What are the effects of propranolol (beta blocker) on pregnancy?

From the Guidelines

Propranolol can be used during pregnancy when the benefits outweigh the risks, particularly for conditions like hypertension, arrhythmias, migraines, or anxiety, as it is generally considered one of the safer beta-blockers for pregnant women, with a long history of use in pregnancy. The typical dosing ranges from 10-40 mg taken 2-4 times daily, depending on the condition being treated. According to the 2020 AHA/ACC guideline for the diagnosis and treatment of patients with hypertrophic cardiomyopathy 1, most beta-blockers, including propranolol, are generally considered safe to use during pregnancy. However, it is essential to note that potential concerns include possible intrauterine growth restriction with long-term use, and newborns should be monitored for hypoglycemia, bradycardia, and respiratory depression for 48-72 hours after birth if the mother was taking propranolol near delivery.

When considering the use of propranolol during pregnancy, it is crucial to weigh the benefits against the risks. The 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults 1 recommends transitioning women with hypertension who become pregnant to methyldopa, nifedipine, and/or labetalol during pregnancy. However, propranolol may still be considered in certain situations, and breastfeeding while taking propranolol is generally considered acceptable as minimal amounts pass into breast milk.

Key considerations for the use of propranolol during pregnancy include:

• Monitoring maternal blood pressure, heart rate, and fetal growth throughout pregnancy
• Using the lowest effective dose possible
• Being aware of potential concerns, such as intrauterine growth restriction and newborn hypoglycemia, bradycardia, and respiratory depression
• Considering alternative treatment options, such as methyldopa, nifedipine, and/or labetalol, as recommended by the 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline 1.

Ultimately, the decision to use propranolol during pregnancy should be made on a case-by-case basis, taking into account the individual patient's needs and medical history, and in consultation with a healthcare provider.

From the FDA Drug Label

Pregnancy Category C: In a series of reproductive and developmental toxicology studies, propranolol was given to rats by gavage or in the diet throughout pregnancy and lactation At doses of 150 mg/kg/day, but not at doses of 80 mg/kg/day (equivalent to the MRHD on a body surface area basis), treatment was associated with embryotoxicity (reduced litter size and increased resorption rates) as well as neonatal toxicity (deaths) There are no adequate and well-controlled studies in pregnant women Intrauterine growth retardation, small placentas, and congenital abnormalities have been reported in neonates whose mothers received propranolol during pregnancy. Neonates whose mothers are receiving propranolol at parturition have exhibited bradycardia, hypoglycemia and/or respiratory depression. Propranolol hydrochloride extended-release capsules should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Key Points:

• Propranolol is classified as Pregnancy Category C.
• There are no adequate and well-controlled studies in pregnant women.
• Potential risks to the fetus include intrauterine growth retardation, small placentas, and congenital abnormalities.
• Neonatal effects may include bradycardia, hypoglycemia, and/or respiratory depression.
• Propranolol should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus 2.

From the Research

Propranolol in Pregnancy

• Propranolol is a beta-adrenoceptor blocking drug that has been used to treat hypertension in pregnancy 3, 4.
• A prospective study comparing propranolol with methyldopa in 28 women with pregnancy-associated hypertension found that both drugs were equally effective in controlling maternal hypertension, but one infant born to a mother receiving propranolol had symptomatic hypoglycaemia 3.
• The pharmacokinetics of propranolol during pregnancy were studied in 6 healthy pregnant volunteers, and it was found that the disposition of propranolol is not altered during pregnancy 4.
• Propranolol and its metabolites were found to cross into breast milk, with the maximum dose likely to be ingested by the infant being approximately 0.1% of the maternal dose 3.

Comparison with Other Antihypertensive Drugs

• Labetalol, another antihypertensive drug, has been found to be effective and well-tolerated in patients with all grades of hypertension, including pregnant women 5.
• A study comparing oral antihypertensive regimens, including labetalol, nifedipine, and methyldopa, found that all three drugs were viable initial options for treating severe hypertension in low-resource settings 6.
• A systematic review of the pharmacokinetics of methyldopa, labetalol, and nifedipine throughout pregnancy found that there is a large heterogeneity in the available studies, and further research is needed to determine the optimal dosing of these drugs during pregnancy 7.

Safety and Efficacy

• Propranolol has been found to be effective in controlling maternal hypertension, but its use has been associated with symptomatic hypoglycaemia in infants 3.
• Labetalol has been found to be effective and well-tolerated in pregnant women, and is considered a valuable option for treating hypertension in this population 5.
• The safety and efficacy of propranolol and other antihypertensive drugs during pregnancy need to be carefully considered, and further research is needed to determine the optimal treatment strategies for hypertension in pregnancy 6, 7, 3, 4, 5.