Dataset Information

Epigenome-wide DNA methylation in placentas from preterm infants: association with maternal socioeconomic status.

ABSTRACT: This study evaluated the hypothesis that prenatal maternal socioeconomic status (SES) adversity is associated with DNA methylation in the placenta. SES adversity was defined by the presence of, as well as a summative count of, four factors: less than college education, single marital status, food and nutritional service assistance, and public health insurance. Epigenome-wide DNA methylation was assessed using the Illumina EPIC array in 426 placentas from a sample of infants born < 28 weeks of gestation from the Extremely Low Gestational Age Newborn cohort. Associations between SES adversity and DNA methylation were assessed with robust linear regressions adjusted for covariates and controlled the false discovery rate at < 10%. We also examined whether such associations were sex specific. Indicators of SES adversity were associated with differential methylation at 33 CpG sites. Of the 33 identified CpG sites, 19 (57.6%) displayed increased methylation, and 14 (42.4%) displayed decreased methylation in association with at least one of the SES adversity factors. Sex differences were observed in DNA methylation associated with summative SES score; in which placentas derived from female pregnancies showed more robust differential CpG methylation than placentas from male pregnancies. Maternal SES adversity was associated with differential methylation of genes with key role in gene transcription and placental function, potentially altering immunity and stress response. Further investigation is needed to evaluate the role of epigenetic differences in mediating the association between maternal socioeconomic status during pregnancy and later life health outcomes in children.

SUBMITTER: Santos HP

PROVIDER: S-EPMC6615526 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Epigenome-wide DNA methylation in placentas from preterm infants: association with maternal socioeconomic status.

Santos Hudson P HP Bhattacharya Arjun A Martin Elizabeth M EM Addo Kezia K Psioda Matt M Smeester Lisa L Joseph Robert M RM Hooper Stephen R SR Frazier Jean A JA Kuban Karl C KC O'Shea T Michael TM Fry Rebecca C RC

Epigenetics 20190521 8

This study evaluated the hypothesis that prenatal maternal socioeconomic status (SES) adversity is associated with DNA methylation in the placenta. SES adversity was defined by the presence of, as well as a summative count of, four factors: less than college education, single marital status, food and nutritional service assistance, and public health insurance. Epigenome-wide DNA methylation was assessed using the Illumina EPIC array in 426 placentas from a sample of infants born < 28 weeks of ge ...[more]

PMID: 31062658

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Project description:BackgroundBronchopulmonary dysplasia (BPD) is a lung disease in premature infants caused by therapeutic oxygen supplemental and characterized by impaired pulmonary development which persists into later life. While advances in neonatal care have improved survival rates of premature infants, cases of BPD have been increasing with limited therapeutic options for prevention and treatment. This study was designed to explore the relationship between gestational age (GA), birth weight, and estimated blood cell-type composition in premature infants and to elucidate early epigenetic biomarkers associated with BPD.MethodsCord blood DNA from preterm neonates that went on to develop BPD (n = 14) or not (non-BPD, n = 93) was applied to Illumina 450 K methylation arrays. Blood cell-type compositions were estimated using DNA methylation profiles. Multivariable robust regression analysis elucidated CpGs associated with BPD risk. cDNA microarray analysis of cord blood RNA identified differentially expressed genes in neonates who later developed BPD.ResultsThe development of BPD and the need for oxygen supplementation were strongly associated with GA (BPD, p < 1.0E-04; O2 supplementation, p < 1.0E-09) and birth weight (BPD, p < 1.0E-02; O2 supplementation, p < 1.0E-07). The estimated nucleated red blood cell (NRBC) percent was negatively associated with birth weight and GA, positively associated with hypomethylation of the tobacco smoke exposure biomarker cg05575921, and high-NRBC blood samples displayed a hypomethylation profile. Epigenome-wide association study (EWAS) identified 38 (Bonferroni) and 275 (false discovery rate 1%) differentially methylated CpGs associated with BPD. BPD-associated CpGs in cord blood were enriched for lung maturation and hematopoiesis pathways. Stochastic epigenetic mutation burden at birth was significantly elevated among those who developed BPD (adjusted p = 0.02). Transcriptome changes in cord blood cells reflected cell cycle, development, and pulmonary disorder events in BPD.ConclusionsWhile results must be interpreted with caution because of the small size of this study, NRBC content strongly impacted DNA methylation profiles in preterm cord blood and EWAS analysis revealed potential insights into biological pathways involved in BPD pathogenesis.

Project description:BackgroundUnbalanced iron homeostasis in pregnancy is associated with an increased risk of adverse birth and childhood health outcomes. DNA methylation has been suggested as a potential underlying mechanism linking environmental exposures such as micronutrient status during pregnancy with offspring health. We performed a meta-analysis on the association of maternal early-pregnancy serum ferritin concentrations, as a marker of body iron stores, and cord blood DNA methylation. We included 1286 mother-newborn pairs from two population-based prospective cohorts. Serum ferritin concentrations were measured in early pregnancy. DNA methylation was measured with the Infinium HumanMethylation450 BeadChip (Illumina). We examined epigenome-wide associations of maternal early-pregnancy serum ferritin and cord blood DNA methylation using robust linear regression analyses, with adjustment for confounders and performed fixed-effects meta-analyses. We additionally examined whether associations of any CpGs identified in cord blood persisted in the peripheral blood of older children and explored associations with other markers of maternal iron status. We also examined whether similar findings were present in the association of cord blood serum ferritin concentrations with cord blood DNA methylation.ResultsMaternal early-pregnancy serum ferritin concentrations were inversely associated with DNA methylation at two CpGs (cg02806645 and cg06322988) in PRR23A and one CpG (cg04468817) in PRSS22. Associations at two of these CpG sites persisted at each of the follow-up time points in childhood. Cord blood serum ferritin concentrations were not associated with cord blood DNA methylation levels at the three identified CpGs.ConclusionMaternal early-pregnancy serum ferritin concentrations were associated with lower cord blood DNA methylation levels at three CpGs and these associations partly persisted in older children. Further studies are needed to uncover the role of these CpGs in the underlying mechanisms of the associations of maternal iron status and offspring health outcomes.

Project description:BackgroundMaternal stress before, during and after pregnancy has profound effects on the development and lifelong function of the infant's neurocognitive development. We hypothesized that the programming of the central nervous system (CNS), hypothalamic-pituitary-adrenal (HPA) axis and autonomic nervous system (ANS) induced by prenatal stress (PS) is reflected in electrophysiological and epigenetic biomarkers. In this study, we aimed to find noninvasive epigenetic biomarkers of PS in the newborn salivary DNA.ResultsA total of 728 pregnant women were screened for stress exposure using Cohen Perceived Stress Scale (PSS), 164 women were enrolled, and 114 dyads were analyzed. Prenatal Distress Questionnaire (PDQ) was also administered to assess specific pregnancy worries. Transabdominal fetal electrocardiograms (taECG) were recorded to derive coupling between maternal and fetal heart rates resulting in a 'Fetal Stress Index' (FSI). Upon delivery, we collected maternal hair strands for cortisol measurements and newborn's saliva for epigenetic analyses. DNA was extracted from saliva samples, and DNA methylation was measured using EPIC BeadChip array (850 k CpG sites). Linear regression was used to identify associations between PSS/PDQ/FSI/Cortisol and DNA methylation. We found epigenome-wide significant associations for 5 CpG with PDQ and cortisol at FDR < 5%. Three CpGs were annotated to genes (Illumina Gene annotation file): YAP1, TOMM20 and CSMD1, and two CpGs were located approximately lay at 50 kb from SSBP4 and SCAMP1. In addition, two differentiated methylation regions (DMR) related to maternal stress measures PDQ and cortisol were found: DAXX and ARL4D.ConclusionsGenes annotated to these CpGs were found to be involved in secretion and transportation, nuclear signaling, Hippo signaling pathways, apoptosis, intracellular trafficking and neuronal signaling. Moreover, some CpGs are annotated to genes related to autism, post-traumatic stress disorder (PTSD) and schizophrenia. However, our results should be viewed as hypothesis generating until replicated in a larger sample. Early assessment of such noninvasive PS biomarkers will allow timelier detection of babies at risk and a more effective allocation of resources for early intervention programs to improve child development. A biomarker-guided early intervention strategy is the first step in the prevention of future health problems, reducing their personal and societal impact.

Dataset Information

Epigenome-wide DNA methylation in placentas from preterm infants: association with maternal socioeconomic status.

Publications

Epigenome-wide DNA methylation in placentas from preterm infants: association with maternal socioeconomic status.

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