Maternal smoking in pregnancy and birth defects: a systematic review based on 173 687 malformed cases and 11.7 million controls

Abstract

BACKGROUND ; There is uncertainty over whether maternal smoking is associated with birth defects. We conducted the first ever comprehensive systematic review to establish which specific malformations are associated with smoking. METHODS ; Observational studies published 1959-2010 were identified (Medline), and included if they reported the odds ratio (OR) for having a non-chromosomal birth defect among women who smoked during pregnancy compared with non-smokers. ORs adjusted for potential confounders were extracted (e.g. maternal age and alcohol), otherwise unadjusted estimates were used. One hundred and seventy-two articles were used in the meta-analyses: a total of 173 687 malformed cases and 11 674 332 unaffected controls. RESULTS ; Significant positive associations with maternal smoking were found for: cardiovascular/heart defects [OR 1.09, 95% confidence interval (CI) 1.02-1.17]; musculoskeletal defects (OR 1.16, 95% CI 1.05-1.27); limb reduction defects (OR 1.26, 95% CI 1.15-1.39); missing/extra digits (OR 1.18, 95% CI 0.99-1.41); clubfoot (OR 1.28, 95% CI 1.10-1.47); craniosynostosis (OR 1.33, 95% CI 1.03-1.73); facial defects (OR 1.19, 95% CI 1.06-1.35); eye defects (OR 1.25, 95% CI 1.11-1.40); orofacial clefts (OR 1.28, 95% CI 1.20-1.36); gastrointestinal defects (OR 1.27, 95% CI 1.18-1.36); gastroschisis (OR 1.50, 95% CI 1.28-1.76); anal atresia (OR 1.20, 95% CI 1.06-1.36); hernia (OR 1.40, 95% CI 1.23-1.59); and undescended testes (OR 1.13, 95% CI 1.02-1.25). There was a reduced risk for hypospadias (OR 0.90, 95% CI 0.85-0.95) and skin defects (OR 0.82, 0.75-0.89). For all defects combined the OR was 1.01 (0.96-1.07), due to including defects with a reduced risk and those with no association (including chromosomal defects). CONCLUSIONS ; Birth defects that are positively associated with maternal smoking should now be included in public health educational materials to encourage more women to quit before or during pregnancy.

Figure 1

Summary of the meta-analyses for maternal smoking in pregnancy and birth defects. The pooled ORs are shown for each body system and specific defects (total number of malformed cases in brackets). CI: confidence interval *Umbilical, inguinal or ventral hernia. ‘Oesophageal fistula’ is ‘oesophageal atresia/tracheoesophageal fistula’.

Figure 2

Forest plots for (a) cardiovascular/heart defects (Kelsey 1978 had no standard error, OR = 1.08), (b) all musculoskeletal defects (two studies had no standard error: Kelsey 1978 OR = 0.93, and Hemminki 1981 OR = 1.35), (c) limb reduction defects, (d) digit anomaly (ie polydactyly, syndactyly and adactyly), (e) clubfoot (Kelsey 1978 had no standard error, OR = 1.22; and the pooled OR excluding Shiono 1986 Kaiser is 1.35, 95% CI 1.17–1.54), and (f) craniosynostosis. Studies are ranked according to size of the odds ratio.

Figure 2

Forest plots for (a) cardiovascular/heart defects (Kelsey 1978 had no standard error, OR = 1.08), (b) all musculoskeletal defects (two studies had no standard error: Kelsey 1978 OR = 0.93, and Hemminki 1981 OR = 1.35), (c) limb reduction defects, (d) digit anomaly (ie polydactyly, syndactyly and adactyly), (e) clubfoot (Kelsey 1978 had no standard error, OR = 1.22; and the pooled OR excluding Shiono 1986 Kaiser is 1.35, 95% CI 1.17–1.54), and (f) craniosynostosis. Studies are ranked according to size of the odds ratio.

Figure 3

Forest plots for (a) facial defects, (b) eye defects only, and (c) cleft lip or palate. Studies are ranked according to size of the odds ratio.

Figure 3

Forest plots for (a) facial defects, (b) eye defects only, and (c) cleft lip or palate. Studies are ranked according to size of the odds ratio.

Figure 4

Forest plots for (a) all gastrointestinal defects (Kelsey 1978 had no standard error, OR = 1.55), (b) gastroschisis, (c) anal atresia, (d) umbilical/ventral/inguinal hernias, (e) all genitourinary defects, and (f) cryptorchidism. Studies are ranked according to size of the odds ratio.

Figure 4

Forest plots for (a) all gastrointestinal defects (Kelsey 1978 had no standard error, OR = 1.55), (b) gastroschisis, (c) anal atresia, (d) umbilical/ventral/inguinal hernias, (e) all genitourinary defects, and (f) cryptorchidism. Studies are ranked according to size of the odds ratio.