Morning sickness

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"nausea and vomiting of pregnancy" management

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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:
DrugClassNotes
Doxylamine + pyridoxine (Diclegis/Diclectin)H1 antihistamine + B6Reintroduced after large prospective studies confirmed no teratogenicity; first-line Rx
PromethazinePhenothiazine dopamine antagonistEffective; may cause drowsiness or dystonia
MetoclopramideDopamine antagonistEffective 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, ChlorpromazinePhenothiazinesUsed 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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