Maternal smoking during pregnancy and infant stress response: Test of a prenatal programming hypothesis

PSYCHONEUROENDOCRINOLOGY

卷:48

Article

Stroud, Laura R.^1,2  Papandonatos, George D.³  Rodriguez, Daniel⁴  McCallum, Meaghan⁵  Salisbury, Amy L.^1,6,7  Phipps, Maureen G.^7,8  Lester, Barry^1,6,7  Huestis, Marilyn A.⁹  Niaura, Raymond¹⁰  Padbury, James F.^6,7  Marsit, Carmen J.¹¹ 

[1] Brown Univ, Warren Alpert Med Sch, Dept Psychiat & Human Behav, Providence, RI 02906 USA

[2] Miriam Hosp, Ctr Behav & Prevent Med, Providence, RI 02906 USA

[3] Brown Univ, Sch Publ Hlth, Dept Biostat, Providence, RI 02903 USA

[4] La Salle Univ, Sch Nursing & Hlth Sci, Dept Publ Hlth & Nutr, Philadelphia, PA 19141 USA

[5] Emory Univ, Dept Psychol, Atlanta, GA 30322 USA

[6] Brown Univ, Warren Alpert Med Sch, Dept Pediat, Providence, RI 02906 USA

[7] Women & Infants Hosp Rhode Isl, Providence, RI 02905 USA

[8] Brown Univ, Warren Alpert Med Sch, Dept Obstet & Gynecol, Providence, RI 02905 USA

[9] NIDA, Intramural Res Branch, NIH, Baltimore, MD 21224 USA

[10] Amer Legacy Fdn, Schroeder Inst Tobacco Res & Policy Studies, Washington, DC 20036 USA

[11] Dartmouth Coll, Dept Pharmacol & Toxicol, Hanover, NH 03755 USA

关键词: Smoking;    Tobacco;    Pregnancy;    Infant;    Cortisol;    Stress;    Epigenetic;    Programming;    Placenta;    NR3C1;   

DOI  :  10.1016/j.psyneuen.2014.05.017

来源: Elsevier

【 摘 要 】

Background: Maternal smoking during pregnancy (MSDP) is associated with early and long-term neurobehavioral deficits; however mechanisms remain unknown. We tested the hypothesis that MSDP programs the hypothalamic pituitary adrenocortical (HPA) axis of the offspring leading to adverse outcomes. In an intensive, prospective study, we investigated associations between MSDP and infant cortisol stress response and explored whether alterations in cortisol response were mediated by epigenetic modulation of the placental glucocorticoid receptor gene (NR3C1). Methods: Participants were 100 healthy mother-infant pairs (53% MSDP-exposed; 42% female) from a low income, racially/ethnically diverse sample (55% minorities). MSDP was assessed by timeline followback interview verified by saliva and meconium cotinine. Infant cortisol responses to a neurobehavioral exam were assessed seven times over the first postnatal month. Methylation of placental NR3C1 promoter exon 1F was assessed using bisulfite pyrosequencing in a subsample (n = 45). Results: MSDP-exposed infants showed significantly and persistently attenuated basal and reactive cortisol levels over the first postnatal month vs. unexposed infants. Exploratory analyses revealed that MSDP was associated with altered methylation of the placental NR3C1 promoter; degree of methylation of the placental NR3C1 was associated with infant basal and reactive cortisol over the first postnatal month and mediated effects of MSDP on infant basal cortisol. Conclusions: Results provide initial support for our hypothesis that MSDP programs offspring HPA (dys)regulation. Epigenetic regulation of placental GR may serve as a novel underlying mechanism. Results may have implications for delineating pathways to adverse outcomes from MSDP. (C) 2014 Elsevier Ltd. All rights reserved.

【 授权许可】

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