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Cross-genetic determination of maternal and neonatal immune mediators during pregnancy.

ABSTRACT: BACKGROUND:The immune system plays a fundamental role in development during pregnancy and early life. Alterations in circulating maternal and neonatal immune mediators have been associated with pregnancy complications as well as susceptibility to autoimmune and neurodevelopmental conditions in later life. Evidence suggests that the immune system in adults not only responds to environmental stimulation but is also under strong genetic control. METHODS:This is the first genetic study of >?700 mother-infant pairs to analyse the circulating levels of 22 maternal mid-gestational serum-derived and 42 neonatal bloodspot-derived immune mediators (cytokines/chemokines) in the context of maternal and fetal genotype. We first estimated the maternal and fetal genome-wide SNP-based heritability (h2g) for each immune molecule and then performed genome-wide association studies (GWAS) to identify specific loci contributing to individual immune mediators. Finally, we assessed the relationship between genetic immune determinants and ASD outcome. RESULTS:We show maternal and neonatal cytokines/chemokines displaying genetic regulation using independent methodologies. We demonstrate that novel fetal loci for immune function independently affect the physiological levels of maternal immune mediators and vice versa. The cross-associated loci are in distinct genomic regions compared with individual-specific immune mediator loci. Finally, we observed an interaction between increased IL-8 levels at birth, autism spectrum disorder (ASD) status, and a specific maternal genotype. CONCLUSIONS:Our results suggest that maternal and fetal genetic variation influences the immune system during pregnancy and at birth via distinct mechanisms and that a better understanding of immune factor determinants in early development may shed light on risk factors for developmental disorders.

SUBMITTER: Traglia M

PROVIDER: S-EPMC6106874 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Cross-genetic determination of maternal and neonatal immune mediators during pregnancy.

Traglia Michela M Croen Lisa A LA Jones Karen L KL Heuer Luke S LS Yolken Robert R Kharrazi Martin M DeLorenze Gerald N GN Ashwood Paul P Van de Water Judy J Weiss Lauren A LA

Genome medicine 20180822 1

<h4>Background</h4>The immune system plays a fundamental role in development during pregnancy and early life. Alterations in circulating maternal and neonatal immune mediators have been associated with pregnancy complications as well as susceptibility to autoimmune and neurodevelopmental conditions in later life. Evidence suggests that the immune system in adults not only responds to environmental stimulation but is also under strong genetic control.<h4>Methods</h4>This is the first genetic stud ...[more]

PMID: 30134952

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Project description:BackgroundVegetarian diets are becoming increasingly popular in the USA. Limited research has examined the health consequences of vegetarian diets during pregnancy. We comprehensively examined associations of vegetarianism during pregnancy with maternal and neonatal outcomes.MethodsWe used data from the Eunice Kennedy Shriver National Institute of Child Health and Human Development's Fetal Growth Studies-Singletons, a prospective multi-site cohort of 1948 low-risk pregnant women of four races/ethnicities (White, Black, Hispanic, Asian/Pacific Islander) in the USA (2009-2013). Vegetarianism was self-reported and also defined based on dietary patterns measured using a self-administered first-trimester food-frequency questionnaire (full [lacto-ovo and vegan], pesco-, semi- and non-vegetarians). Neonatal outcomes included birthweight and neonatal anthropometric measures, small for gestational age, small for gestational age with neonatal morbidity and preterm delivery. Maternal outcomes included gestational weight gain, gestational diabetes, hypertensive disorders of pregnancy and gestational anaemia.ResultsNinety-nine (6.2%) women self-reported being vegetarian. The diet-based definition identified 32 (2.0%) full vegetarians, 7 (0.6%) pesco-vegetarians and 301 (17.6%) semi-vegetarians. Neonates of diet-based full vegetarians had higher odds of being small for gestational age [adjusted odds ratio (ORadj) = 2.51, 95% confidence interval: 1.01, 6.21], but not of being small for gestational age with a postnatal morbidity. Full vegetarians had marginally increased the odds of inadequate second-trimester gestational weight gain (ORadj = 2.24, 95% confidence interval: 0.95, 5.27).ConclusionVegetarian diets during pregnancy were associated with constitutionally smaller neonatal size, potentially via the mothers' reduced gestational weight gain. Notably, vegetarianism was not associated with small-for-gestational-age-related morbidities or other adverse maternal outcomes.

Project description:BackgroundFetal exposure to bisphenols is associated with altered fetal growth, adverse birth outcomes and childhood cardio-metabolic risk factors. Metabolomics may serve as a tool to identify the mechanisms underlying these associations. We examined the associations of maternal bisphenol urinary concentrations in pregnancy with neonatal metabolite profiles from cord blood.MethodsIn a population-based prospective cohort study among 225 mother-child pairs, maternal urinary bisphenol A, S and F concentrations in first, second and third trimester were measured. LC-MS/MS was used to determine neonatal concentrations of amino acids, non-esterified fatty acids (NEFA), phospholipids (PL), and carnitines in cord blood.ResultsNo associations of maternal total bisphenol concentrations with neonatal metabolite profiles were present. Higher maternal average BPA concentrations were associated with higher neonatal mono-unsaturated alkyl-lysophosphatidylcholine concentrations, whereas higher maternal average BPS was associated with lower neonatal overall and saturated alkyl-lysophosphatidylcholine (p-values < 0.05).Trimester-specific analyses showed that higher maternal BPA, BPS and BPF were associated with alterations in neonatal NEFA, diacyl-phosphatidylcholines, acyl-alkyl-phosphatidylcholines, alkyl-lysophosphatidylcholine, sphingomyelines and acyl-carnitines, with the strongest effects for third trimester maternal bisphenol and neonatal diacyl-phosphatidylcholine, sphingomyeline and acyl-carnitine metabolites (p-values < 0.05). Associations were not explained by maternal socio-demographic and lifestyle characteristics or birth characteristics.DiscussionHigher maternal bisphenol A, F and S concentrations in pregnancy are associated with alterations in neonatal metabolite profile, mainly in NEFA, PL and carnitines concentrations. These findings provide novel insight into potential mechanisms underlying associations of maternal bisphenol exposure during pregnancy with adverse offspring outcomes but need to be replicated among larger, diverse populations.

Project description:Findings on maternal 25-hydroxyvitamin D (25[OH]D) and neonatal anthropometry are inconsistent, and may at least be partly due to variations in gestational week (GW) of 25(OH)D measurement and the lack of longitudinal 25(OH)D measurements across gestation. The aim of the current study was to examine the associations of longitudinal measures of maternal 25(OH)D and neonatal anthropometry at birth. This study included 321 mother⁻offspring pairs enrolled in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Fetal Growth Studies⁻Singletons. This study was a prospective cohort design without supplementation and without data on dietary supplementation. Nevertheless, measurement of plasma 25(OH)D reflects vitamin D from different sources, including supplementation. Maternal concentrations of total 25(OH)D were measured at 10⁻14, 15⁻26, 23⁻31, and 33⁻39 GW and categorized as <50 nmol/L, 50⁻75 nmol/L, and >75 nmol/L. Generalized linear models were used to examine associations of 25(OH)D at each time-point with neonate birthweight z-score, length, and sum of skinfolds at birth. At 10⁻14 GW, 16.8% and 49.2% of women had 25(OH)D <50 nmol/L and between 50⁻75 nmol/L, respectively. The association of maternal 25(OH)D with neonatal anthropometry differed by GW and women's prepregnancy BMI (normal (<25.0 kg/m²), overweight/obese (25.0⁻44.9 kg/m²)). All analyses were stratified by prepregnancy BMI status. Among women with an overweight/obese BMI, 25(OH)D <50 nmol/L at 10⁻14 GW was associated with lower birthweight z-score (0.56; 95% CI: -0.99, -0.13) and length (-1.56 cm; 95% CI: -3.07, -0.06), and at 23⁻31 GW was associated with shorter length (-2.77 cm; 95% CI: -13.38, -4.98) and lower sum of skinfolds (-9.18 mm; 95% CI: -13.38, -4.98). Among women with a normal BMI, 25(OH)D <50 nmol/L at 10⁻14 GW was associated with lower sum of skinfolds (-2.64 mm; 95% CI: -5.03, -0.24), at 23⁻31 GW was associated with larger birthweight z-scores (0.64; 95% CI: 0.03, 1.25), and at 33-39 GW with both higher birthweight z-score (1.22; 95% CI: 0.71, 1.73) and longer length (1.94 cm; 95% CI: 0.37, 3.52). Maternal 25(OH)D status during pregnancy was associated with neonatal anthropometric measures, and the associations were specific to GW of 25(OH)D measurement and prepregnancy BMI.

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Cross-genetic determination of maternal and neonatal immune mediators during pregnancy.

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Cross-genetic determination of maternal and neonatal immune mediators during pregnancy.

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