Hyperemesis gravidarum (HG) refers to severe and persistent nausea and vomiting during early pregnancy, resulting in dehydration, ketosis, and even acidosis that require hospitalization. Its incidence is approximately 0.3% to 3.0%.
Etiology
Endocrine Factors
Elevated Levels of Human Chorionic Gonadotropin (hCG)
The timing of the onset and resolution of early pregnancy symptoms aligns with the rise and fall of hCG levels. In addition, women with conditions like molar pregnancy or multiple pregnancies, which are associated with significantly elevated hCG levels, have a higher incidence of severe vomiting. This indicates that hyperemesis gravidarum may be linked to elevated hCG levels.
Elevated Estrogen Levels
An increase in estradiol levels appears to be associated with nausea and vomiting during pregnancy, while lower levels are linked to a reduced likelihood of these symptoms. This indirectly suggests that estrogen may contribute to hyperemesis gravidarum.
Psychological and Social Factors
Women experiencing excessive psychological stress, anxiety, or worry, as well as those living in poor socioeconomic and environmental conditions, have a higher likelihood of developing hyperemesis gravidarum.
Clinical Manifestations
Hyperemesis gravidarum most commonly occurs before 10 weeks of gestation. Typical symptoms begin around 6 weeks of pregnancy, with nausea and vomiting that progressively worsen as the pregnancy advances. By 8 weeks, persistent vomiting often develops, preventing food intake and causing dehydration, electrolyte imbalances, and even acidosis. In severe cases, additional symptoms, such as lethargy, confusion, delirium, coma, or even death, may arise.
Affected women experience weight loss, often exceeding 5% of their pre-pregnancy weight, along with significant wasting, extreme fatigue, dry and cracked lips, dehydrated skin, sunken eyes, and reduced urine output. Liver and kidney function may become impaired, leading to symptoms such as jaundice, elevated bilirubin and transaminase levels, increased blood urea nitrogen and creatinine, and the presence of urinary protein and casts. Severe cases may also result in vitamin B1 deficiency, causing Wernicke encephalopathy.
Diagnosis and Differential Diagnosis
Hyperemesis gravidarum is a diagnosis of exclusion. A thorough medical history should be obtained to rule out other potential causes of vomiting, such as gastrointestinal conditions (e.g., gastrointestinal infections, pancreatitis, cholecystitis, and viral hepatitis), as well as genitourinary diseases (e.g., urinary tract infections or ovarian tumor torsion).
The diagnosis can be made based on typical clinical presentations. Auxiliary examinations may assist in assessing disease severity.
Urinalysis
Tests for urinary ketones, urine output, and specific gravity are used. Midstream urine culture helps to rule out urinary tract infections.
Blood Tests
Blood counts, liver and kidney function, and electrolytes are measured to evaluate disease severity. Liver enzyme levels may be elevated in some patients with hyperemesis gravidarum but typically do not exceed four times the upper normal limit or 300 U/L. Serum bilirubin levels may also be elevated but usually do not exceed 4 mg/dL.
Ultrasound Exam
Ultrasound imaging is used to rule out multiple pregnancies and gestational trophoblastic diseases.
Complications
Hyperthyroidism
Elevated hCG levels during pregnancy may stimulate the thyroid gland to secrete thyroid hormones due to the structural similarity between the beta subunit of hCG and thyroid-stimulating hormone (TSH). This leads to a feedback suppression of TSH levels. As a result, transient hyperthyroidism occurs in 60–70% of women with hyperemesis gravidarum, characterized by decreased TSH levels or elevated free T4 levels. This condition is generally temporary, rarely requiring anti-thyroid medications, and usually resolves by 20 weeks of gestation.
Wernicke Encephalopathy
Wernicke encephalopathy typically arises after about 3 weeks of persistent hyperemesis gravidarum and is caused by severe vitamin B1 deficiency due to prolonged vomiting. Clinical features include nystagmus, visual disturbances, and impaired gait and posture. Advanced cases may progress to stupor, coma, or even death.
Treatment
Pregnant women with persistent vomiting accompanied by ketosis require hospitalization. Treatment includes intravenous fluid replacement, supplementation with multivitamins (particularly B vitamins), correction of dehydration and electrolyte imbalances, appropriate use of antiemetic medications, and prevention and management of complications.
General Management and Psychological Support
Efforts should be made to minimize exposure to triggers that may induce vomiting, such as certain smells or foods. An empty stomach in the morning should be avoided, and small, frequent meals are encouraged.
Correction of Dehydration and Electrolyte Imbalances
For those unable to eat or showing symptoms of dehydration, intravenous fluid replacement, multivitamin supplementation (especially B vitamins), and parenteral nutritional support are necessary. Vitamin B1 should be administered early to prevent Wernicke encephalopathy. Electrolyte levels must be closely monitored during treatment, and timely supplementation is necessary to correct imbalances. The risk of venous thrombosis should also be considered and appropriate preventive measures taken.
Antiemetic Therapy
Potential medications include:
- Vitamin B6 or a combination of Vitamin B6 and Doxylamine:
- Metoclopramide: The use of metoclopramide during early pregnancy has not been associated with an increased risk of fetal structural abnormalities or spontaneous abortion, and there is no significant difference in newborn birth weight compared to control groups.
- Ondansetron: While sufficient evidence for the safety of ondansetron in pregnancy is lacking, studies suggest the absolute risk is low; however, risks and benefits should be carefully weighed.
- Promethazine: The antiemetic efficacy of promethazine is comparable to that of metoclopramide, though promethazine is associated with more side effects.
- Glucocorticoids: Methylprednisolone can alleviate symptoms of hyperemesis gravidarum. However, its use in the first trimester has been associated with an increased risk of fetal cleft palate. As a result, glucocorticoids should not be used as a first-line treatment before 10 weeks of pregnancy and should only be considered as a last-resort antiemetic for refractory hyperemesis gravidarum.
Prognosis
The majority of patients with hyperemesis gravidarum experience significant improvement with active and standardized treatment. Symptoms often resolve naturally as pregnancy progresses, and the overall maternal and fetal outcomes are favorable.