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. 2021 Dec 14;22(1):922.
doi: 10.1186/s13063-021-05865-7.

Investigating N-3 Fatty Acids to prevent Neonatal Tobacco-related outcomeS (INFANTS): study protocol for a double-blind, randomized, placebo-controlled parallel clinical trial of n-3 polyunsaturated fatty acids in pregnant smokers

Harvey J Murff  1   2 , Robert A Greevy  3 , Reesha S Sanghani  4 , Katherine E Hartmann  4 , Tina V Hartert  5 , Cornelia R Graves  6 , Scott S Lee  7 , Hilary A Tindle  7   8
Affiliations

Investigating N-3 Fatty Acids to prevent Neonatal Tobacco-related outcomeS (INFANTS): study protocol for a double-blind, randomized, placebo-controlled parallel clinical trial of n-3 polyunsaturated fatty acids in pregnant smokers

Harvey J Murff et al. Trials. .

Abstract

Background: Tobacco use during pregnancy is the most important modifiable risk factor associated with adverse pregnancy outcomes, increasing the risk of preterm birth, intrauterine growth restriction and sudden infant death syndrome. Fewer than half of pregnant smokers can quit on their own. Identifying safe and effective therapies to prevent tobacco-related adverse pregnancy outcomes and/or increase smoking cessation in pregnant women would have a substantial public health impact. Cigarette smoking is associated with a relative deficiency in circulating n-3 long-chain polyunsaturated fatty acid (n-3 LCPUFA) levels. A recent analysis found that smokers taking n-3 LCPUFAs during pregnancy had a reduction in preterm labor risk when compared to non-smokers. Studies have shown that supplemental n-3 LCPUFAs may also reduce nicotine cravings and daily cigarette use. Thus, smokers may benefit from supplemental n-3 LCPUFAs by lowering the risk of preterm labor and/or increased smoking cessation. To address important remaining knowledge gaps, we propose the Investigating N-3 Fatty Acids to prevent Neonatal Tobacco related outcomeS (INFANTS).

Methods: The INFANTS study is a multicenter, randomized, double-blind, placebo-controlled study that will randomize 400 pregnant smokers to either supplemental n-3 LCPUFAs or placebo. Participants will be enrolled between 12 and 24 weeks' gestation and followed until 6 weeks after delivery. We will recruit from clinical centers throughout Middle Tennessee. We will assess smoking behavior after 12 weeks of supplementation using self-report and validated biomarkers of tobacco exposure. We will measure response to supplementation using biological markers of n-3 LCPUFA status. Our primary endpoint will be preterm labor as reflected by gestational age at delivery. Our secondary endpoint will be change from baseline in cigarettes per day at 12 weeks.

Discussion: This study tests the hypothesis that smoking-induced n-3 LCPUFA deficiencies contribute to tobacco-related adverse pregnancy outcomes and that supplementation of n-3 LCPUFAs in pregnant smokers may prevent these complications. If our study demonstrates that supplemental n-3 LCPUFAs are effective at reducing the risk of tobacco-related adverse neonatal outcomes and/or reducing tobacco use during pregnancy, our results could have an immediate and major impact on pregnancy care and neonatal outcomes.

Trial registration: ClinicalTrials.gov NCT04417595. Registered on April 21, 2020.

Keywords: Placebo-controlled; Pre-term birth; Pregnancy; Red blood cell Membrane phospholipids; Smoking cessation; n-3 long chain poly unsaturated fatty acids (LCPUFA).

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Conflict of interest statement

HAT has been the principal investigator of NIH-supported studies for smoking cessation in which the medication was donated by the manufacturer and has volunteered without pay as part of a scientific advisory panel providing design input for a phase 3 trial of cytisine, a medication for smoking cessation which is not yet FDA approved. The other investigators have no competing interests to declare.

Figures

Fig. 1
Fig. 1
Organization of the INFANTS study
See this image and copyright information in PMC

References

    1. Benowitz NL, Pomerleau OF, Pomerleau CS, Jacob P., 3rd Nicotine metabolite ratio as a predictor of cigarette consumption. Nicotine Tobacco Res. 2003;5(5):621–624. doi: 10.1080/1462220031000158717. - DOI - PubMed
    1. Ellard GA, Johnstone FD, Prescott RJ, Ji-Xian W, Jian-Hua M. Smoking during pregnancy: the dose dependence of birthweight deficits. Br J Obstet Gynaecol. 1996;103(8):806–813. doi: 10.1111/j.1471-0528.1996.tb09878.x. - DOI - PubMed
    1. Li CQ, Windsor RA, Perkins L, Goldenberg RL, Lowe JB. The impact on infant birth weight and gestational age of cotinine-validated smoking reduction during pregnancy. Jama. 1993;269(12):1519–1524. doi: 10.1001/jama.1993.03500120057026. - DOI - PubMed
    1. Mitchell EA, Tuohy PG, Brunt JM, Thompson JM, Clements MS, Stewart AW, et al. Risk factors for sudden infant death syndrome following the prevention campaign in New Zealand: a prospective study. Pediatrics. 1997;100(5):835–840. doi: 10.1542/peds.100.5.835. - DOI - PubMed
    1. Pineles BL, Hsu S, Park E, Samet JM. Systematic review and meta-analyses of perinatal death and maternal exposure to tobacco smoke during pregnancy. American journal of epidemiology. 2016;184(2):87–97. doi: 10.1093/aje/kwv301. - DOI - PMC - PubMed

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