Prenatal exposure to mixtures of heavy metals and neurodevelopment in infants at 6 months.

BACKGROUND: Exposure to mixture of neurotoxic metals such as lead, mercury and cadmium occurs at a specific point of time. When exposed to metal mixtures, one metal may act as an agonist or antagonist to another metal. Thus, it is important to study the effects of exposure to a combination of metals on children's development using advance statistical methods. OBJECTIVES: In this study, we explored the effects of prenatal metal exposure including lead, mercury and cadmium in early pregnancy (12-20 weeks), late pregnancy (>28 weeks), and at birth on neurodevelopment of infants at 6 months of age. METHODS: We included 523 eligible mother-child pairs from the mothers and children environmental health (MOCEH) study, a prospective birth cohort study in Korea. We used linear regression, Bayesian kernel machine regression (BKMR) and generalized additive models (GAM), to evaluate the effects of exposure to metal mixtures on neurodevelopment of infants aged 6 months. The Korean version of Bayley scale of infant and toddler development-II was used to measure the child's neurodevelopment. RESULTS: Linear regression models showed a significant negative effect of lead exposure during late pregnancy on the mental development index (MDI) [ß = -2.51 (-4.92, -0.10)] scores of infants aged 6 months following co-exposure to mercury. Further, linear regression analysis showed a significant interaction between late pregnancy lead and mercury concentrations. BKMR analysis showed similar results as those obtained in linear regression models. These results were also replicated in the GAM. Stratification analysis showed that greater than 50 percentile concentration of mercury in late pregnancy potentiated the adverse effects of lead in late pregnancy on MDI [ß = -4.33 (-7.66, -1.00)] and psychomotor development index (PDI) [ß = -5.30 (-9.13, -1.46)] at 6 months of age. Prenatal cadmium exposure did not show a significant association with MDI and PDI at 6 months in the linear regression or BKMR analysis. CONCLUSION: Based on all the statistical methods used, we demonstrated the effect of combined exposure to metals on the neurodevelopment of infants aged 6 months, with significant interaction between lead and mercury.

Prenatal exposure to perfluorinated compounds affects thyroid hormone levels in newborn girls.

Perfluorinated compounds (PFCs) are ubiquitous in the environment and have been detected in humans and wildlife. Exposure to PFCs has decreased in the United States recently, while exposure to PFCs continues in Asian countries, which represents a public health concern. Various mechanisms by which PFCs affect fetal growth have been proposed, such as activation of peroxisome proliferators, disruption of thyroid hormones and changes in lipid metabolism. However, the overall evidence for an association with thyroid hormones is not strong. Therefore, we examined the effect of various prenatal PFCs on cord blood thyroid hormones: triiodothyronine (T3), thyroxine (T4), thyroid stimulating hormone (TSH) levels, and explored the endocrine disrupting effect of these PFCs on thyroid hormone levels in children according to gender. Two hundred and seventy-nine study participants were selected from among the enrolled participants in the Ewha Birth & Growth Retrospective Cohort, a retrospective birth cohort study conducted at Ewha Womans University Hospital, Seoul, Korea between 2006 and 2010. A generalized linear model was constructed to explore the association of PFCs and thyroid hormones. Further, an analysis stratified by gender was conducted. Our study shows that cord blood perfluoro n-pentanoic acid (PFPeA) was positively associated with cord blood T4 (p=0.01) level. Gender-specific analysis showed that prenatal PFCs: PFPeA and Perfluorohexane sulfonic acid (PFHxS) exposure significantly increased T4 (p<0.01) and T3 (p=0.03), respectively, while perfluorononanoic acid (PFNA) decreased TSH (p=0.04) concentration in newborn girls. Thus, prenatal PFC exposure may disrupt thyroid hormone homeostasis. Thyroid hormones play a crucial role in fetal development and may have gender specific action. Hence, these results are of utmost importance in high-risk groups, such as pregnant women and children.

Prenatal Exposure to Perfluorinated Compounds Affects Birth Weight Through GSTM1 Polymorphism.

OBJECTIVE: The aim of this study was to investigate the effect of genetic polymorphisms on the association of prenatal exposure to perfluorinated compounds (PFCs) with birth weight. METHODS: We analyzed the level of eight PFCs in cord blood and two genetic polymorphisms in maternal blood of 268 subjects. RESULTS: Concentrations of perfluorooctanoic acid, perfluorooctane sulfonate, perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), and perfluoroundecanoic acid (PFUnDA) showed significant association with a decrease in birth weight (P < 0.05). In mothers with glutathione S-transferase M1 (GSTM1) null genotype, concentrations of PFNA, PFDA, and PFUnDA showed significantly negative association with birth weight (P < 0.05). CONCLUSION: Our findings indicated that GSTM1 polymorphism might affect the association between exposure to PFCs and birth weight, suggesting the effect of genetic susceptibility on the relationship between prenatal PFCs exposure and birth outcomes.

Neurodevelopment in Early Childhood Affected by Prenatal Lead Exposure and Iron Intake.

No safe threshold level of lead exposure in children has been recognized. Also, the information on shielding effect of maternal dietary iron intake during pregnancy on the adverse effects of prenatal lead exposure on children's postnatal neurocognitive development is very limited. We examined the association of prenatal lead exposure and neurodevelopment in children at 6, 12, 24, and 36 months and the protective action of maternal dietary iron intake against the impact of lead exposure. The study participants comprise 965 pregnant women and their subsequent offspring of the total participants enrolled in the Mothers and Children's environmental health study: a prospective birth cohort study. Generalized linear model and linear mixed model analysis were performed to analyze the effect of prenatal lead exposure and mother's dietary iron intake on children's cognitive development at 6, 12, 24, and 36 months. Maternal late pregnancy lead was marginally associated with deficits in mental development index (MDI) of children at 6 months. Mothers having less than 75th percentile of dietary iron intake during pregnancy showed significant increase in the harmful effect of late pregnancy lead exposure on MDI at 6 months. Linear mixed model analyses showed the significant detrimental effect of prenatal lead exposure in late pregnancy on cognitive development up to 36 months in children of mothers having less dietary iron intake during pregnancy. Thus, our findings imply importance to reduce prenatal lead exposure and have adequate iron intake for better neurodevelopment in children.