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 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.

Discovering structure in multiple outcomes models for tests of childhood neurodevelopment.

Bayesian model-based clustering provides a powerful and flexible tool that can be incorporated into regression models to better understand the grouping of observations. Using data from the Seychelles Child Development Study, we explore the effect of prenatal methylmercury exposure on 20 neurodevelopmental outcomes measured in 9-year-old children. Rather than cluster individual subjects, we cluster the outcomes within a multiple outcomes model. By using information in the data to nest the outcomes into groups called domains, the model more accurately reflects the shared characteristics of neurodevelopmental domains and improves estimation of the overall and outcome-specific exposure effects by shrinking effects within and between domains selected by the data. The Bayesian paradigm allows for sampling from the posterior distribution of the grouping parameters; thus, inference can be made about group membership and their defining characteristics. We avoid the often difficult and highly subjective requirement of a priori identification of the total number of groups by incorporating a Dirichlet process prior to form a fully Bayesian multiple outcomes model.

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.

Health conditions, functional status and health care utilization in adults with cerebral palsy.

Aim: Health conditions in children with cerebral palsy (CP) are well described, yet health is less defined with advancing age. We examined health conditions, functional status and health care utilization in adults with CP across age groups. Methods: We collected cross-sectional data on health conditions, functional status and utilization from the medical records of adults with CP across a large university-affiliated primary care network using the Rochester Health Status Survey IV (RHSS-IV), a 58-item validated survey. Data from the National Health and Nutrition Examination Survey and National Health Interview Survey provided prevalence estimates for the general population as comparison. Results: Compared to the general population, adults with CP had higher rates of seizure disorder, obesity and asthma across all ages. Adults with CP under 30 years of age had higher rates of hypertension (16.7 versus 5.6%; P = 0.04), urinary incontinence (41.7 versus 10.5%; P < 0.001) and depression (16.7 versus 6.9%; P = 0.07). Conversely, there were lower rates of alcohol misuse, tobacco/nicotine and sexually transmitted illnesses. Independence with all activities of daily living decreased from 37.5% at 18-29 years of age to 22.5% in those 60 and over. Seizure disorders, urinary incontinence and gastroesophageal reflux disease were all independently associated with lower functional status. As expected, health care utilization increased with advancing age. Conclusions: Adults with CP should be monitored for conditions occurring at higher prevalence in CP, as well as common conditions occurring with advancing age. Age-related functional decline should be anticipated, especially with coexisting seizure disorders and urinary incontinence.

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.

Health Conditions and Functional Status in Adults with Autism: A Cross-Sectional Evaluation.

BACKGROUND: Children and adolescents with autism spectrum disorder (ASD) have many well-known health concerns, yet health conditions in adults with ASD remain poorly defined. OBJECTIVE: To examine health conditions and functional status in adults with ASD and identify factors associated with health and functional status across age cohorts. DESIGN AND SUBJECTS: We collected cross-sectional data from 255 adult subjects aged 18 to 71 years with ASD using the Rochester Health Status Survey IV (RHSS-IV), a 58-item validated survey instrument. We used the National Health and Nutritional Examination Survey and National Health Interview Survey to provide comparative prevalence rates in the general population. RESULTS: Compared to the general population, young adults aged 18-29 with ASD had a substantially higher prevalence of seizure disorder (11.2 % vs. 1.4 %; p = 0.002), depression (16.4 % vs. 6.4 %; p = 0.007), hypertension (12.9 % vs. 6.3 %; p = 0.05), and allergies (39.7 % vs. 8.4 %; p < 0.001). In contrast, young adults with ASD had considerably lower rates of sexually transmitted illness (STI) (0.9 % vs. 4.3 %; p = 0.03), tobacco use (5.2 % vs. 31.9 %; p < 0.001), and alcohol misuse (0.9 % vs. 11.9 %; p < 0.001). Adults 40 and over with ASD also had higher rates of seizure disorder (29.2 % vs. 1.7 %; p < 0.001), lower tobacco use (2.8 % vs. 24.5 %; p < 0.001), and lower alcohol misuse (1.4 % vs. 18.2 %; p < 0.001) compared to the general population. Amongst the 55 % of participants with a documented IQ score, 91 % had an intellectual disability (IQ < 70). Within the cohort aged 40 years old and older, only 54.2 % were independent with eating, 43.0 % independent with dressing, and 43.1 % independent with bathing. Lower IQ and depression were associated with lower functional status. CONCLUSIONS: Adults with ASD have a high prevalence of seizure disorders and depression, but low rates of STIs, tobacco use, and alcohol misuse. Within our cohort, the majority of older adults with ASD required some assistance with activities of daily living.

Life course health and healthcare utilization among adults with spina bifida.

AIM: To evaluate the prevalence of organ system disorders and describe healthcare utilization among adults with spina bifida at a regional clinic. METHOD: This study was a structured chart review using the Rochester Health Status Survey-IV. 65 males, 57 females aged 16 to 59 years were seen at the Spina Bifida Center of Central New York between January 2007 and December 2008 (annual hospitalization rate was 15 out of 100). RESULTS: Hospitalizations and acute outpatient visits were associated with having shunted hydrocephalus, whereas visits to the emergency department were associated with having a decubitus ulcer. Logistic regression models revealed that older adults made proportionately fewer visits to primary care providers than younger adults (odds ratio 0.919; p=0.02). Yet for every 1-year increase in age, the odds of being hospitalized increased by 5% (odds ratio 1.051; p=0.03). INTERPRETATION: Adults with spina bifida have multiple organ-system disorders. They have greater difficulty accessing services, and utilize emergency and inpatient healthcare at higher rates than the general population. In the future, adults with spina bifida will require access to more medical care and preventive services if they are to have optimal health, well-being, and functioning.

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.

Early-stage primary school children attending a school in the Malawian School Feeding Program (SFP) have better reversal learning and lean muscle mass growth than those attending a non-SFP school.

In developing countries, schoolchildren encounter a number of challenges, including failure to complete school, poor health and nutrition, and poor academic performance. Implementation of school feeding programs (SFPs) in less developed countries is increasing and yet there is mixed evidence regarding their positive effects on nutrition, education, and cognition at the population level. This study evaluated cognitive and anthropometric outcomes in entry-level primary school children in Malawi with the aim of generating evidence for the ongoing debate about SFPs in Malawi and other developing countries. A total of 226 schoolchildren aged 6-8 y in 2 rural Malawian public primary schools were followed for one school year. Children attending one school (SFP school) received a daily ration of corn-soy blend porridge, while those attending the other (non-SFP school) did not. Baseline and post-baseline outcomes included the Cambridge Neurological Test Automated Battery cognitive tests of paired associate learning, rapid visual information processing and intra-extra dimensional shift, and anthropometric measurements of weight, height, and mid-upper arm circumference (MUAC). At follow-up, the SFP subcohort had a greater reduction than the non-SFP subcohort in the number of intra-extra predimensional shift errors made (mean 18.5 and 24.9, respectively; P-interaction = 0.02) and also showed an increase in MUAC (from 16.3 to 17.0; P-interaction <0.0001). The results indicate that the SFP in Malawi is associated with an improvement in reversal learning and catch-up growth in lean muscle mass in children in the SFP school compared with children in the non-SFP school. These findings suggest that the Malawian SFP, if well managed and ration sizes are sustained, may have the potential to improve nutritional and cognitive indicators of the most disadvantaged children.

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.

Nutritional and cognitive status of entry-level primary school children in Zomba, rural Malawi.

Entry-level Malawian children (n = 226) aged 6-8 years from two public primary schools, one a participant in a national school feeding programme (FP), the other not, were investigated for differences in nutritional and cognitive status. Stunted growth (42%) and underweight (25%) were prevalent, with no significant differences between the schools, although the school attended was a significant predictor of mid-upper arm circumference. Previous attendance at a community-based childcare centre was significantly associated with lower body weight and height. There were no significant differences in memory, reversal learning and attention outcomes between the schools. These findings report no major significant difference in nutrition or cognitive statuses between the schools, and on this basis suggest that both schools were equally in need of FP participation. More inclusive interventions and broadening/review of FP participation criteria are recommended.

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.

Associations between serum taurine concentrations in mothers and neonates and the children's anthropometrics and early neurodevelopment: Results from the Seychelles Child Development Study, Nutrition Cohort 2.

BACKGROUND: High concentrations of taurine are present in the developing human brain and maternal breast milk. Taurine is thought to influence fetal growth and brain development based on experimental rodent studies. As fish is an important dietary source of taurine, we investigated associations between taurine concentrations and child outcomes in a high fish consuming population. OBJECTIVE: To examine associations between maternal and cord serum taurine concentrations and birth anthropometric measures and cognitive development in children at 20 months of age. METHODS: Pregnant women were recruited between 2008 and 2011 as part of Nutrition Cohort 2 (NC2) of the Seychelles Child Development Study (SCDS). Maternal taurine serum concentrations were measured at 28 week's gestation and in cord serum. Child weight, length and head circumference were measured at birth and neurodevelopment was assessed using Bayley Scales of Infant Development II (BSID-II) at 20 months of age. Associations between taurine status, birth measures and neurodevelopmental outcomes were examined (n = 300) using regression models and adjusted for relevant covariates. RESULTS: Mean (SD) maternal and cord taurine concentrations were 124.9 (39.2) µmol/L (range 28.2-253.9 µmol/L) and 187.6 (60.0) µmol/L (range 55.0-417.4 µmol/L) respectively. We found no associations between maternal taurine concentrations and child anthropometric and neurodevelopmental measures (weight ß = -0.001, SE=0.001; length ß = -0.006, SE=0.006; head circumference ß = -0.002, SE=0.002; MDI ß = -0.005, SE=0.015; PDI ß = -0.004, SE=0.016; all P > 0.05), or between cord taurine concentrations and outcomes (weight ß = -0.001, SE<0.000; length ß = -0.001, SE=0.004; head circumference ß < 0.000, SE=0.002; MDI ß = 0.004, SE=0.010; PDI ß = -0.015, SE=0.012; all P > 0.05). CONCLUSION: The Seychellois population have high maternal and cord taurine concentrations owing to their high fish intake and may be considered taurine replete compared to individuals who consume a Westernised diet. This high taurine status may explain why there were no significant associations between maternal and cord taurine concentrations and outcomes after adjusting for covariates.

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.

Varying coefficient function models to explore interactions between maternal nutritional status and prenatal methylmercury toxicity in the Seychelles Child Development Nutrition Study.

Maternal consumption of fish during the gestational period exposes the fetus to both nutrients, especially the long-chain polyunsaturated fatty acids (LCPUFAs), believed to be beneficial for fetal brain development, as well as to the neurotoxicant methylmercury (MeHg). We recently reported that nutrients present in fish may modify MeHg neurotoxicity. Understanding the apparent interaction of MeHg exposure and nutrients present in fish is complicated by the limitations of modeling methods. In this study we fit varying coefficient function models to data from the Seychelles Child Development Nutrition Study (SCDNS) cohort to assess the association of dietary nutrients and children's development. This cohort of mother-child pairs in the Republic of Seychelles had fish consumption averaging 9 meals per week. Maternal nutritional status was assessed for five different nutritional components known to be present in fish (n-3 LCPUFA, n-6 LCPUFA, iron status, iodine status, and choline) and associated with children's neurological development. We also included prenatal MeHg exposure (measured in maternal hair). We examined two child neurodevelopmental outcomes (Bayley Scales Infant Development-II (BSID-II) Mental Developmental Index (MDI) and Psychomotor Developmental Index (PDI)), each administered at 9 and at 30 months. The varying coefficient models allow the possible interactions between each nutritional component and MeHg to be modeled as a smoothly varying function of MeHg as an effect modifier. Iron, iodine, choline, and n-6 LCPUFA had little or no observable modulation at different MeHg exposures. In contrast the n-3 LCPUFA docosahexaenoic acid (DHA) had beneficial effects on the BSID-II PDI that were reduced or absent at higher MeHg exposures. This study presents a useful modeling method that can be brought to bear on questions involving interactions between covariates, and illustrates the continuing importance of viewing fish consumption during pregnancy as a case of multiple exposures to nutrients and to MeHg. The results encourage more emphasis on a holistic view of the risks and benefits of fish consumption as it relates to infant development.