Is the association of maternal smoking and pregnancy-induced hypertension dependent on fetal growth?

Abstract

Maternal smoking during pregnancy is a serious, albeit preventable, cause of perinatal mortality. The risk of preeclampsia, a form of pregnancy-induced hypertension (PIH), however, is decreased by smoking, but the mechanisms remain unclear. Preeclampsia is thought to be the result of placental factors that cause endothelial cell dysfunction, frequently associated with increased blood pressure. Smoking impairs endocrine and transport functions of the placenta that can inhibit fetal growth. We hypothesize that the effect of smoking on risk of PIH/preeclampsia is dependent on its inhibition of placental function as indicated by decreased fetal growth. Our objective was to determine if this association is dependent on decreased fetal growth. A population-based, retrospective cohort study in the United States was performed consisting of nulliparous women who delivered a singleton birth (n=8,025,295) between 1995 and 2002. Fetal growth was defined as birthweight-for-gestational age, and characterized as <1, 1-2, 3-4, 5-9, 10-19…, ≥90th centiles. Risk and relative risk (RR) of PIH before and after adjusting for confounders was estimated. Smoking was associated with decreased risk of PIH with up to a 46% decreased risk of PIH for growth-restricted babies (<10th centile). This association, however, decreased with increasing birthweight centile and was non-significant at ≥20th centile among heavy smokers, at ≥60th centile for moderate and ≥80th centile for light smokers. Smoking was associated with decreased risk of PIH among growth-restricted babies. These findings suggest that smoking may cause lasting damage to the placenta resulting in growth restriction that, in turn, may reduce the production of placental factors that cause PIH.