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 Maternal 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.

Air pollution and DNA methylation: effects of exposure in humans

“…To understand whether in utero air pollution exposure affects DNAm, a number of studies have examined placenta or cord blood samples [33, 34, 41, 42]. One study showed a significant concentration-dependent association between exposure to NO 2 during pregnancy and DNAm at three CpGs in cord blood samples measured using the Illumina 450K platform (Table 1 and Additional file 2: Table S2) [41].…”

“…An alternative to an epidemiological study approach is to compare people living in areas with different air pollution concentrations, for example, an area with lots of industry and high air pollution with a rural area nearby with low air pollution [27, 32–34]. After correction for differences between the populations living in these two locations, comparison allows estimation of the effects of the increased air pollution exposure associated with living in the industrial area.…”

Exposure to NO2, CO, and PM2.5 is linked to regional DNA methylation differences in asthma

“…Asthma is the most frequent chronic disease in children [ 1 ], and its prevalence continues to increase, raising global public health concerns [ 2 – 4 ]. Previous studies found that high prenatal ambient air pollutant (AAP) exposure alters epigenetic programming in utero [ 5 ] and that children are at greater risk of developing asthma when exposed to higher concentrations of AAPs [ 6 ]. This further raises concern and increases the urgency of understanding the relationship between AAP exposures and asthma and finding effective ways to prevent, treat, and/or cure asthma.…”

Environmental Health Research in Africa: Important Progress and Promising Opportunities

“…These markers were often able to distinguish traffic-exposed individuals from controls but only one of the 63 papers from this review was from an African-based study (DeMarini, 2013). Prenatal exposure to air pollution and HIV status of mothers appeared to lead to differential methylation in infants particularly in certain biological pathways related to metabolic processes and viral regulation (Goodrich et al, 2016). Only one study evaluated epigenome-wide DNA methylation and this study found differential methylation in genes related to growth and immune function for infants of aflatoxin-exposed mothers (Hernandez-Vargas et al, 2015).…”

“…Additional outcomes evaluated included markers of oxidative stress, inflammatory cytokines, and chemokines (Cachon et al, 2014), chronic bronchitis from occupational exposures to dust (Hinson et al, 2016), elevated prostate specific antigen (PSA) among young men exposed occupationally to quarry pollutants (Ewenighi et al, 2017), chronic respiratory symptoms among limestone factory workers in Zambia (Bwalya et al, 2011), and allergic rhinitis in urban areas (Flatin et al, 2018). Exacerbation of silicosis due to higher doses of particulate matter exposure, impacts of exposure to prenatal air pollution on DNA methylation in the context of HIV status and antiretroviral treatment (Goodrich et al, 2016), asthma and asthma exacerbations, mortality, cerebrovascular outcomes, cardiovascular outcomes, and daily respiratory mortality were also evaluated.…”