Prenatal and postnatal exposure to tobacco smoking and molecular signatures in children

Abstract

Maternal smoking during pregnancy (MSDP) and postnatal secondhand smoking (SHS) are ongoing public health concerns that are associated with adverse child health outcomes, but not much is known about the underlying molecular mechanisms. We investigated the association between MSDP and placental DNA methylation, and its link with reproductive outcomes through a meta- analysis. We identified 1224 differentially methylated CpGs in placenta, which were enriched for pathways related to inflammation, growth factors and vascularization. Moreover, the methylation of many of these CpGs was associated with gestational age and birth size. We also investigated the association between MSDP and postnatal SHS, and different molecular layers in children: blood DNA methylation and transcription, plasma proteins, and serum and urinary metabolites. In utero exposure, was only associated with child DNA methylation, confirming a persistent MSDP-related signature on the blood epigenome. However, this imprint was not mirrored in the child transcriptome. In contrast, postnatal SHS was related to protein and metabolite levels, which are more dynamic, and likely reflecting short-term exposures. Of note, the MSDP-associated methylome signature was tissue-specific.