What Causes Hyperemesis Gravidarum (HG)?
The hormone Growth and Differentiation Factor 15 (GDF15) is the most likely cause of Hyperemesis Gravidarum. GDF15 is made by the placenta and rises very rapidly early in pregnancy. It causes taste aversion, nausea, and vomiting. Some people with HG have variation in the gene that codes for GDF15 which can cause them to produce abnormal levels of the hormone and/or have abnormal sensitivity to the hormone in pregnancy.
In addition to genetics, there are other factors that can change GDF15 levels which are currently under investigation. The genes that code for the GDF15 receptor (GFRAL), the progesterone receptor (PGR), and the insulin-like growth factor binding protein 7 (IGFBP7) are also associated with HG.
Q: Is there a higher risk of a female baby or twins with HG?
A: There is a slightly higher risk of a female baby or multiples (twins) with HG pregnancies.
HG is too often assumed to be influenced by psychological causes because the physiological causes are just now being determined by collaborative genetics research. Women report seeking medical care for severe nausea and vomiting (HG) presumably due to a flu or GI disorder, never considering the possibility of pregnancy, yet are still told their symptoms are related to a rejection of their pregnancy, or an exaggerated reaction to expected nausea and vomiting of pregnancy.
Identifying and diagnosing early HG can be difficult. Proof, such as severe weight loss, debility, and dehydration, often develop after prolonged symptoms, making it more difficult to manage her symptoms. With our genetic research, we hope to have a test developed to identify those at risk of severe symptoms.
Genetics Research: GDF15 is the most likely cause of Hyperemesis Gravidarum
HER Foundation, in collaboration with Dr. Marlena Fejzo, is the leading HG research team in the world. However, research is limited by lack of funding and priority, so high-quality studies with decisive results are rare. Please support our collaborative research with leading universities.
Early Research and Theories about HG Causes
Hyperemesis gravidarum was recognized several centuries ago, but the first research appears was around the 18th Century. Then, HG was thought to be related to abnormalities, toxins, ulcerations, or infections in a related organ.
Early in the 20th Century, a psychological cause was adopted for HG based on psychoanalytic theories despite the lack of evidence and biased studies. This belief has been passed from generation to generation despite evidence disproving it. Our genetics research proves HG has a biological cause.
Health professionals, researchers and medical texts still suggest HG is a psychosomatic disorder. Consequently, women suffer from inadequate treatment and uncaring health professionals lacking compassion. MORE
Psychological stress and trauma often result from HG, especially if it is inadequately managed, but stress and trauma are not the cause of HG.
Outdated and very poorly designed studies originally suggested HG was caused by hysteria and psychosomatic disorders. Despite controlled studies disproving these erroneous assertions, the myth persists and women with HG suffer as a result. Studies of psychological influences on HG continue to be published. Too many are still denied adequate care and end up terminating a wanted pregnancy.
Not surprisingly, some of these same emotions are well-documented in studies of people experiencing bed rest or other illnesses yet are accepted as normal.
Most if not all women experience secondary psychological effects (e.g.: frustration, feelings of helplessness, fear of death, isolation, depression, trauma, etc.) due to the misery and stress of HG, not to mention the grief from fetal loss which affects about 1 in 3 mothers.
Hormones and HG
Hormonal changes are the most studied theory of HG’s causes, but fail to show consistent results. Most studies focus on hCG, thyroid, and steroid hormones like cortisol, estrogen, and progesterone in early pregnancy because onset and peak of symptoms correlate with elevations in many of these hormones.
A few studies are evaluating hormones that affect appetite such as ghrelin. Research, including our genetic studies, find hormones such as GDF15, which is a marker for cachexia and affects appetite and taste perception, may influence development and severity of HG and resulting weight changes during pregnancy. Future screening for these genes and hormones will provide valuable insight into HG management.
Increases in serum thyroxine levels have been documented in up to 73% of pregnancies complicated by HG. Thyroid hormones are stimulated by the increase in hCG and may result in transient hyperthyroidism. Severity of HG is sometimes linked to the degree of hyperthyroidism. Mutations of hCG or TSH receptors have also been found to be elevated in women with HG.
Gastric Dysfunctions and HG
Researchers have cited changes in gastrointestinal (GI) function that cause nausea and vomiting, as well as GI complications of HG. The causes include fasting, low protein intake, hormones and genes.
- slowed GI movement causing distention, low appetite, and constipation,
- regurgitation of duodenal contents back into the stomach or esophagus even in the absence of food, and
- severe acid reflux.
Research finds gastric pacing, acid-reducing medications, metoclopramide Rx, and high protein and liquid meals reduce symptoms.
- PubMed Research on HG and Gastrointestinal Function
- PubMed Research on Pregnancy and Gastric Motility
Nutritional Deficiencies and HG
Profound and prolonged nutritional deficiencies occur during HG, with some studies finding intake half of required. Yet oral vitamins are rarely tolerated during HG. Deficiencies worsen symptoms and cause additional symptoms such as changes in taste and smell, which may improve after administration of IV vitamins with fluids.
Thiamine, which is depleted within 2 weeks of poor intake or a high carbohydrate diet, may lead to severe nausea and vomiting, neurological and cardiac damage, and even death. Vitamin K deficiency can result in maternal bleeding and fetal embryopathy.