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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 (β 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.

Background The achievement of target 25-hydroxyvitamin D [25(OH)D] concentrations in pregnancy may be altered by maternal obesity. Objective The authors examined the effects of maternal supplementation of 10 μg compared with 20 μg vitamin D3/d on maternal and umbilical cord 25(OH)D. The secondary aim was to investigate the influence of maternal BMI (in kg/m2) on the response of the primary outcomes. Methods The authors performed a 2-arm parallel double-blind randomized trial with 240 pregnant women recruited throughout the year in Northern Ireland. Women were stratified by BMI to receive 10 or 20 µg vitamin D3/d from 12 gestational wk (GW) until delivery. Maternal blood samples collected at 12, 28, and 36 GW and from the umbilical cord were analyzed for total serum 25(OH)D. A total of 166 women completed the study. Results Mean ± SD 25(OH)D at 36 GW was 80.8 ± 28.2 compared with 94.4 ± 33.2 nmol/L (P < 0.001) (10 compared with 20 µg vitamin D3/d, respectively). In those classified with 25(OH)D

Objective Mild to moderate iodine deficiency during pregnancy has been associated with adverse neurodevelopmental outcomes in offspring. Few research studies to date combine assessment of urinary iodine (UIC and/or ICr), biomarkers that best reflect dietary intake, with reported dietary intake of iodine rich foods in their assessment of iodine deficiency. Thus, a systematic review was conducted to incorporate both these important measures. Design Using PRISMA guidelines, a comprehensive search was conducted in three electronic databases (EMBASE®, MedLine® and Web of Science®) from January 1970–March 2021. Quality assessment was undertaken using the Newcastle Ottawa Scale. Eligible studies included reported assessment of iodine status through urinary iodine (UIC and/or ICr) and/or dietary intake measures in pregnancy alongside neurodevelopmental outcomes measured in the children. Data extracted included study author, design, sample size, country, gestational age, child age at testing, cognitive tests, urinary iodine assessment (UIC in μg/L and/or ICr in μg/g), dietary iodine intake assessment and results of associations for the assessed cognitive outcomes. Results Twelve studies were included with nine reporting women as mild-moderately iodine deficient based on World Health Organization (WHO) cut-offs for urinary iodine measurements Conclusion The majority of studies classified pregnant women to be mild-moderately iodine deficient based on urinary iodine assessment (UIC and/or ICr) and/or dietary intakes, with subsequent offspring neurodevelopment implications identified. Although a considerable number of studies did not report an adverse association with neurodevelopmental outcomes, these findings are still supportive of ensuring adequate dietary iodine intakes and urinary iodine monitoring throughout pregnancy due to the important role iodine plays within foetal neurodevelopment. This review suggests that dietary intake data may indicate a stronger association with cognitive outcomes than urinary iodine measurements alone. The strength of this review distinguishes results based on cognitive outcome per urinary iodine assessment strategy (UIC and/or ICr) with dietary data. Future work is needed respecting the usefulness of urinary iodine assessment (UIC and/or ICr) as an indicator of deficiency whilst also taking account of dietary intakes.

This prospective, descriptive study assessed caring practices of pet cat and dog owners in Northern Ireland with a survey questionnaire, focusing primarily on feeding and exercising. Owners of both pet cats and dogs reported that they fed their pets either twice or three times a day (53 and 78% for cats and dogs, respectively). However, in the case of nearly 40% of pet cat owners it transpired that they fed their cat(s) as often as the animal demanded (18.8%) or that food was available all the time (20.7%). Cat owners reported that their pets had access to outdoors (84%) and were not provided with any play time (53.1%). The highest number of pet dogs (46.1%) were reported as being walked daily for less than 1 h, and the highest number (38.4%) were played with daily for less than 1 h. Both cat (60%) and dog (61%) owners perceived the body condition of their animal ‘as it should be’ for animal age/sex. However, both pet cat (76%) and dog (63%) owners reported that neither their pet's bodyweight nor its body condition was monitored. Our results suggest not all pet cat and dog owners are aware of the fundamentals of their animals’ feeding requirements as regards health and many provide insufficient physical activity required for their animals’ health and welfare. The major strengths of the study include the size and geographic distribution of the study population allowing the generalisation of the results to other locations.

BACKGROUND: Fish is a primary source of protein and n-3 PUFA but also contains methylmercury (MeHg), a naturally occurring neurotoxicant to which, at sufficient exposure levels, the developing fetal brain is particularly sensitive. OBJECTIVES: To examine the association between prenatal MeHg and maternal status of n-3 and n-6 PUFA with neurodevelopment, and to determine whether PUFA might modify prenatal MeHg associations with neurodevelopment. METHODS: We examined the Seychelles Child Development Study Nutrition Cohort 2 (NC2) at age 7 y. We used a sophisticated and extensive neurodevelopmental test battery that addressed 17 specific outcomes in multiple neurodevelopmental domains: cognition, executive and psychomotor function, language development, behavior, scholastic achievement, and social communication. Analyses were undertaken on 1237 mother-child pairs with complete covariate data (after exclusions) and a measure of at least 1 outcome. We examined the main and interactive associations of prenatal MeHg exposure (measured as maternal hair mercury) and prenatal PUFA status (measured in maternal serum at 28 weeks' gestation) on child neurodevelopmental outcomes using linear regression models. We applied the Bonferroni correction to account for multiple comparisons and considered P values

Purpose Long-chain polyunsaturated fatty acids (LCPUFA) can be synthesised endogenously from linoleic acid (LA) and α-linolenic acid (ALA) in a pathway involving the fatty acid desaturase (FADS) genes. Endogenous synthesis is inefficient; therefore, dietary intake of preformed LCPUFA from their richest source of fish is preferred. This study investigated the effect of fish consumption on PUFA concentrations in women of childbearing age while stratifying by FADS genotype. The influence of fish consumption on lipid profile, and markers of inflammation and oxidative stress was also examined. Methods Healthy women (n = 49) provided a buccal swab which was analysed for FADS2 genotype (rs3834458; T/deletion). Participants were stratified according to genotype and randomised to an intervention group to receive either no fish (n = 18), 1 portion (n = 14) or 2 portions (n = 17) (140 g per portion) of fish per week for a period of 8 weeks. Serum PUFA was analysed at baseline and post-intervention. Lipid profile, and markers of inflammation and oxidative stress were also analysed. Results Participants consuming 2 portions of fish per week had significantly higher concentrations of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and total n-3 PUFA, and a lower n-6:n-3 ratio compared to those in the no fish or 1 portion per week group (all p Conclusion Consumption of 2 portions of fish per week has beneficial effects on biological n-3 PUFA concentrations in women of childbearing age; however, no effects on oxidative stress, inflammation or lipid profile were observed. This trial was registered at www.clinicaltrials.gov (NCT03765580), registered December 2018.

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, β = 0.205, P = 0.03; TC compared with CC, β = 0.203, P = 0.04) and FADS1-FADS2 (rs3834458, Tdel compared with DelDel, β = 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, β = 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. (Less)

Background Maternal thyroid hormones facilitate optimal foetal neurodevelopment, however the exact role of the thyroid hormones on specific cognitive outcomes is unknown. Objectives This study aimed to investigate associations between maternal thyroid function and neurodevelopmental outcomes at 20 months in the Seychelles Child Development Study (SCDS, n=1535). Methods Maternal free thyroid hormones (fT3, fT4 and fTSH) were assessed at 28 weeks gestation with a range of child cognitive outcomes analysed at 20 months. Dietary iodine intake was analysed for a subset of women through a Food Frequency Questionnaire (FFQ) (n=422), with a median iodine intake of 233µg/d, slightly below the recommended iodine intake for pregnancy as advised by the WHO (>250µg/d). Linear regression analysis was used to test associations between serum concentrations of fT3, fT4 and fTSH and child cognitive outcomes. Thyroid hormones were analysed both as continuous data and also categorised as quintiles. 95% of mothers had optimal thyroid function based on their TSH concentrations. Results Results show that maternal fT3, fT4 and TSH were not significantly associated with any cognitive outcomes at 20 months in this high fish-eating population. However, a positive association, using quintiles for fT3, was reported for Motor Development Index (MDI; a subtest of the Bayley’s Scales of Infant Development), between Q3 vs Q4 (β 0.073; p 0.043) and for Q3 vs Q5 (β value 0.086; p 0.018). Conclusions Thus, it is possible mothers in our cohort, who largely have optimal thyroid function and iodine intakes, are able to regulate thyroid function throughout pregnancy to meet neurodevelopmental needs. However, it is likely that minor imbalances of fT3, as indicated from our quintile analysis, may impact offspring neurodevelopment. Thus, further investigation is warranted, particularly focusing on thyroid hormone fluctuation throughout pregnancy in relation to possible associations with infant neurodevelopment.

Background: Fish contains methylmercury (MeHg) which can cause oxidative stress and neurodevelopmental toxicity at sufficiently high doses. Fish also contains polyunsaturated fatty acids (PUFA) which have both antioxidant (n-3) and oxidant (n-6) properties. Mitochondrial DNA (mtDNA) is sensitive to oxidative stress but has not been previously studied in relation to MeHg exposure or PUFA status. Objective: To investigate the associations between MeHg exposure and PUFA status during pregnancy with relative mitochondrial DNA copy number (RmtDNAcn) in mothers and their newborns. Methods: In total, 1488 mother-child pairs from the Seychelles Child Development Study Nutrition Cohort 2 were included in this study. Total Hg was measured in maternal blood collected at 28 weeks' gestation, maternal hair at delivery, and in fetal cord blood. PUFA (n-3 and n-6) were measured only in maternal blood. RmtDNAcn was measured by qPCR in both maternal and cord blood. Results: Increasing maternal blood Hg (β = 0.001, 95%CI: 0.000, 0.002) and n-3 PUFA concentrations (β = 0.183, 95%CI: 0.048, 0.317) were associated with higher maternal RmtDNAcn. Increasing maternal n-6 PUFA (β = −0.103, 95%CI: −0.145, −0.062) and n-6/n-3 ratio (β = −0.011, 95%CI: −0.017, −0.004) were associated with lower maternal RmtDNAcn. Increasing fetal cord blood Hg was associated with lower fetal RmtDNAcn (β = −0.002, 95%CI: −0.004, −0.000). Neither maternal blood Hg nor PUFA status was associated with fetal RmtDNAcn. Conclusions: Our findings suggest that MeHg and PUFA may influence mitochondrial homeostasis although the magnitude of these associations are small. Future studies should confirm the findings and explore the underlying mechanisms. Keywords: Mitochondrial DNA, Methylmercury, Mercury, Polyunsaturated fatty acids

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 (β = 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.

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-1β, 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 (β = −0.667; p = 0.007) and lower total Th2 (IL-4, IL-10 and IL-13) (β = −0.715; p = 0.036). In the interaction model, MeHg and IL-1β was positive and significantly different from zero in the lowest n-6:n-3 ratio tertile (β = 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.

Emma L Carson,1 L Kirsty Pourshahidi,1 Sharon M Madigan,2 Francina R Baldrick,1 Martin G Kelly,3 Eamon Laird,4 Martin Healy,5 JJ Strain,1 Maria S Mulhern1 1Nutrition Innovation Centre for Food and Health (NICHE), School of Biomedical Sciences, University of Ulster, Coleraine, Co. Londonderry, UK; 2Respiratory Dietitian, Pulmonary Rehabilitation Team, Belfast Health and Social Care Trust, Belfast, UK; 3Respiratory Team, Altnagelvin Hospital, Western Health and Social Care Trust, Londonderry, UK; 4School of Medicine, Trinity College, Dublin, Ireland; 5Department of Biochemistry, Central Pathology Laboratory, St James Hospital, Dublin, Ireland Background: Owing to hospitalization, reduced functional capacity and consequently, less sunlight exposure, suboptimal vitamin D status (25-hydroxyvitamin D [25(OH)D]

Context The metabolism of thyroid hormones, which are essential for normal development, involves many proteins and enzymes. It requires iodine as a key component but is also influenced by several other micronutrients, including selenium, zinc, iron, and vitamin A. Objective This systematic review was designed to investigate the effect of micronutrient status and supplementation on iodine status and thyroid hormone concentrations. Data sources Using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines, electronic databases were searched from their inception to April 2016. Study selection Human studies published in English and reporting data on micronutrient status and iodine status and/or thyroid hormone concentrations were included. Studies that examined the effect of micronutrient supplementation on iodine status and/or thyroid hormone concentrations were also included. Data extraction A predesigned and piloted data extraction form was used to compile data from individual studies. Results A total of 57 studies were included: 20 intervention studies and 37 observational studies. Although observational evidence suggests that concentrations of selenium, zinc, and iron are positively associated with iodine status, data from randomized controlled trials fail to confirm this relationship. Conclusions Further studies are needed to provide greater understanding of the role of micronutrient status in iodine nutrition and thyroid function to ascertain the public health implications for populations worldwide.

Context Polyunsaturated fatty acids (PUFA) are important during pregnancy for fetal development and child health outcomes. The fatty acid desaturase (FADS) genes also influence PUFA status, with the FADS genes controlling how much product (eg, arachidonic acid, eicosapentaenoic acid, and docosahexaenoic acid) is metabolized from the precursor molecules linoleic acid and α-linolenic acid. Objective The current review discusses the influence of FADS genotype on PUFA status of pregnant women, breast milk, and children, and also how FADS may influence child health outcomes. Data sources The Ovid Medline, Scopus, Embase, Cochrane Library, CINAHL Plus, PubMed and Web of Science databases were searched from their inception to September 2018. Data extraction Eligible studies reported FADS genotype and blood concentrations of PUFA during pregnancy, in childhood, breast milk concentrations of PUFA or child health outcomes. Data analysis In pregnant and lactating women, minor allele carriers have higher concentrations of linoleic acid and α-linolenic acid, and lower concentrations of arachidonic acid, in blood and breast milk, respectively. In children, FADS genotype influences PUFA status in the same manner and may impact child outcomes such as cognition and allergies; however, the direction of effects for the evidence to date is not consistent. Conclusion Further studies are needed to further investigate associations between FADS and outcomes, as well as the diet-gene interaction.

Maternal BMI has been shown to be inversely correlated with vitamin D status (25-hydroxyvitamin D (25(OH)D) concentrations) during pregnancy. Pregnant women with obesity and with vitamin D deficiency are at risk of many adverse health outcomes in pregnancy.The aim of this study was to examine differences in maternal vitamin D status across normal weight, overweight and obese pregnant women in early pregnancy.Data collected at baseline from a double-blind randomised vitamin D intervention study (MO-VITD) were used. Pregnant women without pregnancy complications, aged > 18 years and having a singleton pregnancy were recruited between January 2016 and August 2017 at antenatal clinics in the Western Health and Social Care Trust, Northern Ireland. Non-fasting blood samples were collected at 12 weeks gestation and analysed for total serum 25(OH)D, using liquid chromatography tandem mass spectrometry. Data from 239 pregnant women (80 normal weight, 79 overweight, 80 obese) were included in the current analysis.The mean ± SD 25(OH)D concentration of all pregnant women at 12 weeks gestation was 52.0 ± 21.6 nmol/L. Women classed as obese or overweight had significantly lower 25(OH)D concentrations compared to women of normal weight (48.8 ± 20.3 vs 49.8 ± 20.4 vs. 57.5 ± 23.1 nmol/L, P = 0.019; obese, overweight, normal weight respectively). A total of 45% of all pregnant women were found to be either vitamin D deficient (25(OH)D < 25nmol/L; 13%) or insufficient (25–50 nmol/L; 32%) in early pregnancy. BMI was significantly negatively correlated with 25(OH)D concentrations (r = -0.168; P = 0.009). Regression analyses showed that BMI (β = -0.165; P = 0.006), season (β = 0.220; P = < 0.0001), supplement use (β = -0.268; P < 0.0001) and a sun holiday within the previous 6 months (β = -0.180; P = 0.010) were significant predictors of 25(OH)D concentrations. In early pregnancy, 62% of pregnant women reported using a supplement containing vitamin D and 38% reported no supplement use. Supplement users had a significantly higher vitamin D status than non-supplement users in all BMI categories but overall, 37% of supplement users were still classified as vitamin D insufficient. Vitamin D status was significantly lower in winter months compared to summer months. In early pregnancy, especially during winter months, pregnant women with obesity, particularly non-supplement users, are at higher risk of low vitamin D status. Based on the lower vitamin D status observed in early pregnancy in obese women, the effect of BMI on vitamin D supplementation throughout pregnancy needs to be examined.

Optimal maternal polyunsaturated fatty acid (PUFA) status is essential for foetal development. The desaturase enzymes, encoded by the fatty acid desaturase (FADS) genes, are involved in the endogenous synthesis of long chain (LC)PUFA and influence maternal LCPUFA concentrations. The minor allele of various FADS SNPs has been associated with increased maternal concentrations of the precursors linoleic acid (LA) and α-linolenic acid (ALA), and lower concentrations of the LCPUFA arachidonic acid (AA) and docosahexaenoic acid (DHA); however, there is limited research to date on the influence of FADS genotype on cord PUFA status. The aim of the current study was to investigate the influence of maternal and child genetic variation on cord blood PUFA status in a high fish-eating cohort.Cord blood samples collected from mother-child pairs (n = 1088) taking part in the Seychelles Child Development Study (SCDS) Nutrition Cohort 2 (NC2) were analysed for total serum PUFA. Maternal (n = 1088) and child genotype (n = 592) were determined for the FADS SNPs rs174537, rs174561, rs174575, and rs3834458. Regression analysis determined associations between maternal and child FADS genotype and cord PUFA status. In all regression models, the major allele homozygote genotype for each SNP was used as the reference group.Directions of significant associations were as predicted. In mothers, the minor allele homozygote genotype for SNPs rs174537, rs174561 and rs3834458 was associated with lower cord DHA and lower total n-3 PUFA when compared to the major allele homozygous genotype (p < 0.05 for all). The heterozygous genotype was associated with increased concentrations of LA compared to the reference genotype for rs174561 (p = 0.021) and rs383448 (p = 0.023). In children, the heterozygous genotype was associated with lower AA concentrations and lower cord n-6:n-3 ratio for all SNPs (p < 0.05 for all) compared to those with the major allele homozygous genotype. A lower cord AA:LA ratio was also observed for children heterozygous for rs174547, rs174561 and rs174575 (p < 0.05 for all). Contrary to expected, there were no associations between cord PUFA concentrations and child minor allele homozygous genotype.The current study indicates that variation in maternal and child FADS genotype influences cord PUFA concentrations, despite the high intake of preformed dietary LCPUFA from fish in this population. The sample size for minor allele homozygous children was likely too small to observe any statistically significant associations in the current analysis. Further research is needed to determine whether increased dietary intake can compensate for lower PUFA status as a result of FADS genotype.

The association of MeHg exposure through fish consumption on human autoimmunity remains unclear. Fish also contain n-3 long chain polyunsaturated fatty acids (LCPUFA) that are known to regulate inflammation and mitigate autoimmune disease symptoms. We studied the association of low-level exposure to methylmercury (MeHg) through fish consumption in the SCDS. We examined this association at age 19 years in the SCDS Main Cohort (n = 497). We measured MeHg exposure at 3 time points [prenatal, weighted average (6 months to 19 years) and concurrent (19 years) and LCPUFA status and a panel of 13 autoimmune markers at age 19 years. The autoimmune markers included antinuclear antibodies (ANA), anti-dsDNA and anti-RNP, and total (non-specific) immunoglobulins (Ig) IgG, IgA, and IgM. A combined ANA variable was also calculated based on being within or above reference range for any of the ANA markers; 56% of the subjects met this criterion. Multivariable regression models adjusted for prenatal MeHg, sex and waist circumference, with and without adjustment for LCPUFA, were fit for the three MeHg exposure metrics and each immune marker. Mean (SD) prenatal, weighted average and concurrent MeHg was 6.84 (4.55), 7.46 (2.82), and 10.23 (6.02) ppm, respectively. Combined ANA was positively associated with concurrent MeHg following adjustment for the n6:n3 LCPUFA ratio (β = 0.036, 95%; CI: 0.001, 0.073). Prenatal and average MeHg exposures were not significantly associated with any individual ANA. IgM was negatively associated with concurrent (β = -0.016, 95%CI: -0.016, -0.002), and average (β = -0.042, 95%CI: -0.042, -0.009) MeHg exposure in the models adjusted for n-3, n-6 LCPUFA and when separately adjusted for the n6:n3 LCPUFA ratio. Total (19-year) n-3 PUFA status was negatively associated with anti-RNP (β = -20.355, 95%CI: -36.89, -4.34) and IgG (β = -1.384, 95%CI: -2.682, -0.087). Total n-3 LCPUFA was associated with lower markers of autoimmunity. MeHg exposure at 19 years was associated with higher ANA and lower IgM but only following adjustment for LCPUFA. The clinical significance of these findings is unclear and further research is warranted to determine if these associations precede autoimmune disease development.

Pregnant women who are overweight/obese are particularly vulnerable to vitamin D insufficiency owing to higher physiological requirements and lower status (25(OH)D concentrations) associated with obesity. Achieving adequate maternal vitamin D status with current recommendations (10μg/d) remains controversial.This study examined supplementation effects (10μg-vs-20μg vitamin D3/d) throughout pregnancy (12 weeks gestation until delivery) on vitamin D status of normal weight, overweight and obese pregnant women and on cord blood, using a double-blind randomised vitamin D intervention study (MO-VITD). 240 pregnant women were recruited throughout the year at antenatal clinics in Northern Ireland (equal numbers of normal weight (18.5–24.9 kg/m2), overweight (25–29.9 kg/m2), and obese (> 30kg/m2)). Non-fasting maternal blood samples were collected at 12, 28 and 34–36 weeks gestation and from the umbilical cord after delivery and analysed for total serum 25(OH)D using LCMS.A high prevalence of vitamin D insufficiency (25–50nmol/L) was found in the 1st trimester in both treatment groups (41.5% and 48.8%; 10μg vs. 20μg respectively). Maternal 25(OH)D concentrations increased from the 1st to 3rd trimester in both the 10μg/d and 20μg/d groups, with a higher increase in the 20μg group (17.1 ± 24.7 and 28.8 ± 33.3nmol/L, P = 0.002). There was no difference in cord blood 25(OH)D concentrations between treatment groups.Women who started pregnancy with insufficient 25(OH)D concentrations remained insufficient throughout pregnancy in the 10μg/d group (49.9 ± 28.2nmol/L at trimester 3). In the 20μg/d group, women starting pregnancy as insufficient achieved levels of sufficiency in the 2nd (58.9 ± 30.6nmol/L) and 3rd (64.0 ± 35.9nmol/L) trimesters. Women who started pregnancy with sufficient vitamin D status (25(OH)D > 50nmol/L), maintained levels of sufficiency throughout pregnancy irrespective of treatment group (83.1 ± 24.4 and 96.7 ± 30.7 at trimester 3 in 10μg/d and 20 μg/d groups respectively); findings were similar across all BMI categories.Obese women who started pregnancy with an insufficient status were found to have deficient cord blood (25(OH)D < 25 nmol/L) in both the 10μg/d and 20μg/d groups (19.4 ± 20.2 vs. 19.5 ± 9.4nmol/L respectively), whilst obese women who started pregnancy with sufficient status (> 50nmol/L) had cord blood concentrations considered insufficient (40.2 ± 18.4 vs. 44.2 ± 15.6nmol/L; 10μg vs. 20μg groups respectively).Based on our findings of the high prevalence of vitamin D insufficiency in early pregnancy, maternal vitamin D supplementation of 20μg/d is advisable to maintain maternal vitamin D status in pregnant women in Northern Ireland.

Objectives To determine if auditory function is associated with current long chain polyunsaturated fatty acids (LCPUFA) concentrations in a cohort of young adults who consume oceanic fish with naturally acquired methylmercury (MeHg). We measured participants plasma LCPUFA concentrations (total n-3, total n-6 and the n-6:n-3 ratio) and looked for an association with Auditory Brain Response (ABR) latencies and Otoacoustic Emissions (OAE) amplitudes. Design Auditory function of 534 participants from the Seychelles Child Development Study (SCDS) main cohort was examined at 19 years of age. Tests included standard pure-tone audiometry, tympanometry, ABR and both Click-Evoked OAE (CEOAE) and Distortion-Product OAE (DPOAE). Associations of LCPUFA status, measured at the time of examination, and auditory outcomes were examined using covariate-adjusted linear regression models. All models were adjusted for sex, prenatal and current MeHg exposure and hearing status. Results LCPUFA concentrations were similar for both sexes and when comparing participants with normal hearing (90.4 %) to those who had a sensorineural hearing loss in one or both ears (9.6 %). When looking at a subset of only hearing impaired participants, LCPUFA concentrations were similar in those participants who had a mild sensorineural hearing loss as compared with participants that had a moderate sensorineural hearing loss. LCPUFA concentrations were not correlated with current hair MeHg. LCPUFA concentrations were statistically significantly associated with only 6 of 174 ABR and OAE endpoints examined. Four of the 6 significant associations were present in only one sex. In female participants as n-6 concentrations increased, the ABR wave I absolute latency increased for a 60 dBnHL 19 click/sec stimulus. For male participants the interwave I-III latencies for a 60 dBnHL 69 clicks/sec stimulus increased as the n-6:n-3 LCPUFA ratio increased and the interwave I-V interval decreased for a 60 dBnHL 39 clicks/sec stimulus as the n-6 concentration increased. For both sexes interwave latencies were prolonged for the III-V interwave interval for an 80 dBnHL 39 clicks/sec as n-3 LCPUFA concentration increased. As the n-3 LCPUFA concentrations increased, the amplitude of the 6000 Hz DPOAE in the right ear increased for both sexes. As the n-6:n-3 ratio increased, the amplitude of the 1500 Hz DPOAE in the left ear decreased for females. The amplitude of the CEOAE was not associated with n-3, n-6 LCPUFA concentrations or the n-6:n-3 ratio. Conclusion There was no evidence to suggest LCPUFA status was associated with hearing acuity, ABR latencies or OAE amplitudes, even though our participants tended to have higher LCPUFA concentrations as compared to individuals consuming a more western diet. No association was observed between LCPUFA status and a participants hearing status (normal hearing or hearing loss). Although we found a few associations between current plasma LCPUFA status and ABR and OAE auditory endpoints examined, no clear pattern exists. Some of these associations would be considered detrimental resulting in prolonged ABR latencies or smaller OAE amplitudes, while others would be considered beneficial resulting in shortened ABR latencies or larger OAE amplitudes.

Problem Markers of maternal inflammation may determine infant birth outcomes. Method of study Maternal serum samples were collected at 28 weeks gestation (n = 1418) in the Seychelles Child Development Study Nutrition Cohort 2 and analyzed for immune markers by MSD multiplex assay, including cytokines from the Th1 (IFN-γ, IL-1β, IL-2 and TNF-α) and Th2 (IL-4, IL-5, IL-10) subsets, with IL-6, MCP-1, TARC, sFlt-1 and VEGF-D. Associations of log-transformed immune markers with birthweight, length, head circumference and gestational age were assessed by multiple linear regression models, which were adjusted for maternal age, BMI, parity, child sex, gestational age and socioeconomic status. Results Neither total Th1, Th2 nor Th1:Th2 were significantly associated with any birth outcome. However, the angiogenesis marker VEGF-D was predictive of a lower birthweight, (β = −0.058, P = 0.017) and birth length (β = −0.088, P = 0.001) after adjusting for covariates. Higher concentrations of CRP were predictive of a lower birthweight (β = −0.057, P = 0.023) and IL-2 (β = 0.073, P = 0.009) and the chemokine MCP-1 (β = 0.067, P = 0.016) were predictive of a longer gestational age. Conclusions In our cohort of healthy pregnant women, we found no evidence for associations between the Th1 or Th2 inflammatory markers with birth outcomes. However, VEGF-D and CRP appear to predict lower birthweight and IL-2 and MCP-1 a longer gestation. Greater understanding is required of the variation in these immune markers at different gestational stages, as well as the factors which may regulate their balance in healthy pregnancy. n = 233.

Immune dysregulation during pregnancy may influence behavior and neurodevelopment in offspring, but few human studies have tested this hypothesis. Using structural equation modeling, we examined associations between maternal inflammatory markers at 28 weeks gestation and child neurodevelopmental outcomes at 20 months of age in a sample of 1,453 mother-child pairs. We observed several associations between maternal inflammatory markers measured in the late second or early third trimester and child neurodevelopmental outcomes. The direction of association for some markers was unexpected. Further research is warranted to confirm and elucidate the exact nature of these findings.

Background: ATP-binding cassette (ABC) transporters have been associated with methylmercury (MeHg) toxicity in experimental animal models. Aims: To evaluate the association of single nucleotide polymorphisms (SNPs) in maternal ABC transporter genes with 1) maternal hair MeHg concentrations during pregnancy and 2) child neurodevelopmental outcomes. Materials and methods: Nutrition Cohort 2 (NC2) is an observational mother-child cohort recruited in the Republic of Seychelles from 2008–2011. Total mercury (Hg) was measured in maternal hair growing during pregnancy as a biomarker for prenatal MeHg exposure (N = 1313) (mean 3.9 ppm). Infants completed developmental assessments by Bayley Scales of Infant Development II (BSID-II) at 20 months of age (N = 1331). Genotyping for fifteen SNPs in ABCC1, ABCC2 and ABCB1 was performed for the mothers. Results: Seven of fifteen ABC SNPs (ABCC1 rs11075290, rs212093, and rs215088; ABCC2 rs717620; ABCB1 rs10276499, rs1202169, and rs2032582) were associated with concentrations of maternal hair Hg (p

Epidemiologic evidence of an adverse association between exposure to methylmercury (MeHg) from consuming fish and heart rate variability (HRV) is inconclusive. We aimed to evaluate MeHg exposure in relation to HRV parameters in a large cohort of young adults from a high fish consuming population in the Republic of Seychelles. Main Cohort participants in the Seychelles Child Development Study were evaluated at a mean age of 19 years. Prenatal MeHg exposure was determined in maternal hair growing during pregnancy and recent exposure in participant’s hair taken at the evaluation. The evaluation consisted of short (~2 hours) and long (overnight) Holter recordings obtained in 514 and 203 participants, respectively. Multivariable analyses examined the association of prenatal and recent MeHg exposure (in separate models) with time-domain and frequency-domain HRV parameters in different physiologic circumstances: supine position, standing position, mental stress when undergoing a mathematics test, sleep, and long recording. Prenatal MeHg exposure was not associated with any of the 23 HRV parameters studied after adjustment for multiplicity. The recent MeHg showed a trend toward significance only for few variables in the primary model. However, after additional adjustment for activity levels, polyunsaturated fatty acids, and multiplicity none were significant after a Bonferroni adjustment. In conclusion, prenatal and recent MeHg exposure had no consistent pattern of associations to support the hypothesis that they are adversely associated with heart rate variability in this study population that consumes large amounts of fish.

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 (β = 0.036, 95%; CI: 0.001, 0.073). IgM was negatively associated with Y19Hg (β = −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.

Problem: Maternal methylmercury (MeHg) exposure may be associated with immune response during pregnancy. Method of study: In the high fish-eating Seychelles Child Development Study Nutrition Cohort 2, we examined the association between maternal MeHg, polyunsaturated fatty acids (PUFA), and immune markers (Th1:Th2; TNF-α, IL-1β, IFN-γ, IL-2, IL-4, IL-5, IL-10, MCP-1, TARC, sFlt-1, VEGF-D, CRP and IL-6) at 28 weeks’ gestation. Linear regression examined associations between MeHg exposure and immune markers with and without adjustment for PUFA. Results: In all models, as MeHg concentrations increased, the Th1:Th2 ratio, total Th1 and individual Th1 (IL-1β, IL-2, TNF-α) concentrations decreased. MeHg was not associated with total Th2 cytokines but was associated with a decrease in IL-4 and IL-10. MeHg was positively associated with TARC and VEGF-D and negatively associated with CRP. There was a significant interaction between MeHg and the n-6:n-3 ratio, with MeHg associated with a larger decrease in Th1:Th2 at higher n-6:n-3 PUFA ratios. The n-3 PUFA were associated with lower CRP, IL-4 and higher IFN-γ. The n-6 PUFA were associated with higher IL-1β, IL-2, TNF-α, IL-4, IL-10, CRP and IL-6. Conclusion: Maternal MeHg was associated with markers of immune function at 28 weeks’ gestation. A significant interaction between MeHg and the n-6:n-3 ratio on the Th1:Th2 ratio suggests that the n-3 PUFA may mitigate any immunosuppressive associations of MeHg. The n-3 and n-6 PUFA were associated with suppressive and stimulatory immune responses, respectively. Overall, the associations were of small magnitude, and further research is required to determine the clinical significance.

Polyunsaturated fatty acids (PUFA) are essential for neurodevelopment and the developing foetus depends on an optimal maternal status. Fish is a rich source of PUFA. The current study investigated dietary patterns, and associations with PUFA status in a high-fish consuming cohort of pregnant women in the Seychelles. At 28 weeks&rsquo, gestation, pregnant women provided a blood sample, from which serum total PUFA concentrations were measured, A Food Frequency Questionnaire (FFQ) and Fish Use Questionnaire (FUQ) were also completed. Principal component analysis (PCA) of dietary information identified four patterns. Regression analyses found dietary pattern 2, containing foods traditionally eaten in the Seychelles e.g., fish, fruit and vegetables was positively associated with serum docosahexaenoic acid (DHA) (&beta, = 0.134, CI = 0.001, 0.022), and serum total n-3 PUFA (&beta, = 0.139, CI = 0.001, 0.023) concentrations. Dietary pattern 1, high in processed foods, snacks, white meat and eggs, was not significantly associated with any of the serum PUFA concentrations. The FUQ indicated that fatty fish was associated with EPA status (&beta, = 0.180, CI = 0.001, 0.005) in high consumers. The second dietary pattern, consisting of higher consumption of fish and fruit, was positively associated with n-3 PUFA status during pregnancy.

Cow’s milk is the most important dietary source of iodine in the UK and Ireland, and also contributes to dietary selenium intakes. The aim of this study was to investigate the effect of season, milk fat class (whole; semi-skimmed; skimmed) and pasteurisation on iodine and selenium concentrations in Northern Ireland (NI) milk, and to estimate the contribution of this milk to consumer iodine and selenium intakes. Milk samples (unpasteurised, whole, semi-skimmed and skimmed) were collected weekly from two large NI creameries between May 2013 and April 2014 and were analysed by inductively coupled plasma-mass spectrometry (ICP-MS). Using milk consumption data from the National Diet and Nutrition Survey (NDNS) Rolling Programme, the contribution of milk (at iodine and selenium concentrations measured in the present study) to UK dietary intakes was estimated. The mean ± standard deviation (SD) iodine concentration of milk was 475.9 ± 63.5 µg/kg and the mean selenium concentration of milk was 17.8 ± 2.7 µg/kg. Season had an important determining effect on the iodine, but not the selenium, content of cow’s milk, where iodine concentrations were highest in milk produced in spring compared to autumn months (534.3 ± 53.7 vs. 433.6 ± 57.8 µg/kg, respectively; p = 0.001). The measured iodine and selenium concentrations of NI milk were higher than those listed in current UK Food Composition Databases (Food Standards Agency (FSA) (2002); FSA (2015)). The dietary modelling analysis confirmed that milk makes an important contribution to iodine and selenium intakes. This contribution may be higher than previously estimated if iodine and selenium (+25.0 and +1.1 µg/day respectively) concentrations measured in the present study were replicable across the UK at the current level of milk consumption. Iodine intakes were theoretically shown to vary by season concurrent with the seasonal variation in NI milk iodine concentrations. Routine monitoring of milk iodine concentrations is required and efforts should be made to understand reasons for fluctuations in milk iodine concentrations, in order to realise the nutritional impact to consumers.

Long-chain n-6 and n-3 PUFA (LC-PUFA), arachidonic acid (AA) (20:4n-6) and DHA (22:6n-3), are critical for optimal brain development. These fatty acids can be consumed directly from the diet, or synthesized endogenously from precursor PUFA by Δ-5 (encoded by FADS1) and Δ-6 desaturases (encoded by FADS2). The aim of this study was to determine the potential importance of maternal genetic variability in FADS1 and FADS2 genes to maternal LC-PUFA status and infant neurodevelopment in populations with high fish intakes. The Nutrition Cohorts 1 (NC1) and 2 (NC2) are longitudinal observational mother-child cohorts in the Republic of Seychelles. Maternal serum LC-PUFA was measured at 28 weeks gestation and genotyping for rs174537 (FADS1), rs174561 (FADS1), rs3834458 (FADS1-FADS2) and rs174575 (FADS2) was performed in both cohorts. The children completed the Bayley Scales of Infant Development II (BSID-II) at 30 months in NC1 and at 20 months in NC2. Complete data were available for 221 and 1310 mothers from NC1 and NC2 respectively. With increasing number of rs3834458 minor alleles, maternal concentrations of AA were significantly decreased (NC1 p=0.004; NC2 p

Background Dietary sources of vitamin D (both natural and fortified) are increasingly contributing to consumers' vitamin D intake and status. Therefore, the present study aimed to validate a vitamin D food frequency questionnaire (FFQ) for the assessment of habitual vitamin D intake. Methods A total of 49 apparently healthy consenting adults (aged 18-64 years) from the local community were sampled at the end of winter. Dietary intakes were recorded using a 4-day weighed food record (4d-WFR) and a 17-item FFQ based on foods known to contribute to dietary vitamin D intake. Fasting vitamin D status was quantified by serum 25-hydroxyvitamin D [25(OH)D] using liquid chromatography tandem mass spectrometry. The method of triads was applied using these three measurements to determine the overall validity of the FFQ. Results Vitamin D intakes from 4d-WFR ranged between 0.42 and 31.65 μg day(-1), whereas intakes determined from the FFQ ranged from 1.03 to 36.08 μg day(-1). Serum 25(OH)D concentrations ranged between 12.89 and 279.00 nmol L(-1). The mean (SD) difference between the FFQ and 4d-WFR was +1.62 ( 3.86). There were strong correlations between the vitamin D intake estimated by the FFQ and that from the 4d-WFR (r = 0.562) and also with serum 25(OH)D concentrations (r = 0.567). Vitamin D intake estimated from the 4d-WFR was also strongly correlated with serum 25(OH)D concentrations (r = 0.411). The overall validity coefficient calculated using the method of triads was high (0.881). Conclusions The vitamin D FFQ has been validated for use in future studies aiming to assess habitual vitamin D intake.

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 existence of an optimal DHA balance with respect to arachidonic acid for different aspects of neurodevelopment. Am J Clin Nutr doi: 10.3945/ajcn.114.100503.

Background Studies investigating obesity and cardiometabolic risk have focused on ‘at-risk’ populations and methodological inconsistencies have produced equivocal findings. The present cross-sectional study investigated indices of body composition as predictors of cardiometabolic risk and their relationship with inflammation in apparently healthy young adults. Methods A fasting blood sample was taken from consenting adults (160 males, 32 females, aged 18–40 years) for assessment of cardiometabolic risk markers (blood pressure, lipid profiles and insulin resistance) and inflammatory markers (C-reactive protein, tumour necrosis factor-α, interleukin-6, interleukin-10 and adiponectin). Together with anthropometry, fat mass (FM) and fat-free mass (FFM) were determined by dual-energy X-ray absorptiometry. FM was expressed in absolute terms (kg), as well as relative to total body weight (%), height [FM index (FMI, kg m−2)] and FFM (FM : FFM,%). Results Although anthropometric indices were associated with most cardiometabolic risk markers, the strongest relationship was observed with FMI. Relative to having a low cardiometabolic risk (≤2 markers above clinically relevant cut-offs), each kg m−2 increase in FMI, increased the likelihood of having an increased cardiometabolic risk by 29% (odds ratio = 1.29; 95% confidence interval = 1.12–1.49). Inflammatory markers were not associated with body composition or cardiometabolic risk. Conclusions FMI was the strongest predictor of overall cardiometabolic risk but not inflammation per se. However, anthropometric indices, such as body mass index and waist-to-height ratio, remain valuable surrogate measures of adiposity in this group, particularly when risk markers are considered independently.

Introduction: Glutathione (GSH) pathways play a key role the metabolism and elimination of the neurotoxicant methylmercury (MeHg). We hypothesized that maternal genetic variation linked to GSH pathways could influence MeHg concentrations in pregnant mothers and children and thereby also affect early life development. Methods: The GCLM (rs41303970, C/T), GCLC (rs761142, T/G) and GSTP1 (rs1695, A/G) polymorphisms were genotyped in 1449 mothers in a prospective study of the Seychellois population with a diet rich in fish. Genotypes were analyzed in association with maternal hair and blood Hg, fetal blood Hg (cord blood Hg), as well as children's mental (MDI) and motor development (PDI; MDI and PDI assessed by Bayley Scales of Infant Development at 20 months). We also examined whether genotypes modified the association between Hg exposure and developmental outcomes. Results: GCLC rs761142 TT homozygotes showed statistically higher mean maternal hair Hg (4.12 ppm) than G carriers (AG 3.73 and GG 3.52 ppm) (p = 0.037). For the combination of GCLC rs761142 and GCLM rs41303970, double homozygotes TT + CC showed higher hair Hg (4.40 ppm) than G + T carriers (3.44 ppm; p = 0.018). No associations were observed between GSTP1 rs1695 and maternal hair Hg or between any genotypes and maternal blood Hg or cord blood Hg. The maternal GSTP1 rs1695 rare allele (G) was associated with a lower MDI among children (β = −1.48, p = 0.048). We also observed some interactions: increasing Hg in maternal and cord blood was associated with lower PDI among GCLC rs761142 TT carriers; and increasing Hg in hair was associated with lower MDI among GSTP1 rs1695 GG carriers. Conclusions: Maternal genetic variation in genes involved in GSH synthesis is statistically associated with Hg concentrations in maternal hair, but not in maternal or fetal blood. We observed interactions that suggest maternal GSH genetics may modify associations between MeHg exposure and neurodevelopmental outcomes. Keywords: Methylmercury, GCLC, GCLM, GSTP1, Neurodevelopment

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 (

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 (β = 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 (β = 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.