Organophosphate exposures during pregnancy and child neurodevelopment: Recommendations for essential policy reforms.
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ABSTRACT:
SUBMITTER: Hertz-Picciotto I
PROVIDER: S-EPMC6200179 | biostudies-literature | 2018 Oct
REPOSITORIES: biostudies-literature
Publications
Organophosphate exposures during pregnancy and child neurodevelopment: Recommendations for essential policy reforms.
Hertz-Picciotto Irva I Sass Jennifer B JB Engel Stephanie S Bennett Deborah H DH Bradman Asa A Eskenazi Brenda B Lanphear Bruce B Whyatt Robin R
PLoS medicine 20181024 10
In a Policy Forum, Irva Hertz-Picciotto and colleagues review the scientific evidence linking organophosphate pesticides to cognitive, behavioral, and neurological deficits in children and recommend actions to reduce exposures. ...[more]
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Project description:Early child neurodevelopment has major impacts on future human capital and health. However, not much is known about the impacts of prenatal risk factors on child neurodevelopment. This study evaluates the effects of maternal smoking during pregnancy on child neurodevelopment between 3 and 24 months of age and interactions with socioeconomic status (SES). Data from a unique sample of children from South America are employed. Smoking has large adverse effects on neurodevelopment, with larger effects in the low SES sample. The study results highlight the importance of early interventions beginning before and during pregnancy for enhancing child development and future human capital attainment.
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Project description:BackgroundThis study applies multimodal MRI to investigate neurodevelopment in nine-year-old children born to cancer-complicated pregnancies.MethodsIn this cohort study, children born after cancer-complicated pregnancies were recruited alongside 1:1 matched controls regarding age, sex and gestational age at birth (GA). Multimodal MRI was used to investigate whole-brain and subcortical volume, cortical structure (using surface-based morphometry), white matter microstructure (using fixel-based analysis) and functional connectivity (using resting-state blood-oxygen-level-dependant signal correlations). Graph theory probed whole-brain structural and functional organization. For each imaging outcome we conducted two group comparisons: 1) children born after cancer-complicated pregnancies versus matched controls, and 2) the subgroup of children with prenatal chemotherapy exposure versus matched controls. In both models, we used the covariate of GA and the group-by-GA interaction, using false-discovery-rate (FDR) or family-wise-error (FWE) correction for multiple comparisons. Exploratory post-hoc analyses investigated the relation between brain structure/function, neuropsychological outcome and maternal oncological/obstetrical history.FindingsForty-two children born after cancer-complicated pregnancies were included in this study, with 30 prenatally exposed to chemotherapy. Brain organization and functional connectivity were not significantly different between groups. Both cancer and chemotherapy in pregnancy, as compared to matched controls, were associated with a lower travel depth, indicating less pronounced gyrification, in the left superior temporal gyrus (pFDR ≤ 006), with post-hoc analysis indicating platinum derivatives during pregnancy as a potential risk factor (p = .028). Both cancer and chemotherapy in pregnancy were related to a lower fibre cross-section (FCS) and lower fibre density and cross-section (FDC) in the posterior corpus callosum and its tapetal fibres, compared to controls. Higher FDC in the chemotherapy subgroup and higher FCS in the whole study group were observed in the anterior thalamic radiations. None of the psycho-behavioural parameters correlated significantly with any of the brain differences in the study group or chemotherapy subgroup.InterpretationPrenatal exposure to maternal cancer and its treatment might affect local grey and white matter structure, but not functional connectivity or global organization. While platinum-based therapy was identified as a potential risk factor, this was not the case for chemotherapy in general.FundingThis project has received funding from the European Union's Horizon 2020 research and innovation program (European Research council, grant no 647,047), the Foundation against cancer (Stichting tegen kanker, grant no. 2014-152) and the Research Foundation Flanders (FWO, grants no. 11B9919N, 12ZV420N).
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Project description:Cytokines and chemokines are potent modulators of brain development and as such, dysregulation of the maternal immune system can result in deviations in the fetal cytokine balance, altering the course of typical brain development, and putting the individual on a "pathway to pathology". In the current study, we used a multi-variate approach to evaluate networks of interacting cytokines and investigated whether alterations in the maternal immune milieu could be linked to alcohol-related and alcohol-independent child neurodevelopmental delay. This was achieved through the measurement of 40 cytokines/chemokines from maternal blood samples collected during the second and third trimesters of pregnancy. Importantly, during the second trimester we identified network enrichment in levels of cytokines including IFN-?, IL-10, TNF-?, TNF-?, and CRP associated with offspring neurodevelopmental delay. However, as elevations in levels of these cytokines have previously been reported in a wide range of neurodevelopmental disorders including autism spectrum disorder and schizophrenia, we suggest that this cytokine profile is likely not disorder specific, but rather may be an indicator of neurodevelopmental delay in general. By contrast, distinct clusters of activated/inhibited cytokines were identified based on maternal alcohol consumption and child neurodevelopmental outcome. Specifically, cytokines including IL-15, IL-10, MDC, and members of the VEGF sub-family were highest in alcohol-consuming mothers of children with neurodevelopmental delay and were identified in both network analyses and examination of individual cytokines, whereas a differential and unique cytokine profile was identified in the case of alcohol-independent child neurodevelopmental delay. We propose that the current findings could provide a critical step towards the development of early biomarkers and possibly interventions for alcohol-related neurodevelopmental delay. Importantly, the current approach could be informative for understanding mechanisms linking maternal immune system dysfunction and adverse child outcomes in a range of other neurodevelopmental disorders.
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Project description:BackgroundMaternal nutrition during pregnancy and lactation has profound effects on the development and lifelong health of the child. Long-chain PUFAs are particularly important for myelination and the development of vision during the perinatal period.ObjectivesWe conducted a systematic review to examine the relationship between supplementation with omega-3 fatty acids during pregnancy and/or lactation and neurodevelopment in children, to inform the Scientific Report of the 2020 Dietary Guidelines Advisory Committee.MethodsWe identified articles on omega-3 fatty acid supplementation in pregnant and lactating women that included measures of neurodevelopment in their children (0-18 y) by searching PubMed, CENTRAL, Embase, and CINAHL Plus. After dual screening articles for inclusion, we qualitatively synthesized and graded the strength of evidence using pre-established criteria for assessing risk of bias, consistency, directness, precision, and generalizability.ResultsWe included 33 articles from 15 randomized controlled trials (RCTs) and 1 prospective cohort study. Of the 8 RCTs that delivered omega-3 fatty acid dietary supplements during pregnancy alone (200-2200 mg/d DHA and 0-1100 mg/d EPA for approximately 20 wk), 5 studies reported ≥1 finding that supplementation improved measures of cognitive development in the infant or child by 6%-11% (P < 0.05), but all 8 studies also reported ≥1 nonsignificant (P > 0.05) result. There was inconsistent or insufficient evidence for other outcomes (language, social-emotional, physical, motor, or visual development; academic performance; risks of attention deficit disorder, attention-deficit/hyperactivity disorder, autism spectrum disorder, anxiety, or depression) and for supplementation during lactation or both pregnancy and lactation. Populations with a lower socioeconomic status and adolescents were underrepresented and studies lacked racial and ethnic diversity.ConclusionsLimited evidence suggests that omega-3 fatty acid supplementation during pregnancy may result in favorable cognitive development in the child. There was insufficient evidence to evaluate the effects of omega-3 fatty acid supplementation during pregnancy and/or lactation on other developmental outcomes.
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Project description:BackgroundEnvironmental phenols and parabens are endocrine disrupting chemicals (EDCs) with the potential to affect child neurodevelopment including autism spectrum disorders (ASD). Our aim was to assess whether exposure to environmental phenols and parabens during pregnancy was associated with an increased risk of clinical ASD or other nontypical development (non-TD).MethodsThis study included mother-child pairs (N = 207) from the Markers of Autism Risks in Babies - Learning Early Signs (MARBLES) Cohort Study with urinary phenol and paraben metabolites analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) from repeated pregnancy urine samples. Because family recurrence risks in siblings are about 20%, MARBLES enrolls pregnant women who already had a child with ASD. Children were clinically assessed at 3 years of age and classified into 3 outcome categories: ASD, non-TD, or typically developing (TD). Single analyte analyses were conducted with trinomial logistic regression and weighted quantile sum (WQS) regression was used to test for mixture effects.ResultsRegression models were adjusted for pre-pregnancy body mass index, prenatal vitamin use (yes/no), homeowner status (yes/no), birth year, and child's sex. In single chemical analyses phenol exposures were not significantly associated with child's diagnosis. Mixture analyses using trinomial WQS regression showed a significantly increased risk of non-TD compared to TD (OR = 1.58, 95% CI: 1.04, 2.04) with overall greater prenatal phenol and paraben metabolites mixture. Results for ASD also showed an increased risk, but it was not significant.DiscussionThis is the first study to provide evidence that pregnancy environmental phenol exposures may increase the risk for non-TD in a high-risk population.
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