Prenatal nicotine exposure and effects on the health of the newborn

Abstract: Maternal smoking is one of the most important preventable risk factors in pregnancy. Whether it is nicotine or combustion products, or possibly both, that cause the adverse effects is not clear. The common substance in snuff and cigarette smoke is nicotine.The main objective was to study whether it is safe to use snuff in pregnancy, and if cessation of tobacco use influences the risk of adverse effects on the health of the newborn. Methods: Studies I-III were all based on data from the Swedish Medical Birth Register. Information on tobacco use three months before pregnancy and in early pregnancy was obtained from the register and categorized as nonuser, smoker 1 -9 cigarettes/day, smoker≥10 cigarettes/day or snuff user. Most epidemiological studies on tobacco use are based on selfreported information. Snuff use in pregnancy has not been validated previously. In study IV, self-reported snuff use in a cohort of pregnant women was validated by the use of a biomarker of nicotine exposure, cotinine. Results: In study I, the association between smoking or snuff use in pregnancy and risk of neonatal apnea was investigated. Maternal snuff use was associated with an almost twofold risk of neonatal apnea. In contrast, the increased risk of apnea in smokers was not significant after adjustment for gestational age, indicating different mechanisms for nicotine and tobacco smoke. Study II investigated the association between tobacco use and risk of oral cleft malformations. Both maternal smoking and snuff use were associated with increased risk of oral cleft malformations. However, infants of women who had stopped smoking or using snuff before the antenatal booking were not at an increased risk of oral cleft malformations compared to that of nonusers. In study III, the association between maternal smoking, snuff use and preterm birth was studied. Maternal smoking was associated with extremely (<28 weeks), very (28-<32 weeks) and moderately (32-<37 weeks) preterm birth. Snuff use in pregnancy was associated with extremely preterm birth and moderately preterm birth, whereas the association with very preterm birth was of borderline significance. Importantly, with cessation of tobacco use in early pregnancy, there was no increased risk. In Study IV, self-reported snuff use was validated by measuring cotinine in maternal urine and meconium of the newborn. Self-reported use of snuff was found valid in late pregnancy. However, there was a large proportion of misclassification of snuff use in the Medical Birth Register in late pregnancy. Conclusion: Snuff use and smoking in pregnancy are associated with increased risk of adverse effects such as neonatal apnea, oral cleft malformation and extremely preterm birth. Importantly, infants of women who stopped using tobacco were not at an increased risk. This thesis indicates that no forms of nicotine or tobacco are to be regarded as safe to use in pregnancy.