Prenatal exposures and DNA methylation in newborns: a pilot study in Durban, South Africa

Abstract

The in utero environment has the potential to influence epigenetic programming and subsequently the health of offspring. Even though pregnant women living in urban Africa are exposed to multiple chemicals and infectious agents that may impact their developing children, the neonatal epigenome has not been studied in these regions. We assessed whether prenatal exposures to air pollution and maternal human immunodeficiency virus (HIV) are associated with changes to DNA methylation throughout the epigenome using a pilot sample from the Mother and Child Environmental (MACE) birth cohort, of which 36% of the mothers are HIV positive. Families living in a high air pollution region (south Durban, n = 11) and a low air pollution region (north Durban, n = 11) with comparable socioeconomic characteristics were selected for analysis. DNA methylation was quantified in cord blood plasma DNA at >430 000 CpG sites using the Infinium HumanMethylation450 BeadChip. Sites associated with living in south Durban or maternal HIV infection (p < 0.001) were more likely to be hypomethylated and located in CpG islands. Top differentially methylated sites by region of Durban were enriched in pathways related to xenobiotic metabolism, oxygen and gas transport, and sensory perception of chemical stimuli when performing gene set enrichment testing with LRpath. Differentially methylated sites by maternal HIV status were enriched in cytochrome P450s, pathways involved in detection of chemical stimuli, metabolic processes, and viral regulation and processing. Given the small sample size of the study, future work examining the impact of prenatal exposures to air pollution, maternal infection, and antiviral treatment on the epigenome and downstream health implications is merited in Sub-Saharan African populations.

Figure 1. Enrichment of Hypomethylated Sites among High Air Pollution and Maternal HIV Exposure Groups

A statistically significant enrichment of hypomethylated sites was observed when comparing cord blood plasma DNA methylation from individuals A) residing in a high air pollution region (south Durban) compared with the low pollution north Durban and B) with maternal HIV exposure compared with uninfected mothers. Relationships were assessed in models adjusting for gestational age, child’s sex, air pollution group, and maternal HIV status (n=22). Percentage of hypomethylated (direction=negative) and hypermethylated (positive) sites are displayed from the following groups of CpG sites: 1) all sites (n=433,782), 2) p<0.001 (n=420 for air pollution, 689 for HIV), or effect size >1 (log fold-change <−1 or >1; n=781 for air pollution analysis, 514 for HIV). A reference line is drawn at 50%.

Figure 2. Enrichment of Differentially Methylated Sites (DMS) in CpG Islands among High Air Pollution and Maternal HIV Exposure Groups

Among the top DMS (p<0.001) by air pollution exposure region (420 CpG sites) or maternal HIV status (689 sites) in models adjusting for both exposures, gestational age, and sex, there was a statistically significant shift in annotation related to CpG islands compared to the expected proportions based on all probes (‘All CpG Sites’). Specifically, DMS were over-represented in CpG islands and depleted in the ‘open sea’ for both in utero exposures.