North American AED (Antiepileptic Drug) Pregnancy Registry, Boston, Massachusetts, USA.
Medical Genetics and Metabolism Unit, Mass General for Children, Boston, Massachusetts, USA.
Birth Defects Res. 2023 Aug 15;115(14):1274-1283. doi: 10.1002/bdr2.2188. Epub 2023 Jun 30.
Pregnancy registries, designed to assess the safety of medications and vaccines for the exposed mother and fetus, have been developed since the 1990s. Malformations present in the exposed liveborn or stillborn infant or fetuses in elective terminations are the outcome of greatest concern. The experiences of the North American AED (antiepileptic drug) Pregnancy Registry (NAAPR) can be used to identify the challenges and limitations of a pregnancy registry in identifying congenital malformations.
The NAAPR enrolls pregnant women who are taking one or more AEDs for any medical condition, but primarily to prevent seizures, and an unexposed comparison group. Participants are interviewed by clinical research coordinators (CRCs) at enrollment, later in pregnancy and postpartum. Malformations are identified in the mother's reports and her infant's medical records through age 12 weeks. A teratologist, blinded to exposure status, evaluates each potential malformation identified.
Among 10,982 pregnancies enrolled between 1997 and 2022, 282 malformations were identified in the 9677 AED-exposed and 15 among the 1305 unexposed infants. Isolated malformations, such as cleft palate, accounted for 84% of the malformations identified. Increased frequencies of oral clefts and myelomeningocele were associated with exposure to several different AEDs. Copies of reports from many diagnostic studies were not obtained and very few pregnancy losses had autopsies.
The evaluation of the AED-exposed infants in a pregnancy registry is indirect. Improvements rely on the rapport established with the mothers by the CRCs and the mothers' willingness to assist in obtaining information from her infants' physicians.
自 20 世纪 90 年代以来，为了评估药物和疫苗对暴露母亲和胎儿的安全性，已经开发了妊娠登记处。最受关注的是暴露的活产或死产婴儿或选择性终止妊娠的胎儿中存在的畸形。可以利用北美 AED（抗癫痫药物）妊娠登记处（NAAPR）的经验来确定妊娠登记处识别先天性畸形的挑战和局限性。
NAAPR 招募了正在服用一种或多种用于任何医疗状况的 AED 的孕妇，但主要是为了预防癫痫发作，并招募了一个未暴露的对照组。参与者在入组时、妊娠后期和产后由临床研究协调员（CRC）进行访谈。通过母亲的报告和她婴儿的医疗记录，在 12 周龄前识别畸形。一名畸形学专家，对暴露状态不知情，评估每个潜在的畸形。
在 1997 年至 2022 年期间入组的 10982 例妊娠中，在 9677 例 AED 暴露组的婴儿中发现了 282 例畸形，在 1305 例未暴露组的婴儿中发现了 15 例畸形。孤立性畸形，如腭裂，占所识别畸形的 84%。多种不同 AED 暴露与口腔裂和脊髓脊膜膨出的发生率增加有关。许多诊断研究的报告副本未获得，极少数妊娠丢失进行了尸检。
妊娠登记处对 AED 暴露婴儿的评估是间接的。改进依赖于 CRC 与母亲建立的融洽关系，以及母亲愿意协助从她婴儿的医生那里获取信息。
