Is it safe to take Lisinopril (angiotensin-converting enzyme inhibitor) during pregnancy?

Lisinopril is Contraindicated During Pregnancy

Lisinopril must be discontinued immediately if pregnancy is detected or planned due to significant risks of fetal harm, including renal dysplasia, oligohydramnios, pulmonary hypoplasia, and intrauterine growth restriction. 1, 2

Risks of ACE Inhibitors in Pregnancy

• ACE inhibitors like lisinopril are classified as FDA Pregnancy Category D, indicating evidence of human fetal risk 1

• When used during the second and third trimesters, ACE inhibitors can cause:

  • Fetal renal dysfunction 1, 2
  • Oligohydramnios (reduced amniotic fluid) 1, 3
  • Pulmonary hypoplasia 2, 1
  • Skeletal deformations 1
  • Neonatal hypotension 1
  • Skull hypoplasia 1
  • Anuria and renal failure 1
  • Potential neonatal death 1, 4

• Even first-trimester exposure to ACE inhibitors should be avoided, as potential risks cannot be ruled out 2, 5

Alternative Antihypertensive Medications for Pregnancy

• Women who become pregnant or are planning pregnancy should be transitioned to pregnancy-safe alternatives 2, 5

• Recommended first-line alternatives include:

  • Methyldopa (250-500 mg twice daily) 2, 5
  • Long-acting nifedipine (30-90 mg daily) 2, 5
  • Labetalol (100-400 mg twice daily) 2, 5

• These medications have established safety profiles during pregnancy and are specifically recommended by clinical guidelines 2, 5

Management Algorithm for Hypertension in Pregnancy

1. Discontinue lisinopril immediately upon confirmation or planning of pregnancy 1, 2
2. Switch to a pregnancy-safe alternative:
   • First choice: Long-acting nifedipine 5
   • Alternative options: Methyldopa or labetalol 2, 5
3. Target blood pressure: 110-135/85 mmHg 2, 5
4. Monitor closely for:
   • Blood pressure control (deintensify if BP <90/60 mmHg) 2
   • Pedal edema with nifedipine 5
   • Fetal growth and development 2

Evidence from Case Reports

• Case reports document that oligohydramnios caused by ARBs (which have similar effects to ACE inhibitors) can be reversed after discontinuation 3
• However, other case reports show severe complications including renal failure in neonates exposed to ACE inhibitors during pregnancy 6
• Even with successful outcomes in isolated cases, the preponderance of evidence strongly advises against ACE inhibitor use during pregnancy 6, 7

Important Considerations and Pitfalls

• Never continue lisinopril once pregnancy is confirmed or planned 2, 5
• Patients should be counseled about the risks of ACE inhibitor exposure during pregnancy 1
• Avoid atenolol specifically among beta-blockers, as it may impair fetal growth 5, 8
• Diuretics are generally not recommended during pregnancy due to risk of reduced uteroplacental perfusion 5
• If inadvertent exposure occurs during early pregnancy, this is not necessarily an indication for pregnancy termination, but requires immediate medication change and careful monitoring 4