Prenatal Particulate Air Pollution and DNA Methylation in Newborns: An Epigenome-Wide Meta-Analysis

Environ Health Perspect. 2019 May;127(5):57012. doi: 10.1289/EHP4522. Epub 2019 May 31.


Background: Prenatal exposure to air pollution has been associated with childhood respiratory disease and other adverse outcomes. Epigenetics is a suggested link between exposures and health outcomes.

Objectives: We aimed to investigate associations between prenatal exposure to particulate matter (PM) with diameter [Formula: see text] ([Formula: see text]) or [Formula: see text] ([Formula: see text]) and DNA methylation in newborns and children.

Methods: We meta-analyzed associations between exposure to [Formula: see text] ([Formula: see text]) and [Formula: see text] ([Formula: see text]) at maternal home addresses during pregnancy and newborn DNA methylation assessed by Illumina Infinium HumanMethylation450K BeadChip in nine European and American studies, with replication in 688 independent newborns and look-up analyses in 2,118 older children. We used two approaches, one focusing on single cytosine-phosphate-guanine (CpG) sites and another on differentially methylated regions (DMRs). We also related PM exposures to blood mRNA expression.

Results: Six CpGs were significantly associated [false discovery rate (FDR) [Formula: see text]] with prenatal [Formula: see text] and 14 with [Formula: see text] exposure. Two of the [Formula: see text] CpGs mapped to FAM13A (cg00905156) and NOTCH4 (cg06849931) previously associated with lung function and asthma. Although these associations did not replicate in the smaller newborn sample, both CpGs were significant ([Formula: see text]) in 7- to 9-y-olds. For cg06849931, however, the direction of the association was inconsistent. Concurrent [Formula: see text] exposure was associated with a significantly higher NOTCH4 expression at age 16 y. We also identified several DMRs associated with either prenatal [Formula: see text] and or [Formula: see text] exposure, of which two [Formula: see text] DMRs, including H19 and MARCH11, replicated in newborns.

Conclusions: Several differentially methylated CpGs and DMRs associated with prenatal PM exposure were identified in newborns, with annotation to genes previously implicated in lung-related outcomes.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Air Pollutants / adverse effects*
  • Air Pollution / adverse effects
  • Child
  • Child, Preschool
  • DNA Methylation / drug effects*
  • Epigenome*
  • Female
  • Fetal Blood / chemistry*
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Maternal Exposure / adverse effects*
  • Particulate Matter / adverse effects*
  • Pregnancy


  • Air Pollutants
  • Particulate Matter