BMI-defined metabolome improves the prediction of pregnancy complications, birth outcomes, and neurodevelopment in children over anthropometric BMI. The novel, BMI-related PMRSs generated based on the BMI-defined metabolome have the potential to become biomarkers identifying at-risk mothers and their children for timely targeted interventions even at the level of maternal non-obesity and normal weight.

Gestational glyphosate exposure and early childhood neurodevelopment in a Puerto Rico birth cohort

IntroductionN-(phosphonomethyl)glycine, or glyphosate, is a non-selective systemic herbicide widely used in agricultural, industrial, and residential settings since 1974. Glyphosate exposure has been inconsistently linked to neurotoxicity in animals, and studies of effects of gestational exposure among humans are scarce. In this study we investigated relationships between prenatal urinary glyphosate analytes and early childhood neurodevelopment. MethodsMother-child pairs from the PROTECT-CRECE birth cohort in Puerto Rico with measures for both maternal urinary glyphosate analytes and child neurodevelopment were included for analysis (n = 143). Spot urine samples were collected 1–3 times throughout pregnancy and analyzed for glyphosate and aminomethylphosphonic acid (AMPA), an environmental degradant of glyphosate. Child neurodevelopment was assessed at 6, 12, and 24 months using the Battelle Developmental Inventory, 2nd edition Spanish (BDI-2), which provides scores for adaptive, personal-social, communication, motor, and cognitive domains. We used multivariable linear regression to examine associations between the geometric mean of maternal urinary glyphosate analytes across pregnancy and BDI-2 scores at each follow-up. Results were expressed as percent change in BDI-2 score per interquartile range increase in exposure. ResultsPrenatal AMPA concentrations were negatively associated with communication domain at 12 months (%change = −5.32; 95%CI: 9.04, −1.61; p = 0.007), and communication subdomain scores at 12 and 24 months. At 24 months, four BDI-2 domains were associated with AMPA: adaptive (%change = −3.15; 95%CI: 6.05, −0.25; p = 0.038), personal-social (%change = −4.37; 95%CI: 7.48, −1.26; p = 0.008), communication (%change = −7.00; 95%CI: 11.75, −2.26; p = 0.005), and cognitive (%change = −4.02; 95%CI: 6.72, −1.32; p = 0.005). Similar trends were observed with GLY concentrations, but most confidence intervals include zero. We found no significant associations at 6 months. ConclusionsOur results suggest that gestational exposure to glyphosate is associated with adverse early neurodevelopment, with more pronounced delays at 24 months. Given glyphosate's wide usage, further investigation into the impact of gestational glyphosate exposure on neurodevelopment is warranted.

The Benefit of Levothyroxine Replacement in Maternal Subclinical and Overt Hypothyroidism on Early Child Neurodevelopment

The Benefit of Levothyroxine Replacement in Maternal Subclinical and Overt Hypothyroidism on Early Child Neurodevelopment

Cohort profile update: The Canadian Maternal-Infant Research on Environmental Chemicals Child Development study (MIREC-CD PLUS).

The pan-Canadian Maternal-Infant Research on Environmental Chemicals (MIREC) study was established to determine whether maternal environmental chemical exposures were associated with adverse pregnancy outcomes in 2001 pregnant women. The MIREC-Child Development (CD PLUS) study followed this cohort with the goal of assessing the potential effects of prenatal exposures on anthropometry and neurodevelopment in early childhood. MIREC families with children between the ages of 15 months and 5 years who had agreed to be contacted for future research (n = 1459) were invited to participate in MIREC-CD PLUS which combines data collected from an online Maternal Self-Administered Questionnaire with biomonitoring and neurodevelopment data collected from two in-person visits. Between April 2013 and March 2015, 803 children participated in the Biomonitoring visit where we collected anthropometric measures, blood, and urine from the children. The Behavioural Assessment System for Children-2, Behaviour Rating Inventory of Executive Function, MacArthur-Bates Communicative Development Inventories and the Communication subscale of the Adaptive Behaviour Scale from the Bayley Scales of Infant and Toddler Development-III are available on close to 900 children. There were 610 singleton children who completed in-person visits for neurodevelopment assessments including the Social Responsiveness Scale, Wechsler Preschool Primary Scale of Intelligence-III and NEuroPSYchological assessments (NEPSY). Currently, we are following the cohort into early adolescence to measure the impact of early life exposures on endocrine and metabolic function (MIREC-ENDO). Data collection for the MIREC-CD PLUS study is complete and analysis of the data continues. We are now extending the follow-up of the cohort into adolescence to measure the impact of early life exposures on endocrine and metabolic function (MIREC-ENDO). MIREC-CD PLUS is limited by loss to follow-up and the fact that mothers are predominately of higher socioeconomic status and 'White' ethnicity, which limits our generalizability. However, the depth of biomonitoring and clinical measures in MIREC provides a platform to examine associations of prenatal, infancy and childhood exposures with child growth and development.

Impact of levothyroxine therapy for maternal subclinical and overt hypothyroidism on early child neurodevelopment: A prospective cohort study.

Treatment indication of maternal subclinical hypothyroidism (SCH) is undetermined, despite the wide administration of levothyroxine for maternal overt hypothyroidism (OH). This study aimed to evaluate the therapeutic effect of levothyroxine for maternal SCH and OH in real-world practice, with a focus on early child neurodevelopment. Prospective cohort study. Pregnant women diagnosed with SCH at the first antenatal visit were enroled and compared to those diagnosed with OH. Thyroid follow-ups were conducted during pregnancy. Early child neurodevelopment was assessed using the Gesell Development Diagnosis Scale (GDDS) at 1, 3, 6, 12and 24 months of age. From January 2012 to December 2013, a total of 442 pregnant women were included in final analysis, among whom 194 and 248 were assigned to the SCH and OH groups, respectively. The percentage of levothyroxine therapy at the first antenatal visit was significantly lower in the SCH group than that in the OH group (91.24% vs. 97.58%, p < .01), with a similar treatment rate at delivery (99.4% vs. 100%, p > .05). Notably, GDDS scores were lower in the SCH group than those in the OH group at 6 months to 2 years of age, which was confirmed by subgroup analyses and sensitivity analyses. Children born with maternal SCH demonstrated slightly lower neuropsychological scores at 6 months to 2 years of age compared to those with maternal OH in the clinical practice. The therapeutic effect of maternal SCH on the child neurodevelopment requires further exploration.

Gestational glyphosate exposure and early childhood neurodevelopment in a Puerto Rico birth cohort

Gestational glyphosate exposure and early childhood neurodevelopment in a Puerto Rico birth cohort

Umbilical cord serum elementomics of 52 trace elements and early childhood neurodevelopment

Umbilical cord serum elementomics of 52 trace elements and early childhood neurodevelopment

Association between levothyroxine treatment for maternal subclinical hypothyroidism with negative TPOAb and early child neurodevelopment: A prospective real-world clinical trial.

Subclinical hypothyroidism (SCH) during pregnancy is reported to have detrimental impact on pregnancy and child development. However, its treatment indications require further investigation in different thyroid peroxidase antibody (TPOAb) status. This was a secondary analysis of a Chinese prospective cohort in a real-world setting. Pregnant women with gestational SCH were enrolled at the first antenatal visit and grouped by TPOAb positivity. Child neurodevelopment was assessed by the Gesell development diagnosis scale (GDDS) at one, three, six, 12, and 24 months of age. Subgroup analyses and sensitivity analyses were also conducted. ClinicalTrials.gov NCT01744743. From January 2012 to December 2013, a total of 171 participants were enrolled, including 116 of SCH with TPOAb negative (SCH-TPOAb [-]) and 55 of SCH with TPOAb positive (SCH-TPOAb [+]). Compared to women in the SCH-TPOAb (+) group, those in the SCH-TPOAb (-) group had lower thyroid-stimulating hormone (TSH) levels at enrollment and 12-16+6 gestational weeks, and unexpectedly higher TSH levels at 30-34+6 gestational weeks and delivery, with a correspondingly lower levothyroxine dosage throughout pregnancy (all p < 0.05). Offspring in the SCH-TPOAb (-) group displayed lower GDDS scores at one year old than did their counterparts (adjusted p < 0.05), which was possibly related to the worse thyroid function control of maternal SCH-TPOAb (-). No statistically significant difference was found in the GDDS assessments of children at one, three, six, and 24 months of age. These results were also confirmed in subgroup analyses stratified by maternal thyroid characteristics at enrollment, namely TSH levels, free levothyroxine (T4 ) levels, and anti-thyroglobulin antibody (TgAb) status, as well as in sensitivity analyses excluding participants with no levothyroxine treatment at enrollment. In the current clinical practice, infants born to mothers with SCH-TPOAb (-) displayed slightly lower neurodevelopmental scores at one year old than did those born to mothers with SCH-TPOAb (+) but this difference was not seen at two years.

Indoor air pollution exposure and early childhood development in the Upstate KIDS Study

BackgroundLimited human studies have investigated the impact of indoor air pollution on early childhood neurodevelopment among the US population. We aimed to examine the associations between prenatal and postnatal indoor air pollution exposure and early childhood development in a population-based birth cohort. MethodsThis analysis included 4735 mother-child pairs enrolled between 2008 and 2010 in the Upstate KIDS Study. Indoor air pollution exposure from cooking fuels, heating fuels, and passive smoke during pregnancy, and at 12 and 36 months after birth were assessed by questionnaires. Five domains of child development were assessed by the Ages and Stages Questionnaire at 4, 8, 12, 18, 24, 30, and 36 months. Generalized estimating equations were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for potential confounders. ResultsExposure to unclean cooking fuels (natural gas, propane, or wood) throughout the study period was associated with increased odds of failing any development domain (OR = 1.28, 95% CI 1.07, 1.53), the gross motor domain (OR = 1.52, 95% CI: 1.09, 2.13), and the personal-social domain (OR = 1.36, 95% CI: 1.00, 1.85), respectively. Passive smoke exposure throughout the study period increased the odds of failing the problem-solving domain by 71% (OR = 1.71, 95% CI 1.01, 2.91) among children of non-smoking mothers. No association was found between heating fuel use and failing any or specific domains. ConclusionUnclean cooking fuel use and passive smoke exposure during pregnancy and early life were associated with developmental delays in this large prospective birth cohort.

PTFS05-07-23 The Association of Human Milk Macronutrient Content With Early Childhood Growth and Neurodevelopment in Rural Bangladesh

PTFS05-07-23 The Association of Human Milk Macronutrient Content With Early Childhood Growth and Neurodevelopment in Rural Bangladesh

Prenatal and Childhood Exposure to Organophosphate Pesticides and Behavior Problems in Adolescents and Young Adults in the CHAMACOS Study.

We previously reported associations of prenatal exposure to organophosphate (OP) pesticides with poorer neurodevelopment in early childhood and at school age, including poorer cognitive function and more behavioral problems, in the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS), a birth cohort study in an agriculture community. We investigated the extent to which early-life exposure to OP pesticides is associated with behavioral problems, including mental health, in youth during adolescence and early adulthood. We measured urinary dialkylphosphates (DAPs), nonspecific OP metabolites, in urine samples collected from mothers twice during pregnancy (13 and 26 wk) and at five different times in their children (ages 6 months to 5 y). We assessed maternal report and youth report of externalizing and internalizing behavior problems using the Behavior Assessment System for Children, 2nd edition (BASC-2), when the youth were ages 14, 16, and 18 y. Because there was evidence of nonlinearity, we estimated associations across quartiles of DAPs and modeled repeated outcome measures using generalized estimating equations. There were 335 youths with prenatal maternal DAP measures and 14-. 16-, or 18-y BASC-2 scores. Prenatal maternal DAP concentrations (specific gravity-adjusted median, , ) were associated with higher T-scores (more behavior problems) from maternal report, including more hyperactivity [fourth vs. first quartile of exposure ; 95% confidence interval (CI): 0.18, 4.45], aggression (; 95% CI: 0.15, 3.66), attention problems (; 95% CI: 0.26, 5.30), and depression (; 95% CI: 0.08, 5.24). Associations with youth report of externalizing problems were null, and associations with depression were suggestive (fourth vs. first quartile of exposure ; 95% CI: , 4.67). Childhood DAP metabolites were not associated with behavioral problems. We found associations of prenatal, but not childhood, urinary DAP concentrations with adolescent/young adult externalizing and internalizing behavior problems. These findings are consistent with prior associations we have reported with neurodevelopmental outcomes measured earlier in childhood in CHAMACOS participants and suggests that prenatal exposure to OP pesticides may have lasting effects on the behavioral health of youth as they mature into adulthood, including their mental health. https://doi.org/10.1289/EHP11380.

Prenatal iodine supplementation and early childhood neurodevelopment: the PoppiE trial – study protocol for a multicentre randomised controlled trial

IntroductionObservational studies suggest both low and high iodine intakes in pregnancy are associated with poorer neurodevelopmental outcomes in children. This raises concern that current universal iodine supplement recommendations for pregnant...

Aluminum hydroxide exposure induces neurodevelopmental impairment in hESC-derived cerebral organoids

Aluminum (Al) has been classified as a cumulative environmental pollutant that endangers human health. There is increasing evidence to suggest the toxic effects of Al, but the specific action on human brain development remains unclear. Al hydroxide (Al(OH)3), the most common vaccine adjuvant, is the major source of Al and poses risks to the environment and early childhood neurodevelopment. In this study, we explored the neurotoxic effect of 5 μg/ml or 25 μg/ml Al(OH)3 for six days on neurogenesis by utilizing human cerebral organoids from human embryonic stem cells (hESCs). We found that early Al(OH)3 exposure in organoids caused a reduction in the size, deficits in basal neural progenitor cell (NPC) proliferation, and premature neuron differentiation in a time and dose-dependent manner. Transcriptomes analysis revealed a markedly altered Hippo-YAP1 signaling pathway in Al(OH)3 exposed cerebral organoid, uncovering a novel mechanism for Al(OH)3-induced detrimental to neurogenesis during human cortical development. We further identified that Al(OH)3 exposure at day 90 mainly decreased the production of outer radial glia-like cells(oRGs) but promoted NPC toward astrocyte differentiation. Taken together, we established a tractable experimental model to facilitate a better understanding of the impact and mechanism of Al(OH)3 exposure on human brain development.

Associations of prenatal PFAS exposure and early childhood neurodevelopment: Evidence from the Shanghai Maternal-Child Pairs Cohort

Epidemiological data on the effects of perfluoroalkyl and polyfluoroalkyl substances (PFAS) on infant neurodevelopment trajectories are far from being sufficiently addressed. In this study, 1285 mother–child pairs were recruited during 2016–2017. A high-performance liquid chromatography-triple quadrupole mass spectrometer was used to measure 16 PFAS levels in cord serum. Ages and Stages Questionnaires were used to examine children's neurodevelopment at 2, 6, 12, and 24 months of age. Group-based trajectory models were applied to derive the neurodevelopmental trajectories. Children with relatively low scores from 2 to 24 months were classified into a low-score group and were used as a risk group in each domain. Multiple linear regression, logistic regression, and quantile-based g-computation were performed to assess associations of single or mixture PFAS exposures with neurodevelopment and trajectories. Perfluorooctane sulphonate (PFOS), perfluorooctanoic acid (PFOA), perfluorohexanesulfonic acid (PFHxS), and 6:2 chlorinated polyfluorooctane ether sulfonate (6:2Cl-PFESA) were detected in over 90 % samples. PFOA had the highest concentration (median: 4.61 μg/L). Each ln-unit (μg/L) increase of PFAS (e.g., PFOA, PFOS, PFHxS, 6:2Cl-PFESA) was associated with poor scores of communication domain at 6 months, with the effect size ranging from −0.69 to −0.44. PFOS (OR: 1.14, (1.03, 1.26), PFDA (OR:1.08, (1.02, 1.15)), PFHxS (OR:1.31, (1.12, 1.56)), and 6:2Cl-PFESA (OR:1.08, (1.00, 1.16)) were associated with an increased risk of being in the low-score group in the early childhood communication domain's trajectory. Each mixture quartile increment was associated with a 1.60 (−2.76, −0.45) decrease in communication domain scores of 6-month-old infants, and the mixture effect was mainly attributed to PFOS. Each mixture quartile increase was associated with a 1.23-fold (1.03, 1.46) risk of being in the low-score group of the communication domain, and the mixture effect was mainly attributed to PFOS. In conclusion, PFAS and their mixtures might adversely affect childhood neurodevelopment. The gender-specific associations existed in the above associations.

Expansion and commentary on a two generation approach to prenatal opioid exposure - a commentary on Conradt et al. (2023).

Early child neurodevelopment, including psychopathology, is influenced by a myriad of factors and interactions. These factors are both intrinsic to the caregiver-child dyad such as genetics and epigenetics as well as extrinsic such as social environment and enrichment. Additional layers of complexity may be at play within families with parental substance use, as outlined by Conradt et al. (2023) in their review article titled "Prenatal Opioid Exposure: A Two-Generation Approach to Conceptualizing Risk for Child Psychopathology.". Conradt et al. provide an overarching synthesis of many findings related to substance use that goes beyond the in utero exposure to the transgenerational interface of pregnancy and early childhood, including biologic sensitivities such as genetic predisposition, overrepresentation of social risk factors including early adversities of caregivers and poverty, and transgenerational interactional susceptibilities. Altered dyadic interactions may relate to joint changes in neurobehavior and are not isolated from the influence of infant genetics, epigenetics, and environment. The early neurodevelopmental correlates of prenatal substance exposure including risks of childhood psychopathology are then a composite of many different forces. This nuanced reality, described as an "inter-generational cascade," does not centralize parental substance use or prenatal exposure as a singularly causative moment but positions it within the ecologic milieu of the total lived experience.

Prospective associations between various prenatal exposures to maternal psychological stress and neurodevelopment in children within 24 months after birth

BackgroundThere is increasing evidence that prenatal exposure to maternal psychological distress may be a factor influencing offspring neurodevelopment, but stress type-dependent effects of maternal psychological distress on offspring neurodevelopment in early childhood have yet to be fully elucidated. Additionally, although positive maternal mental health exerts potential effects in protecting against adverse health outcomes, few investigators have considered the effects of positive maternal mental health on offspring neurodevelopment in early childhood. AimsTo determine the associations between various prenatal exposures to maternal psychological distress and positive life-event experiences and offspring neurodevelopment within 24 months of age. MethodsA total of 4412 mother-child dyads were recruited from the Shanghai Maternal-Child Pairs Cohort (Shanghai MCPC). Maternal perceived stress, negative life-event stress, positive life-event experiences around the time of conception (i.e., three months prior to and after conception) were assessed at 12–16 gestational weeks, and maternal anxiety and depressive symptoms were assessed at 32–36 gestational weeks. We measured children's neurodevelopment using the Ages and Stages Questionnaire, Third Edition (ASQ-3) at two, six, 12, and 24 months postnatally. We then exploited generalized linear models to estimate the associations between prenatal maternal psychological distress and positive life-event experiences and children's neurodevelopment at the above periods, and generalized linear mixed models were applied to assess the associations between maternal psychological distress and positive life-event experiences and suspected developmental delay (SDD) in children within 24 months after birth based on a longitudinal design. ResultsMaternal perceived stress and negative life-event stress around the time of conception, and anxiety and depressive symptoms during late pregnancy were negatively associated with scores of children's neurodevelopment at two, six, 12, and 24 months of age; while maternal life-event experiences were positively associated with scores of children's neurodevelopment. Longitudinal analysis revealed that higher levels of maternal negative life-event stress and depressive symptoms augmented the risk of SDD in personal-social (OR = 1.435, 1.681). Mothers who experienced higher levels of positive life-event experiences exhibited a reduced risk of SDD in gross motor and personal-social domains (OR = 0.373, 0.350). ConclusionsPrenatal exposure to maternal psychological distress is negatively associated with children's neurodevelopment in early childhood depending upon the type of distress. Maternal positive life-event experiences around the time of conception appeared to present potential benefits for child neurodevelopment.

Correlation between Cord Blood Vitamin D Levels and Problem-Solving Neurodevelopment in Early Childhood: A Cohort Study in Rural Indonesia.

Vitamin D influence on brain development and subsequent postnatal neurodevelopment remains controversial. We explored the correlation between cord blood vitamin D levels and longitudinal neurodevelopment in early childhood. A cohort study was conducted on term infants with no congenital abnormalities, born from pregnant women from a cohort study. Cord blood samples were collected to measure vitamin D. Neurodevelopment was examined three times in infants aged 6, 12 and 24 months using the Ages and Stages Questionnaire-3, which comprises 30 questions of five developmental domains: gross motor, fine motor, communication, problem-solving and social–personal. Statistical analysis was conducted with Spearman’s rank correlation and multiple linear regression. Of the 141 babies born from previous cohort studies, only 116 participants were included. The mean level of cord blood vitamin D was 16.2 ng/mL. The percentage participants with vitamin D deficiency and insufficiency were 12.9 and 65.5, respectively. Cord blood vitamin D and the problem-solving domain for infant aged 12 and 24 months were correlated (r = 0.217 and 0.414, respectively). Multiple linear regression showed a decreased problem-solving domain score of 0.641 associated with decreased vitamin D levels. In conclusion, cord blood vitamin D levels correlated with infant neurodevelopmental status.