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OBJECTIVES: To investigate, using a Mendelian randomisation approach, whether heavier smoking is associated with a range of regional adiposity phenotypes, in particular those related to abdominal adiposity.DESIGN: Mendelian randomisation meta-analyses using a genetic variant (rs16969968/rs1051730 in the CHRNA5-CHRNA3-CHRNB4 gene region) as a proxy for smoking heaviness, of the associations of smoking heaviness with a range of adiposity phenotypes.PARTICIPANTS: 148 731 current, former and never-smokers of European ancestry aged ≥16 years from 29 studies in the consortium for Causal Analysis Research in Tobacco and Alcohol (CARTA).PRIMARY OUTCOME MEASURES: Waist and hip circumferences, and waist-hip ratio.RESULTS: The data included up to 66 809 never-smokers, 43 009 former smokers and 38 913 current daily cigarette smokers. Among current smokers, for each extra minor allele, the geometric mean was lower for waist circumference by -0.40% (95% CI -0.57% to -0.22%), with effects on hip circumference, waist-hip ratio and body mass index (BMI) being -0.31% (95% CI -0.42% to -0.19), -0.08% (-0.19% to 0.03%) and -0.74% (-0.96% to -0.51%), respectively. In contrast, among never-smokers, these effects were higher by 0.23% (0.09% to 0.36%), 0.17% (0.08% to 0.26%), 0.07% (-0.01% to 0.15%) and 0.35% (0.18% to 0.52%), respectively. When adjusting the three central adiposity measures for BMI, the effects among current smokers changed direction and were higher by 0.14% (0.05% to 0.22%) for waist circumference, 0.02% (-0.05% to 0.08%) for hip circumference and 0.10% (0.02% to 0.19%) for waist-hip ratio, for each extra minor allele.CONCLUSIONS: For a given BMI, a gene variant associated with increased cigarette consumption was associated with increased waist circumference. Smoking in an effort to control weight may lead to accumulation of central adiposity. OBJECTIVES: To investigate, using a Mendelian randomisation approach, whether heavier smoking is associated with a range of regional adiposity phenotypes, in particular those related to abdominal adiposity.DESIGN: Mendelian randomisation meta-analyses using a genetic variant (rs16969968/rs1051730 in the CHRNA5-CHRNA3-CHRNB4 gene region) as a proxy for smoking heaviness, of the associations of smoking heaviness with a range of adiposity phenotypes.PARTICIPANTS: 148 731 current, former and never-smokers of European ancestry aged ≥16 years from 29 studies in the consortium for Causal Analysis Research in Tobacco and Alcohol (CARTA).PRIMARY OUTCOME MEASURES: Waist and hip circumferences, and waist-hip ratio.RESULTS: The data included up to 66 809 never-smokers, 43 009 former smokers and 38 913 current daily cigarette smokers. Among current smokers, for each extra minor allele, the geometric mean was lower for waist circumference by -0.40% (95% CI -0.57% to -0.22%), with effects on hip circumference, waist-hip ratio and body mass index (BMI) being -0.31% (95% CI -0.42% to -0.19), -0.08% (-0.19% to 0.03%) and -0.74% (-0.96% to -0.51%), respectively. In contrast, among never-smokers, these effects were higher by 0.23% (0.09% to 0.36%), 0.17% (0.08% to 0.26%), 0.07% (-0.01% to 0.15%) and 0.35% (0.18% to 0.52%), respectively. When adjusting the three central adiposity measures for BMI, the effects among current smokers changed direction and were higher by 0.14% (0.05% to 0.22%) for waist circumference, 0.02% (-0.05% to 0.08%) for hip circumference and 0.10% (0.02% to 0.19%) for waist-hip ratio, for each extra minor allele.CONCLUSIONS: For a given BMI, a gene variant associated with increased cigarette consumption was associated with increased waist circumference. Smoking in an effort to control weight may lead to accumulation of central adiposity.

Background Fetal smoke exposure is a common and key avoidable risk factor for birth complications and seems to influence later risk of overweight. It is unclear whether this increased risk is also present if mothers smoke during the first trimester only or reduce the number of cigarettes during pregnancy, or when only fathers smoke. We aimed to assess the associations of parental smoking during pregnancy, specifically of quitting or reducing smoking and maternal and paternal smoking combined, with preterm birth, small size for gestational age, and childhood overweight. Methods and findings We performed an individual participant data meta-analysis among 229,158 families from 28 pregnancy/birth cohorts from Europe and North America. All 28 cohorts had information on maternal smoking, and 16 also had information on paternal smoking. In total, 22 cohorts were population-based, with birth years ranging from 1991 to 2015. The mothers’ median age was 30.0 years, and most mothers were medium or highly educated. We used multilevel binary logistic regression models adjusted for maternal and paternal sociodemographic and lifestyle-related characteristics. Compared with nonsmoking mothers, maternal first trimester smoking only was not associated with adverse birth outcomes but was associated with a higher risk of childhood overweight (odds ratio [OR] 1.17 [95% CI 1.02–1.35], P value = 0.030). Children from mothers who continued smoking during pregnancy had higher risks of preterm birth (OR 1.08 [95% CI 1.02–1.15], P value = 0.012), small size for gestational age (OR 2.15 [95% CI 2.07–2.23], P value < 0.001), and childhood overweight (OR 1.42 [95% CI 1.35–1.48], P value < 0.001). Mothers who reduced the number of cigarettes between the first and third trimester, without quitting, still had a higher risk of small size for gestational age. However, the corresponding risk estimates were smaller than for women who continued the same amount of cigarettes throughout pregnancy (OR 1.89 [95% CI 1.52–2.34] instead of OR 2.20 [95% CI 2.02–2.42] when reducing from 5–9 to ≤4 cigarettes/day; OR 2.79 [95% CI 2.39–3.25] and OR 1.93 [95% CI 1.46–2.57] instead of OR 2.95 [95% CI 2.75–3.15] when reducing from ≥10 to 5–9 and ≤4 cigarettes/day, respectively [P values < 0.001]). Reducing the number of cigarettes during pregnancy did not affect the risks of preterm birth and childhood overweight. Among nonsmoking mothers, paternal smoking was associated with childhood overweight (OR 1.21 [95% CI 1.16–1.27], P value < 0.001) but not with adverse birth outcomes. Limitations of this study include the self-report of parental smoking information and the possibility of residual confounding. As this study only included participants from Europe and North America, results need to be carefully interpreted regarding other populations. Conclusions We observed that as compared to nonsmoking during pregnancy, quitting smoking in the first trimester is associated with the same risk of preterm birth and small size for gestational age, but with a higher risk of childhood overweight. Reducing the number of cigarettes, without quitting, has limited beneficial effects. Paternal smoking seems to be associated, independently of maternal smoking, with the risk of childhood overweight. Population strategies should focus on parental smoking prevention before or at the start, rather than during, pregnancy., Elise Philips and co-workers investigate parental smoking and associated birth and child outcomes., Author summary Why was this study done? Maternal smoking during pregnancy is an important risk factor for various birth complications and childhood overweight. It is not clear whether this increased risk is also present if mothers smoke during the first trimester only or reduce the number of cigarettes during pregnancy. The associations of paternal smoking with birth and childhood outcomes also remain unknown. What did the researchers do and find? We conducted an individual participant data meta-analysis using data from 229,158 families from 28 pregnancy and birth cohorts from Europe and North America to assess the associations of parental smoking during pregnancy, specifically of quitting or reducing smoking and maternal and paternal smoking combined, with preterm birth, small size for gestational age, and childhood overweight. We observed that smoking in the first trimester only did not increase the risk of preterm birth and small size for gestational age but was associated with a higher risk of childhood overweight, as compared to nonsmoking. Reducing the number of cigarettes during pregnancy, without quitting, was still associated with higher risks of these adverse outcomes. Paternal smoking seems to be associated, independently of maternal smoking, with the risks of childhood overweight. What do these findings mean? Population strategies should focus on parental smoking prevention before or at the start of, rather than during, pregnancy. Future studies are needed to assess the specific associations of smoking in the preconception and childhood periods with offspring outcomes.