Associations between prenatal alcohol and tobacco exposure on Doppler flow velocity waveforms in pregnancy: a South African study

Background: The negative impact of prenatal alcohol and tobacco exposure (PAE and PTE) on fetal development and birth outcomes are well described, yet pathophysiologic mechanisms are less clear. Our aim was to investigate (1) the associations between quantity, frequency and timing (QFT) of PAE and PTE with blood flow velocities in arteries of the fetal-placental-maternal circulation and (2) the extent to which combined effect of QFT of PAE and/or PTE and Doppler flow velocity waveforms (FWV) predict infant birth weight. Methods: The Safe Passage Study is a cohort based in urban Cape Town, South Africa. Recruitment occurred between 2007 and 2015. Information on QFT of PAE and PTE was collected prospectively at up to 4 occasions during pregnancy using a modified Timeline Follow-Back approach. Ultrasound examinations consisted of Doppler flow velocity waveforms of the uterine, umbilical (UA) and fetal middle cerebral arteries for the pulsatility index (PI) at 20–24 and 34–38 weeks. Exclusion criteria included: twin pregnancies, stillbirths, participants exposed to other drugs. The sample was divided into three groups (controls, PAE and PTE) and included 1396 maternal-fetal-dyads assessed during the second trimester; 1398 assessed during the third trimester. Results: PTE was associated with higher UA PI values in second and third trimesters (p < 0.001), compared to the PAE and control group. The total amount of cigarettes smoked during pregnancy was positively correlated with UA PI values (r = 0.087, p < 0.001). There was a positive correlation between cigarettes smoked per day in trimester one (r = 0.091, p < 0.01), and trimester two (r = 0.075, p < 0.01) and UA PI (in trimester two), as well as cigarettes smoked per day in trimester two (r = 0.058, p < 0.05) and trimester three (r = 0.069, p < 0.05) and the UA PI in trimester three. Generalized additive models indicated that PAE in trimester two, PTE in trimester one and Doppler FWV in trimester three were significant predictors of birth weight in this sample. Conclusion: In our study, PTE in trimesters two and three resulted in increased vascular resistance of the placenta. These findings highlight nuance in associations between PAE, PTE and blood flow velocities in arteries of the fetal-placental-maternal circulation and birth weight, suggesting that quantity and timing are important factors in these relationships.