What are the effects of Diphenhydramine (Benadryl) on pregnancy?

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Last updated: March 28, 2025View editorial policy

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From the Guidelines

Benadryl (diphenhydramine) should be used with caution during pregnancy, particularly during the first trimester, due to potential concerns over congenital malformations, such as cleft palate, although recent studies have not detected any increased risk 1. When considering the use of diphenhydramine during pregnancy, it is essential to weigh the potential benefits against the risks.

  • The first trimester is the most critical period for concern about potential congenital malformations due to medication use, as this is when organogenesis occurs 1.
  • While diphenhydramine is often used by pregnant patients, a case-control study suggesting an association with cleft palate has yet to be sufficiently refuted, warranting caution 1.
  • Non-medication approaches, such as avoiding allergens, using saline nasal sprays, or running an air purifier, should be considered first to treat allergy symptoms during pregnancy.
  • If medication is necessary, the lowest effective dose of diphenhydramine should be used for the shortest duration possible, with the typical adult dose being 25-50 mg every 4-6 hours, not exceeding 300 mg in 24 hours.
  • It is crucial to consult with a healthcare provider before taking any medication during pregnancy, as they can provide personalized advice based on the specific health situation and stage of pregnancy.
  • The side effects of diphenhydramine, such as drowsiness, dry mouth, and constipation, may be more pronounced during pregnancy and should be closely monitored 1.

From the FDA Drug Label

If pregnant or breast-feeding, ask a healthcare professional before use The effects of Diphenhydramine (Benadryl) on pregnancy are not explicitly stated in the drug label, except that it advises to ask a healthcare professional before use.

  • The label does not provide information on the safety or risks of using Diphenhydramine during pregnancy.
  • It is recommended to consult a healthcare professional for guidance on using Diphenhydramine during pregnancy 2

From the Research

Effects of Diphenhydramine (Benadryl) on Pregnancy

  • There are no direct studies on the effects of Diphenhydramine (Benadryl) on pregnancy in the provided evidence.
  • However, studies on antihistamines in general provide some insights:
    • First-generation antihistamines, which include Diphenhydramine, are considered less safe than second-generation antihistamines during pregnancy 3, 4.
    • A review of antihistamines used during pregnancy suggests that none of the antihistamines available today have been categorized as safe during pregnancy, and careful risk/benefit assessment should be done before prescribing them 4.
    • A study on the use of loratadine, a second-generation antihistamine, in human pregnancy found that it does not represent a major teratogenic risk 5.
  • It is recommended that all over-the-counter medication use, including antihistamines like Diphenhydramine, should be discussed with patients, and the effects of the symptoms should be balanced with the risks and benefits of each medication 6.
  • Other studies suggest that sympathomimetic decongestants, which are often combined with antihistamines like Diphenhydramine in cold medications, have teratogenic potential when taken during the first trimester of pregnancy 7.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Allergy Medications During Pregnancy.

The American journal of the medical sciences, 2016

Research

A review of antihistamines used during pregnancy.

Journal of pharmacology & pharmacotherapeutics, 2012

Research

Over-the-Counter Medications in Pregnancy.

American family physician, 2014

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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