Maternal fish consumption and child neurodevelopment in Nutrition 1 Cohort: Seychelles Child Development Study.

Maternal fish consumption exposes the fetus to beneficial nutrients and potentially adverse neurotoxicants. The current study investigated associations between maternal fish consumption and child neurodevelopmental outcomes. Maternal fish consumption was assessed in the Seychelles Child Development Study Nutrition Cohort 1 (n 229) using 4-day food diaries. Neurodevelopment was evaluated at 9 and 30 months, and 5 and 9 years with test batteries assessing twenty-six endpoints and covering multiple neurodevelopmental domains. Analyses used multiple linear regression with adjustment for covariates known to influence child neurodevelopment. This cohort consumed an average of 8 fish meals/week and the total fish intake during pregnancy was 106·8 (sd 61·9) g/d. Among the twenty-six endpoints evaluated in the primary analysis there was one beneficial association. Children whose mothers consumed larger quantities of fish performed marginally better on the Kaufman Brief Intelligence Test (a test of nonverbal intelligence) at age 5 years (ß 0·003, 95 % CI (0, 0·005)). A secondary analysis dividing fish consumption into tertiles found no significant associations when comparing the highest and lowest consumption groups. In this cohort, where fish consumption is substantially higher than current global recommendations, maternal fish consumption during pregnancy was not beneficially or adversely associated with children's neurodevelopmental outcomes.

Serum cytokines are associated with n-3 polyunsaturated fatty acids and not with methylmercury measured in infant cord blood in the Seychelles child development study.

BACKGROUND: Maternal fish consumption increases infant methylmercury (MeHg) exposure and polyunsaturated fatty acid (PUFA) concentrations. The n-3 PUFA are regulators of inflammation while MeHg may impact the cord cytokine profile and, subsequently, contribute to immune mediated outcomes. This study aimed to investigate associations between infant MeHg exposure and cord cytokine concentrations while adjusting for cord PUFA. METHODS: We studied participants in the Seychelles Child Development Study (SCDS) Nutrition Cohort 2 (NC2), a large birth cohort in a high fish-eating population. Whole blood MeHg, serum PUFA and serum cytokine concentrations (IFN-γ, IL-1ß, IL-2, IL-12p70, TNF-α, IL-4, IL-10, IL-13, IL-6 and IL-8) were measured in cord blood collected at delivery (n = 878). Linear regression examined associations between infant MeHg exposure and cord cytokines concentrations, with and without adjustment for cord PUFA. An interaction model examined cord MeHg, cytokines and tertiles of the n-6:n-3 ratio (low/medium/high). RESULTS: There was no overall association between cord MeHg (34.08 ± 19.98 µg/L) and cytokine concentrations, with or without adjustment for PUFA. Increased total n-3 PUFA (DHA, EPA and ALA) was significantly associated with lower IL-10 (ß = -0.667; p = 0.007) and lower total Th2 (IL-4, IL-10 and IL-13) (ß = -0.715; p = 0.036). In the interaction model, MeHg and IL-1ß was positive and significantly different from zero in the lowest n-6:n-3 ratio tertile (ß = 0.002, p = 0.03). CONCLUSION: Methylmercury exposure from fish consumption does not appear to impact markers of inflammation in cord blood. The association of cord n-3 PUFA with lower IL-10 and total Th2 cytokines suggests that they may have a beneficial influence on the regulation of the inflammatory milieu. These findings are important for public health advice and deserve to be investigated in follow up studies.

Maternal and child fatty acid desaturase genotype as determinants of cord blood long-chain PUFA (LCPUFA) concentrations in the Seychelles Child Development Study.

Optimal maternal long-chain PUFA (LCPUFA) status is essential for the developing fetus. The fatty acid desaturase (FADS) genes are involved in the endogenous synthesis of LCPUFA. The minor allele of various FADS SNP have been associated with increased maternal concentrations of the precursors linoleic acid (LA) and α-linolenic acid (ALA), and lower concentrations of arachidonic acid (AA) and DHA. There is limited research on the influence of FADS genotype on cord PUFA status. The current study investigated the influence of maternal and child genetic variation in FADS genotype on cord blood PUFA status in a high fish-eating cohort. Cord blood samples (n 1088) collected from the Seychelles Child Development Study (SCDS) Nutrition Cohort 2 (NC2) were analysed for total serum PUFA. Of those with cord PUFA data available, maternal (n 1062) and child (n 916), FADS1 (rs174537 and rs174561), FADS2 (rs174575), and FADS1-FADS2 (rs3834458) were determined. Regression analysis determined that maternal minor allele homozygosity was associated with lower cord blood concentrations of DHA and the sum of EPA + DHA. Lower cord blood AA concentrations were observed in children who were minor allele homozygous for rs3834458 (ß = 0·075; P = 0·037). Children who were minor allele carriers for rs174537, rs174561, rs174575 and rs3834458 had a lower cord blood AA:LA ratio (P < 0·05 for all). Both maternal and child FADS genotype were associated with cord LCPUFA concentrations, and therefore, the influence of FADS genotype was observed despite the high intake of preformed dietary LCPUFA from fish in this population.

Delivery Mode and Child Development at 20 Months of Age and 7 Years of Age in the Republic of Seychelles.

OBJECTIVE: To determine if cesarean delivery is adversely associated with child neurodevelopment as measured at 20 months and 7 years. METHODS: In a prospective cohort study (n = 1328) in the Republic of Seychelles, we examined the association between mode of delivery and 22 measures of child neurodevelopment spanning multiple domains: cognition, executive and psychomotor function, language development, behavior, scholastic achievement, and social communication. Using multivariable linear regression, we evaluated the relationship between delivery mode (Cesarean/vaginal delivery) and each developmental outcome, while controlling for relevant covariates including child sex and age, maternal age, maternal IQ, whether both parents lived with the child, and Hollingshead socioeconomic status. RESULTS: At 20 months, children born via cesarean delivery had slightly higher scores (ß = 0.11, 95% confidence interval: 0.00, 0.21) on the Infant Behavior Questionnaire-Revised Positive Affectivity/Surgency subtest, a measure of infant temperament, as compared to vaginal delivery. Delivery mode was not associated with any of the 7-year developmental outcomes. CONCLUSIONS FOR PRACTICE: Our study does not support the notion that cesarean delivery is associated with child neurodevelopmental outcomes.

Maternal Long-Chain Polyunsaturated Fatty Acid Status, Methylmercury Exposure, and Birth Outcomes in a High-Fish-Eating Mother-Child Cohort.

BACKGROUND: Maternal status of long-chain PUFAs (LC-PUFAs) may be related to fetal growth. Maternal fish consumption exposes the mother to the neurotoxicant methylmercury (MeHg), which, in contrast, may restrict fetal growth. OBJECTIVE: Our aim was to examine relations between maternal LC-PUFA status at 28 wk and birth outcomes (birth weight, length, and head circumference), controlling for MeHg exposure throughout pregnancy, in the Seychelles Child Development Study Nutrition Cohort 2. Our secondary aim was to examine the influence of maternal variation in genes regulating the desaturation of LC-PUFAs [fatty acid desaturase (FADS)] on birth outcomes. METHODS: From nonfasting blood samples collected at 28 wk of gestation, we measured serum total LC-PUFA concentrations and FADS1 (rs174537, rs174561), FADS1-FADS2rs3834458, and FADS2rs174575 genotypes, with hair total mercury concentrations assessed at delivery. Data were available for n = 1236 mother-child pairs. Associations of maternal LC-PUFAs, MeHg, and FADS genotype with birth outcomes were assessed by multiple linear regression models, adjusting for child sex, gestational age, maternal age, BMI, alcohol use, socioeconomic status, and parity. RESULTS: In our cohort of healthy mothers, neither maternal LC-PUFA status nor MeHg exposure were significant determinants of birth outcomes. However, when compared with major allele homozygotes, mothers who were heterozygous for the minor allele of FADS1 (rs174537 and rs174561, GT compared with TT, ß = 0.205, P = 0.03; TC compared with CC, ß = 0.203, P = 0.04) and FADS1-FADS2 (rs3834458, Tdel compared with DelDel, ß = 0.197, P = 0.04) had infants with a greater head circumference (all P < 0.05). Homozygosity for the minor allele of FADS2 (rs174575) was associated with a greater birth weight (GG compared with CC, ß = 0.109, P = 0.04). CONCLUSIONS: In our mother-child cohort, neither maternal LC-PUFA status nor MeHg exposure was associated with birth outcomes. The observed associations of variation in maternal FADS genotype with birth outcomes should be confirmed in other populations.

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.

PUFA Status and Methylmercury Exposure Are Not Associated with Leukocyte Telomere Length in Mothers or Their Children in the Seychelles Child Development Study.

Background: Leukocyte telomere length (TL) is associated with age-related diseases and early mortality, but there is a lack of data on the determinants of TL in early life. Evidence suggests that dietary intake of marine n-3 (ω-3) polyunsaturated fatty acids (PUFAs) is protective of telomere attrition, yet the effect of methylmercury exposure, also found in fish, on TL is unknown.Objective: The aim of this study was to investigate the associations between prenatal PUFA status, methylmercury exposure, and TL in mothers and children in the SCDS (Seychelles Child Development Study), for whom fish consumption is high.Methods: Blood samples collected from 229 mothers (at 28 wk gestation and delivery) and children (at 5 y of age) in the SCDS first nutrition cohort were analyzed for PUFA concentrations. Prenatal mercury was measured in maternal hair collected at delivery. Postnatal mercury was also measured in children's hair samples with the use of a cumulative metric derived from values obtained at 3-5 y of age. Relative TL was measured in blood obtained from mothers at delivery, in cord blood, and in children at 5 y of age by quantitative polymerase chain reaction. Linear regression models were used to investigate the associations between PUFA status, methylmercury exposure, and TL.Results: Neither prenatal PUFA status or methylmercury exposure was associated with TL of the mother or child or with TL attrition rate. However, a higher prenatal n-6:n-3 PUFA ratio was significantly associated with longer TLs in the mothers (ß = 0.001, P = 0.048). Child PUFA status and methylmercury exposure were not associated with child TL. However, higher family Hollingshead socioeconomic status (SES) scores at 9 mo of age were significantly associated with longer TLs in cord blood (ß = 0.005, P = 0.03).Conclusions: We found no evidence that PUFA status or methylmercury exposure are determinants of TL in either the mother or child. However, our results support the hypothesis that family SES may be associated with child TL.

Dietary selenium and mercury intakes from fish consumption during pregnancy: Seychelles Child Development Study Nutrition Cohort 2.

Some health agencies have issued precautionary principle fish advisories to pregnant women based on the presence of methylmercury (MeHg) in fish that could possibly be harmful to the developing fetus. Fish, however, is a rich source of selenium (Se) and other nutrients essential for normal brain development. Selenium is also thought to have a key role in alleviating MeHg toxicity. We estimated the dietary Se and MeHg intakes and dietary Se:Hg molar ratios from the fish consumed in a high fish-eating pregnant cohort where no adverse associations of fish consumption and outcomes has been reported. We used dietary data collected as part of the Seychelles Child Development Study Nutrition Cohort 2 (n = 1419). In this cohort 98% of participants consumed fish, with an average intake of 106.2 g per day. Daily Se intakes from fish consumption were 61.6 µg/ d, within the range recommended during pregnancy. The mean dietary Se:Hg molar ratios was 6. These findings demonstrate that fish consumption exposes pregnant Seychellois women to Se in excess of MeHg. Based on these findings, fish consumption, especially fish with Se:Hg ratios above 1, may help pregnant women achieve optimum dietary Se intakes, which may protect against MeHg toxicity.

Autism spectrum disorder phenotypes and prenatal exposure to methylmercury.

BACKGROUND: There continues to be public concern that mercury exposure and autism spectrum disorder (ASD) may be associated. The primary source of exposure to organic mercury in humans is to methylmercury from fish consumption. We evaluated the association between prenatal methylmercury exposure and ASD phenotype in children and adolescents in the Republic of Seychelles, where fish consumption is high. METHODS: We administered the Social Communication Questionnaire to parents of a cohort of 1784 children, adolescents, and young adults. The Social Responsiveness Scale was administered to teachers of 537 cohort subjects at about 10 years of age. Prenatal exposure to methylmercury was measured in maternal hair samples collected at or near the time of birth. Multivariable regression models evaluated the relationship between prenatal methylmercury exposure and ASD phenotypic scores, adjusting for relevant covariates. RESULTS: The mean prenatal methylmercury exposure for subjects in the analysis was 8.4 ppm (standard deviation [SD] = 5.7). The mean Social Communication Questionnaire score was 8.0 (SD = 4.4). The mean prenatal methylmercury exposure for subjects with Social Responsiveness Scale scores was 6.7 ppm (SD = 4.4) and the mean Social Responsiveness Scale score was 57.6 (SD = 26.8). No consistent association between prenatal methylmercury exposure and ASD screening instrument was found, using linear and nonlinear regression analyses. CONCLUSIONS: Prenatal exposure to methylmercury was not associated with ASD phenotypic behaviors in our cohort of high fish consumers. Our findings contribute to the growing literature suggesting that exposure to methylmercury does not play an important role in the development of ASD phenotypic behavior.

Choline status and neurodevelopmental outcomes at 5 years of age in the Seychelles Child Development Nutrition Study.

Choline is an essential nutrient that is found in many food sources and plays a critical role in the development of the central nervous system. Animal studies have shown that choline status pre- and postnatally can have long-lasting effects on attention and memory; however, effects in human subjects have not been well studied. The aim of the present study was to examine the association between plasma concentrations of free choline and its related metabolites in children and their neurodevelopment in the Seychelles Child Development Nutrition Study, an ongoing longitudinal study assessing the development of children born to mothers with high fish consumption during pregnancy. Plasma concentrations of free choline, betaine, dimethylglycine (DMG), methionine and homocysteine and specific measures of neurodevelopment were measured in 210 children aged 5 years. The children's plasma free choline concentration (9·17 (sd 2·09) µmol/l) was moderately, but significantly, correlated with betaine (r 0·24; P= 0·0006), DMG (r 0·15; P= 0·03), methionine (r 0·24; P= 0·0005) and homocysteine (r 0·19; P= 0·006) concentrations. Adjusted multiple linear regression revealed that betaine concentrations were positively associated with Preschool Language Scale ­ total language scores (ß = 0·066; P= 0·04), but no other associations were evident. We found no indication that free choline concentration or its metabolites, within the normal physiological range, are associated with neurodevelopmental outcomes in children at 5 years of age. As there is considerable animal evidence suggesting that choline status during development is associated with cognitive outcome, the issue deserves further study in other cohorts.

Potential role of selenium in modifying the effect of maternal methylmercury exposure on child neurodevelopment - A review.

Selenium (Se) is an essential trace element for normal neurodevelopment. It is incorporated into multiple selenoenzymes which have roles in the brain and neurological function, the synthesis of thyroid hormones, the antioxidant defense system, DNA synthesis, and reproduction. Fish is a source of both Se and neurotoxic methylmercury (MeHg). Selenium is known to ameliorate the effects of MeHg in experimental animals, but studies in children exposed to both Se and MeHg through prenatal fish consumption have been inconclusive. Research on Se's implications for pregnancy and child neurodevelopment is limited. The aims of this review are to summarize the literature on the biological roles of Se during pregnancy and the potential role in mitigating the effects of MeHg exposure from fish consumption on human health. This review has shown that Se concentrations among pregnant women globally appear insufficient, with the majority of pregnant women reporting Se concentrations below 70 µg/L during pregnancy. The role of Se in child development and its interactions with MeHg in children are inconclusive. Further investigation of the interaction between Se and MeHg in relation to child neurodevelopment in high fish-eating populations is required to fully elucidate effects.

The association of auditory function measures with low-level methylmercury from oceanic fish consumption and mercury vapor from amalgam: The Seychelles Child Development Study Nutrition 1 Cohort.

BACKGROUND: Some authors have reported that low-level exposure to methylmercury (MeHg) adversely impacts measures of auditory function. These reports, however, are not consistent in their findings. Consequently, we examined auditory function in a population exposed to low-level methylmercury (MeHg) exposure from fish consumption and to mercury vapor (Hg0) from dental amalgams. We analyzed their associations with the participants hearing acuity, absolute and interwave ABR latencies, and otoacoustic emissions (distortion product/DPOAE and click evoked/CEOAE). DESIGN: We administered an audiometry test battery to 246 participants from the Seychelles Child Development Study (SCDS) Nutrition Cohort 1 (NC1) at 9 years of age. The test battery included standard pure-tone audiometry, tympanometry, Auditory Brainstem Responses (ABR) and Distortion Product and Click Evoked Otoacoustic Emissions (DPOAE and CEOAE) testing. We measured prenatal MeHg exposure in maternal hair and postnatal MeHg in children's hair. We approximated prenatal Hg0 exposure using maternal amalgam surface area and postnatal Hg0 using children amalgam surface area. Complete exposure records and audiometric data were available on 210 participants and in them we analyzed the association of MeHg and Hg0 exposures with auditory outcomes using covariate-adjusted linear regression models adjusted for sex and tympanometric pressure. RESULTS: Hg exposures were similar for both sexes. Seven of the 210 evaluable participants examined had either a mild (5) or moderate (2) hearing loss. Four had a mild monaural hearing loss and 3 had either a mild (1) or moderate (2) bilateral hearing loss. No participant had greater than a moderate hearing loss in either ear. Hg exposures were higher in participants with either a mild or moderate hearing loss, but these differences were not statistically significant. Among the 210 with complete data, neither prenatal nor postnatal MeHg nor Hg0 exposure was statistically significantly associated with any of the ABR endpoints (p > 0.05 for all 72 associations). Neither prenatal nor postnatal Hg0 exposure was associated with any of the OAE endpoints (p > 0.05). MeHg exposure was statistically associated with 6 of the 56 DPOAE endpoints (p-values between 0.0001 and 0.023), but none of the 40 CEOAE endpoints. Two of the associations occurred with prenatal MeHg exposures and 1 of those would suggest a beneficial effect. Four of the other associations occurred with postnatal MeHg exposures with only 2 found in left ears of both males and females and the other 2 in the left and right ear of females at only one frequency. CONCLUSION: Overall, these data do not present a clear and consistent pattern to suggest that the auditory system is negatively affected by low-level methylmercury exposure due to dietary consumption of oceanic fish or mercury vapor exposure from dental amalgams.

Relationship of mercury and selenium in ocean fish frequently consumed in the Seychelles: A comparison to levels in ocean fish consumed in the US.

We characterized mercury and selenium in the fish consumed in the Seychelles Islands to determine if their levels are similar to fish consumed in the US. A secondary aim was to examine whether fish weight and species predict mercury and selenium in fish consumed in the Seychelles. We measured total mercury (THg) and selenium (Se) content of 10 samples from each of the 19 most frequently consumed fish species in Seychelles and for each calculated the Se:Hg molar ratios and the Selenium Health Benefit Value Index (HBV Se). Linear regression models examined associations with weight and species. Average MeHg levels in fish ranged from less than 0.01 ppm (streamlined spinefoot) to 0.7 ppm (bludger trevally) with an overall mean of 0.21 ± 0.23 ppm. Average Se levels ranged from 0.34 ppm (blue-barred parrot fish) to 0.93 ppm (blue-lined large-eye bream) with a mean of 0.54 ± 0.23 ppm. All fish species had a mean Se:Hg molar ratio > 1 and positive mean HBV Se index values. Weight was strongly predictive of MeHg and Se:Hg molar ratio, both across and within most species, but was less predictive of Se and HBV Se. Our study demonstrated that fish consumed in Seychelles have mercury and selenium content similar to that of fish consumed in the US. Fish in both countries have favorable positive values for Se:Hg molar ratios and HBV Se indexes. Because mercury and selenium concentrations in fish are similar to those in the US but fish consumption is substantially higher in Seychelles, the Seychellois make an ideal population in which to determine if there are adverse effects of prenatal, postnatal, and lifetime low dose MeHg exposure from fish consumption.

Fish consumption and its lipid modifying effects - A review of intervention studies.

Fish is an important source of nutrients, particularly the long chain n-3 polyunsaturated fatty acids (n-3 PUFAs). The incorporation of fish into the diet has been shown to have several health benefits, including lowering the risk of cardiovascular disease (CVD). Elevated plasma lipids are one of the main modifiable risk factors contributing to CVD and may be partly mediated by n-3 PUFAs. Although n-3 PUFAs in the form of supplementation have been shown to exert lipid modifying effects, the effects of fish consumption on the lipid profile have not been well summarised to date. Therefore, the aim of the present review is to discuss the current evidence from intervention studies investigating the effect of fish consumption on the lipid profile in both apparently healthy and non-healthy populations. Existing evidence appears to support the role of fish in promoting a shift towards a less inflammatory lipid profile through raising n-3 PUFAs and potentially lowering n-6 PUFA and triglyceride concentrations in both healthy and non-healthy populations. Fish consumption has a negligible effect on cholesterol concentrations; however, fish consumption may promote a small increase in high density lipoprotein (HDL) cholesterol amongst people with lower HDL at baseline. Limited studies have shown fish consumption to result in shifts in phospholipid and sphingolipid species and structure, albeit it is not yet clear whether these alterations have any meaningful impact on CVD risk. Future well-designed studies that utilise NMR and/or lipidomics analysis are warranted to explore the effects of these shifts in lipid content and structure in the context of disease development. Public health guidance should emphasise the cardioprotective benefits of fish and encourage consumption particularly in the Global North where fish consumption remains low.

Postnatal methylmercury exposure and neurodevelopmental outcomes at 7 years of age in the Seychelles Child Development Study Nutrition Cohort 2.

BACKGROUND: Consumption of fish yields many nutritional benefits, but also results in exposure to methylmercury (MeHg). The developing brain is known to be particularly susceptible to MeHg toxicity in high doses. However, the potential impact of low-level environmental exposure from fish consumption on children's neurodevelopment remains unclear. METHODS: We investigated postnatal MeHg exposure at 7 years and its association with a battery of 17 neurodevelopmental outcomes in a subset of children (n = 376) from 1535 enrolled mother-child pairs in Nutrition Cohort 2 of the Seychelles Child Development Study (SCDS NC2). Each outcome was modeled in relation to postnatal MeHg exposure using linear regression, adjusting for prenatal MeHg exposure, levels of maternal polyunsaturated fatty acids (PUFA), and several other covariates known to be associated with neurodevelopmental outcomes. RESULTS: Median postnatal MeHg exposure at 7 years was 2.5 ppm, while the median prenatal MeHg exposure was 3.5 ppm. We found no statistically significant associations between postnatal MeHg exposure and any of the 17 neurodevelopmental outcomes after adjusting for prenatal MeHg exposure and other covariates. CONCLUSIONS: These findings are consistent with previous cross-sectional analyses of the SCDS Main Cohort. Continued follow-up of the entire NC2 cohort at later ages with repeated exposure measures is needed to further confirm these findings.

KEAP1 polymorphisms and neurodevelopmental outcomes in children with exposure to prenatal MeHg from the Seychelles Child Development Study Nutrition Cohort 2.

BACKGROUND: Humans differ in the metabolism of the neurotoxicant methyl mercury (MeHg). This variation may be partially due to variation in genes encoding the transcription factor Nuclear factor E2-related factor 2 (NRF2) and its negative regulator Kelch-like ECH-Associated Protein 1 (KEAP1), which regulate glutathione and related transporter and antioxidant proteins that play a role in the metabolism and neurotoxicity of MeHg. AIM: To elucidate a potential risk from genetic variation in NFE2L2 (encoding NRF2) and KEAP1 toward prenatal mercury exposure and child neurodevelopmental outcomes at 20 months and 7 years of age in a population with variable prenatal exposure to MeHg from maternal fish consumption. MATERIAL AND METHODS: Nutrition Cohort 2 is a mother-child cohort in the Republic of Seychelles. Children were genotyped for NFE2L2 (rs2364723, rs13001694) and KEAP1 (rs8113472, rs9676881) polymorphisms (N = 1285 after removing siblings). Total mercury (Hg) was measured in cord blood as a biomarker for prenatal MeHg exposure. Child neurodevelopmental outcomes included the Bayley Scales of Infant Development II administered at 20 months of age, and outcomes across multiple neurodevelopmental domains from 14 tests administered in children and 3 instruments completed by parents when children were 7 years of age. RESULTS: The mean cord blood MeHg concentration was 34 (95% CI 11, 75) µg/L. None of the four polymorphisms had a significant association (p < 0.05) with either cord MeHg or neurodevelopmental test results at 20 months. There were no significant associations between either NFE2L2 polymorphism and any developmental test scores. At 7 years, children carrying KEAP1 rs8113472 CA showed significantly worse performance on psychomotor function than children with the CC variant (finger tapping, dominant hand: ß - 1.19, SE 0.34; finger tapping, non-dominant hand: ß - 0.92, SE 0.31) and worse social communication (SCQ Total: ß 0.65, SE 0.27). Children carrying rs8113472 AA, versus children with CC, showed significantly better performance on social communication (SRS Total: ß - 8.88, SE 3.60). Children carrying KEAP1 rs9676881 AG, versus children with GG, showed significantly worse performance on psychomotor function (trailmaking A time: ß 8.66, SE 3.37) and cognition (KBIT Matrices: ß - 0.96, SE 0.36). CONCLUSION: No associations between NFE2L2 and KEAP1 polymorphisms and MeHg concentration were identified. However, at 7 years, KEAP1 polymorphisms were associated with differences in neurodevelopmental outcomes in children from a population with high fish intake.

Maternal PUFA status but not prenatal methylmercury exposure is associated with children's language functions at age five years in the Seychelles.

Evidence from the Seychelles Child Development Nutrition Study suggests that maternal nutritional status can modulate the relationship between prenatal methylmercury (MeHg) exposure and developmental outcomes in children. The aim of this study was to investigate whether maternal PUFA status was a confounding factor in any possible associations between prenatal MeHg exposure and developmental outcomes at 5 y of age in the Republic of Seychelles. Maternal status of (n-3) and (n-6) PUFA were measured in serum collected at 28 wk gestation and delivery. Prenatal MeHg exposure was determined in maternal hair collected at delivery. At 5 y of age, the children completed a comprehensive range of sensitive developmental assessments. Complete data from 225 mothers and their children were available for analysis. Multiple linear regression analyses revealed Preschool Language Scale scores of the children improved with increasing maternal serum DHA [22:6(n-3)] concentrations and decreased with increasing arachidonic acid [20:4(n-6)] concentrations, albeit verbal intelligence improved with increasing (n-6) PUFA concentrations in maternal serum. There were no adverse associations between MeHg exposure and developmental outcomes. These findings suggest that higher fish consumption, resulting in higher maternal (n-3) PUFA status, during pregnancy is associated with beneficial developmental effects rather than detrimental effects resulting from the higher concomitant exposures of the fetus to MeHg. The association of maternal (n-3) PUFA status with improved child language development may partially explain the authors' previous finding of improving language scores, as prenatal MeHg exposure increased in an earlier mother-child cohort in the Seychelles where maternal PUFA status was not measured.

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.

Contribution of child ABC-transporter genetics to prenatal MeHg exposure and neurodevelopment.

BACKGROUND: There is emerging evidence that exposure to prenatal methylmercury (MeHg) from maternal fish consumption during pregnancy can differ between individuals due to genetic variation. In previous studies, we have reported that maternal polymorphisms in ABC-transporter genes were associated with maternal hair MeHg concentrations, and with children's early neurodevelopmental tests. In this study, we add to these findings by evaluating the contribution of genetic variation in children's ABC-transporter genes to prenatal MeHg exposure and early child neurodevelopmental tests. METHODS: We genotyped six polymorphisms (rs2032582, rs10276499 and rs1202169 in ABCB1; rs11075290 and rs215088 in ABCC1; rs717620 in ABCC2) in DNA from cord blood and maternal blood of the Seychelles Child Development Study Nutrition Cohort 2. We determined prenatal MeHg exposure by measuring total mercury (Hg) in cord blood by atomic fluorescence spectrometry. We assessed neurodevelopment in children at approximately 20 months using the Bayley Scales of Infant Development (BSID-II). We used linear regression models to analyze covariate-adjusted associations of child genotype with cord MeHg and BSID-II outcomes (Mental Developmental and Psychomotor Developmental Indexes). We also evaluated interactions between genotypes, cord MeHg, and neurodevelopmental outcomes. All models were run with and without adjustment for maternal genotype. RESULTS: Of the six evaluated polymorphisms, only ABCC1 rs11075290 was associated with cord blood MeHg; children homozygous for the T-allele had on average 29.99 µg/L MeHg in cord blood while those homozygous for the C-allele had on average 38.06 µg/L MeHg in cord blood (p < 0.001). No polymorphisms in the children were associated with either subscale of the BSID. However, the association between cord MeHg and the Mental Developmental Index (MDI) of the BSID differed significantly across the three genotypes of ABCB1 rs10276499 (2df F-test, p = 0.045). With increasing cord MeHg, the MDI decreased (slope=-0.091, p = 0.014) among children homozygous for the rare C-allele. CONCLUSIONS: These findings support the possibility that child ABC genetics might influence prenatal MeHg exposure.

Socioeconomic position and cognitive function in the Seychelles: a life course analysis.

OBJECTIVE: Poorer socioeconomic conditions early in life have been linked with memory, attention and learning deficits in adulthood, as well as with specific areas of educational achievement. It remains unclear, however, whether these distal associations are mediated by more current socioeconomic factors. In this study, we sought to confirm the relation between early-life socioeconomic position (SEP) and adult cognitive function, and to examine potential mediation by contemporaneous SEP. METHODS: Data from 463 young adults from the Main Cohort of the Seychelles Child Development Study were analyzed using subtests of the Cambridge Neurological Test Automated Battery and the Woodcock Johnson Test of Scholastic Achievement in relation to maternal Hollingshead Social Status Index scores at study enrollment (infancy), follow-up at 107 months, and follow-up at 17 years. RESULTS: Findings include evidence of a link between infant-period SEP and 17-year memory, which was not mediated by childhood and 17-year SEP. Verbal and mathematical achievement at 17 years was associated with SEP at all points in the life course. CONCLUSIONS: SEP at different points during the young-adult life course may affect different cognitive domains later in life, which may provide targets for societal investment in ensuring adequate family resources throughout childhood and adolescence.