Is diphenhydramine (Benadryl) safe to use during pregnancy?

Safety of Diphenhydramine During Pregnancy

Diphenhydramine should be used with caution during pregnancy, particularly in the first trimester, due to concerns about a possible association with cleft palate, although recent studies have not conclusively confirmed this risk. 1

Safety Profile and Risks

• Both first-generation and second-generation antihistamines generally have good safety records during pregnancy, but specific concerns exist for diphenhydramine 1
• The FDA drug label for diphenhydramine recommends consulting a healthcare professional before use during pregnancy 2
• Although diphenhydramine is frequently used during pregnancy, there is some concern over a case-control study suggesting an association with cleft palate that has not been sufficiently refuted 1
• The most critical time for concern about potential congenital malformations is the first trimester, when organogenesis occurs 1

Evidence Quality and Recommendations

• Recent studies have not detected significant increased risk for congenital malformations with diphenhydramine use during pregnancy, but caution is still advised 1
• A 2009 study examining associations between maternal antihistamine use and birth defects found that of 364 associations investigated, 24 had elevated odds ratios, with 8 involving diphenhydramine, though most were of weak to moderate magnitude 3
• Diphenhydramine has been used in combination with metoclopramide for treating hyperemesis gravidarum (severe nausea and vomiting during pregnancy) with acceptable safety profiles 4

Alternative Antihistamine Options

• Chlorpheniramine has been recommended as a first-choice antihistamine during pregnancy due to its observed safety and longevity of use 5
• Cetirizine and loratadine (FDA Pregnancy Category B drugs) have more accumulated safety data than some other antihistamines and may be preferred options 5
• Second-generation antihistamines have confirmed safety through large birth registries, case-control studies, and cohort studies 1

Clinical Approach to Antihistamine Use in Pregnancy

• When antihistamine treatment is necessary during pregnancy, consider:
  1. Non-pharmacological approaches first 5
  2. Antihistamines with better documented safety profiles (chlorphenamine, cetirizine, or loratadine) over diphenhydramine 5
  3. If diphenhydramine is used, avoid first trimester if possible 1

Common Pitfalls and Considerations

• Assuming all antihistamines have equivalent safety profiles during pregnancy is incorrect 5
• Combining antihistamines with oral decongestants should be avoided during the first trimester due to potential risks 1
• Sedative effects of diphenhydramine may be more pronounced during pregnancy, affecting maternal functioning and safety 2
• Over-the-counter medications (including diphenhydramine) are used by most pregnant women, often without medical consultation, which may increase risk 6

Monitoring and Follow-up

• If diphenhydramine must be used during pregnancy, monitor for:
  • Maternal side effects including marked drowsiness and sedation 2
  • Fetal development through routine prenatal care 1
• Consider switching to safer alternative antihistamines if treatment is needed throughout pregnancy 5