Interaction Between Maternal Smoking Cessation Timing and Preexisting Hypertension on Fetal Growth Restriction: A...

Maternal smoking is a major preventable cause of fetal growth restriction (FGR). Although cessation reduces risk, the benefit depends on its timing, and the role of preexisting hypertension-sharing vascular-placental mechanisms-remains underexplored.

We conducted a population-based retrospective cohort study using US birth data (2020-2024). Maternal smoking was divided as nonsmokers, quit before pregnancy, quit in the first trimester, quit in the second trimester, or persistent smokers. FGR was defined using birth-weight-based percentiles derived from the NICHD fetal growth standards (<3rd, <5th, and <10th). Poisson regression with inverse probability of treatment weighting (IPTW) was used to estimate adjusted risk ratios (aRRs). Effect modification by preexisting hypertension was examined on multiplicative and additive scales.

Among 17,381,709 singleton live births, FGR-3rd incidence increased across groups (3.3%, 4.5%, 6.1%, 7.5%, and 10.0%, respectively), showing a dose-response gradient. Compared with nonsmokers, the IPTW-aRRs for FGR-3rd were 1.20 (95% CI:1.17-1.23), 1.61 (1.57-1.66), 2.03 (1.95-2.11) and 2.01 (1.99-2.04) for women who quit before pregnancy, in the first trimester, in the second trimester, and persistent smokers. Preexisting hypertension increased absolute FGR risk but modified associations on the multiplicative scale, with attenuated relative risks among hypertensive women. No meaningful interaction was observed on additive scale. Notably, hypertensive women who quit before pregnancy achieved FGR risks comparable to hypertensive nonsmokers (aRR=0.98, 0.88-1.08). Similar patterns were observed for <5th and <10th percentiles.

Earlier smoking cessation is associated with lower risk of FGR. Preexisting hypertension modifies associations on the multiplicative scale, where relative risks were attenuated among hypertensive women, but not on the additive scale, suggesting the independence on the additive scale (a lack of departure from risk additivity). These findings support integrating smoking cessation into preconception and antenatal care, especially for high-risk women.