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American Journal of Epidemiology Advance Access originally published online on October 19, 2005
American Journal of Epidemiology 2005 162(11):1108-1113; doi:10.1093/aje/kwi323
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American Journal of Epidemiology Copyright © 2005 by the Johns Hopkins Bloomberg School of Public Health All rights reserved; printed in U.S.A.

Original Contribution

Plasma C-Reactive Protein in Early Pregnancy and Preterm Delivery

Waranuch Pitiphat1,2,3, Matthew W. Gillman4,5, Kaumudi J. Joshipura1,2, Paige L. Williams6, Chester W. Douglass1,2 and Janet W. Rich-Edwards1,4,7

1 Department of Epidemiology, Harvard School of Public Health, Boston, MA
2 Department of Oral Health Policy and Epidemiology, Harvard School of Dental Medicine, Boston, MA
3 Department of Community Dentistry, Faculty of Dentistry, Khon Kaen University, Khon Kaen, Thailand
4 Department of Ambulatory Care and Prevention, Harvard Medical School and Harvard Pilgrim Health Care, Boston, MA
5 Department of Nutrition, Harvard School of Public Health, Boston, MA
6 Department of Biostatistics, Harvard School of Public Health, Boston, MA
7 The Channing Laboratory, Harvard Medical School and Brigham and Women's Hospital, Boston, MA

Correspondence to Dr. Waranuch Pitiphat, Faculty of Dentistry, Khon Kaen University, Khon Kaen 40002, Thailand (e-mail: waranuch{at}kku.ac.th).

Systemic maternal infections have been associated with preterm delivery. The authors examined the association of C-reactive protein (CRP), a marker of inflammation, with preterm delivery. This nested case-control study was conducted within Project Viva in Massachusetts between 1999 and 2002. Subjects were 117 women who delivered preterm (<37 weeks' gestation) and 117 controls (term deliveries) matched on age, race/ethnicity, and smoking status. High-sensitivity CRP assays were performed on early-pregnancy (5.3–19.3 weeks' gestation) plasma samples. Odds ratios and 95% confidence intervals were estimated by using conditional logistic regression adjusted for matching factors, gestational age at blood collection, and prepregnancy body mass index. Median concentration of CRP was 3.2 mg/liter in cases versus 2.4 mg/liter in controls. No significant association was found between quartiles of CRP and preterm delivery. However, CRP levels exceeding the threshold defined in the literature were associated with increased risk of preterm delivery (odds ratio = 2.55, 95% confidence interval: 1.05, 6.02 for CRP ≥8 mg/liter). The association was stronger among cases who experienced spontaneous delivery (odds ratio = 4.64, 95% confidence interval: 0.94, 22.96) versus indicated delivery (odds ratio = 1.42, 95% confidence interval: 0.44, 4.61). These findings suggest that very high CRP levels in early pregnancy are associated with preterm delivery.

biological markers; C-reactive protein; case-control studies; pregnancy; premature birth


Abbreviations: CI, confidence interval; CRP, C-reactive protein; OR, odds ratio


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