Child Neurodevelopment Outcomes Research Articles

Prenatal exposure to metals and metalloids and child neurodevelopment outcomes in Puerto Rico

Prenatal exposure to metals and metalloids and child neurodevelopment outcomes in Puerto Rico

Association of fluoride exposure with disease burden and neurodevelopment outcomes in children in South Korea

Association of fluoride exposure with disease burden and neurodevelopment outcomes in children in South Korea

Brain structural and functional outcomes in the offspring of women experiencing psychological distress during pregnancy.

In-utero exposure to maternal psychological distress is increasingly linked with disrupted fetal and neonatal brain development and long-term neurobehavioral dysfunction in children and adults. Elevated maternal psychological distress is associated with changes in fetal brain structure and function, including reduced hippocampal and cerebellar volumes, increased cerebral cortical gyrification and sulcal depth, decreased brain metabolites (e.g., choline and creatine levels), and disrupted functional connectivity. After birth, reduced cerebral and cerebellar gray matter volumes, increased cerebral cortical gyrification, altered amygdala and hippocampal volumes, and disturbed brain microstructure and functional connectivity have been reported in the offspring months or even years after exposure to maternal distress during pregnancy. Additionally, adverse child neurodevelopment outcomes such as cognitive, language, learning, memory, social-emotional problems, and neuropsychiatric dysfunction are being increasingly reported after prenatal exposure to maternal distress. The mechanisms by which prenatal maternal psychological distress influences early brain development include but are not limited to impaired placental function, disrupted fetal epigenetic regulation, altered microbiome and inflammation, dysregulated hypothalamic pituitary adrenal axis, altered distribution of the fetal cardiac output to the brain, and disrupted maternal sleep and appetite. This review will appraise the available literature on the brain structural and functional outcomes and neurodevelopmental outcomes in the offspring of pregnant women experiencing elevated psychological distress. In addition, it will also provide an overview of the mechanistic underpinnings of brain development changes in stress response and discuss current treatments for elevated maternal psychological distress, including pharmacotherapy (e.g., selective serotonin reuptake inhibitors) and non-pharmacotherapy (e.g., cognitive-behavior therapy). Finally, it will end with a consideration of future directions in the field.

Linear growth beyond 24 months and child neurodevelopment in low- and middle-income countries: a systematic review and meta-analysis

AimTo synthesize available evidence on the association between change in linear growth (height for age z score, HAZ) beyond the first two years of life with later child neurodevelopment outcomes in Low- and middle-income countries (LMICs).MethodsWe searched PubMed, Web of Science, and EMBASE for cohort studies on the association between change in HAZ after age two and neurodevelopment outcomes in middle or late childhood. Data extraction was done independently by two reviewers.ResultsA total of 21 studies, that included 64,562 children from 13 LMICs were identified. Each unit increase in change in HAZ above two years is associated with a + 0.01 increase (N = 8 studies, 27,393 children) in the cognitive scores at 3.5 to 12 years of age and a + 0.05-standard deviation (SD) increase (95% CI 0.02 to 0.08, N = 3 studies, 17,830 children) in the language score at 5 to 15 years of age. No significant association of change in HAZ with motor (standardized mean difference (SMD) 0.04; 95% CI: -0.10, 0.18, N = 1 study, 966 children) or socio-emotional scores (SMD 0.00; 95% CI: -0.02, 0.01, N = 4 studies, 14,616 participants) was observed.ConclusionChanges in HAZ after the first two years of life appear to have a small or no association with child neurodevelopment outcomes in LMICs.

Prenatal/Early-Life Exposure to Polycyclic Aromatic Hydrocarbons (PAHs) and Adverse Neurodevelopment Outcomes in Children: A Systematic Review and Meta-Analysis

Prenatal/Early-Life Exposure to Polycyclic Aromatic Hydrocarbons (PAHs) and Adverse Neurodevelopment Outcomes in Children: A Systematic Review and Meta-Analysis

Associations between maternal thyroid function in pregnancy and child neurodevelopmental outcomes at 20 months in the Seychelles Child Development Study, Nutrition Cohort 2 (SCDS NC2).

Maternal thyroid hormones facilitate optimal foetal neurodevelopment; however, the exact role of the thyroid hormones on specific cognitive outcomes is unknown. The present study aimed to investigate associations between maternal thyroid function and neurodevelopmental outcomes in the Seychelles Child Development Study (SCDS) Nutrition 2 cohort (n 1328). Maternal free thyroid hormones (fT3, fT4 and fTSH) were assessed at 28 weeks' gestation with a range of child cognitive outcomes analysed at 20 months. Dietary iodine intake was analysed for a subset of women through a Food Frequency Questionnaire. Linear regression analysis was used to test associations between serum concentrations of maternal thyroid hormones and child neurodevelopment outcomes. Thyroid hormones were analysed as continuous data and categorised as quintiles. 95% of mothers had optimal thyroid function based on fTSH concentrations. Overall, the present study shows that maternal thyroid function is not associated with neurodevelopmental outcomes in this high fish-eating population. However, a positive association, using quintiles for fT3, was reported for the Mental Developmental Index, between Q3 v. Q4 (β 0⋅073; P 0⋅043) and for Q3 v. Q5 (β value 0⋅086; P 0⋅018). To conclude, mothers in our cohort, who largely have optimal thyroid function and iodine intakes, appear able to regulate thyroid function throughout pregnancy to meet neurodevelopmental needs. However, it is possible that minor imbalances of fT3, as indicated from our secondary analysis, may impact offspring neurodevelopment. Further investigation of the relationship between maternal thyroid function and infant neurodevelopment is warranted, particularly in populations with different dietary patterns and thereby iodine intakes.

Antenatal Depressive Symptoms and Neurodevelopment Outcomes in Children at 30 Months. A Study From South India.

BackgroundPrevalence of antenatal depression in low and middle income countries is high. However studies examining the association between maternal antenatal depression and early childhood development from these countries are scarce. The objective of the study was to examine the association between antenatal depressive symptoms assessed serially during pregnancy and child neurodevelopment outcomes in mother–child dyads part of a randomized control trial of maternal B12 supplementation during pregnancy.MethodSubjects were 203 women who had participated in the placebo-controlled, randomized trial of vitamin B12 supplementation during pregnancy and 6 weeks post-partum on whom serial assessments of depressive symptoms in each of the trimesters were available. Cognitive, receptive language, expressive language, fine motor skills and gross motor skills were assessed at 30 months using the Bayley’s Scale of Infant Development-3rd edition (BSID-III). Antenatal depressive symptoms were assessed at three trimesters using the Kessler’s 10 Psychological Distress Scale (K10). Women were classified into three categories: not depressed (K10 <6 in all trimesters), with intermittent depressive symptoms (K10 ≥6 in at least one trimester) and with persistent depressive symptoms (K10 score ≥6 in at least 2 trimesters).Results112 (55.2%) of the women did not have depressive symptoms, 58 (28.6%) had intermittent depressive symptoms and 33 (16.2%) had persistent depressive symptoms. The children of women with intermittent antenatal depressive symptoms scored lower on the receptive language domain on BSID-III compared to children of women who were not depressed on univariate analysis, but not on bivariate regression analysis. Women with persistent depressive symptoms had lower educational attainment (p = 0.004), lower social support (p = 0.006) and used more emotional coping strategies (p = 0.005) compared to the not depressed group.ConclusionsA significant number of women in south India had antenatal depressive symptoms. Findings from this study suggest a possible association between antenatal depressive symptoms and receptive language in children. Larger studies including women with clinical depression are needed to confirm these findings.

Modelling factors for Aboriginal and Torres Strait Islander child neurodevelopment outcomes: A latent class analysis.

The Australian Early Development Census (AEDC) provides a measure of early child development upon school entry. Understanding which combination of factors influences Aboriginal child neurodevelopment is important to inform policy and practice. The primary objective was to use latent class analysis (LCA) to model AEDC profiles and identify the highest need profiles. The secondary objective was to determine the associations of these high need profiles on the likelihood of a child becoming developmentally vulnerable. We designed a prospective population-based birth cohort study (n=2715) using linked data sets with information on Aboriginal cohort children, and their mothers and siblings in Western Australia. Specific developmental indicators in the 2009 and 2012 AEDC were used to assess developmental vulnerability. LCA methods were used to determine need profiles and their association with developmental vulnerability. 49.3% of Aboriginal children were vulnerable on at least one developmental domain, and 37.5% were vulnerable on two or more domains. LCA found six unique profiles. High needs family, High needs young mother, and Preterm infant comprised 42% of the cohort and were considered to have high need configurations. These groups were at least 1.7 times as likely to have children who had at least one or two developmental vulnerabilities compared with the Healthy family group. Many Aboriginal children in Western Australia enter school with at least one developmental vulnerability. This study highlights a range of unique profiles that can be used to empower Aboriginal families for change and develop targeted programmes for improving the early development of young Aboriginal children.

Prenatal and postnatal polycyclic aromatic hydrocarbons (PAH) exposure and behavioral development in early adolescence.

OPS 22: Behavioral effects of chemical exposures, Room 117, Floor 1, August 27, 2019, 4:30 PM - 5:30 PM Background/Aim: Exposure to polycyclic aromatic hydrocarbons (PAHs) has been linked with neurodevelopment outcomes in children. The aim of our study was to assess the relationship between exposure to PAHs in prenatal period as well as in early childhood and behavioral outcomes during the early adolescence. Methods: 168 adolescents (girls: 51.2%) from birth cohort, for whom PAHs exposure data (both prenatally and age of 3 years) were available and Child Behavioral Checklist (CBCL) was completed by mother between ages of 12 and 15 years. The multivariable Poisson regression model was used to estimate the betas for the association between the raw score for all CBCL outcomes and PAH exposure dichotomized according to median. Results: The median PAH exposure levels in the population under the study were 21.6 ng/m3 in prenatal period and 22.8 ng/m3 for the assessment in are of 3 years. Adolescents below the median for total prenatal PAH exposure compared to those above, were more likely to be withdrawn/depressed (beta=0.30; p=0.016), have somatic complaints (beta=0.44; p=0.002), present Rule-breaking (beta=0.65; p<0.001) and Aggressive behaviors (beta=0.29; p=0.001) as well as both summary outcomes - externalizing (beta=0.39; p<0.001) and internalizing problems (beta=0.27; p<0.001). While the highest exposure to PAHs at age of 3 years was related to Rule-Breaking (beta=0.55; p<0.001) and Aggressive behaviors (beta=0.26; p=0.003) and Externalizing problems (beta=0.33; p<0.001). Conclusions: The high exposure PAHs in prenatal period as well as during early childhood was related to higher likelihood of aggressive and rule-breaking behaviors during early adolescence.

Prenatal mercury exposure and child neurodevelopment outcomes at 18 months: Results from the Mediterranean PHIME cohort.

Neurotoxicity due to acute prenatal exposure to high-dose of mercury (Hg) is well documented. However, the effect of prenatal exposure to low Hg levels on child neurodevelopment and the question about "safety" of fish-eating during pregnancy remain controversial. International comparisons of Hg concentrations in mother-child biological samples and neurodevelopmental scores embedded in birth cohort studies may provide useful evidence to explore this issue. The Mediterranean (Italy, Slovenia, Croatia, and Greece) cohort study included 1308 mother-child pairs enrolled in the Public Health Impact of long-term, low-level, Mixed Element exposure in a susceptible population EU Sixth Framework Programme (PHIME). Maternal hair and venous blood, cord blood and breast milk samples were collected, and total Hg (THg) levels were measured. Demographic and socioeconomic information, lifestyles and nutritional habits were collected through questionnaires at different phases of follow-up. Children at 18 months of age underwent neurodevelopmental testing using the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III). Multivariate linear and logistic regressions were performed, for each country, to assess the association between THg and BSID-III scores, obtaining adjusted β coefficients and odds ratios (ORs). These values were used to conduct a meta-analysis, to explore possible heterogeneity among countries and to obtain combined estimates of the association between THg exposure and BSID-III scores. Median THg (ng/g) was: 704 in maternal hair, 2.4 in maternal blood, 3.6 in cord blood, and 0.6 in breast milk. THg concentrations were highest in Greece and lowest in Slovenia. BSID-III neurodevelopmental scores were higher in Croatia and Slovenia. The meta-analysis of multivariate linear models found an overall positive association between language composite score and receptive communication scaled score and increasing THg in maternal hair (n = 1086; β = 0.55; 95%CI: 0.05-1.05 and n = 1075; β = 0.12; 95%CI: 0.02-0.22, respectively). The meta-analysis of logistic regression models showed that the overall adjusted OR between THg in cord blood and suboptimal gross motor score was borderline significant (n = 882; OR = 1.03; 95%CI: 1.00-1.07). Heterogeneity was found across the four sub-cohorts for language composite score in maternal blood, and for fine motor scaled score in cord blood and breast milk. Language composite score and THg concentrations in maternal venous blood were positively related (n = 58; β = 4.29; CI95% (-0.02, 8.60)) in Croatia and an increase of 1 ng/g of THg in maternal venous blood was associated with a reduced risk for children to fall in the lowest quintile of language score by 31% (n = 58; OR = 0.69; CI 95%: 0.37, 1.01). The comparison of β coefficients obtained by multiple linear regression model showed an inverse association between fine motor score and THg concentrations in cord blood for Croatia (n = 54; β = -0.53; CI 95%: -1.10, 0.04) and Slovenia (n = 225; β = -0.25; CI 95%: -0.49, -0.01). In Slovenia THg level in breast milk was associated with suboptimal fine motor performance (n = 195; OR = 5.25; CI 95%: 1.36, 21.10). This study showed an inverse relation between THg levels and developmental motor scores at 18 months, although the evidence was weak and partially internally and externally inconsistent. No evidence of detrimental effects of THg was found for cognitive and language outcomes at these concentrations and age.

Impact of maternal nutritional supplementation in conjunction with a breastfeeding support program during the last trimester to 12 weeks postpartum on breastfeeding practices and child development at 30 months old.

BackgroundMaternal nutrition during pregnancy and breastfeeding is important for the healthy growth and development of the fetus and infant.PurposeThis study aimed to evaluate the long-term effects of a maternal milk supplementation (MMS) in conjunction with a breastfeeding support program on breastfeeding practices including duration of any breastfeeding and exclusive breastfeeding and child neurodevelopment outcomes at 30 months old.MethodsWe followed up the offspring of 204 Vietnamese women who completed a randomized controlled trial where the intervention group received MMS with a breastfeeding support program from the last trimester to 12 weeks postpartum while the control group received standard care. At 30 months postpartum, information on child feeding practices was collected and child neurodevelopment was assessed by the Bayley Scales of Infant and Toddler Development (Bayley-III).ResultsThere was no significant difference in the duration of any breastfeeding (ABF) from birth between the groups. However, the intervention group had longer exclusive breastfeeding (EBF) duration (p = 0.0172), higher EBF rate at 6 months (p = 0.0093) and lower risk of discontinuing EBF (p = 0.0071) than the control. Children in the intervention group had significantly higher Bayley-III composite scores in the domains of cognitive (p = 0.0498) and motor (p = 0.0422) functions, as well as a tendency toward better social-emotional behavior (p = 0.0513) than children in the control group. The association between maternal intervention and child development was attenuated after further adjustment for birth weight but not EBF duration, suggesting that improvements in child development may be partially attributed to the benefits of prenatal nutrition supplementation on birth outcomes.ConclusionsMMS with breastfeeding support during late pregnancy and early postpartum significantly improved EBF practices. The intervention was also associated with improvements in neurodevelopment in children at 30 months old.

Postcardiac surgery neurodevelopmental evaluation in children with congenital heart disease

Background Congenital heart disease (CHD) is one of the most common congenital anomalies. It may carry risk of neurodevelopment (ND) delay. Open heart surgery has been widely introduced to those patients. The outcome of this surgery on patient’s development is unclear. Objective The aim was to evaluate ND outcomes in children with CHD who underwent open heart surgery. Patients and methods Fifty children with CHD were enrolled in this study: 23 were surgically repaired (group 1) and 27 had no surgical intervention (group 2). Twenty normal children of matched age and sex were enrolled in the study as controls (group 3). Bayley-III test was used to compare the ND parameters in all groups. Results ND aspects showed lower significant differences in groups 1 and 2 when matched with the control group (P 0.05). Conclusion CHD carries the risk of ND delay, and exposure to open heart surgery increases this risk.

Are there early inflammatory biomarkers that affect neurodevelopment in infancy?

Few studies have investigated the relationship between post-natal inflammatory biomarkers at early age and child neurodevelopment outcomes. The main aim of this study was to examine the relationship between IL-6, IL-1β, IL-4 cytokines, as well as cortisol at 6 and 12months of age, and neurodevelopment and psychological problems at 30months of age.The study was conducted on a sample of 51 full-term newborns who were followed up at 6, 12, and 30months of age. Infant neurodevelopment was assessed using the Bayley Scales of Infant Development-II, psychological problems were assessed with the Child Behavior Checklist 1.5–5 (CBCL 1.5–5) and the mother's emotional symptoms were assessed with the General Health Questionnaire-28. When the infants were 6 and 12months old, IL-6, IL-1β, IL-4 cytokines, and cortisol were measured in blood samples. The results showed that higher IL-6 at 12months predicted higher scores in internalizing (emotionally reactive, anxious/depressed, withdrawn and attention problems) and externalizing problems (aggressive behavior) at 30months. By contrast, high levels of IL-1β at 6months were related to worse motor skills. Inflammatory biomarkers were not related to mental performance. IL-6 and IL-1β could be early markers of later psychological problems and psychomotor disabilities.

Association of maternal thyroid function during early pregnancy with offspring IQ and brain morphology in childhood: a population-based prospective cohort study

Thyroid hormone is involved in the regulation of early brain development. Since the fetal thyroid gland is not fully functional until week 18-20 of pregnancy, neuronal migration and other crucial early stages of intrauterine brain development largely depend on the supply of maternal thyroid hormone. Current clinical practice mostly focuses on preventing the negative consequences of low thyroid hormone concentrations, but data from animal studies have shown that both low and high concentrations of thyroid hormone have negative effects on offspring brain development. We aimed to investigate the association of maternal thyroid function with child intelligence quotient (IQ) and brain morphology. In this population-based prospective cohort study, embedded within the Generation R Study (Rotterdam, Netherlands), we investigated the association of maternal thyroid function with child IQ (assessed by non-verbal intelligence tests) and brain morphology (assessed on brain MRI scans). Eligible women were those living in the study area at their delivery date, which had to be between April 1, 2002, and Jan 1, 2006. For this study, women with available serum samples who presented in early pregnancy (<18 weeks) were included. Data for maternal thyroid-stimulating hormone, free thyroxine, thyroid peroxidase antibodies (at weeks 9-18 of pregnancy), and child IQ (assessed at a median of 6·0 years of age [95% range 5·6-7·9 years]) or brain MRI scans (done at a median of 8·0 years of age [6·2-10·0]) were obtained. Analyses were adjusted for potential confounders including concentrations of human chorionic gonadotropin and child thyroid-stimulating hormone and free thyroxine. Data for child IQ were available for 3839 mother-child pairs, and MRI scans were available from 646 children. Maternal free thyroxine concentrations showed an inverted U-shaped association with child IQ (p=0·0044), child grey matter volume (p=0·0062), and cortex volume (p=0·0011). For both low and high maternal free thyroxine concentrations, this association corresponded to a 1·4-3·8 points reduction in mean child IQ. Maternal thyroid-stimulating hormone was not associated with child IQ or brain morphology. All associations remained similar after the exclusion of women with overt hypothyroidism and overt hyperthyroidism, and after adjustment for concentrations of human chorionic gonadotropin, child thyroid-stimulating hormone and free thyroxine or thyroid peroxidase antibodies (continuous or positivity). Both low and high maternal free thyroxine concentrations during pregnancy were associated with lower child IQ and lower grey matter and cortex volume. The association between high maternal free thyroxine and low child IQ suggests that levothyroxine therapy during pregnancy, which is often initiated in women with subclinical hypothyroidism during pregnancy, might carry the potential risk of adverse child neurodevelopment outcomes when the aim of treatment is to achieve high-normal thyroid function test results. The Netherlands Organisation for Health Research and Development (ZonMw) and the European Community's Seventh Framework Programme.

Neurodevelopment outcomes in children exposed to organic mercury from multiple sources in a tin-ore mine environment in Brazil.

Methylmercury (from fresh-water fish) and ethylmercury [from thimerosal-containing vaccines (TCVs)] are the most prevalent source of neurotoxic exposure during early life in families consuming fish and using these vaccines. But children living in Amazonian mining environments are exposed to additional toxic metals in waste materials. We studied mercury (Hg) exposure and neurodevelopment in 294 children (105 boys and 189 girls) from Bom Futuro (Rondonia, Brazil), the epicenter of a tin-ore open-pit mine. Hair-Hg (HHg) concentrations and total ethylmercury (from TCVs) were taken from infants and respective mothers during pregnancy. We used bivariate analysis to determine the effect of sex and linear mixed models to assess the association of prenatal and postnatal organic Hg exposures with children's Bayley Scales of Infant Development (BSID) as psychomotor developmental index and mental developmental index (MDI) at 6 and 24months of age as well as milestones achievements (age of walking and age of talking). Significant differences between boys and girls were observed for both MDI score (p=0.0073) and MDI score (p=0.0288) at 6months but not at 24months. Regression analysis showed that only in boys was there a significant interaction between MDI score with family income (β=0.288, p=0.018) and with birth weight (β=-0.216, p=0.036) at 6months; at 24months, however, only boys showed a significant association of both MDI score (β=-0.222, p=0.045) and MDI score (β=-0.222, p=0.045) with neonatal HHg. In boys, age of walking was associated with HHg (β=0.188, p=0.019) and breastfeeding (β=-0.282, p=0.000), whereas for girls, age of walking was only associated with breastfeeding (β=-0.275, p=0.001). In this mining environment, with only a weak association for prenatal Hg exposure, there was a significant sex difference in neurodevelopment, with boys showing more sensitivity related to BSID delays.