Pregabalin May be Linked to Birth Defects, But to What Extent?

Researchers caution that Pregabalin, an agent approved by the FDA to treat epilepsy, fibromyalgia, and neuropathic pain, may be associated with an increased risk of major birth defects after first trimester exposure, though results are inconclusive.

Results of a small study suggest that pregabalin—the agent approved by the FDA to treat epilepsy, fibromyalgia, and neuropathic pain and commonly used off-label to treat generalized anxiety disorder and other mental health issues—appears to be associated with an increased risk of major birth defects after first trimester exposure.

Published online on May 18, 2016 in the American Academy of Neurology’s Neurology, the multicenter, observational prospective cohort study was conducted to compare pregnancy outcomes in women exposed to pregabalin with those of matched controls (not exposed to any medications known to be teratogenic or to any antiepileptic drugs).

Teratology Information Services systematically collected data between 2004 and 2013 in seven countries from 164 women who took pregabalin while pregnant—115 to treat neuropathic pain; 39 for psychiatric disorders, including depression, anxiety, bipolar disorder, and psychosis; five to treat epilepsy; and one for restless legs syndrome—and compared them to 656 controls. The women or their practitioners were contacted again after their expected due dates.

Among the women who took pregabalin, 77% started taking the drug before they became pregnant, all stopped taking the drug at an average of 6 weeks into their pregnancies, and 13% were also taking another anti-seizure medication.

Women who took pregabalin during the first trimester of their pregnancies were three times more likely to give birth to children with major birth defects when compared with controls, after exclusion of chromosomal aberration syndrome, and when cases with exposure during the first trimester of pregnancy were analyzed separately. Indeed, seven of 116 women who took pregabalin (6.0%) had babies with major birth defects, compared with 12 of 580 controls (2.1%).

Major birth defects observed in the study included heart defects and structural problems with the central nervous system and other organs. Women who took pregabalin were six times more likely to have a pregnancy with a major defect of the central nervous system when compared with those who did not take the drug (4/125 pregnancies, or 3.2% vs. 3/570 pregnancies, or 0.5%).

Women in the pregabalin group also had a lower rate of live births when compared with controls (71.9% vs 85.2%), mostly due to a higher rate of elective (9.8% vs. 5.0%) and medically indicated (5.5% vs. 1.8%) pregnancy terminations. However, pregabalin exposure was not associated with a significantly higher risk of spontaneous abortion in the Cox proportional cause-specific hazards model.

“We can’t draw any definitive conclusions from this study…” said lead author Ursula Winterfeld, PhD, citing its small sample size and some of the women’s use of other medications, “…but these results do signal that there may be an increased risk for major birth defects after taking pregabalin during the first trimester of pregnancy.”

Winterfeld, a pharmacist and clinical pharmacologist in the Department of Clinical Pharmacology at the Teratogen Information Service and Lausanne University Hospital in Switzerland, cautions: “Pregabalin should be prescribed for women of child-bearing age only after making sure that the benefits of the drug outweigh the risks and after counseling them about using effective birth control. In cases where women have taken pregabalin during pregnancy, extra fetal monitoring may be warranted.”