USE OF ANGIOTENSIN CONVERTING ENZYME INHIBITORS IN PREGNANCY

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(Date of issue: July 2021, Version: 4)

This is a UKTIS monograph for use by health care professionals. For case-specific advice please contact UKTIS on 0344 892 0909. To report an exposure please download and complete a pregnancy reporting form. Please encourage all women to complete an online reporting form.

A corresponding patient information leaflet on ACE inhibitor use in pregnancy is available at www.medicinesinpregnancy.org.

Summary

Angiotensin converting enzyme (ACE) is an important constituent of the renin angiotensin system (RAS) which regulates fluid volume and controls vascular tone. ACE inhibitors (ACE-I) decrease the activity of ACE to counteract its vasoactive effects, thereby reducing blood pressure. ACE-I are used for the treatment of hypertension, heart failure, nephropathy, and in the prophylaxis of cardiovascular events.

ACE-I fetopathy following exposure to ACE-I in the second and third trimesters of pregnancy is well-described and may include oligohydramnios, renal tubular dysgenesis, neonatal anuria, hypocalvaria, pulmonary hypoplasia, persistent patent ductus arteriosus, mild-to-severe intrauterine growth restriction, and fetal or neonatal death. It is proposed that these effects occur as a result of a direct effect on the fetal RAS which begins to function from approximately 26 weeks gestation. A small prospective case series has suggested that the risk period for ACE-I fetopathy is with exposure beyond 20 weeks gestation. Due to data limitations, the absolute risk of ACE-I fetopathy is unclear.

Due to the risk of ACE-I fetopathy, use of ACE-I in the second and third trimesters is generally contraindicated and should only be reserved for cases of severe maternal illness that cannot be managed using alternative drugs.

There is currently no reliable evidence that exposure to ACE-Is in the first trimester increases the risk of overall infant congenital malformation, or, more specifically, of cardiovascular or CNS malformation. A small number of uncontrolled studies have suggested possible associations with urogenital anomalies, but further research to confirm or refute these observations is required.

Although some studies have described increased risks of miscarriage, preterm delivery and impaired fetal growth following early pregnancy exposure to ACE-I, similar findings have been observed in women taking other antihypertensive medications. As such, these findings are considered confounded by the underlying maternal condition, and there is currently no reliable evidence that first trimester ACE-I exposure directly increases the risk of these outcomes.

The National Institute for Health and Care Excellence (NICE) guidelines state that antihypertensive treatment with ACE-I should be stopped upon recognition of pregnancy and alternatives offered.  NICE guidelines identify labetalol as the first-line antihypertensive for use during pregnancy, with nifedipine or methyldopa being possible alternatives, depending on any pre-existing treatment, side effect profiles, risks (including fetal effects), and the woman's preference. Where prolonged first trimester exposure has occurred, attendance of the routine 20-week anomaly scan is encouraged. Where prolonged second or third trimester exposure has occurred, assessment and management by a specialist in fetal medicine is indicated. Women of childbearing age who are taking an ACE-I should be fully informed of the potential fetal risks and should ideally seek advice before becoming pregnant. Other risk factors may also be present which may increase the risk of adverse pregnancy outcome. Clinicians are reminded to consider these factors when performing risk assessments.

This document is regularly reviewed and updated. Only use full UKTIS monographs downloaded directly from TOXBASE.org to be sure you are using the most up-to-date version. The summaries of these monographs are openly available on UKTIS.org

This is a summary of the full UKTIS monograph for health care professionals and should not be used in isolation. The full UKTIS monograph and access to any hyperlinked related documents is available to health care professionals at www.toxbase.org.

If you have a patient with exposure to a drug or chemical and require assistance in making a patient-specific risk assessment, please telephone UKTIS on 0344 892 0909 to discuss the case with a teratology specialist.

If you would like to report a pregnancy to UKTIS please click here to download our pregnancy reporting form. Please encourage all women to complete an online reporting form.

Disclaimer: Every effort has been made to ensure that this monograph was accurate and up-to-date at the time of writing, however it cannot cover every eventuality and the information providers cannot be held responsible for any adverse outcomes of the measures recommended. The final decision regarding which treatment is used for an individual patient remains the clinical responsibility of the prescriber. This material may be freely reproduced for education and not for profit purposes within the UK National Health Service, however no linking to this website or reproduction by or for commercial organisations is permitted without the express written permission of this service. This document is regularly reviewed and updated. Only use UKTIS monographs downloaded directly from TOXBASE.org or UKTIS.org to ensure you are using the most up-to-date version.