Gabapentinoids exposure in early pregnancy and risk of congenital anomalies a ConcePTION European case-malformed control study

Introduction: The use of gabapentinoids (pregabalin/gabapentin) is increasing during pregnancy, but data on their potential teratogenic effects is lacking. This study assessed the risk of congenital anomalies (CA) following exposure to gabapentinoids during the first trimester of pregnancy.
Material & Methods: A literature review found that coarctation of aorta, orofacial clefts, nervous system, eye, genital and urinary anomalies were associated with gabapentinoid exposure. Using EUROmediCAT data, we conducted a case malformed-control study to test these associations based on 253,911 registrants with CAs among livebirths, fetal deaths from 20 weeks gestational age and terminations of pregnancy for fetal anomaly in 12 European countries, 1995–2020. Cases were registrants with the six above-listed CAs while malformed-controls were registrants with other non-genetic CAs or genetic conditions. An exploratory analysis of the remaining CAs was performed comparing the odds of exposure in registrants with a specific non-genetic CA to the odds of exposure among the remaining non-genetic CAs or genetic conditions. We performed analyses for specific gabapentinoids separately, and as a class. Subgroups with ≥ 3 exposed cases were analyzed. Reporting odds ratios adjusted (aROR) for year of birth, maternal age and registry, with 95% Confidence Intervals (95% CI) were estimated.
Results: 39 registrants were exposed to gabapentinoids: pregabalin and gabapentin exposure was recorded for 22 and 17 registrants, respectively. Due to small numbers of exposed cases, only nervous system and urinary anomalies were analyzed, but no significant increase in exposure was found. However, exposure to any gabapentinoids was significantly reported more frequently among ventricular septal defect cases (VSD) compared with non-genetic and genetic controls (aROR 2.14, 95%CI: 1.00–4.57 and aROR 3.07, 95%CI: 1.07–8.80 respectively; 11 exposed cases).
Conclusion: Our study did not confirm the previous signals identified with first trimester exposure to gabapentinoids, but identified a new signal (VSD) that needs further investigation.