USE OF ANGIOTENSIN CONVERTING ENZYME INHIBITORS IN PREGNANCY

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(Date of issue: April 2018, Version: 3)

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

There is no good evidence that exposure to ACE-I in the first trimester increases the risk of congenital malformation in general or of cardiovascular malformations specifically. A single study suggested a possible increased risk of renal malformations and there are limited and conflicting data on the risk of central nervous system malformations. Further studies are required to confirm or refute these findings.

There are limited data suggesting that first trimester ACE-I may be associated with increased risks of miscarriage, preterm delivery and decreased birth weight. However, similar effects have been observed in women taking antihypertensives other than ACE-I.

The National Institute for Health and Care Excellence (NICE) guidelines state that treatment with ACE-I should be stopped in pregnant women and alternatives offered. UKTIS recommends that where prolonged first trimester exposure has occurred, a 20-week anomaly scan should focus on cardiovascular, renal, and neurological development, in addition to the routine anatomical checks. Prolonged use of ACE-I into the second and third trimesters should be under the supervision of a maternal and fetal medicine specialist. 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 UKTIS monographs downloaded directly from TOXBASE.org or UKTIS.org to be sure you are using the most up-to-date version.

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.