A Bayesian partial membership model for multiple exposures with uncertain group memberships

We present a Bayesian partial membership model that estimates the associations between an outcome, a small number of latent variables, and multiple observed exposures where the number of latent variables is specified a priori. We assign one observed exposure as the sentinel marker for each latent variable. The model allows non-sentinel exposures to have complete membership in one latent group, or partial membership across two or more latent groups. MCMC sampling is used to determine latent group partial memberships for the non-sentinel exposures, and estimate all model parameters. We compare the performance of our model to competing approaches in a simulation study and apply our model to inflammatory marker data measured in a large mother-child cohort of the Seychelles Child Development Study (SCDS). In simulations, our model estimated model parameters with little bias, adequate coverage, and tighter credible intervals compared to competing approaches. Under our partial membership model with two latent groups, SCDS inflammatory marker classifications generally aligned with the scientific literature. Incorporating additional SCDS inflammatory markers and more latent groups produced similar groupings of markers that also aligned with the literature. Associations between covariates and birth weight were similar across latent variable models and were consistent with earlier work in this SCDS cohort. Supplementary materials accompanying this paper appear online.</p

Maternal serum cytokine concentrations in healthy pregnancy and preeclampsia

The maternal immune response is essential for successful pregnancy, promoting immune tolerance to the fetus while maintaining innate and adaptive immunity. Uncontrolled, increased proinflammatory responses are a contributing factor to the pathogenesis of preeclampsia. The Th1/Th2 cytokine shift theory, characterised by bias production of Th2 anti-inflammatory cytokine midgestation, was frequently used to reflect the maternal immune response in pregnancy. This theory is simplistic as it is based on limited information and does not consider the role of other T cell subsets, Th17 and Tregs. A range of maternal peripheral cytokines have been measured in pregnancy cohorts, albeit the changes in individual cytokine concentrations across gestation is not well summarised. Using available data, this review was aimed at summarising changes in individual maternal serum cytokine concentrations throughout healthy pregnancy and evaluating their association with preeclampsia. We report that TNF-α increases as pregnancy progresses, IL-8 decreases in the second trimester, and IL-4 concentrations remain consistent throughout gestation. Lower second trimester IL-10 concentrations may be an early predictor for developing preeclampsia. Proinflammatory cytokines (TNF-α, IFN-γ, IL-2, IL-8, and IL-6) are significantly elevated in preeclampsia. More research is required to determine the usefulness of using cytokines, particularly IL-10, as early biomarkers of pregnancy health

Associations between maternal thyroid function in pregnancy and child neurodevelopmental outcomes at 20 months in the Seychelles Child Development Study, Nutrition Cohort 2 (SCDS NC2)

Maternal thyroid hormones facilitate optimal foetal neurodevelopment; however, the exact role of the thyroid hormones on specific cognitive outcomes is unknown. The present study aimed to investigate associations between maternal thyroid function and neurodevelopmental outcomes in the Seychelles Child Development Study (SCDS) Nutrition 2 cohort (n 1328). 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. Linear regression analysis was used to test associations between serum concentrations of maternal thyroid hormones and child neurodevelopment outcomes. Thyroid hormones were analysed as continuous data and categorised as quintiles. 95% of mothers had optimal thyroid function based on fTSH concentrations. Overall, the present study shows that maternal thyroid function is not associated with neurodevelopmental outcomes in this high fish-eating population. However, a positive association, using quintiles for fT3, was reported for the Mental Developmental Index, between Q3 v. Q4 (β 0⋅073; P 0⋅043) and for Q3 v. Q5 (β value 0⋅086; P 0⋅018). To conclude, mothers in our cohort, who largely have optimal thyroid function and iodine intakes, appear able to regulate thyroid function throughout pregnancy to meet neurodevelopmental needs. However, it is possible that minor imbalances of fT3, as indicated from our secondary analysis, may impact offspring neurodevelopment. Further investigation of the relationship between maternal thyroid function and infant neurodevelopment is warranted, particularly in populations with different dietary patterns and thereby iodine intakes

Polyunsaturated fatty acid 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 ofmarine n-3 (v-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. Postnatalmercury was alsomeasured in children's hair samples with the use of a cumulativemetric derived from values obtained at 3-5 y of age. Relative TL wasmeasured 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 ratiowas significantly associated with longer TLs in the mothers (β = 0.001, P = 0.048). Child PUFA status andmethylmercury exposurewere not associated with child TL. However, higher family Hollingshead socioeconomic status (SES) scores at 9 mo of agewere significantly associatedwith 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

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 β = − 0.001, SE=0.001; length β = − 0.006, SE=0.006; head circumference β = − 0.002, SE=0.002; MDI β = − 0.005, SE=0.015; PDI β = − 0.004, SE=0.016; all P > 0.05), or between cord taurine concentrations and outcomes (weight β = − 0.001, SE<0.000; length β = − 0.001, SE=0.004; head circumference β < 0.000, SE=0.002; MDI β = 0.004, SE=0.010; PDI β = − 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