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Prenatal determinants of cord blood total immunoglobulin E levels in Mexican newborns.

ABSTRACT: Asthma and allergic diseases have increased worldwide; however, etilogic factors for this increase are still poor. Prenatal consumptions of fatty acids are hypothesized, although few clinical trials in developing countries have been performed. This study was designed to identify predictors of immunoglobulin E (IgE) levels in cord blood of Mexican newborns. Total IgE was measured in umbilical cord blood from 613 infants whose mothers participated in a double-blind randomized controlled trial of 400 mg of docosahexaenoic acid or placebo from 18 to 22 weeks gestation through delivery. During pregnancy, information on sociodemographic characteristics, environmental exposures, and perceived maternal stress were obtained; a maternal blood sample was also collected to determine atopy via specific IgE levels. Logistic regression models were used to identify the main prenatal predictors of detectable total IgE levels in cord blood. IgE was detectable in cord blood from 344 (53.7%) infants; the main predictors in multivariate analyses were maternal atopy (odds ratio [OR] = 1.69; 95% CI, 1.19-2.42; p < 0.05) and pesticide use in the home (OR = 1.49; 95% CI, 1.04-2.14; p < 0.05). When stratified by maternal atopy, season of birth was a significant predictor in the atopic group only (OR = 2.48; 95% CI, 1.00-6.16; p < 0.05), and pesticide use was a significant predictor for infants born to nonatopic mothers (OR = 1.64; 95% CI, 1.07-2.51; p < 0.05). No differences were seen in the proportion of infants with detectable IgE by treatment group. Prenatal supplementation with omega-3 polyunsaturated fatty acid did not alter the detectable cord blood IgE levels. Maternal atopy and pesticide use during pregnancy are strong predictors of cord blood IgE levels in newborns. Clinical trial NCT00646360, www.clinicaltrials.gov.

SUBMITTER: Hernandez E

PROVIDER: S-EPMC3973815 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundPer- and polyfluoroalkyl substances (PFAS) are environmentally persistent chemicals widely detected in women of reproductive age. Prenatal PFAS exposure is associated with adverse health outcomes in children. We hypothesized that DNA methylation changes may result from prenatal PFAS exposure and may be linked to offspring cardio-metabolic phenotype.ObjectivesWe estimated associations of prenatal PFAS with DNA methylation in umbilical cord blood. We evaluated associations of methylation at selected sites with neonatal cardio-metabolic indicators.MethodsAmong 583 mother-infant pairs in a prospective cohort, five PFAS were quantified in maternal serum (median 27 wk of gestation). Umbilical cord blood DNA methylation was evaluated using the Illumina HumanMethylation450 array. Differentially methylated positions (DMPs) were evaluated at a false discovery rate (FDR)<0.05 and differentially methylated regions (DMRs) were identified using comb-p (Šidák-adjusted p<0.05). We estimated associations between methylation at candidate DMPs and DMR sites and the following outcomes: newborn weight, adiposity, and cord blood glucose, insulin, lipids, and leptin.ResultsMaternal serum PFAS concentrations were below the median for females in the U.S. general population. Moderate to high pairwise correlations were observed between PFAS concentrations (ρ=0.28-0.76). Methylation at one DMP (cg18587484), annotated to the gene TJAP1, was associated with perfluorooctanoate (PFOA) at FDR< 0.05. Comb-p detected between 4 and 15 DMRs for each PFAS. Associated genes, some common across multiple PFAS, were implicated in growth (RPTOR), lipid homeostasis (PON1, PON3, CIDEB, NR1H2), inflammation and immune activity (RASL11B, RNF39), among other functions. There was suggestive evidence that two PFAS-associated loci (cg09093485, cg09637273) were associated with cord blood triglycerides and birth weight, respectively (FDR< 0.1).DiscussionDNA methylation in umbilical cord blood was associated with maternal serum PFAS concentrations during pregnancy, suggesting potential associations with offspring growth, metabolism, and immune function. Future research should explore whether DNA methylation changes mediate associations between prenatal PFAS exposures and child health outcomes. https://doi.org/10.1289/EHP6888.

Project description:Exposure to phthalates has been shown to impede the human endocrine system, resulting in deleterious effects on pregnant women and their children. Phthalates modify DNA methylation patterns in infant cord blood. We examined the association between prenatal phthalate exposure and DNA methylation patterns in cord blood in a Korean birth cohort. Phthalate levels were measured in 274 maternal urine samples obtained during late pregnancy and 102 neonatal urine samples obtained at birth, and DNA methylation levels were measured in cord blood samples. For each infant in the cohort, associations between CpG methylation and both maternal and neonate phthalate levels were analyzed using linear mixed models. The results were combined with those from a meta-analysis of the levels of phthalates in maternal and neonatal urine samples, which were also analyzed for MEOHP, MEHHP, MnBP, and DEHP. This meta-analysis revealed significant associations between the methylation levels of CpG sites near the CHN2 and CUL3 genes, which were also associated with MEOHP and MnBP in neonatal urine. When the data were stratified by the sex of the infant, MnBP concentration was found to be associated with one CpG site near the OR2A2 and MEGF11 genes in female infants. In contrast, the concentrations of the three maternal phthalates showed no significant association with CpG site methylation. Furthermore, the data identified distinct differentially methylated regions in maternal and neonatal urine samples following exposure to phthalates. The CpGs with methylation levels that were positively associated with phthalate levels (particularly MEOHP and MnBP) were found to be enriched genes and related pathways. These results indicate that prenatal phthalate exposure is significantly associated with DNA methylation at multiple CpG sites. These alterations in DNA methylation may serve as biomarkers of maternal exposure to phthalates in infants and are potential candidates for investigating the mechanisms by which phthalates impact maternal and neonatal health.

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Prenatal determinants of cord blood total immunoglobulin E levels in Mexican newborns.

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