Laura R Stroud1, George D Papandonatos2, Nancy C Jao3, Raymond Niaura4, Stephen Buka5, Neal L Benowitz6. 1. Department of Psychiatry and Human Behavior, Warren Alpert Medical School, Brown University, Box G-BH, Providence, RI 02912, United States; Center for Behavioral and Preventive Medicine, The Miriam Hospital, Coro West, Suite 309, 164 Summit Avenue, Providence, RI 02906, United States. Electronic address: Laura_Stroud@brown.edu. 2. Department of Biostatistics, School of Public Health, Brown University, G-S121-7, 121 South Main Street, Providence, RI 02912, United States. Electronic address: George_Papandonatos@brown.edu. 3. Department of Psychiatry and Human Behavior, Warren Alpert Medical School, Brown University, Box G-BH, Providence, RI 02912, United States; Center for Behavioral and Preventive Medicine, The Miriam Hospital, Coro West, Suite 309, 164 Summit Avenue, Providence, RI 02906, United States. Electronic address: Nancy_Jao@brown.edu. 4. Departments of Social and Behavioral Sciences and Epidemiology, School of Global Public Health, New York University, 708 Broadway, New York, NY 10003, United States. Electronic address: Niaura@nyu.edu. 5. Department of Epidemiology, School of Public Health, Brown University, Box G-S121-2, 121 South Main Street, Providence, RI 02912, United States. Electronic address: Stephen_Buka@brown.edu. 6. Department of Medicine, School of Medicine, University of California, San Francisco, 1001 Potrero Avenue, San Francisco, CA 94110, United States. Electronic address: Neal.Benowitz@uscsf.edu.
Abstract
BACKGROUND: Maternal cigarette smoking is an important modifiable risk factor for low birth weight in the US. We investigated the maternal nicotine metabolite ratio (NMR; trans-3'-hydroxycotinine/cotinine) - a genetically-informed biomarker of nicotine clearance - as a moderator of links between prenatal cigarette use and birth weight. We also explored the role of race in these associations. METHODS: Participants were 454 pregnant women (Mage = 25 years; 11% Black) who smoked cigarettes and their 537 infants from the Collaborative Perinatal Project. Cigarettes smoked per day were assessed at each prenatal visit; maternal NMR was assayed from third trimester serum. Birth weight was obtained from medical records. Generalized estimating equations were used to evaluate associations between cigarette smoking, NMR, race, and birth weight. RESULTS: NMR moderated continuous associations between cigarettes per day over pregnancy and infant birth weight (p = .025). Among women who smoked at moderate levels (<15 cigarettes per day), those with slower NMR showed ~50-100 g decrements in birth weight versus those with faster NMR., while there were no significant associations between NMR and birth weight among women who smoked 15+ cigarettes per day. Although effects of NMR on birthweight were similar for Black and white women, Black women showed significantly slower NMR (p < .001). CONCLUSIONS: This is the first demonstration that the maternal nicotine metabolism phenotype moderates associations between maternal smoking during pregnancy and birth weight. Infants of women with slower nicotine metabolism - including disproportionate representation of Black women - may be at heightened risk for morbidity from maternal smoking.
BACKGROUND: Maternal cigarette smoking is an important modifiable risk factor for low birth weight in the US. We investigated the maternal nicotine metabolite ratio (NMR; trans-3'-hydroxycotinine/cotinine) - a genetically-informed biomarker of nicotine clearance - as a moderator of links between prenatal cigarette use and birth weight. We also explored the role of race in these associations. METHODS: Participants were 454 pregnant women (Mage = 25 years; 11% Black) who smoked cigarettes and their 537 infants from the Collaborative Perinatal Project. Cigarettes smoked per day were assessed at each prenatal visit; maternal NMR was assayed from third trimester serum. Birth weight was obtained from medical records. Generalized estimating equations were used to evaluate associations between cigarette smoking, NMR, race, and birth weight. RESULTS: NMR moderated continuous associations between cigarettes per day over pregnancy and infant birth weight (p = .025). Among women who smoked at moderate levels (<15 cigarettes per day), those with slower NMR showed ~50-100 g decrements in birth weight versus those with faster NMR., while there were no significant associations between NMR and birth weight among women who smoked 15+ cigarettes per day. Although effects of NMR on birthweight were similar for Black and white women, Black women showed significantly slower NMR (p < .001). CONCLUSIONS: This is the first demonstration that the maternal nicotine metabolism phenotype moderates associations between maternal smoking during pregnancy and birth weight. Infants of women with slower nicotine metabolism - including disproportionate representation of Black women - may be at heightened risk for morbidity from maternal smoking.
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