Is Benadryl (diphenhydramine) safe to use during pregnancy?

Safety of Benadryl (Diphenhydramine) During Pregnancy

Diphenhydramine (Benadryl) should be used with caution during pregnancy and only when the potential benefit justifies the risk, as it has been associated with possible birth defects including cleft palate.

Risk Classification and Safety Profile

• Diphenhydramine is classified as FDA Pregnancy Category B, which means animal studies have not demonstrated risk to the fetus, but there are no adequate studies in pregnant women 1
• The drug label for diphenhydramine specifically states: "If pregnant or breast-feeding, ask a healthcare professional before use" 2
• Although diphenhydramine is frequently used during pregnancy and has generally good overall safety data, some studies have raised concerns about potential risks 1

Specific Concerns

• Administration of diphenhydramine has been associated with the development of cleft palate in some studies 1
• A 2009 study identified 8 associations between diphenhydramine use and birth defects, though these were mostly of weak to moderate magnitude 3
• More recent research from 2017 suggests that H1 antihistamines as a class are not associated with increased risk of major malformations (OR 1.07; 95% CI 0.98-1.16) or other adverse fetal outcomes 4

Recommendations for Use During Pregnancy

• Second-generation antihistamines may be preferable first-line options during pregnancy when available, as they have fewer sedating effects and comparable safety data 1
• If an antihistamine is needed during pregnancy, the benefits of treatment should be weighed against the potential risks 1
• For allergic conditions requiring treatment during pregnancy, consider:
  • Using the lowest effective dose for the shortest duration necessary 1
  • Selecting medications with more established safety profiles when possible 1
  • Avoiding combination products that contain decongestants, especially in the first trimester 1

Common Pitfalls to Avoid

• Avoid combining diphenhydramine with oral decongestants, especially during the first trimester, as decongestants have been associated with congenital malformations such as gastroschisis and small intestinal atresia 1
• Do not use diphenhydramine primarily as a sleep aid during pregnancy when alternatives might be safer 2
• Be aware that diphenhydramine can cause marked drowsiness, which may be exacerbated during pregnancy 2

Alternative Options

• For allergic rhinitis during pregnancy, intranasal corticosteroids (particularly budesonide, which is Pregnancy Category B) may be safer first-line options 1
• Sodium cromolyn is considered a safe treatment for allergic rhinitis in pregnancy (Pregnancy Category B) 1
• For severe allergic reactions requiring treatment during pregnancy, the benefit of diphenhydramine treatment likely outweighs the potential risks 1

While diphenhydramine has been widely used during pregnancy, the evidence suggests caution is warranted, particularly in the first trimester when organogenesis occurs. Treatment decisions should prioritize maternal health while minimizing potential risks to the developing fetus.