Hyperemesis gravidarum (HG) is a pregnancy complication that is characterized by severe nausea, vomiting, weight loss, and possibly dehydration. Feeling faint may also occur. It is considered a more severe form of morning sickness. Symptoms often get better after the 20th week of pregnancy but may last the entire pregnancy duration. The exact causes of hyperemesis gravidarum are unknown. Risk factors include the first pregnancy, multiple pregnancy, obesity, prior or family history of HG, and trophoblastic disorder. A December 2023 study published in Nature indicated a link between HG and abnormally high levels of the hormone GDF15, as well as increased sensitivity to that specific hormone. Diagnosis is usually made based on the observed signs and symptoms. HG has been technically defined as more than three episodes of vomiting per day, such that weight loss of 5% or three kilograms has occurred and ketones are present in the urine. Other potential causes of the symptoms should be excluded, including urinary tract infection, and an overactive thyroid. Treatment includes drinking fluids and a bland diet. Recommendations may include electrolyte-replacement drinks, thiamine, and a higher protein diet. Some people require intravenous fluids. With respect to medications, pyridoxine or metoclopramide are preferred. Prochlorperazine, dimenhydrinate, ondansetron (sold under the brand-name Zofran) or corticosteroids may be used if these are not effective. Hospitalization may be required due to the severe symptoms associated. Psychotherapy may improve outcomes. Evidence for acupressure is poor. While vomiting in pregnancy has been described as early as 2000 BCE, the first clear medical description of HG was in 1852, by Paul Antoine Dubois. HG is estimated to affect 0.3–2.0% of pregnant women, although some sources say the figure can be as high as 3%. While previously known as a common cause of death in pregnancy, with proper treatment this is now very rare. Those affected have a lower risk of miscarriage but a higher risk of premature birth. Some pregnant women choose to have an abortion due to HG symptoms.
Signs and symptoms When vomiting is severe, it may result in the following:
Loss of 5% or more of pre-pregnancy body weight Dehydration, causing ketosis, and constipation Nutritional disorders, such as vitamin B1 (thiamine) deficiency, vitamin B6 (pyridoxine) deficiency or vitamin B12 (cobalamin) deficiency Metabolic imbalances such as metabolic ketoacidosis or thyrotoxicosis Physical and emotional stress Difficulty with activities of daily living Symptoms can be aggravated by hunger, fatigue, prenatal vitamins (especially those containing iron), and diet. Many women with HG are extremely sensitive to odors in their environment; certain smells may exacerbate symptoms. Excessive salivation, also known as sialorrhea gravidarum, is another symptom experienced by some women. Hyperemesis gravidarum tends to occur in the first trimester of pregnancy and lasts significantly longer than morning sickness. While most women will experience near-complete relief of morning sickness symptoms near the beginning of their second trimester, some people with HG will experience severe symptoms until they give birth to their baby, and sometimes even after giving birth. A small percentage rarely vomit, but the nausea still causes most (if not all) of the same issues that hyperemesis with vomiting does.
Complications
Pregnant woman Failure to treat or inadequate treatment of HG can lead to one or more of the following:
anemia hyponatremia Wernicke's encephalopathy kidney failure central pontine myelinolysis coagulopathy atrophy Mallory–Weiss tears hypoglycemia jaundice malnutrition pneumomediastinum rhabdomyolysis deconditioning deep vein thrombosis pulmonary embolism splenic avulsion vasospasms of cerebral arteries Depression and post-traumatic stress disorder are common secondary complications of HG, and emotional support can be beneficial.
Infant The effects of HG on the fetus are mainly due to electrolyte imbalances caused by HG in the mother. Women with severe hyperemesis who gain less than 7 kilograms (15 lb) during pregnancy tend to have newborns with lower birth weight or are smaller for gestational age. They also tend to give birth before 37 weeks of gestation. In contrast, infants of women with hyperemesis who have a pregnancy weight gain of more than 7 kilograms (15 lb) appear similar to infants from uncomplicated pregnancies. There is no significant difference in the neonatal death rate in infants born to mothers with HG compared to infants born to mothers who do not have HG. Children born to mothers with undertreated HG have a fourfold increase in neurobehavioral diagnoses.
Causes Though the exact cause of HG is unknown, there are numerous theories. It is thought that HG is caused by a combination of factors, many of which may vary between women, some of which include a genetic predisposition. Women with family members who have had HG are more likely to develop the disease. One factor is an adverse reaction to the hormonal changes of pregnancy, in particular, elevated levels of beta human chorionic gonadotropin (β-hCG). This theory would also explain why hyperemesis gravidarum is most frequently encountered in the first trimester (often around 8–12 weeks of gestation), as β-hCG levels are highest at that time and decline afterward. Another postulated cause of HG is an increase in maternal levels of estrogens (decreasing intestinal motility and gastric emptying leading to nausea/vomiting).
Pathophysiology
Although the pathophysiology of HG is unclear, one of the most commonly accepted theories suggests that levels of β-hCG are associated with it. Leptin, a hormone that inhibits hunger, may also play a role. Possible pathophysiological processes involved are summarized in the following table:
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