No link seen between enzyme-inducing anticonvulsants, perinatal bleeding

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Takeaway

  • Maternal use of anticonvulsants that induce cytochrome P450 enzymes near the time of delivery did not increase the risks for postpartum hemorrhage or neonatal bleeding complications.

Why this matters

  • Inducers of cytochrome P450 enzymes can alter vitamin K metabolism, and some cross the placenta.
  • Only selected anticonvulsants are enzyme-inducing.

Key results

  • Maternal use of enzyme-inducing anticonvulsants vs other anticonvulsants in the last month of pregnancy did not increase risk for:
    • Postpartum hemorrhage (2.6% vs 3.6%; adjusted relative risk, 0.77; 95% CI, 0.58-1.00);
    • Neonatal bleeding complications (3.1% vs 3.5%; adjusted relative risk, 0.83; 95% CI, 0.64-1.08).
  • Findings were similar with less restrictive definition of exposure window (days’ supply ending from 30 days before delivery to any time after delivery) and in analyses limited to women with epilepsy.

Study design

  • Population-based cohort study of 11,572 Medicaid-insured pregnant women having a liveborn infant during 2000-2010 with an anticonvulsant prescription that overlapped the delivery.
  • Anticonvulsants inducing cytochrome P450 enzymes: carbamazepine (Tegretol, others), phenobarbital, phenytoin (Dilantin, others), oxcarbazepine (Trileptal, others), topiramate (Topamax, others).
  • Main outcomes: postpartum hemorrhage, neonatal bleeding complications.
  • Funding: National Institute of Mental Health; Swiss National Science Foundation.

Limitations

  • Actual use of anticonvulsants was unknown.
  • Unmeasured and residual confounding.
  • Uncertain generalizability.