The Swedish health registries were used to investigate a possible effect of maternal smoking on the incidence of multiple malformations. Among 1413811 infants born in 1983-96 and with known smoking exposure in early pregnancy, 26619 with isolated malformations and 1409 with two or more malformations were selected. After controlling for year of birth, maternal age, parity and educational level, a statistically significant association between maternal smoking and multiple malformations was found (OR 1.15; 95% CI 1.02, 1.29). Among isolated malformations, the estimated OR for maternal smoking was close to unity (OR 1.02; 95% CI 0.99, 1.05), but a strong heterogeneity of the magnitude of the association between maternal smoking and the different malformations was found. Among multimalformed, no such heterogeneity was indicated. The ORs for maternal smoking were calculated for all possible pairwise combinations of 44 selected malformations, but no association between maternal smoking and any specific combination could be detected. The ORs for maternal smoking among probable cases of VATER, CHARGE or OEIS non-random associations, respectively, were estimated, but no association was indicated between maternal smoking and any of the malformation complexes. The results of the present study indicate that maternal smoking is associated with a non-specific increased risk of multiple malformations, but further research is needed before such an inference can be made.
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