Pregnancy protection in women of child-bearing age prescribed ACE inhibitors, ARBs or statins - A nationwide cohort study

Abstract Background Cardiometabolic disorders, including hypertension, type-2 diabetes, and hyperlipidemia are increasingly prevalent among younger people. Consequently, women of child-bearing age may be prescribed renin-angiotensin system (RAS) inhibitors and statins. Both angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are known teratogens. Statins are considered possibly teratogenic. In Denmark, ACEIs and ARBs have a ‘Do not use’ recommendation in pregnancy while statins ‘Should not be used’ in pregnancy. Previous studies have reported widespread use of RAS inhibitors without concomitant contraception among women of child-bearing age. This study investigated the situation in Denmark. Purpose To examine prescribing patterns of RAS inhibitors and statins alongside use of concomitant contraception among women of child-bearing age in Denmark. Methods Using nationwide Danish registers, women aged 15–50 years initiating ACEIs, ARBs and statins during 1995–2021 were identified and use of concomitant contraception was evaluated. Contraception was categorized as oral pill, implant, intrauterine device (IUD), or non-use. The duration of protection was assumed to be 1 year for oral contraceptives, 2 years for implants and 4 years for IUDs. Where multiple types of contraceptives were retrieved by individual patients, they were categorized as taking the contraceptive retrieved most recently. Data on non-prescription contraceptives were unavailable, e.g., condoms. Women unable to conceive due to infertility were excluded. Results 79 547 women (median age: 44 years; [interquartile range (IQR): 39–47]) on ACEIs, 64 326 women (median age: 44 years [IQR: 38–48]) on ARBs, and 71 499 women (median age: 45 years [IQR: 40–48]) on statins were included (Figure 1). Correspondingly, 69.1%, 62.8%, and 73.5% were not on contraceptives when starting treatment. Among women prescribed contraception: 70.2%/56.2%/63.1% were on oral contraceptives, 25.3%/30.9%/26.6% had IUDs and 4.5%/12.9%/10.3% had implants, respectively (Figure 1). Younger patients aged 15–29 years were least likely to be unprotected with 41.8%/29.7%/33.4% being unprotected. Among women aged 25 to 35 years the percentage of unprotected women was 51.3%/41.1%/47.7%. Older patients were more likely to have IUDs. Conclusion Substantial numbers of women of child-bearing age were prescribed ACEIs, ARBs and statins from 1995–2021. Most were not prescribed contraceptives. The lack of prescribed pregnancy protection was prevalent even among the youngest women aged 15–29 years and women aged 25 to 35 years, who are the most likely to become pregnant—inferring a potential risk of teratogenic exposure during pregnancy (Figure 2). Subsequent studies should investigate the extent of exposure to ACEIs, ARBs, and statins during pregnancy and the impact of the exposure on pregnancy outcomes.Figure 1 Contraceptive useFigure 2 Study rationale