Which beta‑blockers are safe to use during the third trimester of pregnancy?

Beta-Blockers Safe in Third Trimester Pregnancy

Metoprolol, propranolol, and labetalol are the safest beta-blockers for use during the third trimester of pregnancy, while atenolol should be avoided due to evidence of fetal growth restriction. 1, 2

Recommended Beta-Blockers

First-Line Agents

• Labetalol is considered the preferred beta-blocker during pregnancy, with the most extensive safety data and the advantage of combined alpha-beta blockade providing vasodilation 3, 4, 5
• Metoprolol has a Class I recommendation for prophylactic therapy during pregnancy with Level B evidence, indicating it is generally safe in the third trimester 1
• Propranolol carries a Class IIa recommendation with Level B evidence and is considered safe, though slightly less preferred than metoprolol 1

Additional Options

• Bisoprolol and pindolol are also considered generally safe during pregnancy, though with less extensive documentation 2
• Sotalol may be considered if other agents fail, though experience is more limited 1

Beta-Blockers to Avoid

Atenolol is contraindicated (Class III recommendation) and classified as FDA Category D due to documented associations with:

• Intrauterine growth restriction when used in the first trimester 1
• Lower fetal birth weights compared to other beta-blockers 6
• Higher prevalence of preterm delivery 1

The evidence against atenolol is particularly strong, with comparative studies showing significantly lower birth weights (2750g with atenolol vs 3280g with labetalol, p<0.001) 6

Clinical Considerations for Third Trimester Use

Safety Profile

• None of the recommended beta-blockers have been associated with teratogenicity 3
• Prospective randomized studies have failed to demonstrate higher incidence of fetal complications with beta-blockers (metoprolol, propranolol, labetalol) compared to placebo 1
• Most beta-blockers are considered safe for breastfeeding mothers, including labetalol, metoprolol, and nifedipine 5

Monitoring Requirements

• Closer monitoring of fetal growth and surveillance for fetal bradycardia may be considered for pregnant women on beta-blockers 2
• Serial echocardiography is reasonable during the second or third trimester when hemodynamic load is highest 2

Potential Adverse Effects

Rare cases of adverse fetal effects have been reported with beta-blockers, including:

• Fetal bradycardia 1
• Neonatal hypoglycemia 1, 7
• Premature labor 1
• Metabolic abnormalities 1

However, these effects may be secondary to fetal distress in high-risk pregnancies rather than direct drug effects 1

Theoretical Advantages

Beta-blockers with selective β1 properties (like metoprolol) are theoretically preferable because they may interfere less with peripheral vasodilation and uterine relaxation compared to non-selective agents 1

Common Pitfalls to Avoid

• Do not use atenolol at any stage of pregnancy due to documented fetal harm 1, 8
• Avoid amiodarone (FDA Category D) except for life-threatening arrhythmias resistant to other drugs 1
• While beta-blockers should ideally be avoided in the first trimester if possible, they can be safely used throughout the third trimester when indicated 1