ACE Inhibitors and ARBs Are Absolutely Contraindicated During Pregnancy
ACE inhibitors and ARBs must not be used during pregnancy due to fetotoxicity, particularly affecting the fetal renal system in the second and third trimesters, and should be discontinued immediately upon pregnancy confirmation or ideally when planning conception. 1, 2, 1
Specific Risks by Trimester
Second and Third Trimester Exposure (Well-Established Fetotoxicity)
The risks during later pregnancy are unequivocal and severe 1:
- Renal dysfunction and failure - the primary mechanism of harm
- Oligohydramnios (reduced amniotic fluid)
- Intrauterine growth restriction
- Premature birth
- Fetal and neonatal death
- Skull hypoplasia and limb contractures
- Persistent pulmonary hypoplasia
- Neonatal hypotension and renal failure
ARBs carry similar risks to ACE inhibitors, with case reports documenting comparable adverse effects 1, 3. Recent data suggests ARBs may actually carry a higher risk of fetopathy (11.5%) compared to ACE inhibitors (3.9%) when exposed after gestational week 20 4.
First Trimester Exposure (Emerging Evidence of Risk)
While historically considered safer, recent evidence indicates first-trimester exposure may increase congenital anomaly risk 5:
- A 2024 prospective registry study found ACE inhibitor use during the first trimester was associated with a 3.2-fold increased risk of congenital anomalies (95% CI 1.0-9.6) 5
- However, this risk may be confounded by underlying maternal conditions (hypertension, diabetes, obesity, advanced maternal age) rather than the medication itself 6
- Some studies show increased miscarriage rates with first-trimester exposure 7
The evidence remains somewhat conflicting, with some studies finding no convincing excess of major malformations 8, 7, but the consensus is clear: avoid these medications even in the first trimester when possible 5.
Long-Term Outcomes in Exposed Children
A critical 2026 study revealed that sequelae of fetal RAAS inhibitor exposure may manifest years after birth, not just in the neonatal period 4:
- Among children without neonatal fetopathy, 1.5% developed hypertension or required antihypertensive treatment during follow-up (median 4 years)
- This suggests ongoing surveillance of exposed children is warranted
Clinical Management Algorithm
For Women Planning Pregnancy:
- Discontinue ACE inhibitors/ARBs when planning conception - there is no need to stop months in advance, but switch between weeks 8-10 after conception at the latest 2, 6
- Transition to pregnancy-safe alternatives BEFORE withdrawing contraception 1, 2
- Achieve blood pressure control (≤130/80 mmHg) before conception 9
Safe Alternatives During Pregnancy (First-Line):
- Labetalol (oral)
- Methyldopa (oral)
- Long-acting nifedipine (extended-release formulation)
- Other β-blockers: acebutolol, metoprolol, pindolol, propranolol 2, 10
If Pregnancy Discovered While Taking ACE Inhibitor/ARB:
Discontinue immediately upon pregnancy confirmation 9. The only exception is severe renal dysfunction where shared decision-making about continuing until conception occurs may be considered, but the medication must still be stopped immediately once pregnancy is confirmed 9.
Critical Caveats
- Direct renin inhibitors are also contraindicated during pregnancy 1
- Mineralocorticoid receptor antagonists are contraindicated 10
- The fetotoxicity is specifically related to renal system damage 2
- Women with hypertensive disorders during pregnancy have 4-fold increased risk of developing chronic hypertension and doubled risk of ischemic heart disease later in life, requiring long-term cardiovascular risk monitoring 11
Postpartum Considerations
- ACE inhibitors (specifically enalapril and captopril) are considered safe during lactation 2
- Methyldopa should be avoided postpartum due to risk of postnatal depression 11
- Women can be transitioned back to ACE inhibitors/ARBs after delivery if not breastfeeding, or to enalapril/captopril if breastfeeding 2
The bottom line: Preconception counseling is essential for all women of reproductive age taking ACE inhibitors or ARBs 2, 5. These medications offer no safe window during pregnancy and must be replaced with methyldopa, nifedipine, or labetalol before conception or immediately upon pregnancy recognition.