By Lucy Piper
First trimester exposure to pregabalin may be associated with an increased risk of major birth defects (MBDs), an observational study suggests.
The data from eight Teratology Information Services in seven countries on 164 exposed pregnancies showed that the risk of MBDs was increased a significant threefold compared with 656 unexposed pregnancies.
After limiting the findings to just first trimester exposure and excluding chromosomal aberration syndromes, the rate of major congenital malformations was 6.0% among 116 infants exposed to pregabalin as neonates versus 2.1% among 580 unexposed infants. These included four chromosomal and eight structural anomalies affecting the central nervous system (CNS), or the skeletal, cardiac, and skin or vascular systems.
"Our results raise a signal for a possible increase in the rate of MBD after pregabalin treatment during the first trimester of pregnancy", say researcher Ursula Winterfield (Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland) and colleagues.
The rate of CNS malformations alone was also significantly higher following pregabalin exposure, increased sixfold, at 3.2% compared with 0.5%.
The researchers note that in all four cases of CNS malformations, the mother had been concurrently taking other substances during pregnancy in addition to pregabalin and genetic causes have not been ruled out, but they add: "[G]iven that pregabalin is a centrally acting agent, the possibility that these findings may signal a teratogenic effect in humans needs to be considered."
Other secondary outcomes included rates of live births, spontaneous abortions, preterm deliveries and delivery gestational age and birth weight. Of these, only the rate of live births was lower in the pregabalin-exposed group and this was primarily due to a higher rate of elective and medically indicated pregnancy terminations, suggestive of unplanned pregnancies.
Women were mainly taking pregabalin to treat neuropathic pain, but other indications included psychiatric disorders, epilepsy and restless leg syndrome.
The average daily dose of pregabalin was 150 mg; 77% of women started treatment before becoming pregnant and discontinued at a median gestational age of 6 weeks. However, more than half of the patients continued treatment beyond this point and 33% beyond 7 weeks. First trimester pregabalin exposure occurred in 96% of patients.
Winterfield and colleagues acknowledge in Neurology that the small sample size and differences across groups in maternal conditions and exposure to concomitant medication mean definitive conclusions cannot be drawn from their findings.
But despite these limitations, Page Pennell (Harvard Medical School, Boston, Massachusetts, USA) and Kimford Meador (Stanford University School of Medicine, Palo Alto, California, USA) say in a related editorial that "this study reflects the prescribing pattern for pregabalin".
They recommend: "Each woman receiving a prescription for a neuropsychiatric indication should receive counselling about the potential risk-benefit ratio for her individually, effective birth control until pregnancy is desired, and increased monitoring during pregnancy and for her child through early neurodevelopment."
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Neurology 2016; Advance online publication