What are the safe management options for heartburn and nausea in a pregnant woman (any trimester)?

Management of Heartburn and Nausea in Pregnancy

For heartburn in pregnancy, start with lifestyle modifications and calcium-containing antacids, escalating to H2-receptor antagonists (ranitidine preferred) if needed, reserving PPIs only for severe refractory cases; for nausea, begin with vitamin B6 and dietary changes, then add doxylamine-pyridoxine combination, followed by metoclopramide or promethazine for persistent symptoms, while avoiding ondansetron before 10 weeks gestation due to small but measurable teratogenic risks. 1, 2, 3

Heartburn Management Algorithm

First-Line: Lifestyle Modifications

• Elevate the head of the bed to reduce nighttime symptoms 1
• Consume 5-6 small, frequent meals daily rather than 3 large meals to reduce gastric distension and lower esophageal sphincter pressure 1
• Avoid trigger foods including spicy, fatty, acidic, and fried foods, as well as coffee, alcohol, chocolate, citrus, and carbonated beverages 1
• Avoid lying down for 2-3 hours after meals to minimize reflux episodes 1
• Weight loss is recommended for overweight or obese patients 1

Second-Line: Antacids

• Calcium-containing antacids (such as calcium carbonate) are the preferred first-line medication, with high-level evidence supporting safety and efficacy due to minimal fetal exposure from nonsystemic absorption 1, 4
• Nonparticulate antacids like sodium citrate or sodium bicarbonate are also safe throughout pregnancy 1
• These can be used as needed for symptom relief at any trimester 1, 4

Third-Line: Sucralfate

• Sucralfate 1g orally three times daily if symptoms persist despite lifestyle modifications and antacids 1, 4
• This agent has minimal systemic absorption, making it particularly safe 1

Fourth-Line: H2-Receptor Antagonists

• Ranitidine 150mg twice daily is the preferred H2RA, with documented efficacy and safety even in the first trimester 1, 5, 6
• H2RAs are more effective than placebo and should be used before escalating to PPIs 1
• All H2RAs except nizatidine can be used (nizatidine shows fetal harm in animal studies) 7, 6

Fifth-Line: Proton Pump Inhibitors (Reserve for Severe Cases)

• PPIs should be reserved exclusively for women with intractable symptoms or complicated reflux disease that has failed all other therapies 1, 5, 7
• Lansoprazole may be the preferred PPI due to its safety profile in animal studies and case reports in human pregnancies 1, 5
• All PPIs are FDA category B except omeprazole (category C), though pantoprazole shows no association with major malformations in observational studies 8, 7, 6
• Use with particular caution in the first trimester 1

Trimester-Specific Considerations

• First trimester: Prioritize lifestyle modifications, antacids, and sucralfate; use H2RAs only if clearly needed 1
• Second and third trimesters: Ranitidine can be safely used for severe symptoms 1
• Throughout pregnancy, avoid twice-daily PPI dosing empirically—if symptoms require this level of suppression, consider treatment failure and evaluate further 1

---

Nausea and Vomiting Management Algorithm

Assessment of Severity

• Use the PUQE (Pregnancy-Unique Quantification of Emesis) score: mild (≤6), moderate (7-12), severe (≥13) 2, 3
• Nausea typically begins at 4-6 weeks, peaks at 8-12 weeks, and subsides by week 20 2, 3
• Early intervention is critical to prevent progression to hyperemesis gravidarum, which affects 0.3-2% of pregnancies 2, 3

First-Line: Lifestyle and Dietary Modifications (Mild PUQE ≤6)

• Eat small, frequent, bland meals (BRAT diet: bananas, rice, applesauce, toast) 3
• Choose high-protein, low-fat meals 3
• Avoid spicy, fatty, acidic, and fried foods 3
• Avoid strong food odors that trigger symptoms 2

Second-Line: Vitamin B6 and Antihistamines (Moderate PUQE 7-12)

• Vitamin B6 (pyridoxine) 10-25 mg every 8 hours is safe and effective, but keep total daily dose ≤100 mg/day to avoid peripheral neuropathy 2, 3
• Doxylamine-pyridoxine combination (Diclectin/Diclegis) is the FDA-approved first-line pharmacologic therapy, with delayed-release formulation of doxylamine 10mg + pyridoxine 10mg 2, 3
• Alternative H1-receptor antagonists include promethazine and dimenhydrinate if doxylamine is unavailable 2, 3

Third-Line: Metoclopramide or Promethazine (Severe PUQE ≥13)

• Metoclopramide 5-10 mg orally every 6-8 hours is the preferred third-line agent, with meta-analysis of 33,000 first-trimester exposures showing no significant increase in major congenital defects (OR 1.14,99% CI 0.93-1.38) 2, 3
• Metoclopramide should be administered 3-4 times daily rather than once daily for optimal symptom control 2
• Promethazine is a safe alternative H1-receptor antagonist with extensive clinical experience throughout pregnancy 2
• Withdraw metoclopramide if extrapyramidal symptoms develop 2

Fourth-Line: Ondansetron (Use with Caution Before 10 Weeks)

• Ondansetron 8 mg orally every 8-12 hours can be used as second-line agent, but exercise caution before 10 weeks gestation due to small absolute risk increases: cleft palate (0.03% increase from 11 to 14 per 10,000 births) and ventricular septal defects (0.3% increase) 2, 3
• ACOG recommends case-by-case decision-making for ondansetron use before 10 weeks 2
• After 10 weeks, ondansetron is safer and can be used more liberally 2

Severe Cases Requiring Hospitalization (Hyperemesis Gravidarum)

• IV hydration with normal saline (0.9% NaCl) plus potassium chloride guided by daily electrolyte monitoring 2
• Always provide thiamine supplementation (100 mg IV for minimum 7 days, then 50 mg daily maintenance) BEFORE any dextrose administration to prevent Wernicke encephalopathy 2, 3
• IV metoclopramide 10 mg administered slowly over 1-2 minutes every 6-8 hours is the preferred IV antiemetic 2
• IV ondansetron 0.15 mg/kg per dose (maximum 16 mg) infused over 15 minutes can be used when metoclopramide is ineffective 2

Last Resort: Corticosteroids (Refractory Hyperemesis Only)

• Methylprednisolone 16 mg IV every 8 hours for up to 3 days, then taper over 2 weeks to lowest effective dose (maximum 6 weeks duration) 2
• Avoid corticosteroids before 10 weeks gestation due to small risk of cleft palate 2, 3
• At 20 weeks gestation, methylprednisolone is safer and reduces rehospitalization rates in severe cases 2

---

Critical Safety Considerations and Pitfalls

Common Pitfalls to Avoid

• Don't assume all heartburn requires medication—many cases respond adequately to lifestyle modifications alone 1
• Don't withhold treatment entirely out of excessive caution—untreated severe symptoms can progress to hyperemesis gravidarum with its own maternal and fetal risks 1
• Don't delay pharmacologic treatment for nausea waiting for dietary modifications alone—early treatment prevents progression to severe disease 2
• Don't use metoclopramide as monotherapy for GERD (it's not recommended for GERD syndromes, Grade D recommendation) 1

Medications to Avoid

• Avoid metoclopramide and ondansetron before 10 weeks gestation for hyperemesis due to possible risks, though they may be considered in later pregnancy 1, 2
• Avoid neurokinin-1 (NK-1) antagonists like aprepitant and second-generation antipsychotics like olanzapine unless absolutely necessary due to limited safety data 2

When to Escalate Care

• Troublesome dysphagia warrants endoscopy with biopsy to evaluate for eosinophilic esophagitis or other pathology 1
• Red flags requiring immediate evaluation: severe epigastric pain, persistent vomiting with weight loss >5% of prepregnancy weight, signs of dehydration, or inability to tolerate oral intake 1, 2
• Check thyroid function tests in hyperemesis gravidarum patients, as biochemical hyperthyroidism is common 2
• Monitor electrolytes, liver enzymes (elevated in 40-50% of hyperemesis cases), and nutritional deficiencies 2, 3

Supportive Measures

• Consider enteral or parenteral nutrition if weight loss persists despite pharmacotherapy 2
• Electrolyte replacement and nutritional support are crucial for severe symptoms 3
• Coordination by multidisciplinary team at tertiary care center may be necessary for refractory cases 3