The Use of Angiotensin Converting Enzyme Inhibitors during the First Trimester of Pregnancy

Abstract

Background: The direct effects of angiotensin converting enzyme inhibitor (ACEI) medications on the fetus are difficult to determine since these medicines are usually administered to women presenting with high-risk pregnancies. The aim of this study was to provide an overview of the dispensing patterns, demographic characteristics and pregnancy outcomes of women dispensed an ACEI during pregnancy. Methods:Exposed pregnancies were all births in Western Australia, 2002Australia, -2005 where the mother was dispensed an ACEI under the Australian Pharmaceutical Benefits Scheme, compared with all other births during the same period.Result: From 2002 to 2005, there were 96,698 births in Western Australia. At least one form of ACEI was dispensed to 95 pregnant women (0.1%) and a further 677 pregnant women (0.7%) were dispensed an antihypertensive medication that was not an ACEI. Women dispensed an ACEI in the first trimester were more likely to be obese (aOR 33.4; 95% CI: 19.5-57.2), to have gestational diabetes (aOR 2.6; 1.3-5.4), to have a preterm delivery (aOR 2.8; 1.4-5.6), and to have smoked during their pregnancy (aOR 1.9; 1.2-3.0). The children of women dispensed an ACEI were more likely to have a major birth defect (aOR 2.6; 1.3-5.2). The risk of a major uro-genital birth defect (aOR 4.8; 2.0-11.7) was increased. Conclusion:Although ACEIs are contraindicated, pregnant women continue to be dispensed these medications. This study provides a profile of these women and their pregnancy outcomes. A clear change in the pattern of dispensing ACEIs later in pregnancy was apparent for these women. A greater number of women were dispensed ACEIs during trimester 1, followed by a marked reduction in dispenses in trimester 2 and trimester 3. Although the number of children affected is small, our data suggests that an increased risk of uro-genital defects may arise with maternal ACEI use in the first trimester.

Adverse pregnancy outcomes associated with first‐trimester exposure to angiotensin‐converting enzyme inhibitors or angiotensin II receptor blockers: A systematic review and meta‐analysis

“…A total of 19 articles, published between 1992 and 2018, were included for data extraction, with 18 articles that enabled quantitative analysis (Figure 1). Characteristics of 19 studies are presented in Table 1 32‐50 : 15 are observational cohort studies, three are case‐control studies, and one is a randomized‐controlled trial, all of which were classified as ‘sufficient quality’ or ‘low risk of bias’ studies (Table S1). Relevant studies were conducted in North America (n = 9), Europe (n = 9), or Australia (n = 2).…”

Increased risk of major congenital malformations in early pregnancy use of angiotensin‐converting‐enzyme inhibitors and angiotensin‐receptor‐blockers: a meta‐analysis

“…A total of 14 observational studies reporting on 6234 pregnancies with exposure to ACE‐I or ARB in the first trimester, 4104 pregnancies with exposure to other oral antihypertensives, and 1,872,733 pregnancies without exposure were included in at least one meta‐analysis 4,6–10,19–26 . Table 1 shows the characteristics of all studies included.…”

“…They concluded that the use of ACE‐Is and ARBs in the first trimester did not further increase the risk over and above other antihypertensives and this increased risk was due either to the use of antihypertensives in general or due to the characteristics of the hypertensive women taking them 3 . Since then, at least five additional large population‐based cohort studies have been published on the topic, each showing conflicting results 6–10 …”

pyHeart4Fish: Chamber-specific heart phenotype quantification of zebrafish in high-content screens

“…Exposure to several chemicals and pharmaceuticals during pregnancy and early infancy negatively impacts development. Studies estimate a prevalence of 1%-4% of OPEN ACCESS EDITED BY Megha Kumar, Centre for Cellular & Molecular Biology (CCMB), India congenital defects caused by adverse drug effects (Hernandez et al, 2012;Colvin and Walters, 2016;Uguz, 2020). Approximately 55%-90% of women receive at least one prescription drug during pregnancy (Huybrechts et al, 2018;Dathe and Schaefer, 2019).…”