Hyperemesis gravidarum
Encyclopedia
Hyperemesis gravidarum is a severe form of morning sickness
, with "unrelenting, excessive pregnancy-related nausea and/or vomiting that prevents adequate intake of food and fluids." Hyperemesis is considered a rare complication of pregnancy
but, because nausea
and vomiting
during pregnancy exist on a continuum, there is often not a good diagnosis between common morning sickness
and hyperemesis. Estimates of the percentage of pregnant women afflicted range from 0.3% to 2.0%.
hyper-, meaning excessive, and emesis, meaning vomiting, as well as the Latin gravida, meaning pregnant. Therefore, hyperemesis gravidarum means "excessive vomiting in pregnancy."
. This theory would also explain why hyperemesis gravidarum is most frequently encountered in first trimester (often around 8 – 12 weeks of gestation), as HCG levels are highest at that time and decline afterward.
It is thought that estrogen produces nausea and regurgitation of stomach acids in some women. There is also evidence that leptin
may play a role in HG.
A recent study gives "preliminary evidence" that there may be a genetic component.
Symptoms of morning sickness, and HG, can be aggravated by the following factors: hunger, fatigue, prenatal vitamins (especially those containing iron), odors, and diet.
Some women with HG lose as much as 30% of their body weight. Many sufferers of HG are extremely sensitive to odors in their environment; certain smells may exacerbate symptoms. This is known as hyperolfaction
. Ptyalism
, or hypersalivation, is another symptom experienced by some women suffering from HG.
As compared to morning sickness, HG tends to begin somewhat earlier in the pregnancy and last significantly longer. While most women will experience near-complete relief of morning sickness symptoms near the beginning of their second trimester, some sufferers of HG will experience severe symptoms until they give birth to their baby, and sometimes even after giving birth. An overview of the significant differences between morning sickness and HG can be found at Hyperemesis or Morning Sickness: Overview.
, central pontine myelinolysis
, coagulopathy
, atrophy
, Mallory-Weiss syndrome
, hypoglycemia
, jaundice
, malnutrition
, Wernicke's encephalopathy
, pneumomediastinum
, rhabdomyolysis
, deconditioning
, splenic avulsion, and vasospasms of cerebral arteries. Depression
is a common secondary complication of HG.
On rare occasions a woman can die from hyperemesis; Charlotte Bronté
is a presumed victim of the disease.
, small for gestational age
, and born before 37 weeks gestation. In contrast, infants of women with hyperemesis that have a pregnancy weight gain of more than 7 kg appear similar as infants from uncomplicated pregnancies. No long-term follow-up studies have been conducted on children of hyperemetic women.
Update: Studies show that 38% or so of children whose mothers were exposed to HG end up with a higher chance of having anxiety, being bipolar, and acquiring other behavioral as they get older.
Fever, abdominal pain, or late onset of nausea and vomiting usually indicate another condition, such as appendicitis
, gallbladder disorders
, gastritis
, hepatitis
, or infection.
medications and intravenous rehydration. If medication and IV hydration are insufficient, nutritional support may be required.
Management of HG can be complicated because not all women respond to treatment. In some instances, women with HG may be able to avoid hospitalization by eating a special diet of clear liquids and bland food rich in carbohydrates, and eating before rising in the morning; while these may be of some assistance, they are unlikely to resolve the disorder on their own. Hypnosis has relieved symptoms in some cases. Wristbands used for motion sickness and seasickness have been shown by one study to be effective in treating some cases of HG; these are worn around the wrist at a traditional acupuncture point, 3 finger-widths from the joint, and are available at many pharmacies. There is evidence that ginger
may be effective in treating pregnancy-related nausea; however, in general this is ineffective in cases of HG.
(Vitamin B1) must be considered to reduce the risk of Wernicke's encephalopathy
. A and B vitamins are depleted within two weeks, so extended malnutrition indicates a need for evaluation and supplementation. In addition, mineral levels should be monitored and supplemented; of particular concern are sodium
and potassium
.
After IV rehydration is completed, patients in general progress to frequent small liquid or bland meals. After rehydration, treatment focuses on managing symptoms to allow normal intake of food. However, cycles of hydration and dehydration can occur, making continuing care necessary. Home care is available in the form of a PICC line for hydration and nutrition (called total parenteral nutrition
). Home treatment is often less expensive than long-term and/or repeated hospital stays.
The standard treatment in most of the world is Benedictin (also sold under the trademark name Diclectin), a combination of doxylamine
succinate and vitamin B6
. However, due to a series of birth-defect lawsuits in the United States against its maker, Merrill Dow, Benedictin is not currently on the market in the U.S. (None of the lawsuits were successful, and numerous independent studies and the Food and Drug Administration
(FDA) have concluded that Benedictin does not cause birth defects.) Its component ingredients are available over-the-counter (doxylamine succinate is the active ingredient in many sleep medications), and some doctors will recommend this treatment to their patients.
Antiemetic
drugs, especially ondansetron
(Zofran), are effective in many women. The major drawback of ondansetron has been its cost. In severe cases of HG, the Zofran pump may be more effective than tablets. Zofran is also available in ODT (oral disintegrating tablet), which can be easier for women who have trouble swallowing due to the nausea. Promethazine (Phenergan) has been shown to be safe, at least in rats and may be used during pregnancy with minimal/no side-effects. Metoclopramide
is sometimes used in conjunction with antiemetic drugs; however, it has a somewhat higher incidence of side-effects. Other medications less commonly used to treat HG include Marinol, corticosteroids, and antihistamines.
Other medications that are frequently prescribed for HG are Compazine, Tigan, Phenergan, and Reglan. These can be given orally or intraveneously, or administered as a rectal suppository. They are considered safe for use during pregnancy.
Anecdotal evidence suggests that the use of marijuana, or of the pharamaceutical extract Marinol, can relieve the symptoms of HG, in a similar way to treating nausea in people with Cancer and AIDS. However, due to the criminalisation of cannabis, there have been no clinical trials into its effectivess or risks to the fetus.
However, use of marijuana has been shown to increase the risk for central nervous system growth impairment, low birth weight and size of infants, and preterm deliveries, all of which are associated with poor infant outcomes.
Morning sickness
Morning sickness, also called nausea gravidarum, nausea, vomiting of pregnancy , or pregnancy sickness is a condition that affects more than half of all pregnant women. Related to increased oestrogen levels, a similar form of nausea is also seen in some women who use hormonal contraception or...
, with "unrelenting, excessive pregnancy-related nausea and/or vomiting that prevents adequate intake of food and fluids." Hyperemesis is considered a rare complication of pregnancy
Pregnancy
Pregnancy refers to the fertilization and development of one or more offspring, known as a fetus or embryo, in a woman's uterus. In a pregnancy, there can be multiple gestations, as in the case of twins or triplets...
but, because nausea
Nausea
Nausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...
and vomiting
Vomiting
Vomiting is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose...
during pregnancy exist on a continuum, there is often not a good diagnosis between common morning sickness
Morning sickness
Morning sickness, also called nausea gravidarum, nausea, vomiting of pregnancy , or pregnancy sickness is a condition that affects more than half of all pregnant women. Related to increased oestrogen levels, a similar form of nausea is also seen in some women who use hormonal contraception or...
and hyperemesis. Estimates of the percentage of pregnant women afflicted range from 0.3% to 2.0%.
Etymology
Hyperemesis gravidarum is from the GreekGreek language
Greek is an independent branch of the Indo-European family of languages. Native to the southern Balkans, it has the longest documented history of any Indo-European language, spanning 34 centuries of written records. Its writing system has been the Greek alphabet for the majority of its history;...
hyper-, meaning excessive, and emesis, meaning vomiting, as well as the Latin gravida, meaning pregnant. Therefore, hyperemesis gravidarum means "excessive vomiting in pregnancy."
Causes
The cause of HG is unknown. The leading theories state that it is an adverse reaction to the hormonal changes of pregnancy. In particular, Hyperemesis may be due to raised levels of beta HCG (human chorionic gonadotrophin) as it is more common in multiple pregnancies and in gestational trophoblastic diseaseGestational trophoblastic disease
Gestational trophoblastic disease is a term used for a group of pregnancy-related tumours. These tumours are rare, and they appear when cells in the womb start to grow out of control. The cells that form gestational trophoblastic tumours are called trophoblasts and come from tissue that grows to...
. This theory would also explain why hyperemesis gravidarum is most frequently encountered in first trimester (often around 8 – 12 weeks of gestation), as HCG levels are highest at that time and decline afterward.
It is thought that estrogen produces nausea and regurgitation of stomach acids in some women. There is also evidence that leptin
Leptin
Leptin is a 16 kDa protein hormone that plays a key role in regulating energy intake and energy expenditure, including appetite and metabolism. It is one of the most important adipose derived hormones...
may play a role in HG.
A recent study gives "preliminary evidence" that there may be a genetic component.
Symptoms of morning sickness, and HG, can be aggravated by the following factors: hunger, fatigue, prenatal vitamins (especially those containing iron), odors, and diet.
Symptoms
When HG is severe and/or inadequately treated, it may result in:- Loss of 5% or more of pre-pregnancy body weight
- DehydrationDehydrationIn physiology and medicine, dehydration is defined as the excessive loss of body fluid. It is literally the removal of water from an object; however, in physiological terms, it entails a deficiency of fluid within an organism...
, causing ketosisKetosisKetosis is a state of elevated levels of ketone bodies in the body. It is almost always generalized throughout the body, with hyperketonemia, that is, an elevated level of ketone bodies in the blood. Ketone bodies are formed by ketogenesis when the liver glycogen stores are depleted...
, and constipationConstipationConstipation refers to bowel movements that are infrequent or hard to pass. Constipation is a common cause of painful defecation... - Nutritional deficiencies
- Metabolic imbalances
- Altered sense of taste
- Sensitivity of the brain to motion
- Food leaving the stomach more slowly
- Rapidly changing hormone levels during pregnancy
- Stomach contents moving back up from the stomach
- Physical and emotional stress of pregnancy on the body
- Subconjunctival hemorrhageSubconjunctival hemorrhagethumb|right|250px| A stress induced subconjunctival hemorrhage in the left eye one week after hemorrhaging. Same hemorrhage four weeks after hemorrhaging. Some of the blood in the [[sclera]] has turned yellow, like a bruise....
(broken blood vessels in the eyes) - Difficulty with daily activities
- Hallucinations
Some women with HG lose as much as 30% of their body weight. Many sufferers of HG are extremely sensitive to odors in their environment; certain smells may exacerbate symptoms. This is known as hyperolfaction
Olfaction
Olfaction is the sense of smell. This sense is mediated by specialized sensory cells of the nasal cavity of vertebrates, and, by analogy, sensory cells of the antennae of invertebrates...
. Ptyalism
Drooling
Drooling is when saliva flows outside the mouth...
, or hypersalivation, is another symptom experienced by some women suffering from HG.
As compared to morning sickness, HG tends to begin somewhat earlier in the pregnancy and last significantly longer. While most women will experience near-complete relief of morning sickness symptoms near the beginning of their second trimester, some sufferers of HG will experience severe symptoms until they give birth to their baby, and sometimes even after giving birth. An overview of the significant differences between morning sickness and HG can be found at Hyperemesis or Morning Sickness: Overview.
For the pregnant woman
If inadequately treated, HG can cause renal failureRenal failure
Renal failure or kidney failure describes a medical condition in which the kidneys fail to adequately filter toxins and waste products from the blood...
, central pontine myelinolysis
Central pontine myelinolysis
Central pontine myelinolysis is neurological disease caused by severe damage of the myelin sheath of nerve cells in the brainstem, more precisely in the area termed the pons, predominately of iatrogenic etiology...
, coagulopathy
Coagulopathy
Coagulopathy is a condition in which the blood’s ability to clot is impaired. This condition can cause prolonged or excessive bleeding, which may occur spontaneously or following an injury or medical and dental procedures.The normal clotting process depends on the interplay of various proteins in...
, atrophy
Atrophy
Atrophy is the partial or complete wasting away of a part of the body. Causes of atrophy include mutations , poor nourishment, poor circulation, loss of hormonal support, loss of nerve supply to the target organ, disuse or lack of exercise or disease intrinsic to the tissue itself...
, Mallory-Weiss syndrome
Mallory-Weiss syndrome
Mallory–Weiss syndrome or gastro-esophageal laceration syndrome refers to bleeding from tears in the mucosa at the junction of the stomach and esophagus, usually caused by severe retching, coughing, or vomiting.-Causes:...
, hypoglycemia
Hypoglycemia
Hypoglycemia or hypoglycæmia is the medical term for a state produced by a lower than normal level of blood glucose. The term literally means "under-sweet blood"...
, jaundice
Jaundice
Jaundice is a yellowish pigmentation of the skin, the conjunctival membranes over the sclerae , and other mucous membranes caused by hyperbilirubinemia . This hyperbilirubinemia subsequently causes increased levels of bilirubin in the extracellular fluid...
, malnutrition
Malnutrition
Malnutrition is the condition that results from taking an unbalanced diet in which certain nutrients are lacking, in excess , or in the wrong proportions....
, Wernicke's encephalopathy
Wernicke's encephalopathy
Wernicke encephalopathy is a syndrome characterised by ataxia, ophthalmoplegia, confusion, and impairment of short-term memory.It is caused by lesions in the medial thalamic nuclei, mammillary bodies, periaqueductal and periventricular brainstem nuclei, and superior cerebellar vermis, often...
, pneumomediastinum
Pneumomediastinum
Pneumomediastinum is a condition in which air is present in the mediastinum...
, rhabdomyolysis
Rhabdomyolysis
Rhabdomyolysis is a condition in which damaged skeletal muscle tissue breaks down rapidly. Breakdown products of damaged muscle cells are released into the bloodstream; some of these, such as the protein myoglobin, are harmful to the kidneys and may lead to kidney failure...
, deconditioning
Deconditioning
Deconditioning is adaptation of an organism to less demanding environment, or, alternatively, the decrease of physiological adaptation to normal conditions...
, splenic avulsion, and vasospasms of cerebral arteries. Depression
Clinical depression
Major depressive disorder is a mental disorder characterized by an all-encompassing low mood accompanied by low self-esteem, and by loss of interest or pleasure in normally enjoyable activities...
is a common secondary complication of HG.
On rare occasions a woman can die from hyperemesis; Charlotte Bronté
Charlotte Brontë
Charlotte Brontë was an English novelist and poet, the eldest of the three Brontë sisters who survived into adulthood, whose novels are English literature standards...
is a presumed victim of the disease.
For the fetus
Infants of women with severe hyperemesis that gain less than 7 kg (15.4 lb) during pregnancy tend to be of lower birth weightBirth weight
Birth weight is the body weight of a baby at its birth.There have been numerous studies that have attempted, with varying degrees of success, to show links between birth weight and later-life conditions, including diabetes, obesity, tobacco smoking and intelligence.-Determinants:There are...
, small for gestational age
Small for gestational age
Small for gestational age babies are those who are smaller in size than normal for the baby's sex and gestational age, most commonly defined as a weight below the 10th percentile for the gestational age.-Terminology:...
, and born before 37 weeks gestation. In contrast, infants of women with hyperemesis that have a pregnancy weight gain of more than 7 kg appear similar as infants from uncomplicated pregnancies. No long-term follow-up studies have been conducted on children of hyperemetic women.
Update: Studies show that 38% or so of children whose mothers were exposed to HG end up with a higher chance of having anxiety, being bipolar, and acquiring other behavioral as they get older.
Diagnosis
Women experiencing hyperemesis gravidarum often are dehydrated and lose weight despite efforts to eat. The nausea and vomiting begins in the first or second month of pregnancy. It is extreme and is not helped by normal measures.Fever, abdominal pain, or late onset of nausea and vomiting usually indicate another condition, such as appendicitis
Appendicitis
Appendicitis is a condition characterized by inflammation of the appendix. It is classified as a medical emergency and many cases require removal of the inflamed appendix, either by laparotomy or laparoscopy. Untreated, mortality is high, mainly because of the risk of rupture leading to...
, gallbladder disorders
Cholecystitis
-Signs and symptoms:Cholecystitis usually presents as a pain in the right upper quadrant. This is known as biliary colic. This is initially intermittent, but later usually presents as a constant, severe pain. During the initial stages, the pain may be felt in an area totally separate from the site...
, gastritis
Gastritis
Gastritis is an inflammation of the lining of the stomach, and has many possible causes. The main acute causes are excessive alcohol consumption or prolonged use of nonsteroidal anti-inflammatory drugs such as aspirin or ibuprofen. Sometimes gastritis develops after major surgery, traumatic...
, hepatitis
Hepatitis
Hepatitis is a medical condition defined by the inflammation of the liver and characterized by the presence of inflammatory cells in the tissue of the organ. The name is from the Greek hepar , the root being hepat- , meaning liver, and suffix -itis, meaning "inflammation"...
, or infection.
Treatment
Because of the potential for severe dehydration and other complications, HG is in general treated as a medical emergency. Treatment of HG may include antiemeticAntiemetic
An antiemetic is a drug that is effective against vomiting and nausea. Antiemetics are typically used to treat motion sickness and the side effects of opioid analgesics, general anaesthetics, and chemotherapy directed against cancer....
medications and intravenous rehydration. If medication and IV hydration are insufficient, nutritional support may be required.
Management of HG can be complicated because not all women respond to treatment. In some instances, women with HG may be able to avoid hospitalization by eating a special diet of clear liquids and bland food rich in carbohydrates, and eating before rising in the morning; while these may be of some assistance, they are unlikely to resolve the disorder on their own. Hypnosis has relieved symptoms in some cases. Wristbands used for motion sickness and seasickness have been shown by one study to be effective in treating some cases of HG; these are worn around the wrist at a traditional acupuncture point, 3 finger-widths from the joint, and are available at many pharmacies. There is evidence that ginger
Ginger
Ginger is the rhizome of the plant Zingiber officinale, consumed as a delicacy, medicine, or spice. It lends its name to its genus and family . Other notable members of this plant family are turmeric, cardamom, and galangal....
may be effective in treating pregnancy-related nausea; however, in general this is ineffective in cases of HG.
IV hydration
IV hydration often includes supplementation of electrolytes as persistent vomiting frequently leads to a deficiency. Likewise, supplementation for lost thiamineThiamine
Thiamine or thiamin or vitamin B1 , named as the "thio-vitamine" is a water-soluble vitamin of the B complex. First named aneurin for the detrimental neurological effects if not present in the diet, it was eventually assigned the generic descriptor name vitamin B1. Its phosphate derivatives are...
(Vitamin B1) must be considered to reduce the risk of Wernicke's encephalopathy
Wernicke's encephalopathy
Wernicke encephalopathy is a syndrome characterised by ataxia, ophthalmoplegia, confusion, and impairment of short-term memory.It is caused by lesions in the medial thalamic nuclei, mammillary bodies, periaqueductal and periventricular brainstem nuclei, and superior cerebellar vermis, often...
. A and B vitamins are depleted within two weeks, so extended malnutrition indicates a need for evaluation and supplementation. In addition, mineral levels should be monitored and supplemented; of particular concern are sodium
Sodium
Sodium is a chemical element with the symbol Na and atomic number 11. It is a soft, silvery-white, highly reactive metal and is a member of the alkali metals; its only stable isotope is 23Na. It is an abundant element that exists in numerous minerals, most commonly as sodium chloride...
and potassium
Potassium
Potassium is the chemical element with the symbol K and atomic number 19. Elemental potassium is a soft silvery-white alkali metal that oxidizes rapidly in air and is very reactive with water, generating sufficient heat to ignite the hydrogen emitted in the reaction.Potassium and sodium are...
.
After IV rehydration is completed, patients in general progress to frequent small liquid or bland meals. After rehydration, treatment focuses on managing symptoms to allow normal intake of food. However, cycles of hydration and dehydration can occur, making continuing care necessary. Home care is available in the form of a PICC line for hydration and nutrition (called total parenteral nutrition
Total parenteral nutrition
Parenteral nutrition is feeding a person intravenously, bypassing the usual process of eating and digestion. The person receives nutritional formulae that contain nutrients such as glucose, amino acids, lipids and added vitamins and dietary minerals...
). Home treatment is often less expensive than long-term and/or repeated hospital stays.
Medications
While no medication is considered completely risk-free for use during pregnancy, there are several that are commonly used to treat HG and are believed to be safe.The standard treatment in most of the world is Benedictin (also sold under the trademark name Diclectin), a combination of doxylamine
Doxylamine
Doxylamine is one of the many sedating antihistamines used by itself as a short-term sedative, and in combination with other drugs as a night-time cold and allergy relief drug...
succinate and vitamin B6
Vitamin B6
Vitamin B6 is a water-soluble vitamin and is part of the vitamin B complex group. Several forms of the vitamin are known, but pyridoxal phosphate is the active form and is a cofactor in many reactions of amino acid metabolism, including transamination, deamination, and decarboxylation...
. However, due to a series of birth-defect lawsuits in the United States against its maker, Merrill Dow, Benedictin is not currently on the market in the U.S. (None of the lawsuits were successful, and numerous independent studies and the Food and Drug Administration
Food and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
(FDA) have concluded that Benedictin does not cause birth defects.) Its component ingredients are available over-the-counter (doxylamine succinate is the active ingredient in many sleep medications), and some doctors will recommend this treatment to their patients.
Antiemetic
Antiemetic
An antiemetic is a drug that is effective against vomiting and nausea. Antiemetics are typically used to treat motion sickness and the side effects of opioid analgesics, general anaesthetics, and chemotherapy directed against cancer....
drugs, especially ondansetron
Ondansetron
Ondansetron is a serotonin 5-HT3 receptor antagonist used mainly as an antiemetic , often following chemotherapy. Its effects are thought to be on both peripheral and central nerves...
(Zofran), are effective in many women. The major drawback of ondansetron has been its cost. In severe cases of HG, the Zofran pump may be more effective than tablets. Zofran is also available in ODT (oral disintegrating tablet), which can be easier for women who have trouble swallowing due to the nausea. Promethazine (Phenergan) has been shown to be safe, at least in rats and may be used during pregnancy with minimal/no side-effects. Metoclopramide
Metoclopramide
Metoclopramide is an antiemetic and gastroprokinetic agent. It is commonly used to treat nausea and vomiting, to facilitate gastric emptying in people with gastroparesis, and as a treatment for the gastric stasis often associated with migraine headaches.-Medical uses:Metoclopramide is commonly...
is sometimes used in conjunction with antiemetic drugs; however, it has a somewhat higher incidence of side-effects. Other medications less commonly used to treat HG include Marinol, corticosteroids, and antihistamines.
Other medications that are frequently prescribed for HG are Compazine, Tigan, Phenergan, and Reglan. These can be given orally or intraveneously, or administered as a rectal suppository. They are considered safe for use during pregnancy.
Anecdotal evidence suggests that the use of marijuana, or of the pharamaceutical extract Marinol, can relieve the symptoms of HG, in a similar way to treating nausea in people with Cancer and AIDS. However, due to the criminalisation of cannabis, there have been no clinical trials into its effectivess or risks to the fetus.
However, use of marijuana has been shown to increase the risk for central nervous system growth impairment, low birth weight and size of infants, and preterm deliveries, all of which are associated with poor infant outcomes.