Why is captopril (Angiotensin-Converting Enzyme inhibitor) contraindicated in pregnancy?

Captopril Contraindication in Pregnancy

Captopril is absolutely contraindicated during pregnancy because it can cause severe fetal injury and death, particularly when used during the second and third trimesters. 1

Mechanism of Fetal Harm

• ACE inhibitors like captopril cross the placenta and directly interfere with the fetal renin-angiotensin system, which is critical for normal fetal kidney development and function 1
• This interference leads to decreased fetal renal blood flow, reduced fetal urine production, and subsequent oligohydramnios (reduced amniotic fluid) 2, 3

Specific Fetal and Neonatal Complications

• Renal system abnormalities:

  • Renal dysgenesis (abnormal kidney development) 4
  • Reversible or irreversible renal failure 1, 5
  • Anuria (absence of urine production) 1

• Skeletal and developmental issues:

  • Skull hypoplasia (underdevelopment) 1
  • Limb contractures due to oligohydramnios 1, 3
  • Craniofacial deformation 1

• Pulmonary complications:

  • Lung hypoplasia (underdevelopment) due to oligohydramnios 1, 3
  • Respiratory distress syndrome 3

• Other serious complications:

  • Intrauterine growth retardation 1, 3
  • Hypotension in the newborn 1
  • Patent ductus arteriosus 5, 3
  • Intrauterine fetal death in severe cases 1

Regulatory Classification

• The FDA classifies captopril as Category D, indicating there is positive evidence of human fetal risk, but the potential benefit may outweigh the risk in life-threatening situations 4
• When pregnancy is detected, captopril should be discontinued as soon as possible 1

Alternative Antihypertensive Medications in Pregnancy

• Recommended first-line alternatives for hypertension in pregnancy:

  • Methyldopa 4, 6
  • Labetalol 4, 6
  • Nifedipine (calcium channel blocker) 4, 2, 6

• These medications have established safety profiles in pregnancy and are specifically recommended for pregnant women with hypertension 4, 6

Clinical Management Considerations

• All women of childbearing potential should be counseled about the risks of ACE inhibitors before starting therapy 1
• If a woman becomes pregnant while taking captopril, it should be discontinued immediately 1
• Even first-trimester exposure warrants close monitoring, though the risk appears greatest in the second and third trimesters 1
• After discontinuation of captopril during pregnancy, amniotic fluid levels may return to normal, as demonstrated in case reports 2

Special Situations

• For women with heart failure or other conditions requiring ACE inhibitor therapy who become pregnant, alternative medications must be substituted 4
• In rare cases where no alternative to ACE inhibitors exists, mothers should be fully informed of the risks, and serial ultrasound examinations should be performed to assess the amniotic environment 1

Remember that while some small studies have explored low-dose, short-acting ACE inhibitors in specific high-risk pregnancy situations 7, the overwhelming evidence and guidelines strongly contraindicate their routine use due to the significant risk of fetal harm 1, 3.