Abstract
BackgroundThe adverse health effects of early life exposure to tobacco smoking have been widely reported. In spite of this, the underlying molecular mechanisms of in utero and postnatal exposure to tobacco smoke are only partially understood. Here, we aimed to identify multi-layer molecular signatures associated with exposure to tobacco smoke in these two exposure windows.MethodsWe investigated the associations of maternal smoking during pregnancy and childhood secondhand smoke (SHS) exposure with molecular features measured in 1203 European children (mean age 8.1 years) from the Human Early Life Exposome (HELIX) project. Molecular features, covering 4 layers, included blood DNA methylation and gene and miRNA transcription, plasma proteins, and sera and urinary metabolites.ResultsMaternal smoking during pregnancy was associated with DNA methylation changes at 18 loci in child blood. DNA methylation at 5 of these loci was related to expression of the nearby genes. However, the expression of these genes themselves was only weakly associated with maternal smoking. Conversely, childhood SHS was not associated with blood DNA methylation or transcription patterns, but with reduced levels of several serum metabolites and with increased plasma PAI1 (plasminogen activator inhibitor-1), a protein that inhibits fibrinolysis. Some of the in utero and childhood smoking-related molecular marks showed dose-response trends, with stronger effects with higher dose or longer duration of the exposure.ConclusionIn this first study covering multi-layer molecular features, pregnancy and childhood exposure to tobacco smoke were associated with distinct molecular phenotypes in children. The persistent and dose-dependent changes in the methylome make CpGs good candidates to develop biomarkers of past exposure. Moreover, compared to methylation, the weak association of maternal smoking in pregnancy with gene expression suggests different reversal rates and a methylation-based memory to past exposures. Finally, certain metabolites and protein markers evidenced potential early biological effects of postnatal SHS, such as fibrinolysis.
Highlights
The adverse health effects of early life exposure to tobacco smoking have been widely reported
Study population The study included 1203 children, aged 6 to 11 years, from the Human Early Life Exposome (HELIX) project that had complete information on pregnancy and childhood exposure to tobacco smoking and data on at least one omics platform [24]. These children were from longitudinal cohorts in 6 European countries, 90.1% were of European ancestry, 54.5% were males, and 51.5% were born from highly educated mothers (Table 1)
Our study investigated the in utero and postnatal effects of exposure to tobacco smoke on 4 molecular layers, assessed through a harmonized protocol, in 1203 children across Europe
Summary
The adverse health effects of early life exposure to tobacco smoking have been widely reported. The in utero period and the first years of human life are crucial for the development and maturation of organs [1]. Insults during these periods may result in later adverse health consequences, which might persist during the whole lifespan. Maternal smoking during pregnancy represents one of the most important avoidable risk factors, and its shortand long-term adverse effects on offspring, including prematurity, lower birth weight, increased risk of asthma and obesity, and impaired neurodevelopment, have been widely reported [3, 4]. SHS has been related to increased risk of asthma, lower respiratory infections, and sudden infant death syndrome [4, 6]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
