Joint Effect of Maternal Tobacco Smoking and Pregestational Diabetes on Preterm Births and Congenital Anomalies: A Population-Based Study in Northern Italy.

Smoking and pregestational diabetes (PGD) are recognized risk factors for adverse pregnancy outcomes, but to date, no population-based study has investigated their joint effects. Using hospital discharges, we identified all women with PGD delivering in Emilia-Romagna region during 2007-2010 matched 1 : 5 with parturients without diabetes. Our study endpoints were preterm births and congenital anomalies. We measured interaction between PGD and maternal smoking, by calculating excess prevalence and prevalence ratio due to interaction, relative excess risk due to interaction (RERI), attributable proportion (AP), and the synergy index (S). Analyses were performed in the overall study population and in the subgroup whose PGD was validated through diabetes registers. The study included 992 women with PGD (10.5% smokers) and 4788 comparison women (11.9% smokers). The effects of PGD and maternal tobacco smoking were greater than additive for both preterm birth (excess prevalence due to interaction = 11.7%, excess ratio due to interaction = 1.5, RERI = 2.39, AP = 0.51, S = 2.82) and congenital anomalies (excess prevalence due to interaction = 2.2%, excess ratio due to interaction = 1.3, RERI = 1.33, AP = 0.49, S = 5.03). Joint effect on both endpoints was confirmed in the subgroup whose PGD status was validated. In conclusion, we found that maternal tobacco smoking and PGD intensify each other's effect on preterm birth and congenital anomalies.