A small observational study of first trimester maternal exposure to pregabalin found a potential increased risk for major birth defects.
The drug, used to treat neuropathic pain and partial-onset seizures, is often used off-label in women, according to a previous Swedish study. Although there is limited data for the use of pregabalin in pregnancy, animal studies have linked its use to reproductive toxicity. With many pregnancies unplanned, the risk of exposure to the developing fetus is high.
Ursula Winterfeld, PhD, of the Division of Pharmacology at the Centre Hospitalier in Lusanne, Switzerland and colleagues conducted a multicenter, observational prospective cohort study to compare outcomes in pregnant women exposed to pregabalin and matched controls. The data was obtained from the Teratology Information Services of 8 European countries from 2004 to 2013. The study included 164 patients with maternal exposure to pregabalin and 656 matched controls. Treatment indications included restless leg syndrome (n=1), epilepsy (n=5), psychiatric disorders (n=39), and neuropathic pain (n=115).
The median pregabalin dose was 150 mg daily and was initiated prior to pregnancy in 77% of patients. Pregabalin was discontinued at a median gestational age of 6 weeks. However, 61% of patients continued pregabalin after 6 weeks and 33% continued after 7 weeks of gestation. Most exposures were during the first trimester (96%). Concomitant treatment with an additional antiepileptic drug was observed in 13% of patients.
Overall, major birth defects were observed more often in the pregabalin group (9.6% vs 2.8%, OR 3.7, 95% CI: 1.5-8.6, P<.001). When cases with chromosomal syndromes were excluded and limited to first trimester exposure, the rate of major birth defects remained higher in the pregabalin group (6% vs 2.1%, OR 3.0, 95% CI: 1.2-7.9, P=.03). The pregabalin group also had a lower rate of live births than the control group (71.9% vs 85.2%, P<.001). This difference was mostly attributed to a higher rate of medically-indicated and elective terminations. Exposure was not significantly associated with a higher risk of spontaneous abortion in Cox proportional analysis (HR 1.60, 95% CI: 0.95-2.71, P=.08).
“In our opinion, the significant increase in the rate of major malformations observed in this study should already imply that pregabalin prescription be avoided whenever possible during pregnancy,” Dr Winterfeld and co-author Theirry Buclin, MD, told Neurology Advisor. “In patients of childbearing age, effective contraception should be advised when prescribing pregabalin, and its indication must be carefully re-examined in cases of desired or established pregnancy.”
Still, the authors recognized that the results are limited and “need to be confirmed by further independent studies before pregabalin deserves to be put with certainty among malformation-inducing drugs,” they said.
In an accompanying editorial, Page Pennell, MD, of Harvard Medical School and Kimford J. Meador, MD, of Stanford University School of Medicine, noted that the study was limited by a small sample size and the differences between the study and control groups, including medical conditions, medication use, tobacco use, and gestational age at contact. The results “provide a signal of concern that MCMs are higher in pregnancies of women on pregabalin with a variety of other factors compared to a control population,” they wrote.
Further research is needed to confirm the findings, the authors said, and patients should be counseled on the potential risks and benefits of neuropsychiatric medications prior to pregnancy.
- Winterfeld U, Merlob P, Baud D, et al. Pregnancy outcome following maternal exposure to pregabalin may call for concern. Neurology 2016; doi:10.1212/WNL.0000000000002767.
- Pennell PB and Meador KJ. A common medication for neuropsychiatric illnesses may cause common problems in pregnancy. Neurology 2016; doi:10.1212/WNL.0000000000002780.