title: Prenatal glucocorticoids and maternal smoking during pregnancy independently program adult nicotine dependence in daughters: a 40-year prospective study.
abstract: BACKGROUND
  Maternal smoking during pregnancy (MSDP) is an independent risk factor for offspring nicotine dependence (ND), but mechanisms remain unknown. We investigated prenatal glucocorticoid (cortisol) and androgen (testosterone) associations with offspring ND over 40 years and the possibility that prenatal glucocorticoids and androgens would mediate links between MSDP and offspring ND.
  
  
  METHODS
  Participants were 1086 mother-adult offspring pairs (59% female) from the New England Family Study, a 40-year longitudinal follow-up of the Collaborative Perinatal Project. MSDP was assessed prospectively at each prenatal visit. Maternal cortisol, testosterone, and cotinine (nicotine metabolite) were assayed from third trimester maternal sera. Offspring lifetime ND was assessed via structured interview.
  
  
  RESULTS
  Significant bivariate associations emerged for: 1) MSDP/cotinine and lifetime ND; and 2) maternal cortisol and lifetime ND, for daughters only. In multivariate models, maternal cortisol and MSDP/cotinine remained significantly and independently associated with increased odds of lifetime ND of daughters. However, cortisol did not mediate the MSDP-lifetime ND relation. No associations emerged between maternal testosterone and offspring ND.
  
  
  CONCLUSIONS
  Results provide the first evidence in support of prenatal glucocorticoid programming of adult ND over 40 years in daughters only. Our study highlights two independent prenatal pathways leading to increased risk for ND in daughters: elevated prenatal glucocorticoids and MSDP/nicotine exposure. Daughter-specific effects of glucocorticoid and MSDP programming over 40 years highlight the breadth and persistence of sexually dimorphic programming effects in humans. Results do not support androgen programming of offspring ND.
authors.affiliation: Department of Psychiatry and Human Behavior, Alpert Medical School, School of Public Health, Brown University, Providence, Rhode Island. Electronic address: lstroud1@lifespan.org.
authors.forename: Laura R
authors.initials: LR
authors.lastname: Stroud
authors.forename: George D
authors.initials: GD
authors.lastname: Papandonatos
authors.forename: Edmond
authors.initials: E
authors.lastname: Shenassa
authors.forename: Daniel
authors.initials: D
authors.lastname: Rodriguez
authors.forename: Raymond
authors.initials: R
authors.lastname: Niaura
authors.forename: Kaja Z
authors.initials: KZ
authors.lastname: LeWinn
authors.forename: Lewis P
authors.initials: LP
authors.lastname: Lipsitt
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Buka
mesh_terms: D000328:Adult; D003367:Cotinine / Q000097:blood; D005260:Female; D005938:Glucocorticoids / Q000009:adverse effects*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008137:Longitudinal Studies; D033261:Maternal-Fetal Relations; D008875:Middle Aged; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000097:blood / Q000503:physiopathology*; D012189:Retrospective Studies; D012907:Smoking / Q000009:adverse effects*; D013739:Testosterone / Q000097:blood; D014029:Tobacco Use Disorder / Q000097:blood / Q000503:physiopathology*
chemical_list: D005938:Glucocorticoids; D013739:Testosterone; D003367:Cotinine; D006854:Hydrocortisone
keywords: Androgen; cortisol; cotinine; glucocorticoid; maternal smoking during pregnancy; nicotine dependence; programming; testosterone
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