Ascertainment of malformations in pregnancy registries: Lessons learned in the North American AED Pregnancy Registry.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

The North American Antiepileptic Drug Pregnancy Registry: A Canadian Subgroup Analysis.

BACKGROUND: The North American AED Pregnancy Registry (NAAPR) provides crucial data for understanding the risks of antiepileptic drug (AED) exposure in pregnancy. This study aims to quantify the Canadian contribution to NAAPR and compare AED usage in pregnancy in Canada and the USA. METHODS: Enrollment rate ratios (ERR) to NAAPR, adjusted for the populations of women of childbearing age, were calculated for the USA, Canada, and for the different Canadian provinces. Methods of enrollment to NAAPR and AED usage were compared between the two countries using chi-squared tests. RESULTS: Between 1997 and 2019, 10,215 pregnant women enrolled into NAAPR: 4.1% were Canadian (n = 432, ERR = 0.39, CI95% = 0.35-0.43). Within Canada, no patients were enrolled from the three northern territories or from Prince Edward Island. While fewer patients than expected enrolled from Quebec (ERR = 0.35, CI95% = 0.19-0.58), Nova Scotia had the highest enrollment rate (ERR = 1.55; CI95% = 0.66-3.11). Compared with their American peers, Canadians were less likely to have been enrolled by their healthcare provider and more likely to have been enrolled via social media (p < 0.01). Canadian women were more likely to be taking carbamazepine (24% vs. 15%; p < 0.01) or valproic acid (8% vs. 4%; p < 0.01). CONCLUSION: The proportion of Canadian enrollees into NAAPR was less than expected based on the relative population size of Canadian women of reproductive age. Greater Canadian enrollment to NAAPR would contribute to ongoing worldwide efforts in assessing the risks of AEDs use in pregnant women and help quantify rates of AED usage, major congenital malformations, and access to subspecialized epilepsy care within Canada.