Is metoprolol safe to use during pregnancy?

Metoprolol Can Be Used in Pregnancy, But It Is NOT a First-Line Agent

Metoprolol is acceptable for use during pregnancy when first-line agents (nifedipine or labetalol) are contraindicated or ineffective, but it carries a dose-dependent risk of fetal growth restriction and should be avoided as initial therapy. 1

Why Metoprolol Is Not First-Line

The most recent 2025 guidelines from Circulation explicitly recommend extended-release nifedipine and labetalol as first-line antihypertensive medications during pregnancy 1. Metoprolol is not mentioned among these preferred agents. The guidelines specifically warn that atenolol should not be used due to risk of fetal growth restriction 1, and while metoprolol is not explicitly contraindicated like atenolol, the beta-blocker class carries similar concerns.

The 2011 ESC guidelines note that metoprolol is recommended as an acceptable option 2, but this predates the more recent evidence showing dose-dependent fetal risks.

Evidence on Metoprolol Safety

FDA Classification and Animal Data

The FDA labels metoprolol as Pregnancy Category C 3. Key findings:

• Animal studies showed no teratogenic potential (no birth defects)
• However, embryotoxicity and fetotoxicity occurred at doses 50 mg/kg in rats and 25 mg/kg in rabbits
• Effects included increased preimplantation loss, decreased viable fetuses, decreased neonatal survival, and growth delay in utero
• "There are no adequate and well-controlled studies in pregnant women" 3
• The drug should be used "only if clearly needed" 3

Human Data Shows Dose-Dependent Fetal Growth Restriction

The most concerning finding is a clear dose-response relationship between metoprolol and small-for-gestational-age (SGA) infants:

• A 2022 study of 540 pregnancies in women with heart disease found that high-dose beta-blocker use (86.5% metoprolol) carried a five-fold increased risk of SGA infants (adjusted OR 4.89,95% CI 2.22-10.78) 4
• Low-dose beta-blocker use showed a two-fold increased risk (adjusted OR 1.75,95% CI 0.83-3.72), though not statistically significant 4
• Overall, 19.8% of beta-blocker exposed infants were SGA compared to 9.5% in non-exposed controls 4

A 2020 prospective cohort study comparing 294 metoprolol/bisoprolol-exposed neonates found:

• 24.1% were SGA compared to 10.2% with methyldopa (OR 2.5,95% CI 1.2-5.2) and 9.9% in non-hypertensive controls (OR 4.3,95% CI 2.6-7.1) 5
• Increased preterm birth risk compared to non-hypertensive pregnancies (OR 2.2,95% CI 1.3-3.8) 5
• Neonatal adverse outcomes (bradycardia, hypoglycemia, respiratory disorders) occurred in 11.5% but were not statistically significantly different from controls 5

Older Data Was More Favorable

A 1978 study of 101 hypertensive pregnancies treated with metoprolol showed lower perinatal mortality (2.0% vs 8.0% with hydralazine) and lower fetal growth retardation (11.7% vs 16.3%) 6. However, this older evidence is superseded by more recent, larger studies with better methodology.

Clinical Algorithm for Use

When to Consider Metoprolol:

1. First-line agents (nifedipine, labetalol) are contraindicated (e.g., severe reactive airway disease precludes labetalol)
2. First-line agents are ineffective or poorly tolerated
3. Specific cardiac indications exist (e.g., Long QT syndrome, where beta-blockers reduce arrhythmic events) 7
4. Patient was stable on metoprolol pre-pregnancy for cardiac disease

If Using Metoprolol:

• Use the lowest effective dose to minimize fetal growth restriction risk 4
• Implement serial fetal growth ultrasounds every 3-4 weeks starting at 24-28 weeks gestation 4, 5
• Monitor for fetal bradycardia with regular fetal heart rate assessments
• Plan for close neonatal monitoring at birth for bradycardia, hypoglycemia, and respiratory issues 5
• Consider switching to first-line agents if feasible

Absolute Contraindications to Beta-Blockers in Pregnancy:

• None specific to metoprolol, but avoid atenolol specifically 1
• Standard beta-blocker contraindications apply (severe bradycardia, heart block, decompensated heart failure)

Critical Caveats

• Metoprolol is NOT teratogenic - it does not cause birth defects 3, 5
• The primary risk is fetal growth restriction, which is dose-dependent and potentially related to both the medication and underlying maternal hypertension 4, 5
• Women should immediately inform their doctor upon confirming pregnancy if taking metoprolol 3
• The drug crosses the placenta and is excreted in breast milk in small quantities 3
• Postpartum, consider switching to once-daily agents (nifedipine, amlodipine, enalapril) for better adherence 1