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

  Mostrar afiliaciones +
• Localización: Environmental health perspectives, ISSN 0091-6765, Vol. 125, Nº. 4, 2017, págs. 760-766
• Idioma: inglés
• DOI: 10.1289/EHP333
• Enlaces
  • Texto completo
• Resumen

  • 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

• Referencias bibliográficas
  • Benowitz, NL. (1996). Cotinine as a biomarker of environmental tobacco smoke exposure.. Epidemiol Rev. 18. 188-204
  • Besingi, W, Johansson, A. (2014). Smoke-related DNA methylation changes in the etiology of human disease.. Hum Mol Genet. 23. 2290-2297
  • Bibikova, M, Barnes, B, Tsan, C, Ho, V, Klotzle, B, Le, JM. (2011). High density DNA methylation array with single CpG site resolution.. Genomics....
  • Chen, YA, Lemire, M, Choufani, S, Butcher, DT, Grafodatskaya, D, Zanke, BW. (2013). Discovery of cross-reactive probes and polymorphic CpGs...
  • Dempsey, D, Jacob, P, Benowitz, NL. (2002). Accelerated metabolism of nicotine and cotinine in pregnant smokers.. J Pharmacol Exp Ther. 301....
  • (2014). DHHS, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking...
  • Dietz, PM, Homa, D, England, LJ, Burley, K, Tong, VT, Dube, SR. (2011). Estimates of nondisclosure of cigarette smoking among pregnant and...
  • Fan, J, Lv, J. (2008). Sure independence screening for ultrahigh dimensional feature space.. J R Stat Soc Series B Stat Methodol. 70. 849-911
  • (2011). Robust regression in R. In:. Sage. Thousand Oaks, CA.
  • (2009). Springer. New York, NY.
  • Irgens, LM. (2000). The Medical Birth Registry of Norway. Epidemiological research and surveillance throughout 30 years.. Acta Obstet Gynecol...
  • Jacobsen, BK, Thelle, DS. (1988). The Tromsø Heart Study: responders and non-responders to a health questionnaire, do they differ?. Scand...
  • Joubert, BR, Felix, JF, Yousefi, P, Bakulski, KM, Just, AC, Breton, C. (2016). DNA methylation in newborns and maternal smoking in pregnancy:...
  • Joubert, BR, Håberg, SE, Bell, DA, Nilsen, RM, Vollset, SE, Midttun, Ø. (2014). Maternal smoking and DNA methylation in newborns:. Cancer...
  • Küpers, LK, Xu, X, Jankipersadsing, SA, Vaez, A, la Bastide-van Gemert, S, Scholtens, S. (2015). DNA methylation mediates the effect of maternal...
  • Kvalvik, LG, Nilsen, RM, Skjærven, R, Vollset, SE, Midttun, Ø, Ueland, PM. (2012). Self-reported smoking status and plasma cotinine concentrations...
  • (2016).
  • Magnus, P, Irgens, LM, Haug, K, Nystad, W, Skjærven, R, Stoltenberg, C. (2006). Cohort profile: the Norwegian Mother and Child Cohort Study...
  • Metz, CE. (1978). Basic principles of ROC analysis.. Semin Nucl Med. 8. 283-298
  • Midttun, Ø, Hustad, S, Ueland, PM. (2009). Quantitative profiling of biomarkers related to B-vitamin status, tryptophan metabolism and inflammation...
  • Moran, S, Arribas, C, Esteller, M. (2016). Validation of a DNA methylation microarray for 850,000 CpG sites of the human genome enriched in...
  • Mund, M, Louwen, F, Klingelhoefer, D, Gerber, A. (2013). Smoking and pregnancy—a review on the first major environmental risk factor of the...
  • Murin, S, Rafii, R, Bilello, K. (2011). Smoking and smoking cessation in pregnancy.. Clin Chest Med. 32. 75-91
  • Richmond, RC, Simpkin, AJ, Woodward, G, Gaunt, TR, Lyttleton, O, McArdle, WL. (2015). Prenatal exposure to maternal smoking and offspring...
  • Roessler, J, Lehmann, U. (2015). Quantitative DNA methylation analysis by pyrosequencing®.. Methods Mol Biol. 1315. 175-188
  • Rønningen, KS, Paltiel, L, Meltzer, HM, Nordhagen, R, Lie, KK, Hovengen, R. (2006). The biobank of the Norwegian Mother and Child Cohort Study:...
  • Sandoval, J, Heyn, H, Moran, S, Serra-Musach, J, Pujana, MA, Bibikova, M. (2011). Validation of a DNA methylation microarray for 450,000 CpG...
  • Shaw, GM, Carmichael, SL, Vollset, SE, Yang, W, Finnell, RH, Blom, H. (2009). Mid-pregnancy cotinine and risks of orofacial clefts and neural...
  • Shenker, NS, Ueland, PM, Polidoro, S, van Veldhoven, K, Ricceri, F, Brown, R. (2013). DNA methylation as a long-term biomarker of exposure...
  • Teschendorff, AE, Marabita, F, Lechner, M, Bartlett, T, Tegner, J, Gomez-Cabrero, D. (2013). A beta-mixture quantile normalization method...
  • Tibshirani, R. (1996). Regression shrinkage and selection via the lasso.. J R Stat Soc Series B Stat Methodol. 58. 267-288
  • Wani, K, Aldape, KD. (2016). PCR techniques in characterizing DNA methylation.. Methods Mol Biol. 1392. 177-186
  • Wiencke, JK, Bracci, PM, Hsuang, G, Zheng, S, Hansen, H, Wrensch, MR. (2014). A comparison of DNA methylation specific droplet digital PCR...
  • Wu, MC, Joubert, BR, Kuan, PF, Håberg, SE, Nystad, W, Peddada, SD. (2014). A systematic assessment of normalization approaches for the Infinium...