IntroductionThe causal relationship between maternal second-hand smoke (SHS) exposure during pregnancy and small for gestational-age (SGA) has been affirmed, but the mechanism is still unclear. Previous studies have found that the placenta remarkably affects fetal intrauterine growth and that SHS exposure during pregnancy impairs placental growth and decreases placental weight. Therefore, the placenta may mediate the association between maternal SHS exposure during pregnancy and SGA. This study explores whether and to what extent the association between maternal SHS exposure during pregnancy and SGA is mediated by the placenta. MethodsWe investigated 562 pregnant women delivering SGA newborns (cases) and 1581 delivering appropriate-for-gestational-age newborns (controls) in this case–control study. Information on maternal SHS exposure during pregnancy, socio-demographic characteristics and obstetric conditions, including placental weight, were collected at the Maternity and Child Health Care Hospitals of Shenzhen and Foshan in Guangdong, China. Linear and hierarchical logistic regression models were fitted to examine the mediation effects of placental weight on the association between maternal SHS exposure during pregnancy and SGA. ResultsAfter controlling for ethnicity, maternal age, educational level, family income, pre-pregnancy body mass index (BMI), parity, gestational age and newborn gender, maternal SHS exposure during pregnancy was associated with a higher SGA risk (adjusted odds ratio (OR) = 1.26; 95% confidence interval (CI) = 1.03–1.55) and lower placental weight (standard deviation (SD) = −0.15, SE = 0.04). Regression models illustrated that placental weight partially mediated (49.6%; 95% CI = 35.9–63.3%) the association between SHS exposure during pregnancy and SGA. DiscussionOur findings suggest that the placenta plays an intermediary role in how maternal prenatal SHS exposure affects fetal growth.