Morning sickness
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Morning Sickness (Nausea and Vomiting of Pregnancy)
Overview
"Morning sickness" is a misnomer - only about 2% of affected women have symptoms restricted to the morning, while 80% are symptomatic throughout the day. Nausea and vomiting of pregnancy (NVP) complicates 50-90% of pregnancies, making it one of the most common complaints in early pregnancy.
- Symptoms typically begin ~39 days after the last menstrual period (often before the woman knows she is pregnant)
- Peak around 9-11 weeks' gestation
- Usually resolve by 20-22 weeks, though symptoms persist into late pregnancy in ~45% of cases
- A pregnancy test should be done in any fertile woman with new-onset nausea and vomiting
Pathogenesis
The cause is not fully established, but several factors are implicated:
- hCG (human chorionic gonadotropin) - symptom severity parallels hCG levels; higher hCG (molar pregnancies, multiple gestations) correlates with more severe symptoms
- Estrogen and progesterone slow gastric emptying, contributing to nausea
- Vitamin B6 (pyridoxine) deficiency - reduced levels have been observed in NVP
- Serotonin receptor gene polymorphisms (HTR3C) - a genetic basis has been identified
- Helicobacter pylori - serological association with hyperemesis gravidarum reported (though active infection studies are mixed)
- Hormones including leptin, prostaglandin E2, and androgens have also been implicated
Risk Factors
- First pregnancy (primigravida)
- Younger maternal age
- Multiple gestation
- Molar pregnancy
- Pre-existing GERD
- Overweight
- Low socioeconomic status
- History of motion sickness or oral contraceptive intolerance
- Family history (hereditary tendency)
Interestingly, NVP is associated with better fetal outcomes in typical cases - lower rates of miscarriage, preterm birth, congenital heart defects, cleft palate, and fetal demise.
Hyperemesis Gravidarum
The severe end of the spectrum. Defined as intractable vomiting with:
- Weight loss >5% of prepregnancy weight
- Electrolyte imbalance (particularly hypokalemia)
- Dehydration and ketonemia/ketonuria
Occurs in 0.3-5% of pregnancies and is the most common cause of hospitalization in the first half of pregnancy in the US (second only to preterm labor).
Serious complications include:
- Wernicke's encephalopathy (thiamine deficiency)
- Osmotic demyelination syndrome
- Mallory-Weiss tears
- Retinal hemorrhage
- Thromboembolism
- Low birth weight and preterm delivery
Before diagnosing hyperemesis gravidarum, rule out other causes of vomiting: peptic ulcer disease, cholecystitis, appendicitis, pyelonephritis, pancreatitis, ectopic pregnancy, hepatitis, fatty liver of pregnancy, HELLP syndrome.
Workup: CBC, comprehensive metabolic panel, thyroid function tests, serum lipase, urinalysis (for ketones), serum beta-hCG.
Treatment
Step 1 - Lifestyle and non-pharmacological (first-line):
- Small, frequent meals; avoid triggers and strong odors
- Ginger extract - RCT evidence supports benefit over placebo regardless of dose or preparation
- Pyridoxine (Vitamin B6) - symptomatic benefit in trials
- Acupressure (P6 wrist point) - supportive evidence; acupuncture also shown effective in recent meta-analysis (Jin et al., 2024, PMID 39214380)
Step 2 - Pharmacotherapy:
| Drug | Class | Notes |
|---|---|---|
| Doxylamine + pyridoxine (Diclegis/Diclectin) | H1 antihistamine + B6 | Reintroduced after large prospective studies confirmed no teratogenicity; first-line Rx |
| Promethazine | Phenothiazine dopamine antagonist | Effective; may cause drowsiness or dystonia |
| Metoclopramide | Dopamine antagonist | Effective but higher adverse effect profile |
| Ondansetron (Zofran) | 5-HT3 antagonist (serotonin) | 8 mg IV or 4 mg PO TID; no dystonia; comparable to promethazine |
| Prochlorperazine, Chlorpromazine | Phenothiazines | Used in hospitalized patients |
Step 3 - Severe/refractory hyperemesis:
- IV fluid repletion: 5% glucose in lactated Ringer's or normal saline
- IV electrolyte correction (thiamine before glucose to prevent Wernicke's)
- Glucocorticoids (methylprednisolone) - for severe refractory cases
- Enteral/parenteral nutrition - when symptoms are life-threatening
Admission Criteria
- Uncertain diagnosis
- Intractable vomiting unresponsive to outpatient management
- Persistent ketonuria or electrolyte abnormalities after repletion
- Weight loss >10% of prepregnancy weight
Sources:
- Sleisenger and Fordtran's Gastrointestinal and Liver Disease, p. 1351-1362
- Tintinalli's Emergency Medicine: A Comprehensive Study, p. 1032-1055
- Yamada's Textbook of Gastroenterology, 7th ed., p. 2290-2299
- Katzung's Basic and Clinical Pharmacology, 16th ed., p. 444
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