Nine studies were included in the review (total n not reported): six were cohort studies and three were case-control studies. Quality scores ranged from 70% to 93%.
Cohort studies: The rate of cardiac malformations in the exposed groups (n=3,428) was 1.14% compared to 1.09% in the control groups (n=62,981). The weighted average difference in rates was 0.3% (95% CI -0.1% to 0.7%) and nonsignificant (p=0.19). There was sufficient statistical power to detect significance at a rate as low as 1.26%; the authors stated that the rate in the general population had been reported as having a 95% CI of 0.7 to 1.19
Case control studies: There was no statistically significant difference between the cases and the controls in rates of cardiac malformations (OR 1.18, 95% CI 0.88 to 1.59; n>30,000). The authors calculated that an additional 170,351 patients would be required to achieve statistical significance.
There was no evidence of significant statistical heterogeneity in either the cohort or the case control studies.
There was no evidence of publication bias.