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.

Postnatal growth following prenatal lead exposure and calcium intake.

BACKGROUND: The effects on postnatal growth of maternal exposure to low levels of lead during pregnancy have not been well established. In addition, information is limited regarding the protective effect of dietary calcium intake during pregnancy against the effect of lead for fetal and postnatal growth. We investigated the relationship between prenatal exposure to lead and growth at birth and 6, 12, and 24 months postnatal, and evaluated the role of calcium intake against the effect of lead. METHODS: A total of 1150 pregnant women, and their subsequent offspring, enrolled in a prospective birth cohort study (Mothers and Children's Environmental Health Study), were evaluated. Multivariable regression analysis was conducted to estimate the effects of prenatal maternal blood lead levels on growth at each follow-up. RESULTS: The blood lead levels of participating mothers were <5.0 µg/dL and mean levels were 1.25 µg/dL during the early (before 20 gestational weeks) and late (at delivery) gestational periods. Prenatal exposure to lead, particularly in late pregnancy, was significantly associated with a reduction in infantile growth at 24 months. When pregnant women had dietary calcium intake at mean or upper level, the association was not significant. In contrast, lower than mean level of calcium intake intensified the adverse effect of prenatal lead exposure on growth in children. CONCLUSIONS: Prenatal lead exposure <5.0 µg/dL adversely affects postnatal growth and low calcium intake aggravates the effect, indicating more stringent control of lead and sufficient intake of calcium are necessary to help children's health.

Waist circumference percentiles in 2-18 year old Indian children.

OBJECTIVES: To develop reference percentile curves in Indian children for waist circumference (WC), and to provide a cutoff of WC percentile to identify children at risk for metabolic syndrome (MS). STUDY DESIGN: A multicenter, cross-sectional study was performed in 5 major Indian cities. Height, weight, and blood pressure (BP) were measured in 10,842 children (6065 boys). Elevated BP was defined as either systolic BP or diastolic BP >95th percentile. WC was measured with the child standing using a stretch-resistant tape. Sex-specific reference percentiles were computed using the LMS method which constructs reference percentiles adjusted for skewness. To determine optimal cutoffs for WC percentiles, a validation sample of 208 children was assessed for MS risk factors (ie, anthropometry, BP, blood lipids), and receiver operating characteristic (ROC) curve analysis was performed. RESULTS: Age- and sex-specific WC percentiles (5th, 10th, 15th, 25th, 50th, 75th, 85th, 90th, and 95th) are presented. WC values increased with age in both the boys and the girls. The median WC at age >15 years was greater in boys compared with girls. ROC analysis suggested the 70th percentile as a cutoff for MS risk (sensitivity, 0.84 in boys and 0.82 in girls; specificity, 0.85 in both boys and girls; area under the ROC curve, 0.88 in boys and 0.92 in girls). CONCLUSION: Age- and sex-specific reference curves for WC for Indian children and cutoff values of 70th WC percentile for screening for MS risk are provided.

Beneficial effect of iron pot cooking on iron status.

OBJECTIVES: To develop iron rich snacks using locally available iron rich foods and analyze their iron content when cooked in iron pots. Further, the efficacy of the developed snacks, cooked in iron pots was examined on the hemoglobin status of pre-school children through a three month randomized trial. METHODS: Four iron rich snacks (mean iron content 2.1mg/serving) were cooked in iron pots and 27 preschool children (mean age 2.9 ± 0.9 y, 12 boys) were supplemented with the snacks for 4 mo. Anthropometry and dietary intake data were collected. Hemoglobin, serum iron and transferrin saturation were assessed. RESULTS: An increase of 16.2 % in the iron content was found in the snacks cooked in iron pots than cooked in Teflon coated non-stick pots. After 4 mo of supplementation, a significant increase of 7.9 % was seen in the hemoglobin of the children. CONCLUSION: This pilot study demonstrated that iron rich recipes cooked in iron pot have a beneficial effect on iron status of children. Therefore, such food based strategies have the potential to alleviate iron deficiency anemia not only in children but also in other vulnerable sections of society like in pregnant women.