Perinatal & Pediatric
Continuation of ACE inhibitor dispensing into the first trimester and risk of non-live birth and major congenital malformations: a target trial emulation using US claims data Jeremy Brown* Jeremy Brown Brown Brown Brown Brown King’s College London
Background
ACE inhibitor exposure in the second and third trimester of pregnancy is considered a cause of fetopathy, but it is unclear whether first trimester exposure increases the risk of malformations. We emulated a target trial using US MarketScan commercial insurance claims data to estimate the effect of continuation of ACE inhibitor dispensing into the first trimester on the risk of non-live birth and major congenital malformations (MCM).
Methods
Eligible individuals were pregnant women aged 16-55 years with an ACE inhibitor dispensation in the 90 days prior to conception. Treatment strategies were discontinuation defined by no further dispensations vs. at least one further dispensation within a grace period from conception to end of remaining drug supply + 4 weeks. Pregnancies were cloned and then censored when non-compliant with the assigned strategy. Censoring weights were estimated by pooled logistic regression adjusted for potential confounders.
Results
There were 6,070 eligible pregnancies with an ACE inhibitor dispensation in the 90 days prior to conception. Among 4,315 live births, 1,679 (38.9%) received an ACE inhibitor dispensation within the grace period. Compared to discontinuers the relative risk was 1.12 (95% CI 1.03-1.22) for spontaneous abortions, 1.81 (1.48-2.28) for elective terminations, 1.19 (1.11-1.28) for any non-live birth, and 1.08 (0.74-1.54) for MCM prevalence. No specific pattern of MCM was identified. The proportion of terminations accompanied by a fetal anomaly claim was not higher in continuers vs. discontinuers (2.4%, 6/255 vs. 5.7%, 9/158).
Discussion
Findings provide some reassurance regarding risk of MCM with unintentional exposure to ACE inhibitors in the first trimester. Potential explanations for an increase in elective terminations include more unplanned pregnancies among continuers, termination due to concerns around ACE inhibitor fetotoxicity, and ACE inhibitor continuation among women planning to terminate.
