Evaluating association of smoking status during pregnancy with adverse birth outcomes using urinary cotinine concentration: The Japan environment and Children's study (JECS)

Urinary cotinine concentration (UCC) reflects smoking status. However, in pregnant women, its association with adverse birth outcomes related to fetal growth is not widely known. Thus, we aimed to explore this relationship by focusing on dose-response relationships. We investigated 86,638 pregnant women enrolled between 2011 and 2014 in a prospective cohort study in Japan and observed three birth outcomes (preterm birth, low birth weight, and small-for-gestational age). We measured UCC in the second or third trimester, and categorized the partici-pants using cut-off values (negative cotinine concentration, passive cotinine concentration, and active cotinine concentration corresponding to non-smokers, passive smokers, and active smokers, respectively). Logistic regression analyses were conducted to evaluate the risks, and dose-response relationships were visualized using restricted cubic spline curves. Analyses based on self-reported smoking status were also performed. We found that in low active and highly active cotinine concentrations, the adjusted odds ratios (aORs) of birth outcomes were significantly increased (preterm birth, 1.24 [95% CI 1.06-1.46], 1.39 [95% CI 1.19-1.62]; low birth weight, 1.40 [95% CI 1.24-1.58], 2.27 [95% CI 2.05-2.53]; small-for-gestational age, 1.35 [95% CI 1.19-1.52], 2.39 [95% CI 2.16-2.65]). Restricted cubic spline curves demonstrated risk elevations in the active cotinine concentration range. Our research revealed dose-response relationships between UCC during pregnancy and the risks of preterm birth, low birth weight, and small-for-gestational age. Measurement of UCC to ascertain smoking status during pregnancy may be a useful approach for predicting the risks of these birth outcomes.