Smoking during pregnancy and its effect on placental weight: A Mendelian randomization study

Abstract

Background: The causal relationship between maternal smoking in pregnancy and reduced offspring birth weight is well established and is likely due to impaired placental function. However, observational studies have given conflicting results on the association between smoking and placental weight. We aimed to estimate the causal effect of newly pregnant mothers quitting smoking on their placental weight at the time of delivery. Methods: We used one-sample Mendelian randomization, drawing data from the Avon Longitudinal Study of Parents and Children (ALSPAC) (up to N = 805) and the Norwegian Mother, Father and Child Cohort Study (MoBa) (up to N = 4475). The analysis was performed in pre-pregnancy smokers only, due to the specific role of the genetic instrument SNP rs1051730 (CHRNA5-CHRNA3-CHRNB4) in affecting smoking cessation but not initiation. Results: Fixed effect meta-analysis showed a 175 g [95%CI: 16, 334] higher placental weight for pre-pregnancy smoking mothers who continued smoking at the beginning of pregnancy, compared with those who stopped smoking. Using the number of cigarettes smoked per day in the first trimester as the exposure, the causal estimate was a 12 g [95%CI: 2,22] higher placental weight per cigarette per day. Results were similar when the smoking exposures were measured at the end of pregnancy. Using the residuals of birth weight regressed on placental weight as the outcome, we showed weak evidence of lower offspring birth weight relative to the placental weight for continuing smoking. Conclusion: Our results suggest that continued smoking during pregnancy causes higher placental weights.

Exploring and accounting for genetically driven effect heterogeneity in Mendelian Randomization

“…We restricted our analysis to unrelated mothers with available genetic information. Additionally, we excluded multiple births and preterm births (pregnancy duration ≤ 37 weeks) [25]. The analysis data set had a sample size of 7752 individual mothers.…”