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Taking pregabalin (Lyrica) during pregnancy may be associated with a higher risk of major birth defects, researchers found.

In a prospective, nonrandomized study, women who took pregabalin while pregnant were more likely to have babies with major birth defects (6.0%) compared with women who did not take the drug (2.1%; odds ratio 3.0, P=0.03), , of Lausanne University Hospital in Switzerland, and colleagues reported in the journal Neurology.

Women who'd taken the drug also had a lower live birth rate compared with the control group (71.9% versus 85.2%, P=0.0001).

The study authors concluded that women taking pregabalin during pregnancy perhaps may need more advanced fetal monitoring.

The FDA currently classifies the drug as pregnancy category C, indicating that teratogenic effects have been seen in animal studies but there are "no adequate and well controlled studies in pregnant women." Whether the agency will revise pregabalin's label on the basis of the new study remains to be seen.

, of UH Rainbow Babies and Children's Hospital in Cleveland, who was not involved in the study, said it raises important questions, but is "not definitive proof" that pregabalin causes these birth defects because the study was small, doesn't hone in on a single defect or syndrome and included many mothers-to-be who were also taking other medications. He said it warranted further research.

"They did the study as best they could with the data they had. It's a good study, but it has its limitations," Wiznitzer told 番茄社区. "The bottom line is that women in their childbearing years need to know what they're taking and they need to know what benefits and risks are."

"When studying the myriad of outcomes, it is not always possible to clearly distinguish the effects of one medication from concomitant medications, maternal disease or associated behaviors," commented , of Brigham and Women's Hospital in Boston, in an accompanying Neurology editorial.

Winterfeld and her team worked with eight different teratology information services offices to collect patient data prospectively from 2004 to 2013 in six European countries. They compared 164 pregabalin-exposed pregnancies with 656 controls matched on teratology information center, age, year, and pregnancy stage.

Pregabalin was started before pregnancy in 77% of the patients taking it. The median daily dose was 150 mg. Although the median gestational age of discontinuation for pregabalin was 6 weeks, 61% of these patients continued after week six, and 33% continued taking it beyond the seventh week. The low-median exposure duration was 6 weeks.

Pregabalin is approved for treating partial onset seizures, neuropathic pain, and fibromyalgia. Pregabalin was prescribed mainly for pain and psychiatric disorders including depression, anxiety, bipolar disorder, and psychosis. Although records for only 3% of the pregabalin group included an epilepsy diagnosis, 13% of the group were also taking another antiepileptic drug during pregnancy.

When the analysis was limited to pregabalin monotherapy during only the first trimester of pregnancy, Winterfeld and colleagues found that 15% of pregabalin-exposed infants had major birth defects compared to 2.8% of those unexposed (OR 6.5, P=0.02.)

Major birth defects seen in the study included four chromosomal problems and eight structural problems. Structures affected included the central nervous system, the skeletal system, the cardiac system and the skin or vascular system.

Pregabalin usage was also associated with a significantly higher risk for elective or medically necessary pregnancy termination (hazard ratio 2.81, P<0.001). Spontaneous abortions were not significantly more common with pregabalin, though.

In the 13 newborns who were exposed to pregabalin until delivery, five neonatal complications were reported. Four babies were born with isolated respiratory distress, withdrawal syndrome, or clavicle fracture. The fifth, whose mother took aspirin until 36 weeks followed by enoxaparin until 38 weeks, developed respiratory distress, hypotonia, shock with metabolic acidosis, hepatic cytolysis, and renal insufficiency. It died at 6 weeks old.

The study's main limitation was its lack of a disease-matched control group. But other limitations included the different sources for outcome data, lack of family histories, varying follow-up times, and small sample size for monotherapy. Many of the women in the pregabalin group whose children were born with birth defects were taking multiple prescription drugs during pregnancy.

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