Investigators did not identify a significantly higher risk of congenital malformations in a cohort of women exposed to pregabalin during the first trimester of pregnancy, according to a study published in Neurology.
Previous research has indicated a possible association between major congenital malformations in the fetuses of mothers who were treated with pregabalin during pregnancy.
Elisabetta Patorno, MD, DrPH, of Brigham and Women’s Hospital and Harvard Medical School in Boston, Massachusetts, and colleagues conducted a cohort nested study using data from the US Medicaid Analytic eXtract (MAX) to examine possible associations between major congenital malformations and first-trimester pregabalin exposure.
The cohort included more than 1.3 million pregnancies with a living infant between 2000 and 2010. The investigators identified 477 pregnancies that were exposed to pregabalin during the first trimester (0.04%). This group tended to have a high prevalence of an indicated use for seizures, epilepsy, or pain; had more comorbidities; were older; and were more often white.
Of 477 infants exposed to pregabalin, the investigators identified 28 infants (5.9%) with congenital malformations compared with a rate of 3.3% in infants not exposed to pregabalin. This was associated with a crude relative risk of 1.80 (95% CI, 1.26-2.58) for major congenital malformations in infants exposed to pregabalin. However, the relative risk became 1.16 (95% CI, 0.81-1.67) after propensity score adjustment.
Similar data was obtained from MarketScan, a database of commercial insurance claims, in which 174 infants with exposure to pregabalin had a relative risk of 1.03 (95% CI, 0.56-1.90). Pooling the data produced a relative risk of 1.33 (95% CI, 0.83-2.15) for any pregabalin exposure and a relative risk of 1.02 (95% CI, 0.69-1.51) for pregabalin monotherapy.
The investigators addressed several limitations of the study, including exposure misclassification and outcome misclassification by only including women who filled 2 or more prescriptions and using very specific outcome definitions for the coded diagnoses claims. Further, the study was limited to live births and did not include data on terminated births. The data was also not analyzed for dose-dependent effects because of the limited sample size.
“We did not confirm the suggested increased risk of congenital malformations in pregnancies exposed to pregabalin during the first trimester after carefully accounting for potential confounding variables in either the primary analysis of 1.3 million pregnancies in MAX or the replication sample of >400,000 pregnancies in MarketScan,” the investigators concluded.
Disclosures: The authors report multiple relationships with industry. Please see the study for a full list of disclosures.
Patorno E, Bateman BT, Huybrechts KF, et al. Pregabalin use early in pregnancy and the risk of major congenital malformations. Neurology. 2017;88(21):2020-2025.