The safety of oral hypoglycemic agents in the first trimester of pregnancy: a meta-analysis.

OBJECTIVE: To examine the relationship between first-trimester exposure to oral hypoglycemic agents (OHAs), congenital anomalies and neonatal mortality, accounting for the potential confounding effect of maternal glycemic control. METHOD: A meta-analysis was conducted by searching the literature for studies reporting on women with type II diabetes mellitus, first-trimester exposure to OHAs and either major malformations and/or neonatal mortality. Glycemic control monitoring was noted. Studies were reviewed by two reviewers and disagreement was resolved by consensus. Odds ratios and risk differences were calculated to determine the risk of major malformations and neonatal mortality between those exposed and those not exposed to OHAs. RESULTS: Ten studies met the inclusion criteria. There was no significant difference in the rates of major malformations between those exposed and those not exposed to OHAs; the odds ratio was 1.05 (95% CI 0.65 to 1.70) and the risk difference was 0.00 (95% CI -0.03 to 0.03). For studies reporting glycemic control, the odds ratio for major malformations between those exposed and those not exposed to OHAs was 1.06 (95% CI 0.62 to 1.81). For neonatal death, the odds ratio was 1.16 (95% CI 0.67 to 2.00) and the risk difference was -0.03 (95% CI -0.17 to 0.12). The studies did not provide sufficient detail to determine which OHA(s) were associated with adverse neonatal outcomes. CONCLUSIONS: First-trimester exposure to OHAs did not significantly increase rates of major malformations or neonatal death. However, the studies were heterogeneous and care must be taken in interpreting the results. Further studies are needed to address the safety of OHAs in the first trimester with concomitant good glycemic control.