Diphenhydramine
MedicationBenadryl, Dormin, Unisom, Sominex, Nytol
First-generation antihistamine
Research strength: 3 / 5
MotherToBaby reports that early-pregnancy studies disagree: a few suggested more birth defects, while others found no increase and no consistent pattern. In a US case-control study of 41,148 pregnancies, Hansen et al. found scattered positive results across 340 comparisons of 14 antihistamines, but no strong overall evidence of a link; diphenhydramine was not significantly linked to oral clefts. MotherToBaby reports one study found no higher miscarriage chance with antihistamines, including diphenhydramine, and Aldridge et al. likewise found no association in a first-trimester antihistamine cohort, not a diphenhydramine-only study. AAFP says first-generation antihistamines can be used throughout pregnancy, while the NHS does not normally recommend diphenhydramine because daytime drowsiness and dizziness may worsen. The Benadryl label asks a health professional before use during pregnancy. Ask your provider about your situation.
Last reviewed: 2026-10-16
Sources
- MotherToBaby: Diphenhydramine fact sheetTeratology service
- American Family Physician: Over-the-Counter Medications in Pregnancy
- NHS: Pregnancy, breastfeeding and fertility while taking or using diphenhydramineUK government
- Hansen et al., 2020: National Birth Defects Prevention StudyUS government
- Aldridge et al., 2014: First-trimester antihistamine exposure and pregnancy outcomesUS government
- DailyMed: BENADRYL diphenhydramine hydrochloride tablet label, KenvueDrug company label
Research strength: 2 / 5
MotherToBaby says occasional use at recommended doses is not expected to increase preterm birth or low birth weight. Its fact sheet does not give a separate second-trimester estimate. AAFP says first-generation antihistamines, including diphenhydramine, can be used throughout pregnancy without higher rates of major outcomes; its statement is class-level. The NHS does not normally recommend diphenhydramine in pregnancy because it may cause daytime drowsiness or dizziness, and the Benadryl label asks a health professional before use. Ask your provider about your situation.
Last reviewed: 2026-10-16
Sources
- MotherToBaby: Diphenhydramine fact sheetTeratology service
- American Family Physician: Over-the-Counter Medications in Pregnancy
- NHS: Pregnancy, breastfeeding and fertility while taking or using diphenhydramineUK government
- DailyMed: BENADRYL diphenhydramine hydrochloride tablet label, KenvueDrug company label
Research strength: 3 / 5
MotherToBaby says occasional use at recommended doses is not expected to increase preterm birth or low birth weight, but it gives no separate third-trimester estimate. MotherToBaby reports rare third-trimester contractions and very rare fetal death, usually after higher-than-recommended doses or longer-than-recommended use; Brost et al. described painful contractions after suspected overdose. MotherToBaby reports a few temporary newborn withdrawal symptoms after daily use throughout pregnancy, while a 2000 case report describes a newborn sedated after maternal use before delivery. MotherToBaby and the temazepam label describe one stillbirth after the combination and say the cause is unknown; MotherToBaby advises against combining diphenhydramine and temazepam during pregnancy. AAFP supports first-generation antihistamine use throughout pregnancy, while the NHS does not normally recommend diphenhydramine because of maternal drowsiness and dizziness, and the Benadryl label asks a health professional before use. Ask your provider about your situation.
Last reviewed: 2026-10-16
Sources
- MotherToBaby: Diphenhydramine fact sheetTeratology service
- American Family Physician: Over-the-Counter Medications in Pregnancy
- NHS: Pregnancy, breastfeeding and fertility while taking or using diphenhydramineUK government
- Brost et al., 1996: Diphenhydramine overdose during pregnancyUS government
- Miller, 2000: Diphenhydramine toxicity in a newborn, case reportUS government
- DailyMed: Temazepam capsule labelDrug company label
- DailyMed: BENADRYL diphenhydramine hydrochloride tablet label, KenvueDrug company label
Diphenhydramine — Breastfeeding
Research strength: 2 / 5
MotherToBaby says diphenhydramine passes into milk in small amounts and that occasional or short-term use is not expected to increase infant side effects. LactMed says occasional doses of 25 mg or less are not expected to affect breastfed infants, while larger or longer use may affect the infant or reduce milk supply, especially before supply is established or with pseudoephedrine. In a 1993 study, 8 of 85 infants whose mothers used various antihistamines had reported minor effects, mostly irritability; the abstract does not give a diphenhydramine-specific rate. The NHS says use it only occasionally or for a short time and avoid bed-sharing while taking tablets or liquid; NHS SPS prefers non-sedating options and advises avoiding diphenhydramine combination products if possible, especially with newborns. The Benadryl label asks a health professional before breastfeeding use. Ask your provider about your situation.
Last reviewed: 2026-10-16
Sources
- MotherToBaby: Diphenhydramine fact sheetTeratology service
- LactMed: DiphenhydramineUS government
- NHS: Pregnancy, breastfeeding and fertility while taking or using diphenhydramineUK government
- NHS SPS: Using antihistamines during breastfeedingUK government
- NHS SPS: Diphenhydramine in paracetamol combination products during breastfeedingUK government
- Ito et al., 1993: Prospective follow-up of adverse reactions in breast-fed infantsUS government
- DailyMed: BENADRYL diphenhydramine hydrochloride tablet label, KenvueDrug company label
Pregnancy
MotherToBaby reports that early-pregnancy birth-defect studies do not agree and no consistent pattern has emerged. Hansen et al. (2020) analyzed 41,148 pregnancies, 14 antihistamines, and 64 birth-defect groups; 20 of 340 comparisons had significant positive results, and the authors found no strong evidence of an overall antihistamine-birth-defect link. Diphenhydramine had scattered results, but the study did not find a significant association with oral clefts. This was a case-control study of early pregnancy, not proof that every outcome or exposure level has been ruled out. Aldridge et al. (2014) followed 2,685 pregnancies, including 377 with first-trimester antihistamine use. The study did not detect an association with spontaneous abortion (adjusted hazard ratio 0.88, 95% CI 0.64 to 1.21); its exposure was any antihistamine, not diphenhydramine alone. Etwel et al. (2017) reviewed 37 studies of first-trimester H1 antihistamine exposure and did not find an increased risk of major malformations or other measured outcomes at the class level. Kallen (2002) analyzed 17,266 women, 17,776 deliveries, and 18,197 infants exposed to antihistamines in early pregnancy; the article reported normal malformation rates in the nausea and vomiting group, but did not isolate diphenhydramine. AAFP summarizes first-generation antihistamines as usable throughout pregnancy, but the larger controlled studies primarily address early pregnancy. MotherToBaby reports occasional recommended-dose use is not expected to increase preterm birth or low birth weight, without providing a separate estimate for each later trimester. Reports of contractions and very rare fetal death in the third trimester usually involved higher-than-recommended doses or longer-than-recommended use. Brost et al. (1996) described painful contractions in a pregnant patient with urine diphenhydramine levels suggesting overdose. MotherToBaby reports a few temporary newborn symptoms after daily use throughout pregnancy. The fact sheet does not provide a separate dose or case count for these reports. Miller (2000) described a newborn as very depressed at birth and apparently sedated after maternal diphenhydramine use before delivery. The temazepam label cites one stillbirth at term after the two medicines were taken together and says a cause-and-effect relationship has not been determined. MotherToBaby advises against the combination.
Breastfeeding
MotherToBaby and the NHS say diphenhydramine passes into milk in small amounts and that occasional or short-term use is unlikely to cause infant side effects in a healthy baby. LactMed states that occasional doses of 25 mg or less would not be expected to cause adverse effects, while larger doses or more prolonged use may affect the infant or decrease milk supply, particularly before lactation is established or with pseudoephedrine. LactMed reports no relevant published infant drug levels as of its September 2025 revision. Ito et al. (1993) prospectively followed 838 breastfed infants: mothers of 85 infants had used antihistamines, and 8 of those infants had reported minor effects, most often irritability; none of the reactions required medical care. Diphenhydramine was among the medicines used; the abstract reports antihistamines as a group. NHS SPS reports very limited and conflicting evidence about antihistamines and milk production. Its guidance prefers non-sedating antihistamines for healthy full-term infants and advises avoiding combination products containing diphenhydramine if possible, especially while breastfeeding a newborn.
Diphenhydramine is a first-generation H1 antihistamine used for allergy symptoms, nausea, motion sickness, and sleep. MotherToBaby lists Benadryl, Dormin, Unisom, Sominex, and Nytol as brand names. Some products sold under the same brand contain more than one ingredient, so the exact product label matters. The current BENADRYL tablet label identifies diphenhydramine hydrochloride 25 mg as its active ingredient.
What was tested
Pregnancy evidence includes a large case-control study of early-pregnancy antihistamine exposure, prospective cohorts, a systematic review and meta-analysis, and case reports. Most controlled outcome evidence is observational and class-level; it does not provide a distinct estimate for every trimester or dose pattern. Breastfeeding evidence includes an older milk-level report summarized by LactMed and a prospective infant follow-up study that reports antihistamine-class results, not a diphenhydramine-specific rate. The 2025 randomized vertigo study excluded pregnant participants, the 2026 restless-legs review was not a pregnancy exposure study, and the 2026 postpartum-depression network meta-analysis studied treatment efficacy rather than fetal or infant safety.
Pregnancy use: routine caution versus fetal-outcome evidence
- Source A says
- The NHS says diphenhydramine can be used in pregnancy but is not normally recommended because daytime drowsiness and dizziness may worsen. The BENADRYL label asks pregnant people to ask a health professional before use. (NHS: Pregnancy, breastfeeding and fertility while taking or using diphenhydramine, DailyMed: BENADRYL diphenhydramine hydrochloride tablet label, Kenvue)
- Source B says
- AAFP says first-generation H1 antihistamines, including diphenhydramine, can be used throughout pregnancy without increased rates of several major outcomes. MotherToBaby reports no consistent birth-defect pattern and says occasional recommended-dose use is not expected to raise preterm birth or low birth weight. (American Family Physician: Over-the-Counter Medications in Pregnancy, MotherToBaby: Diphenhydramine fact sheet, Hansen et al., 2020: Use of antihistamine medications during early pregnancy and selected birth defects)
- Why they differ
- The NHS focuses on the medicine's sedating side effects for the pregnant person, while AAFP and MotherToBaby summarize pregnancy outcome data. The AAFP conclusion is class-level, and the controlled outcome evidence is mostly observational and concentrated in early pregnancy. The sources therefore differ in how cautiously they advise routine use, not in a demonstrated fetal injury from occasional recommended-dose use.
- What the evidence shows overall
- The pregnancy outcome evidence and AAFP review support use at recommended doses, while the NHS caution focuses on maternal drowsiness and dizziness. The evidence remains mostly observational and does not settle every trimester or exposure pattern. The summaries retain the NHS caution and the separate high-dose, repeated-use, and temazepam concerns.
How cautious to be with diphenhydramine while breastfeeding, especially for a newborn
- Source A says
- LactMed says small occasional doses of 25 mg or less would not be expected to cause adverse effects, and the NHS says occasional or short-term use may be used while breastfeeding a healthy baby, with monitoring and no bed-sharing while taking tablets or liquid. (LactMed: Diphenhydramine, NHS: Pregnancy, breastfeeding and fertility while taking or using diphenhydramine)
- Source B says
- NHS SPS prefers non-sedating antihistamines and says combination products containing diphenhydramine should be avoided if possible, especially with a newborn while breastfeeding is being established. (NHS SPS: Using antihistamines during breastfeeding, NHS SPS: Using paracetamol during breastfeeding, diphenhydramine combination section)
- Why they differ
- LactMed and the NHS discuss occasional single-agent use, while the SPS warning is especially directed at combination products and newborns during early milk supply establishment. Infant-specific evidence is limited, and the sources emphasize different ages, doses, and product types.
- What the evidence shows overall
- The sources address different situations, but both support caution when the infant is a newborn, doses are larger or repeated, or a combination product is used. The public abstract reports antihistamine-class outcomes rather than a diphenhydramine-specific rate, and milk-supply effects at usual oral doses remain uncertain.
- MotherToBaby says to speak with healthcare providers before changing or stopping a medicine and to discuss which antihistamine is best if regular use is needed. (MotherToBaby)
- LactMed says non-sedating antihistamines are preferred alternatives and that a single bedtime dose after the last feeding may be adequate for many women while minimizing effects. (LactMed)
- The NHS says occasional or short-term use may be considered for a healthy breastfed baby and says not to share a bed while taking diphenhydramine tablets or liquid. (NHS)
- NHS SPS says combination products containing diphenhydramine should be avoided if possible, especially with a newborn while breastfeeding is being established. (NHS Specialist Pharmacy Service)
- The BENADRYL label says to ask a health professional before use if pregnant or breastfeeding. (DailyMed BENADRYL label)
General research, not specific to pregnancy.
The current BENADRYL label warns that marked drowsiness may occur and that alcohol, sedatives, and tranquilizers can increase drowsiness. FDA's diphenhydramine communication warns that doses above the label amount can cause serious heart problems, seizures, coma, or death.
- The BENADRYL label says not to use another product containing diphenhydramine, including a product used on the skin, and cautions people to take care when driving or operating machinery. (DailyMed: BENADRYL diphenhydramine hydrochloride tablet label, Kenvue)
- FDA's 2020 communication says taking more than the recommended dose can cause serious heart problems, seizures, coma, or death. (FDA Drug Safety Communication: High doses of diphenhydramine (Benadryl))
- EMA PRAC's July 2025 review of diphenhydramine and paracetamol fixed-dose combinations found their benefit-risk balance unchanged and kept the current authorization terms. PRAC requested a cumulative review of QT-prolongation cases associated with diphenhydramine, including cases at therapeutic doses. This review concerned combination products and was not a pregnancy-specific action. (EMA PRAC minutes, July 2025: Diphenhydramine and paracetamol combination products)
- MotherToBaby: Diphenhydramine fact sheetTeratology serviceSecondaryPage dated 2024-12-01
- LactMed: DiphenhydramineUS governmentSecondaryPage dated 2025-09-15Independent check
- American Family Physician: Over-the-Counter Medications in PregnancySecondaryIndependent check
- NHS: Pregnancy, breastfeeding and fertility while taking or using diphenhydramineUK governmentSecondaryIndependent check
- NHS SPS: Using paracetamol during breastfeeding, diphenhydramine combination sectionUK governmentSecondaryPage dated 2024-10-11Independent check
- NHS SPS: Using antihistamines during breastfeedingUK governmentSecondaryPage dated 2026-02-05Independent check
- DailyMed: BENADRYL diphenhydramine hydrochloride tablet label, KenvueDrug company labelTertiaryPage dated 2026-07-28
- Hansen et al., 2020: Use of antihistamine medications during early pregnancy and selected birth defectsUS governmentPrimaryIndependent check
- Aldridge et al., 2014: First-trimester antihistamine exposure and pregnancy outcomesUS governmentPrimaryIndependent check
- Etwel et al., 2017: H1 antihistamines and pregnancy outcomes, systematic review and meta-analysisUS governmentPrimaryIndependent check
- Kallen, 2002: Use of antihistamine drugs in early pregnancy and delivery outcomeUS governmentPrimaryIndependent check
- Ito et al., 1993: Prospective follow-up of adverse reactions in breast-fed infants exposed to maternal medicationUS governmentPrimaryIndependent check
- Brost et al., 1996: Diphenhydramine overdose during pregnancy: lessons from the pastUS governmentPrimaryIndependent check
- Miller, 2000: Diphenhydramine toxicity in a newborn, case reportUS governmentPrimaryIndependent check
- DailyMed: Temazepam capsule labelDrug company labelTertiaryPage dated 2026-01-14Independent check
- FDA Drug Safety Communication: High doses of diphenhydramine (Benadryl)US governmentSecondaryPage dated 2025-02-20
- EMA PRAC minutes, July 2025: Diphenhydramine and paracetamol combination productsEU agencySecondaryPage dated 2025-10-31Independent checkEuropean guidance
Last reviewed 2026-10-16
Independent check 2026-10-16
Not yet clinician-reviewed
Ask your provider about your situation.