DNA Methylation Score as a Biomarker in Newborns for Sustained Maternal Smoking during Pregnancy.
Maternal smoking during pregnancy, especially when sustained, leads to numerous adverse health outcomes in offspring. Pregnant women disproportionately underreport smoking and smokers tend to have lower follow-up rates to repeat questionnaires. Missing, incomplete, or inaccurate data on presence and duration of smoking in pregnancy impairs identification of novel health effects and limits adjustment for smoking in studies of other pregnancy exposures. An objective biomarker in newborns of maternal smoking during pregnancy would be valuable.



We developed a biomarker of sustained maternal smoking in pregnancy using common DNA methylation platforms.



Using a dimension reduction method, we developed and tested a numeric score in newborns to reflect sustained maternal smoking in pregnancy from data on cotinine, a short-term smoking biomarker measured mid-pregnancy, and Illumina450K cord blood DNA methylation from newborns in the Norwegian Mother and Child Cohort Study (MoBa).



This score reliably predicted smoking status in the training set (n= 1,057; accuracy = 96%, sensitivity = 80%, specificity = 98%). Sensitivity (58%) was predictably lower in the much smaller test set (n= 221), but accuracy (91%) and specificity (97%) remained high. Reduced birth weight, a well-known effect of maternal smoking, was as strongly related to the score as to cotinine. A three-site score had lower, but acceptable, performance (accuracytrain= 82%, accuracytest= 83%).



Our smoking methylation score represents a promising novel biomarker of sustained maternal smoking during pregnancy easily calculated with Illumina450K or IlluminaEPIC data. It may help identify novel health impacts and improve adjustment for smoking when studying other risk factors with more subtle effects.
Epidemiology Branch, National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH), Department of Health and Human Services (DHHS), Research Triangle Park, North Carolina, USA.
Sarah E
SE
Reese
Shanshan
S
Zhao
Michael C
MC
Wu
Bonnie R
BR
Joubert
Christine L
CL
Parr
Siri E
SE
Håberg
Per Magne
PM
Ueland
Roy M
RM
Nilsen
Øivind
Ø
Midttun
Stein Emil
SE
Vollset
Shyamal D
SD
Peddada
Wenche
W
Nystad
Stephanie J
SJ
London
D000328:Adult; D015415:Biomarkers / Q000097:blood*; D001724:Birth Weight; D015331:Cohort Studies; D003367:Cotinine / Q000097:blood; D019175:DNA Methylation; D005260:Female; D005312:Fetal Blood / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn; D018811:Maternal Exposure / Q000706:statistics & numerical data*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012907:Smoking / Q000453:epidemiology*
D015415:Biomarkers; D003367:Cotinine