Methylmercury and long chain polyunsaturated fatty acids are associated with immune dysregulation in young adults from the Seychelles child development study.

BACKGROUND: Exposure to the environmental toxicant mercury (Hg) has been associated with immune dysregulation, including autoimmune disease, but few human studies have examined methylmercury (MeHg) exposure from fish consumption. OBJECTIVES: We examined associations between MeHg exposure and biological markers of autoimmunity and inflammation while adjusting for long chain polyunsaturated fatty acids (LCPUFA). METHOD: At age 19 years, hair total Hg (Y19Hg), LCPUFA status, a panel of 13 antinuclear antibodies (ANA), total serum immunoglobulins (Ig) IgG, IgA, and IgM and serum markers of inflammation (IL-1, IL-2, IL-6, IL-10, C-reactive protein (CRP), IFN-γ, TNF-α) were measured in the Seychelles Child Development Study (SCDS) Main Cohort (n = 497). Multivariable regression models investigated the association between Y19Hg and biomarkers, adjusting for prenatal total hair Hg (MatHg) and other relevant covariates, and with and without adjustment for LCPUFA. RESULTS: With each 1 ppm increase in Y19Hg (mean 10.23 (SD 6.02) ppm) we observed a 4% increased odds in a positive Combined ANA following adjustment for the n6:n3 LCPUFA ratio (ß = 0.036, 95%; CI: 0.001, 0.073). IgM was negatively associated with Y19Hg (ß = -0.016, 95%CI: 0.016, -0.002) in models adjusted for n-3, n-6 LCPUFA and when separately adjusted for the n-6:n-3 LCPUFA ratio. No associations were observed with MatHg. Total n-3 LCPUFA status was associated with reduced odds of a positive anti-ribonuclear protein (RNP) A. The n-3 LCPUFA were negatively associated with IL-6, IL-10, CRP, IFN-γ, TNF-α and positively with TNF-α:IL-10. There were positive associations between the n-6:n-3 ratio and IL-6, IL-10, CRP, IFN-γ, TNF-α and a negative association with TNF-α:IL-10. DISCUSSION: The Y19Hg exposure was associated with higher ANA and lower IgM albeit only following adjustment for the n-3 LCPUFA or the n-6:n-3 LCPUFA ratio. The clinical significance of these findings is unclear, but warrant follow up at an older age to determine any relationship to the onset of autoimmune disease.

Maternal Vitamin D Status and the Relationship with Neonatal Anthropometric and Childhood Neurodevelopmental Outcomes: Results from the Seychelles Child Development Nutrition Study.

Vitamin D has an important role in early life; however, the optimal vitamin D status during pregnancy is currently unclear. There have been recent calls for pregnant women to maintain circulating 25-hydroxyvitamin D (25(OH)D) concentrations >100 nmol/L for health, yet little is known about the long-term potential benefits or safety of achieving such high maternal 25(OH)D concentrations for infant or child health outcomes. We examined maternal vitamin D status and its associations with infant anthropometric and later childhood neurocognitive outcomes in a mother-child cohort in a sun-rich country near the equator (4.6° S). This study was conducted in pregnant mothers originally recruited to the Seychelles Child Development Nutrition Study. Blood samples (n = 202) taken at delivery were analysed for serum 25-hydroxyvitamin D (25(OH)D) concentrations. Multiple linear regression models assessed associations between maternal 25(OH)D and birth weight, infant head circumference, and neurocognitive outcomes in the children at age 5 years. Mothers were, on average, 27 years of age, and the children's average gestational age was 39 weeks. None of the women reported any intake of vitamin D supplements. Maternal 25(OH)D concentrations had a mean of 101 (range 34-218 nmol/L) and none were deficient (<30 nmol/L). Maternal 25(OH)D concentrations were not associated with child anthropometric or neurodevelopmental outcomes. These findings appear to indicate that a higher vitamin D status is not a limiting factor for neonatal growth or neurocognitive development in the first 5 years of life. Larger studies with greater variability in vitamin D status are needed to further explore optimal cut-offs or non-linear associations (including for maternal health) that might exist among populations with sub-optimal exposure.

Prenatal exposure to methyl mercury from fish consumption and polyunsaturated fatty acids: associations with child development at 20 mo of age in an observational study in the Republic of Seychelles.

BACKGROUND: Fish is a rich source of n-3 polyunsaturated fatty acids (PUFAs) but also contains the neurotoxicant methyl mercury (MeHg). PUFAs may modify the relation between prenatal MeHg exposure and child development either directly by enhancing neurodevelopment or indirectly through the inflammatory milieu. OBJECTIVE: The objective was to investigate the associations of prenatal MeHg exposure and maternal PUFA status with child development at 20 mo of age. DESIGN: The Seychelles Child Development Study Nutrition Cohort 2 is an observational study in the Republic of Seychelles, a high-fish-eating population. Mothers were enrolled during pregnancy and their children evaluated at 20 mo of age by using the Bayley Scales of Infant Development II (BSID-II), the MacArthur Bates Communicative Development Inventories (CDI), and the Infant Behavior Questionnaire-Revised. There were 1265 mother-child pairs with complete data. RESULTS: Prenatal MeHg exposure had no direct associations with neurodevelopmental outcomes. Significant interactions were found between MeHg and PUFAs on the Psychomotor Developmental Index (PDI) of the BSID-II. Increasing MeHg was associated with lower PDI but only in children of mothers with higher n-6/n-3. Among mothers with higher n-3 PUFAs, increasing MeHg was associated with improved PDI. Higher maternal docosahexaenoic acid (DHA) was associated with improved CDI total gestures (language development) but was significantly adversely associated with the Mental Development Index (MDI), both with and without MeHg adjustment. Higher n-6:n-3 ratios were associated with poorer scores on all 3 CDI outcomes. CONCLUSIONS: We found no overall adverse association between prenatal MeHg exposure and neurodevelopmental outcomes. However, maternal PUFA status as a putative marker of the inflammatory milieu appeared to modify the associations of prenatal MeHg exposure with the PDI. Increasing DHA status was positively associated with language development yet negatively associated with the MDI. These findings may indicate the existence of an optimal DHA balance with respect to arachidonic acid for different aspects of neurodevelopment.

Prenatal exposure to methylmercury and LCPUFA in relation to birth weight.

BACKGROUND: Epidemiologic studies have been inconclusive regarding the impact of coexposure to long chain polyunsaturated fatty acids (LCPUFA) and methylmercury (MeHg) from fish consumption during pregnancy on measures of fetal development. OBJECTIVES: We evaluated the association between birth weight and prenatal maternal LCPUFA status and MeHg exposure in the Republic of Seychelles. METHODS: We measured LCPUFA in maternal whole blood collected at 28 weeks of gestation and following delivery and MeHg in maternal hair obtained at delivery. There were 230 births with complete data on birth weight and covariates. Multiple linear regression models controlled for infant sex, gestational age, maternal age, smoking during pregnancy, intrapartum weight gain, prepregnancy body mass index, maternal socioeconomic status, parity, gestational diabetes, and alcohol use during pregnancy. RESULTS: The average birth weight was 3252 g (range 1654-4450) and the average gestational age was 39 weeks (range 34-41). Prenatal MeHg exposure and maternal LCPUFA status were not associated with birth weight. Infant sex and length of gestation were the only predictors, with male sex and increased gestational age consistently associated with greater birth weight. CONCLUSIONS: These findings do not support a relationship between prenatal exposure to LCPUFA and/or MeHg from fish consumption and birth weight.

Neurophysiologic measures of auditory function in fish consumers: associations with long chain polyunsaturated fatty acids and methylmercury.

BACKGROUND: Determining if associations exist between child neurodevelopment and environmental exposures, especially low level or background ones, is challenging and dependent upon being able to measure specific and sensitive endpoints. Psychometric or behavioral measures of CNS function have traditionally been used in such studies, but do have some limitations. Auditory neurophysiologic measures examine different nervous system structures and mechanisms, have fewer limitations, can more easily be quantified, and might be helpful additions to testing. To date, their use in human epidemiological studies has been limited. We reviewed the use of auditory brainstem responses (ABR) and otoacoustic emissions (OAE) in studies designed to determine the relationship of exposures to methyl mercury (MeHg) and nutrients from fish consumption with neurological development. We included studies of experimental animals and humans in an effort to better understand the possible benefits and risks of fish consumption. OBJECTIVES: We reviewed the literature on the use of ABR and OAE to measure associations with environmental exposures that result from consuming a diet high in fish. We focused specifically on long chain polyunsaturated fatty acids (LCPUFA) and MeHg. METHODS: We performed a comprehensive review of relevant studies using web-based search tools and appropriate search terms. RESULTS: Gestational exposure to both LCPUFA and MeHg has been reported to influence the developing auditory system. In experimental studies supplemental LCPUFA is reported to prolong ABR latencies and human studies also suggest an association. Experimental studies of acute and gestational MeHg exposure are reported to prolong ABR latencies and impair hair cell function. In humans, MeHg exposure is reported to prolong ABR latencies, but the impact on hair cell function is unknown. CONCLUSION: The auditory system can provide objective measures and may be useful in studying exposures to nutrients and toxicants and whether they are associated with children's neurodevelopment.

Intakes and adequacy of potentially important nutrients for cognitive development among 5-year-old children in the Seychelles Child Development and Nutrition Study.

OBJECTIVE: To assess the nutritional adequacy of Seychellois children in relation to nutrients reported to be important for cognitive development. DESIGN: Dietary intakes were assessed by 4 d weighed food diaries and analysed using dietary analysis software (WISP version 3·0; Tinuviel Software, UK). Individual nutrient intakes were adjusted to usual intakes and, in order to investigate adequacy, were compared with the UK Estimated Average Requirements for children aged 4-6 years. SETTING: Children 5 years old were followed up as part of the Seychelles Child Development Nutrition Study (SCDNS), located in the high-fish-consuming population of Mahé, Republic of Seychelles. SUBJECTS: Analysis was carried out on a sample of 229 children (118 boys, 111 girls). RESULTS: Children consumed a diet of which fortified cereal and milk products contributed the most to nutrient intakes. The majority (≥80 %) of children met requirements for several nutrients important for child development including Fe, folate and Se. Adjusted dietary intakes of Cu, Zn, iodine, niacin and vitamin A were below the Estimated Average Requirement or Recommended Nutrient Intake. Mean adjusted energy intakes (boys 4769 kJ/d (1139·84 kcal/d), girls 4759 kJ/d (1137·43 kcal/d)) were lower than the estimated energy requirement (boys 5104 kJ/d (1220 kcal/d), girls 5042 kJ/d (1205 kcal/d)) for 88 % of boys and 86 % of girls. CONCLUSIONS: Nutrition was adequate for most children within the SCDNS cohort. Low intakes of some nutrients (including Zn, niacin and vitamin A) could reflect nutritional database inaccuracies, but may require further investigation. The study provides valuable information on the adequacy of intakes of nutrients which could affect the growth and development of Seychellois children.

A longitudinal analysis of prenatal exposure to methylmercury and fatty acids in the Seychelles.

BACKGROUND: Maternal fish consumption during pregnancy exposes the fetus simultaneously to methylmercury (MeHg) and long chain polyunsaturated fatty acids (LCPUFA). Data from the Seychelles Child Development Nutrition Study (SCDNS) showed a negative association of MeHg with child development when children were 30 months of age, only when controlling for LCPUFA. Concomitantly, n-3 LCPUFA were found to have a significant positive association only at 9 months. These findings suggest that the effects of MeHg and LCPUFA may vary with age over the first few years of life. We address this by including outcomes at two ages and adjusting for the child's age at testing. METHODS: A longitudinal analysis utilizing linear mixed models was performed to assess the associations of maternal hair total mercury (THg, a biomarker for MeHg) and maternal LCPUFA with children's Bayley Scales of Infant Development Psychomotor Developmental Index (BSID-II PDI) at 9 and 30 months of age, and to determine whether these associations change over time. Data from 228 children were included. RESULTS: Maternal hair MeHg had a negative effect on BSID PDI, while maternal n-3 LCPUFA had a positive effect. These effects did not change significantly from 9 to 30 months in this analysis. CONCLUSIONS: The longitudinal analysis provides increased power for estimating the relationships of prenatal MeHg and LCPUFA exposures during child development. Significant associations of these exposures in opposite directions confirm the importance of LCPUFA in development and the need to adjust for maternal nutrition when studying prenatal MeHg exposure.

Iron status in pregnant women in the Republic of Seychelles.

OBJECTIVE: To establish the Fe status of pregnant women and their neonates in the Republic of Seychelles. DESIGN: A prospective study. SETTING: Republic of Seychelles. SUBJECTS: Pregnant women were recruited and blood samples taken at enrolment and post-delivery along with cord blood samples. Ferritin and soluble transferrin receptor (sTfR) were measured in maternal (n 220) and cord blood (n 123) samples. RESULTS: Maternal Fe deficiency (ferritin < 15 ng/ml, sTfR > 28 nmol/l) was present in 6 % of subjects at enrolment and in 20 % at delivery. There was no significant decrease in maternal ferritin. A significant increase in sTfR was observed between enrolment and delivery (P < 0.001). Maternal BMI and use of Fe supplements at 28 weeks' gestation were associated with improved maternal Fe status at delivery, whereas parity had a negative effect on sTfR and ferritin at delivery. CONCLUSIONS: Fe status of pregnant Seychellois women was, on average, within normal ranges. The incidence of Fe deficiency throughout pregnancy in this population was similar to that in a Westernised population. Increased awareness of the importance of adequate Fe intake during pregnancy, particularly in multiparous women, is warranted.