A gestational vulnerability window for smoking exposure and the increased risk o preterm birth: how timing and intensity of maternal smoking matter

Background: Reducing the incidence of preterm birth is a national priority. Maternal cigarette smoking is strongly and consistently associated with preterm birth. The objective of this study was to examine prenatal exposure based on combined measures of timing (by trimester) and intensity level (the number of cigarettes smoked per day) of maternal smoking to identify a pregnancy period with the highest risk of preterm birth. Methods: A sample of 2,485,743 singleton births was drawn from the 2010 National Center of Health Statistics (NCHS) linked birth/infant death file of US residents in 33 states that implemented the revised 2003 birth certificate. Nine mutually exclusive smoking status categories were created to assess prenatal exposure across pregnancy in association with preterm birth. Gestational age was based on the obstetric estimate. Multiple logistic regression analyses were conducted to compare the odds of preterm birth among women who smoked at different intensity levels in the second or third trimester with those who smoked only in the first trimester. Results: Overall, 7.95% of women had a preterm birth; 8.90% of low intensity (less than a pack/day) smokers in the first trimester only, 12.99% of low and 15.38% of high intensity (pack a day or more) smokers in the first two trimesters, and 10.56% of low and 1135% of high intensity smokers in all three trimesters delivered preterm. First and second trimester high (aOR 1.85, 95% CI: 1.66, 2.06) and low intensity smokers (aOR 1.51, 95% CI: 1.41, 1.61) had higher odds of preterm birth compared to those who smoked less than a pack a day only in the first trimester, but the odds did not increase for all three trimester smokers relative to the first and second trimester smokers. In sensitivity analysis, adjustment for exposure misclassification error corrected data and testing for effect modification by maternal race/ethnicity found no significant interaction. Conclusions: This study documented a biologically plausible vulnerability window for smoking exposure and the increased risk of preterm birth. For women who do not modify their smoking behavior preconception, preterm birth risk of smoking remains low until late in the first trimester.