DNA Methylation Score as a Biomarker in Newborns for Sustained Maternal Smoking during Pregnancy

• Sarah E. Reese ^[5] ; Shanshan Zhao ^[1] ; Michael C. Wu ^[4] ; Bonnie R. Joubert ^[6] ; Christine L. Parr ^[7] ; Siri E. Håberg ^[2] ; Per Magne Ueland ^[3] ; Roy M. Nilsen ^[3] ; Øivind Midttun ^[8] ; Stein Emil Vollset ^[9] ; Shyamal D. Peddada ^[1] ; Wenche Nystad ^[10] ; Stephanie J. London ^[5]
  1. [1] National Institute of Environmental Health Sciences

     National Institute of Environmental Health Sciences

     Township of Durham, Estados Unidos

     
  2. [2] Norwegian Institute of Public Health

     Norwegian Institute of Public Health

     Noruega

     
  3. [3] University of Bergen

     University of Bergen

     Noruega

     
  4. [4] Fred Hutchinson Cancer Research Center

     Fred Hutchinson Cancer Research Center

     City of Seattle, Estados Unidos

     
  5. [5] 1 Epidemiology Branch, and
  6. [6] 4 Population Health Branch, NIEHS, NIH, DHHS, Research Triangle Park, North Carolina, USA
  7. [7] 1 Epidemiology Branch, and; 5 Department of Chronic Diseases, and
  8. [8] 11 Bevital A/S, Bergen, Norway
  9. [9] 9 Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway; 12 Center for Disease Burden, Norwegian Institute of Public Health, Oslo/Bergen, Norway
  10. [10] 5 Department of Chronic Diseases, and

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• Localización: Environmental health perspectives, ISSN 0091-6765, Vol. 125, Nº. 4, 2017, págs. 760-766
• Idioma: inglés
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  • 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.

    Reese SE, Zhao S, Wu MC, Joubert BR, Parr CL, Håberg SE, Ueland PM, Nilsen RM, Midttun Ø, Vollset SE, Peddada SD, Nystad W, London SJ. 2017. DNA methylation score as a biomarker in newborns for sustained maternal smoking during pregnancy. Environ Health Perspect 125:760–766; http://dx.doi.org/10.1289/EHP333