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Associations of maternal quitting, reducing, and continuing smoking during pregnancy with longitudinal fetal growth: Findings from Mendelian randomization and parental negative control studies

PLoS medicine, 2019-11, Vol.16 (11), p.e1002972 [Peer Reviewed Journal]

COPYRIGHT 2019 Public Library of Science ;COPYRIGHT 2019 Public Library of Science ;2019 Brand et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. ;2019 Brand et al 2019 Brand et al ;ISSN: 1549-1676 ;ISSN: 1549-1277 ;EISSN: 1549-1676 ;DOI: 10.1371/journal.pmed.1002972 ;PMID: 31721775

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Title:
Associations of maternal quitting, reducing, and continuing smoking during pregnancy with longitudinal fetal growth: Findings from Mendelian randomization and parental negative control studies
Author: Brand, Judith S ; Gaillard, Romy ; West, Jane ; McEachan, Rosemary R C ; Wright, John ; Voerman, Ellis ; Felix, Janine F ; Tilling, Kate ; Lawlor, Deborah A
Minelli, Cosetta
Subjects: Adult ; Analysis ; Anthropometry ; Biology and Life Sciences ; Birth weight ; Birth Weight - drug effects ; Cigarette smoking ; Cigarette Smoking - adverse effects ; Cigarettes ; Circumferences ; Drug addiction ; Epidemiology ; Error analysis ; Female ; Femur ; Fetal Development ; Fetal Growth Retardation - etiology ; Fetal Weight ; Fetus ; Fetuses ; Funding ; Genetic research ; Genetics ; Genotypes ; Gestation ; Gestational Age ; Growth ; Hospitals ; Humans ; Infant, Newborn ; Infant, Small for Gestational Age ; Maternal Exposure - adverse effects ; Medical research ; Medical schools ; Medicine and Health Sciences ; Mendelian Randomization Analysis ; Netherlands - epidemiology ; Pediatrics ; People and Places ; Physical Sciences ; Pleiotropy ; Population ; Pregnancy ; Pregnancy Trimester, First - drug effects ; Pregnant women ; Prenatal development ; Prenatal Exposure Delayed Effects - etiology ; Prospective Studies ; Randomization ; Response rates ; Risk factors ; Smokers ; Smoking ; Smoking and women ; Smoking Cessation - psychology ; Social Sciences ; Studies ; Trajectory analysis ; Ultrasonic imaging ; Ultrasound ; United Kingdom - epidemiology ; Women smokers ; Womens health
Is Part Of: PLoS medicine, 2019-11, Vol.16 (11), p.e1002972
Description: Maternal smoking during pregnancy is an established risk factor for low infant birth weight, but evidence on critical exposure windows and timing of fetal growth restriction is limited. Here we investigate the associations of maternal quitting, reducing, and continuing smoking during pregnancy with longitudinal fetal growth by triangulating evidence from 3 analytical approaches to strengthen causal inference. We analysed data from 8,621 European liveborn singletons in 2 population-based pregnancy cohorts (the Generation R Study, the Netherlands 2002-2006 [n = 4,682]) and the Born in Bradford study, United Kingdom 2007-2010 [n = 3,939]) with fetal ultrasound and birth anthropometric measures, parental smoking during pregnancy, and maternal genetic data. Associations with trajectories of estimated fetal weight (EFW) and individual fetal parameters (head circumference, femur length [FL], and abdominal circumference [AC]) from 12-16 to 40 weeks' gestation were analysed using multilevel fractional polynomial models. We compared results from (1) confounder-adjusted multivariable analyses, (2) a Mendelian randomization (MR) analysis using maternal rs1051730 genotype as an instrument for smoking quantity and ease of quitting, and (3) a negative control analysis comparing maternal and mother's partner's smoking associations. In multivariable analyses, women who continued smoking during pregnancy had a smaller fetal size than non-smokers from early gestation (16-20 weeks) through to birth (p-value for each parameter < 0.001). Fetal size reductions in continuing smokers followed a dose-dependent pattern (compared to non-smokers, difference in mean EFW [95% CI] at 40 weeks' gestation was -144 g [-182 to -106], -215 g [-248 to -182], and -290 g [-334 to -247] for light, moderate, and heavy smoking, respectively). Overall, fetal size reductions were most pronounced for FL. The fetal growth trajectory in women who quit smoking in early pregnancy was similar to that of non-smokers, except for a shorter FL and greater AC around 36-40 weeks' gestation. In MR analyses, each genetically determined 1-cigarette-per-day increase was associated with a smaller EFW from 20 weeks' gestation to birth in smokers (p = 0.01, difference in mean EFW at 40 weeks = -45 g [95% CI -81 to -10]) and a greater EFW from 32 weeks' gestation onwards in non-smokers (p = 0.03, difference in mean EFW at 40 weeks = 26 g [95% CI 5 to 47]). There was no evidence that partner smoking was associated with fetal growth. Study limitations include measurement error due to maternal self-report of smoking and the modest sample size for MR analyses resulting in unconfounded estimates being less precise. The apparent positive association of the genetic instrument with fetal growth in non-smokers suggests that genetic pleiotropy may have masked a stronger association in smokers. A consistent linear dose-dependent association of maternal smoking with fetal growth was observed from the early second trimester onwards, while no major growth deficit was found in women who quit smoking early in pregnancy except for a shorter FL during late gestation. These findings reinforce the importance of smoking cessation advice in preconception and antenatal care and show that smoking reduction can lower the risk of impaired fetal growth in women who struggle to quit.
Publisher: United States: Public Library of Science
Language: English
Identifier: ISSN: 1549-1676
ISSN: 1549-1277
EISSN: 1549-1676
DOI: 10.1371/journal.pmed.1002972
PMID: 31721775
Source: Public Library of Science (PLoS) Journals Open Access
Geneva Foundation Free Medical Journals at publisher websites
MEDLINE
PubMed Central
SWEPUB Freely available online
ProQuest Central
DOAJ Directory of Open Access Journals

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Associations of maternal quitting, reducing, and continuing smoking during pregnancy with longitudinal fetal growth: Findings from Mendelian randomization and parental negative control studies

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