Systematic review and meta-analysis of miscarriage and maternal exposure to tobacco smoke during pregnancy.

We conducted a systematic review and meta-analysis to characterize the relationship between smoking and miscarriage. We searched the PubMed database (1956-August 31, 2011) using keywords and conducted manual reference searches of included articles and reports of the US Surgeon General. The full text of 1,706 articles was reviewed, and 98 articles that examined the association between active or passive smoking and miscarriage were included in the meta-analysis. Data were abstracted by 2 reviewers. Any active smoking was associated with increased risk of miscarriage (summary relative risk ratio = 1.23, 95% confidence interval (CI): 1.16, 1.30; n = 50 studies), and this risk was greater when the smoking exposure was specifically defined as during the pregnancy in which miscarriage risk was measured (summary relative risk ratio = 1.32, 95% CI: 1.21, 1.44; n = 25 studies). The risk of miscarriage increased with the amount smoked (1% increase in relative risk per cigarette smoked per day). Secondhand smoke exposure during pregnancy increased the risk of miscarriage by 11% (95% CI: 0.95, 1.31; n = 17 studies). Biases in study publication, design, and analysis did not significantly affect the results. This finding strengthens the evidence that women should not smoke while pregnant, and all women of reproductive age should be warned that smoking increases the risk of miscarriage.