What are the recommended treatments, including non‑pharmacologic measures and safe medications, for nausea (morning sickness) in a pregnant woman?

Treatment of Nausea in Pregnancy

Start with dietary modifications and vitamin B6 (10-25 mg every 8 hours), then escalate to doxylamine-pyridoxine combination if symptoms persist, followed by metoclopramide for refractory cases, reserving ondansetron for severe symptoms after 10 weeks gestation. 1, 2, 3, 4

Initial Non-Pharmacologic Management

Early intervention is critical because it may prevent progression to hyperemesis gravidarum, which affects 0.3-2% of pregnancies and can lead to hospitalization. 1, 3 The PUQE (Pregnancy-Unique Quantification of Emesis) score should be used to assess severity: mild (≤6), moderate (7-12), or severe (≥13). 2, 3

Dietary and lifestyle modifications include:

• Small, frequent meals (6-8 per day) rather than three large meals 3
• BRAT diet (bananas, rice, applesauce, toast) for bland, easily digestible options 3
• High-protein, low-fat meals to minimize gastric irritation 3
• Avoid spicy, fatty, acidic, and fried foods 3
• Identify and eliminate specific triggers like strong food odors 3

Stepwise Pharmacologic Treatment Algorithm

First-Line: Vitamin B6 and Doxylamine

Vitamin B6 (pyridoxine) 10-25 mg orally every 8 hours is the initial pharmacologic treatment, safe at doses up to 100 mg/day. 2, 3, 4 However, chronic doses exceeding 100 mg/day can cause peripheral neuropathy and should be avoided. 2

If vitamin B6 alone is insufficient, escalate to doxylamine-pyridoxine combination (Diclectin/Diclegis) 10 mg/10 mg delayed-release formulation, which is the only FDA-approved medication specifically for nausea and vomiting in pregnancy with a pregnancy safety rating of A. 2, 4, 5 The American College of Obstetricians and Gynecologists (ACOG) recommends this as preferred first-line pharmacologic therapy. 2

Ginger supplementation 250 mg capsules four times daily can be added as an adjunct safe option. 3

Second-Line: Metoclopramide

Metoclopramide 5-10 mg orally every 6-8 hours (3-4 times daily, not once daily) should be used when first-line therapy fails. 1, 2, 4 This is the preferred third-line agent based on the American Gastroenterological Association (AGA) recommendations. 2

A meta-analysis of 33,000 first-trimester exposures showed no significant increase in major congenital defects (odds ratio 1.14,99% CI 0.93-1.38). 2, 4 Metoclopramide has fewer side effects than promethazine, including less drowsiness, dizziness, and dystonia. 2, 4 ACOG advises withdrawing metoclopramide if extrapyramidal symptoms develop. 2

Third-Line: Antihistamines

Promethazine is a safe H1-receptor antagonist throughout pregnancy with extensive clinical experience, indicated when vitamin B6 and doxylamine are insufficient. 2 Other antihistamines like dimenhydrinate and meclizine are safe alternatives. 2

Fourth-Line: Ondansetron (Use with Caution)

Ondansetron 8 mg orally every 8-12 hours should be reserved for refractory cases, particularly after 10 weeks gestation. 2, 4 ACOG recommends case-by-case decision-making for use before 10 weeks due to small absolute risk increases: cleft palate increases from 11 to 14 per 10,000 births (0.03% absolute increase) and ventricular septal defects increase by 0.3% absolute. 2, 4

Despite these concerns, the European Society for Medical Oncology (ESMO) states ondansetron may be safely administered during the first trimester when benefits outweigh risks in severe cases. 2

Severe/Refractory Cases: IV Therapy and Corticosteroids

For patients requiring hospitalization with severe symptoms (PUQE ≥13), persistent vomiting despite oral antiemetics, dehydration, electrolyte abnormalities, or weight loss >5% of prepregnancy weight: 2

IV management includes:

• Normal saline (0.9% NaCl) with potassium chloride guided by daily electrolyte monitoring 2
• Thiamine 100 mg IV (as part of vitamin B complex) BEFORE any dextrose administration to prevent Wernicke encephalopathy, then 50 mg daily maintenance 1, 2, 4
• IV metoclopramide 10 mg slowly over 1-2 minutes every 6-8 hours as preferred IV antiemetic 2
• IV ondansetron 0.15 mg/kg per dose (maximum 16 mg) over 15 minutes if metoclopramide fails 2

Methylprednisolone 16 mg IV every 8 hours for up to 3 days, then taper over 2 weeks should be reserved as last resort for severe, refractory hyperemesis gravidarum only. 1, 2, 4 This should be avoided before 10 weeks gestation due to small risk of cleft palate, but at 20 weeks gestation the risk is substantially lower. 2, 4 Limit maximum duration to 6 weeks. 2

Critical Clinical Pearls

• Early pharmacologic treatment prevents progression to severe disease—do not delay waiting for dietary modifications alone to work. 2, 3
• Thiamine supplementation is essential in prolonged vomiting to prevent Wernicke encephalopathy. 1, 2, 4
• Monitor for dehydration signs: orthostatic hypotension, decreased skin turgor, dry mucous membranes. 2
• Check electrolytes, liver enzymes (elevated in 40-50% of hyperemesis cases), and thyroid function tests in severe cases. 2
• Enteral or parenteral nutrition may be necessary if weight loss persists despite pharmacotherapy. 2

Common Pitfalls to Avoid

• Do not dismiss nausea and vomiting as an inconsequential part of pregnancy—it has significant physical and psychological morbidity. 6
• Do not delay treatment—progression to hyperemesis gravidarum becomes more difficult to control and may require hospitalization. 1, 7
• Do not use ondansetron as first-line therapy before 10 weeks—metoclopramide has superior safety profile in early pregnancy. 2, 4
• Do not give dextrose before thiamine—this can precipitate Wernicke encephalopathy. 2
• Do not exceed 100 mg/day of vitamin B6 chronically—risk of peripheral neuropathy. 2