Hyperemesis gravidarum is a severe form of nausea and vomiting in pregnancy. It generally begins in the first trimester of pregnancy, at around 6 to 8 weeks of gestation, and resolves for most people by 20 weeks of gestation, although it can persist until delivery.^[1] Hyperemesis gravidarum is different from morning sickness, which is a common form of nausea and vomiting during pregnancy that is mild to moderate in nature and occurs in about 80% of pregnancies. Conversely, hyperemesis gravidarum affects about 1% to 3% of pregnancies.^[2]

Hyperemesis gravidarum is a leading cause of hospitalization during pregnancy and can result in dehydration, weight loss, electrolyte imbalances, and nutritional deficiencies.^[3] It can also negatively affect psychosocial well-being, provoking feelings of depression and anxiety.^[4] In very serious cases, it can adversely affect the fetus and is associated with preterm birth, low birth weight babies, and small for gestational age babies.^[5]

The main signs and symptoms are severe nausea, frequent vomiting, increased salivation, and a loss of appetite, with few to no symptom-free days; symptoms usually begin around 6 weeks of gestation. This can lead to weight loss, electrolyte imbalances, nutritional deficiencies, and symptoms of dehydration such as dizziness, headache, lightheadedness, lethargy, decreased urination, and heart palpitations.^[6] Frequent vomiting can cause damage to the esophagus, and in very serious cases, prolonged nutritional deficiencies and electrolyte imbalances, which can cause neurological and cardiovascular damage or even maternal and fetal death; however, these grave outcomes are increasingly rare with access to medical treatments.^[7] Although most symptoms resolve around 20 weeks of gestation, some people have nausea and vomiting until the third trimester or even until delivery.^[8][9]

Hyperemesis gravidarum can also have psychosocial impacts, such as reduced quality of life, depression, anxiety, inability to work or perform daily activities, job loss, fear of future pregnancies, and even considering or actually terminating the current pregnancy.^[10][11][12] These negative effects on mental health can persist into the post-partum period, sometimes causing post-traumatic stress disorder.^[13]

There is no universal definition for hyperemesis gravidarum. It is usually diagnosed based on a combination of signs and symptoms that are not due to other causes and begin early in pregnancy, including persistent and severe nausea and vomiting, dehydration, weight loss (≥5% of pre-pregnancy weight), inability to eat and drink normally, strong limitation of daily activities, and the presence of ketones in the urine.^[3][14]

In order to rule out other causes and determine the severity of the condition (which informs treatment), a clinician may perform an assessment, evaluate certain signs (like weight and blood pressure), order laboratory tests (to check hydration status, electrolyte balance, liver chemistries, nutritional status, thyroid function, etc.), and complete an obstetric ultrasound to check the health of the fetus.^[15]

Medical treatments for hyperemesis gravidarum focus on symptom management and prevention of complications. This usually involves rehydration (e.g., intravenous fluids), nutritional support, and anti-nausea medications. Depending on the severity of the condition, hospitalization may be required.^[15]

There are a variety of medications used to control nausea and vomiting, and some people require a combination of medications to better manage their symptoms. Some common medications for hyperemesis gravidarum include promethazine (a dopamine and serotonin antagonist and antihistamine), ondansetron (a serotonin antagonist), and metoclopramide (a dopamine and serotonin antagonist that can increase lower esophageal sphincter tone and gastric emptying). Corticosteroid medications, like prednisone, are sometimes used, but their safety in pregnancy has been questioned. Although doxylamine/pyridoxine is a first-line medication for morning sickness, it has not been studied in hyperemesis gravidarum.^[1][3]

If there are signs and symptoms of dehydration, intravenous fluids are often required to rehydrate the body and correct vitamin deficiencies and electrolyte imbalances. Tube feeding may be required for nutritional support in people with hyperemesis gravidarum who are unable to maintain weight with oral food intake.^[3][16]

The vomiting associated with hyperemesis gravidarum can result in the depletion of important vitamins, including thiamine (vitamin B1) and vitamin K, which can lead to further neurological and cardiovascular complications.^[7] Repletion of these vitamins will generally be included in standard medical care, but supplementation may also be recommended to maintain adequate levels.

As in all pregnancies, supplementation with a prenatal vitamin is recommended to ensure baseline vitamin and mineral requirements are being met. Certain vitamins and minerals can also be administered intramuscularly or intravenously if nausea and vomiting prevent oral intake.

Pyridoxine (vitamin B6) and ginger are effective for treating mild to moderate nausea and vomiting in pregnancy, but they have not been found to be effective for the severe nausea and vomiting of hyperemesis gravidarum.^[1][17]

Maintaining adequate food intake during hyperemesis gravidarum can be challenging. To improve tolerance, eating small, frequent meals may be helpful. Foods that are bland and high in protein or carbohydrates tend to be better tolerated, while foods with a strong odor or high-fat foods may worsen symptoms. Ultimately, any foods and beverages that are pregnancy-safe and tolerated should be consumed.^[6]

Low-quality evidence suggests that acupuncture and acupressure may help to reduce nausea and the need for medications.^[1][6] In particular, the PC6 or NeiGuan point is the most thoroughly studied for nausea and vomiting and is located on the underside of the wrist, approximately 3 cm above the wrist crease between two tendons.^[18] Pressure can be applied manually or by utilizing a wristband device. There is also data suggesting that hypnotherapymay be a helpful adjunctive treatment for certain people,^[19][20] as can psychotherapy.^[17]

The causes of hyperemesis gravidarum are poorly understood and likely multifactorial. Genetics appear to play an important role, as risk increases substantially if a sister or mother experienced hyperemesis gravidarum during pregnancy.^[21] In fact, a genome-wide association study found that two genes, GDF15 and IGFBP7, are associated with hyperemesis gravidarum. These genes are involved in the formation of the placenta and appetite regulation.^[22] Hormonal changes during pregnancy, particularly increased human chorionic gonadotropin but also changes in progesterone, estrogen, and thyroid hormones, have been found to be associated with an increased risk of hyperemesis gravidarum in some research. It is speculated that people with hyperemesis gravidarum may have higher than normal levels of these hormones; however, the data are inconsistent, and clear associations between levels of these hormones and risk of hyperemesis gravidarum are lacking.^[3][15][23]