DNA methylation score as a biomarker in newborns for sustained maternal smoking during pregnancy

Sarah E. Reese, Shanshan Zhao, Michael C. Wu, Bonnie R. Joubert, Christine L. Parr, Siri E. Håberg, Per Magne Ueland, Roy M. Nilsen, Øivind Midttun, Stein Emil Vollset, Shyamal D. Peddada, Wenche Nystad, Stephanie J. London

Research output: Contribution to journalArticle

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Abstract

Background: 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. Objectives: We developed a biomarker of sustained maternal smoking in pregnancy using common DNA methylation platforms. Methods: 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). Results: 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%). Conclusions: 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.

LanguageEnglish (US)
Pages760-766
Number of pages7
JournalEnvironmental Health Perspectives
Volume125
Issue number4
DOIs
StatePublished - Apr 1 2017

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DNA Methylation
Biomarkers
Smoking
Mothers
Newborn Infant
Pregnancy
Cotinine
Health
Fetal Blood
Birth Weight
Methylation
Pregnant Women
Cohort Studies

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Health, Toxicology and Mutagenesis

Cite this

Reese, S. E., Zhao, S., Wu, M. C., Joubert, B. R., Parr, C. L., Håberg, S. E., ... London, S. J. (2017). DNA methylation score as a biomarker in newborns for sustained maternal smoking during pregnancy. Environmental Health Perspectives, 125(4), 760-766. DOI: 10.1289/EHP333

DNA methylation score as a biomarker in newborns for sustained maternal smoking during pregnancy. / Reese, Sarah E.; Zhao, Shanshan; Wu, Michael C.; Joubert, Bonnie R.; Parr, Christine L.; Håberg, Siri E.; Ueland, Per Magne; Nilsen, Roy M.; Midttun, Øivind; Vollset, Stein Emil; Peddada, Shyamal D.; Nystad, Wenche; London, Stephanie J.

In: Environmental Health Perspectives, Vol. 125, No. 4, 01.04.2017, p. 760-766.

Research output: Contribution to journalArticle

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' Environmental Health Perspectives, vol. 125, no. 4, pp. 760-766. DOI: 10.1289/EHP333
Reese SE, Zhao S, Wu MC, Joubert BR, Parr CL, Håberg SE et al. DNA methylation score as a biomarker in newborns for sustained maternal smoking during pregnancy. Environmental Health Perspectives. 2017 Apr 1;125(4):760-766. Available from, DOI: 10.1289/EHP333
Reese, Sarah E. ; Zhao, Shanshan ; Wu, Michael C. ; Joubert, Bonnie R. ; Parr, Christine L. ; Håberg, Siri E. ; Ueland, Per Magne ; Nilsen, Roy M. ; Midttun, Øivind ; Vollset, Stein Emil ; Peddada, Shyamal D. ; Nystad, Wenche ; London, Stephanie J./ DNA methylation score as a biomarker in newborns for sustained maternal smoking during pregnancy. In: Environmental Health Perspectives. 2017 ; Vol. 125, No. 4. pp. 760-766
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abstract = "Background: 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. Objectives: We developed a biomarker of sustained maternal smoking in pregnancy using common DNA methylation platforms. Methods: 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). Results: 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{\%}). Conclusions: 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.",
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T1 - DNA methylation score as a biomarker in newborns for sustained maternal smoking during pregnancy

AU - Reese,Sarah E.

AU - Zhao,Shanshan

AU - Wu,Michael C.

AU - Joubert,Bonnie R.

AU - Parr,Christine L.

AU - Håberg,Siri E.

AU - Ueland,Per Magne

AU - Nilsen,Roy M.

AU - Midttun,Øivind

AU - Vollset,Stein Emil

AU - Peddada,Shyamal D.

AU - Nystad,Wenche

AU - London,Stephanie J.

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N2 - Background: 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. Objectives: We developed a biomarker of sustained maternal smoking in pregnancy using common DNA methylation platforms. Methods: 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). Results: 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%). Conclusions: 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.

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