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American Journal of Epidemiology Advance Access originally published online on April 10, 2009
American Journal of Epidemiology 2009 169(11):1319-1326; doi:10.1093/aje/kwp061
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American Journal of Epidemiology © The Author 2009. Published by the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org.

ORIGINAL CONTRIBUTIONS

Stress Pathways to Spontaneous Preterm Birth: The Role of Stressors, Psychological Distress, and Stress Hormones

Michael S. Kramer, John Lydon, Louise Séguin, Lise Goulet, Susan R. Kahn, Helen McNamara, Jacques Genest, Clément Dassa, Moy Fong Chen, Shakti Sharma, Michael J. Meaney, Steven Thomson, Stan Van Uum, Gideon Koren, Mourad Dahhou, Julie Lamoureux and Robert W. Platt

Correspondence to Dr. Michael S. Kramer, Montreal Children's Hospital, 2300 Tupper Street (Les Tourelles), Montreal, Quebec H3H 1P3, Canada (e-mail: michael.kramer{at}mcgill.ca).

Received for publication October 28, 2008. Accepted for publication February 18, 2009.

The authors investigated a large number of stressors and measures of psychological distress in a multicenter, prospective cohort study of spontaneous preterm birth among 5,337 Montreal (Canada)-area women who delivered from October 1999 to April 2004. In addition, a nested case-control analysis (207 cases, 444 controls) was used to explore potential biologic pathways by analyzing maternal plasma corticotrophin-releasing hormone (CRH), placental histopathology, and (in a subset) maternal hair cortisol. Among the large number of stress and distress measures studied, only pregnancy-related anxiety was consistently and independently associated with spontaneous preterm birth (for values above the median, adjusted odds ratio = 1.8 (95% confidence interval: 1.3, 2.4)), with a dose-response relation across quartiles. The maternal plasma CRH concentration was significantly higher in cases than in controls in crude analyses but not after adjustment (for concentrations above the median, adjusted odds ratio = 1.1 (95% confidence interval: 0.8, 1.6)). In the subgroup (n = 117) of participants with a sufficient maternal hair sample, hair cortisol was positively associated with gestational age. Neither maternal plasma CRH, hair cortisol, nor placental histopathologic features of infection/inflammation, infarction, or maternal vasculopathy were significantly associated with pregnancy-related anxiety or any other stress or distress measure. The biologic pathways underlying stress-induced preterm birth remain poorly understood.

anxiety; corticotropin-releasing hormone; hydrocortisone; premature birth; stress, physiological; stress, psychological

Abbreviations: CI, confidence interval; CRH, corticotrophin-releasing hormone; OR, odds ratio; PPROM, preterm prelabor rupture of membranes; SD, standard deviation


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