Lisinopril During Pregnancy: Why It's Not Recommended

What does the evidence say about lisinopril during pregnancy?

1. ACE inhibitors like lisinopril should be avoided during the second and third trimesters of pregnancy, when they can reduce fetal urine production and lead to low amniotic fluid, poor lung development, growth restriction, and kidney problems in the newborn. 1
2. It is not known whether lisinopril increases the chance of birth defects when taken in the first trimester, and the background rate of birth defects in any pregnancy is about 3%. 2
3. A meta-analysis covering more than 4 million pregnancies found that first-trimester-only exposure to ACE inhibitors or ARBs was associated with a higher rate of overall congenital malformations (odds ratio 1.94) and a higher rate specifically of heart-related malformations (odds ratio 3.02). 3
4. A separate large cohort study found that after accounting for the mother's underlying high blood pressure and other health conditions, first-trimester ACE inhibitor exposure was not linked to a higher rate of birth defects, suggesting some of the earlier signal may reflect the underlying condition itself rather than the medication. 4
5. Lisinopril clears from the body in roughly 72 hours in adults who are not pregnant, and providers can use that timeline alongside prenatal ultrasound monitoring of amniotic fluid and fetal kidney development when planning a switch to a different blood pressure medication. 1

Is lisinopril safe in each trimester?

• First trimester. It is not known whether lisinopril raises the risk of birth defects in the first trimester. Some newer research found a higher rate of malformations with first-trimester ACE inhibitor exposure, while other large studies found no increased risk once the mother's underlying health conditions were factored in.
• Second trimester. ACE inhibitors including lisinopril should be avoided starting in the second trimester. This is when the fetal kidneys are producing amniotic fluid, and blocking that system can cause low fluid levels and related complications.
• Third trimester. Continued use in the third trimester carries the same risks as the second: low amniotic fluid, poor lung development, and a risk of low blood pressure or kidney problems in the newborn right after birth, some of them serious.