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Perinatal & Pediatric

Smoking during pregnancy and second and third-generation health outcomes in a population-based multigenerational cohort Michelle Pearl* Michelle Pearl Kimberly Berger Alan Hubbard Peyton Jacob Gayle Windham Marty Kharrazi

Background: Smoking tobacco during pregnancy directly exposes the fetus (second generation [G2]) and their early reproductive cells (third generation [G3]) in addition to the pregnant person (first generation [G1]). Limited studies from mostly White cohorts have reported changes in G2 cardiometabolic health and G3 asthma, birthweight and neurodevelopment associated with in utero exposure to G1 smoking. We investigated the health effects of G1 smoking on pre-pregnancy obesity and chronic hypertension in G2, and very-preterm birth (<32 weeks gestation) and autism spectrum disorder (ASD) in G3, in White and Black cohorts.

Methods: Race-stratified case-cohort samples were drawn from all California birth records from 2007-2011 (G3) linked to mothers’ California birth and newborn screening records since 1982 (G2; n=1,225 White; n=1,203 Black). G2 and G3 health outcomes were obtained from linked birth, screening, hospital discharge, and developmental services records. Stored G2 newborn blood spots were analyzed for the tobacco biomarker cotinine, with levels ≥ 10 ng/mL indicating in utero exposure to G1 smoking. Odds ratios were estimated with logistic regression adjusting for G1 neighborhood poverty, age, and parity.

Results: Thirty percent of White and Black G2 subjects were exposed in utero to G1 smoking. G3 very preterm birth was elevated among White G2 subjects exposed to G1 smoking, compared to those with cotinine <10 ng/mL (OR=1.41 [95% CI 1.13, 1.76]). This association was not observed among Black G2 subjects. No associations were observed for G2 pre-pregnancy obesity, G2 chronic hypertension or G3 ASD.

Conclusion: In this first study of multigenerational smoking effects to focus on Black women, no associations were found with selected second and third generation outcomes among Black women. The observation of increased very-preterm birth in the third generation in relation to in utero exposure to tobacco smoking within the White cohort warrants further investigation.