Hyperemesis Gravidarum: Practice Essentials, Background, Pathophysiology Hyperemesis Gravidarum Author: Dotun A Ogunyemi, MD; Chief Editor: Christine Isaacs, MD more... Share Overview Practice Essentials Hyperemesis gravidarum is the most severe form of nausea and vomiting in pregnancy, characterized by persistent nausea and vomiting associated with ketosis and weight loss (>5% of prepregnancy weight). This condition may cause volume depletion, electrolytes and acid-base imbalances, nutritional deficiencies, and even death. Severe hyperemesis requiring hospital admission occurs in 0.3-2% of pregnancies. [ 1 ] Signs and symptoms The defining symptoms of hyperemesis gravidarum are gastrointestinal in nature and include nausea and vomiting. Other common symptoms include ptyalism (excessive salivation), fatigue, weakness, and dizziness. Patients may also experience the following: Sleep disturbance See Clinical Presentation for more detail. Diagnosis Physical examination in women with suspected hyperemesis gravidarum is usually unremarkable. Findings may be more helpful if the patient has unusual complaints suggestive of other disorders (eg, bleeding, abdominal pain).

Examination includes the following: Vital signs, including standing and lying blood pressure and pulse Volume status (eg, mucous membrane condition, skin turgor, neck veins, mental status) General appearance (eg, nutrition, weight) Thyroid evaluation Neurologic evaluation Laboratory tests Initial laboratory studies used in the evaluation of women with hyperemesis gravidarum should include the following: Urinalysis for ketones and specific gravity Serum levels of electrolytes and ketones Liver enzymes and bilirubin levels [ 2 ] Amylase/lipase levels Thyroid stimulating hormone, free thyroxine levels [ 3 ] Urine culture The following imaging studies may be used to assess women with hyperemesis gravidarum: Obstetric ultrasonography: Usually warranted to evaluate for multiple gestations or trophoblastic disease Upper abdominal ultrasonography: If clinically indicated, to evaluate the pancreas and/or biliary tree Abdominal computed tomography scanning or magnetic resonance imaging: If appendicitis is suspected as a cause of nausea and vomiting in pregnancy Additional imaging studies may be warranted if the patient’s clinical presentation is atypical (eg, nausea and/or vomiting beginning after 9-10 wk of gestation, nausea and/or vomiting persisting after 

20-22 wk, acute severe exacerbation) or if another disorder is suggested based on the history or physical examination findings.

Procedures In patients with abdominal pain or upper gastrointestinal bleeding, upper gastrointestinal endoscopy appears to be safe in pregnancy, although careful monitoring is suggested. See Workup for more detail. Management Initial management in pregnant women with hyperemesis gravidarum should be conservative and may include reassurance, dietary recommendations, and support. Alternative therapies may include acupressure and hypnosis. [ 4 ] Pharmacotherapy The only FDA-approved drug for treating nausea and vomiting in pregnancy is doxylamine/pyridoxine. However, antihistamines, antiemetics of the phenothiazine class, and promotility agents (eg, metoclopramide) have also been used to manage nausea and vomiting during pregnancy. In cases refractory to standard therapy, ondansetron and steroids may be considered.

The following medications may be used in women with hyperemesis gravidarum: Vitamins (eg, pyridoxine) Antiemetics (eg, doxylamine-pyridoxine, prochlorperazine, promethazine, chlorpromazine, trimethobenzamide, metoclopramide, ondansetron) corticosteroids (eg, methylprednisolone) Antihistamines (eg, meclizine, diphenhydramine) Surgery In some refractory severe cases of hyperemesis gravidarum, if maternal survival is threatened, or if hyperemesis gravidarum is causing severe physical and psychological burden, termination of the pregnancy should be considered. [ 5 ] See Treatment and Medication for more detail. Next: Background Nausea and vomiting in pregnancy is extremely common. Hyperemesis gravidarum (HEG) is the most severe form of nausea and vomiting in pregnancy. A continuous spectrum of the severity of nausea and vomiting ranges from the nausea and vomiting that occurs in most pregnancies to the severe disorder of hyperemesis gravidarum. Studies estimate that nausea and vomiting occurs in 50-90% of pregnancies.

The nausea and vomiting associated with pregnancy usually begins by 9-10 weeks of gestation, peaks at 11-13 weeks, and resolves in most cases by 12-14 weeks. In 1-10% of pregnancies, symptoms may continue beyond 20-22 weeks. [ 6 , 7 ] Normal nausea and vomiting may be an evolutionary protective mechanism—it may protect the pregnant woman and her embryo from harmful substances in food, such as pathogenic microorganisms in meat products and toxins in plants, with the effect being maximal during embryogenesis (the most vulnerable period of pregnancy). This is supported by studies showing that women who had nausea and vomiting were less likely to have miscarriages and stillbirth. [ 8 , 9 ] Hyperemesis gravidarum is characterized by persistent nausea and vomiting associated with ketosis and weight loss (>5% of prepregnancy weight). Hyperemesis gravidarum may cause volume depletion, electrolytes and acid-base imbalances, nutritional deficiencies, and even death. Severe hyperemesis requiring hospital admission occurs in 0.3-2% of pregnancies.

[ 1 ] Previous Next: Pathophysiology The physiologic basis of hyperemesis gravidarum is controversial. Hyperemesis gravidarum appears to occur as a complex interaction of biological, psychological, and sociocultural factors. Several proposed theories are discussed below. Hormonal changes Women with hyperemesis gravidarum often have high hCG levels that cause transient hyperthyroidism. hCG can physiologically stimulate the thyroid gland thyroid-stimulating hormone (TSH) receptor. hCG levels peak in the first trimester. Some women with hyperemesis gravidarum appear to have clinical hyperthyroidism. However, in a larger portion (50-70%), TSH is transiently suppressed and the free thyroxine (T4) index is elevated (40-73%) with no clinical signs of hyperthyroidism, circulating thyroid antibodies, or enlargement of the thyroid. In transient hyperthyroidism of hyperemesis gravidarum, thyroid function normalizes by the middle of the second trimester without antithyroid treatment. Clinically overt hyperthyroidism and thyroid antibodies are usually absent.

[ 1 , 9 , 10 , 11 ] A report on a unique family with recurrent gestational hyperthyroidism associated with hyperemesis gravidarum showed a mutation in the extracellular domain of the TSH receptor that made it responsive to normal levels of hCG. Thus, cases of hyperemesis gravidarum with a normal hCG may be due to varying hCG isotypes. [ 12 , 13 ] A positive correlation between the serum hCG elevation level and free T4 levels has been found, and the severity of nausea appears to be related to the degree of thyroid stimulation. hCG may not be independently involved in the etiology of hyperemesis gravidarum but may be indirectly involved by its ability to stimulate the thyroid. For these patients, hCG levels were linked to increased levels of immunoglobulin M, complement, and lymphocytes. Thus, an immune process may be responsible for increased circulating hCG or isoforms of hCG with a higher activity for the thyroid.

Critics of this theory note that (1) nausea and vomiting are not usual symptoms of hyperthyroidism, (2) signs of biochemical hyperthyroidism are not universal in cases of hyperemesis gravidarum, and (3) some studies have failed to correlate the severity of symptoms with biochemical abnormalities. [ 14 , 15 , 16 ] Some studies link high estradiol levels to the severity of nausea and vomiting in patients who are pregnant, while others find no correlation between estrogen levels and the severity of nausea and vomiting in pregnant women. Previous intolerance to oral contraceptives is associated with nausea and vomiting in pregnancy. Progesterone also peaks in the first trimester and decreases smooth muscle activity; however, studies have failed to show any connection between progesterone levels and symptoms of nausea and vomiting in pregnant women. Lagiou et al studied prospectively 209 women with nausea and vomiting who showed that estradiol levels were positively correlated while prolactin levels were inversely associated with nausea and vomiting in pregnancy and no correlation existed with estriol, progesterone, or sex-hormone binding globulin.

[ 17 ] Gastrointestinal dysfunction The stomach pacemaker causes rhythmic peristaltic contractions of the stomach. Abnormal myoelectric activity may cause a variety of gastric dysrhythmias, including tachygastrias and bradygastrias. Gastric dysrhythmias have been associated with morning sickness. The presence of dysrhythmias was associated with nausea while normal myoelectrical activity was present in the absence of nausea. Mechanisms that cause gastric dysrhythmias include elevated estrogen or progesterone levels, thyroid disorders, abnormalities in vagal and sympathetic tone, and vasopressin secretion in response to intravascular volume perturbation. Many of these factors are present in early pregnancy. These pathophysiologic factors are hypothesized to be more severe or the gastrointestinal tract more sensitive to the neural/humoral changes in those who develop hyperemesis gravidarum. [ 18 ] Levels of the plasma gut satiety hormones peptide YY (PYY) and pancreatic polypeptide (PP) may play a role in hyperemesis gravidarum and pregnancy-related weight changes.

[ 19 ] In a prospective case-control study of 60 women (30 women with hyperemesis gravidarum, 30 control women), Köşüş et al found that affected women had significantly elevated plasma PYY and PP levels relative to the control group, and that PP levels were the the most important diagnostic and prognostic factors of hyperemesis gravidarum. [ 19 ] Hepatic dysfunction Abnormal liver function studies are noted in approximately 3% of pregnancies, and pregnancy-related diseases are the most frequent causes of liver dysfunction during pregnancy. [ 20 ] There appears to be a trimester-specific occurrence of liver disease during pregnancy. [ 20 ] Liver disease, usually consisting of mild serum transaminase elevation, occurs in almost 50% of patients with hyperemesis gravidarum. Impairment of mitochondrial fatty acid oxidation (FAO) has been hypothesized to play a role in the pathogenesis of maternal liver disease associated with hyperemesis gravidarum.

It has been suggested that women heterozygous for FAO defects develop hyperemesis gravidarum associated with liver disease while carrying fetuses with FAO defects due to accumulation of fatty acids in the placenta and subsequent generation of reactive oxygen species. Alternatively, it is possible that starvation leading to peripheral lipolysis and increased load of fatty acids in maternal-fetal circulation, combined with reduced capacity of the mitochondria to oxidize fatty acids in mothers heterozygous for FAO defects, can also cause hyperemesis gravidarum and liver injury while carrying nonaffected fetuses. Metabolic derangement Metabolic disturbance may have a role in the pathogenesis of hyperemesis gravidarum. [ 21 ] Ergin et al noted that affected women had deficiencies in native and total thiol, and this deficiency was correlated with the severity of the disease. They noted that the dynamic serum thiol-disulfide homeostasis balance shifted to the oxidative side. [ 21 ] Lipid alterations Jarnfelt-Samsioe et al found higher levels of triglycerides, total cholesterol, and phospholipids in women with hyperemesis gravidarum compared with matched, nonvomiting, pregnant and nonpregnant controls.

This may be related to the abnormalities in hepatic function in pregnant women. However, Ustun et al found decreased levels of total cholesterol, LDL cholesterol, apoA and apoB in women with hyperemesis gravidarum compared with controls. [ 22 , 23 ] Infection Helicobacter pylori is a bacterium found in the stomach that may aggravate nausea and vomiting in pregnancy. Studies have found conflicting evidence of the role of H pylori in hyperemesis gravidarum. Recent studies in the United States have not shown association with hyperemesis gravidarum. However, persistent nausea and vomiting beyond the second trimester may be due to an active peptic ulcer caused by H pylori infection. [ 24 , 25 ] Vestibular and olfaction Hyperacuity of the olfactory system may be a contributing factor to nausea and vomiting during pregnancy. Many pregnant women report the smell of cooking food, particularly meats, as triggers to nausea. Striking similarities between hyperemesis gravidarum and motion sickness suggest that unmasking of subclinical vestibular disorders may account for some cases of hyperemesis gravidarum.

[ 26 , 27 ] Genetic In studies examining the familial link of hyperemesis gravidarum, research suggests a possible genetic aspect to hyperemesis. A study was performed looking at 544,087 pregnancies from Norway’s mandatory birth registry from 1967-2005. This study demonstrated that daughters born from a pregnancy complicated by hyperemesis had a 3% risk of having hyperemesis in their own pregnancy. Women who were born after an unaffected pregnancy had a risk of 1.1%. [ 28 ] In surveys administered to mothers who had pregnancies complicated by hyperemesis, higher rates of hyperemesis were reported among their relatives. This was particularly so in their sisters. [ 29 ] Overall, the data suggest that a genetic predisposition may play a role in the development of hyperemesis gravidarum. Biochemical research Hyperemesis gravidarum is associated with overactivation of sympathetic nerves and enhanced production of tumor necrosis factor (TNF)-alpha.

[ 30 ] Increased adenosine levels have also been noted; since adenosine is an established suppressor of excessive sympathetic nerves activation and cytokine production, the increase in plasma adenosine in hyperemesis gravidarum may be modulatory. [ 31 ] Trophoblast-derived cytokines have been reported to induce secretion of hCG. Immunoglobulins C3 and C4 and lymphocyte counts are significantly higher in women with hyperemesis gravidarum. T-helper 1/T-helper 2 balance is decreased in women with hyperemesis gravidarum, which results in increased humoral immunity. Increased fetal DNA has been found in the maternal plasma of women with hyperemesis gravidarum, and the increased DNA is speculated to be derived from trophoblasts that have been destroyed by the hyperactive maternal immune system. Thus, hyperemesis gravidarum may be mediated by immunologic aberrations in pregnancy. [ 32 , 33 , 34 , 35 ] In a more recent study, Biberoglu et al suggest that changes in lipid peroxidation and T-cell activation may be a cause of or compensatory reaction to hyperemesis gravidarum.

[ 36 ] The investigations noted significantly elevated levels of serum malondialdehyde (MDA) and glutathione peroxidase (GPx) in 40 pregnant women with hyperemesis gravidarum compared to 40 unaffected, healthy pregnant women. Psychological issues Physiological changes associated with pregnancy interact with each woman's psychologic state and cultural values. Psychologic responses may interact with and exacerbate the physiology of nausea and vomiting during pregnancy. Nonetheless, hyperemesis gravidarum is typically the cause of, as opposed to the result of, psychologic stress. In very unusual instances, cases of hyperemesis gravidarum could represent psychiatric illness, including conversion or somatization disorder or major depression . [ 37 , 38 , 39 , 40 ] Previous Next: Etiology In a review of 1,301 cases of hyperemesis gravidarum from Canada, Fell et al showed that medical complications of hyperthyroid disorders, psychiatric illness, previous molar disease, gastrointestinal disorders, pregestational diabetes, and asthma were significantly independent risk factors for hyperemesis gravidarum, whereas maternal smoking and maternal age older than 30 years decreased the risk.

Pregnancies with female fetuses and multiple fetuses were also at increased risk. [ 41 , 42 ] In some studies, women from low to middle socioeconomic class, women with lower levels of education, women with previous pregnancies with nausea and vomiting, women in their first pregnancy, and women with previous intolerance to oral contraceptives more commonly experience nausea and vomiting during pregnancy. Nausea and vomiting during pregnancy is also more common with multiple-gestation pregnancies. Other factors that have been proposed include ethnicity, occupational status, fetal anomalies, increased body weight, nausea and vomiting in a prior pregnancy, history of infertility, interpregnancy interval, corpus luteum in right ovary, and prior intolerance to oral contraceptives. Risk factors for hyperemesis gravidarum may include the following: Previous pregnancies with hyperemesis gravidarum Greater body weight Next: Prognosis Hyperemesis gravidarum is self-limited and, in most cases, improves by the end of the first trimester. However, symptoms may persist through 20-22 weeks of gestation and, in some cases, until delivery.

Morbidity/mortality Hyperemesis gravidarum was a significant cause of maternal death before 1940. In Great Britain, mortality decreased from 159 deaths per million births from 1931-1940 to 3 deaths per million births from 1951-1960. Charlotte Brontë is thought to have died of hyperemesis gravidarum in 1855. In the United States, 7 deaths from hyperemesis gravidarum were reported in the 1930s. Today, although hyperemesis gravidarum is still associated with significant morbidity, it is still a rare cause of maternal mortality. A large population-based study of 999,161 women with singleton births by Fossum et al found no association between hyperemesis gravidarum and increased risk of long-term mortality. [ 43 ] Note the following: Many hours of productive work are lost because of nausea and vomiting during pregnancy. Nearly 50% of employed women believe that their work is affected, and up to 25% require time off from work.

Hyperemesis gravidarum is a debilitating illness that can cause severe suffering, which profoundly affects both patients and their families. In about half of the women there is an adverse effect on spousal relationships, and 55% have feelings of depression. In one study of 140 women with hyperemesis gravidarum, 27% required multiple hospitalizations. The financial burden of hyperemesis gravidarum on the American health system has been estimated as approximately $130 million dollars per year, excluding physician fees. Women with hyperemesis gravidarum who have a low pregnancy weight gain (< 15.4 lb or 7 kg) have increased risk for delivering neonates of low birth weight, delivering neonates who are small for gestational age, preterm delivery, and a 5-minute Apgar score of less than 7. Complications Alex Fong, MD Staff Physician, Obstetrics and Gynecology Department, Cedars-Sinai Medical Center Alex Fong, MD is a member of the following medical societies: American Medical Association Disclosure: Nothing to disclose.

Tiffany Chen Herrero, MD Resident Physician, Department of Obstetrics and Gynecology, Cedars Sinai Medical Center Disclosure: Nothing to disclose. Specialty Editor Board Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference Disclosure: Received salary from Medscape for employment. for: Medscape.

Richard S Legro, MD Professor, Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology, Pennsylvania State University College of Medicine; Consulting Staff, Milton S Hershey Medical Center Richard S Legro, MD is a member of the following medical societies: American College of Obstetricians and Gynecologists , Society of Reproductive Surgeons , American Society for Reproductive Medicine , Endocrine Society , Phi Beta Kappa Disclosure: Received honoraria from Korea National Institute of Health and National Institute of Health (Bethesda, MD) for speaking and teaching; Received honoraria from Greater Toronto Area Reproductive Medicine Society (Toronto, ON, CA) for speaking and teaching; Received honoraria from American College of Obstetrics and Gynecologists (Washington, DC) for speaking and teaching; Received honoraria from National Institute of Child Health and Human Development Pediatric and Adolescent Gynecology Research Thi.

Chief Editor Christine Isaacs, MD Associate Professor, Department of Obstetrics and Gynecology, Division Head, General Obstetrics and Gynecology, Medical Director of Midwifery Services, Virginia Commonwealth University School of Medicine Christine Isaacs, MD is a member of the following medical societies: American College of Obstetricians and Gynecologists Disclosure: Nothing to disclose. Additional Contributors Suzanne R Trupin, MD, FACOG Clinical Professor, Department of Obstetrics and Gynecology, University of Illinois College of Medicine at Urbana-Champaign; CEO and Owner, Women's Health Practice; CEO and Owner, Hada Cosmetic Medicine and Midwest Surgical Center Disclosure: Nothing to disclose. Acknowledgements The authors and editors of Medscape Drugs & Diseases gratefully acknowledge the contributions of previous author Giulia A Michelini, MD, to the development and writing of this article. Hyperemesis Gravidarum: Nausea During Pregnancy | Cleveland Clinic Share Facebook Twitter Linkedin Email Print Health & Wellness Programs Did you know Cleveland Clinic offers wellness and educational programs that can help you have a healthy pregnancy? Learn more What is hyperemesis gravidarum? Hyperemesis gravidarum is an uncommon disorder in which extreme, persistent nausea and vomiting occur during pregnancy.

This condition might lead to dehydration. What causes hyperemesis gravidarum? The condition might be caused by rapidly rising serum levels of hormones such as HCG (human chorionic gonadotropin) and estrogen. Extreme nausea and vomiting during pregnancy might indicate a multiple pregnancy(the woman is carrying more than one baby) or hydatidiform mole (abnormal tissue growth that is not a true pregnancy). What are the risk factors for hyperemesis gravidarum? A risk factor is something that increases a person’s chance of getting a disease or condition. Risk factors do not necessarily mean that a person will develop a condition. In the case of hyperemesis gravidarum, the following are risk factors: Hyperemesis gravidarum during an earlier pregnancy Being overweight The presence of trophoblastic disease, which involves the abnormal growth of cells inside the uterus What are the symptoms of hyperemesis gravidarum? Hyperemesis gravidarum usually occurs during the first trimester of pregnancy.

A woman might have hyperemesis gravidarum if she is pregnant and she vomits: More than three to four times per day So much that she loses more than 10 pounds So much that she feels dizzy and lightheaded So much that she is becoming dehydrated How is hyperemesis gravidarum diagnosed? A doctor will ask about symptoms, take a medical history, and perform a physical exam. In addition, the doctor might order certain lab tests to help in making a diagnosis. How is hyperemesis gravidarum treated? The type of treatment that is required depends on how ill a woman becomes. Possible treatments might include: Preventive measures: These might include a pressure-point wristband — similar to those used for motion sickness — vitamin B6, and/or ginger. Small frequent meals: Nausea and vomiting might be treated with dry foods (such as crackers), small frequent meals, and emotional support. Intravenous fluids: It is important for a pregnant woman to maintain her fluid intake. Intravenous(IV) fluids might be needed if a woman continues to vomit throughout pregnancy. In severe cases, the woman might require hospitalization and given IV fluids.

IV fluids might be discontinued when a woman is able to take in fluids by mouth. Total parenteral nutrition: The most severe cases of hyperemesis gravidarum might require that complex, balanced solutions of nutrients be given through an IV throughout pregnancy. This is called total parenteral nutrition (TPN). Medicines: Medicine to prevent nausea is used when vomiting is persistent and poses possible risks to the mother or baby. If a woman cannot take medicines by mouth, the drugs might be administered through an IV or a suppository. Medicines used to prevent nausea include Promethazine, Meclizine, and Droperidol. Can hyperemesis gravidarum be prevented? Although there are no known ways to completely prevent hyperemesis gravidarum, the following measures might help keep morning sickness from becoming severe: Eating small, frequent meals Waiting until nausea has improved before taking iron supplements Using a pressure-point wrist band, vitamin B6, and/or ginger, as recommended by a doctor References: The HER Foundation. About Hyperemesis Gravidarum Accessed 11/4/2016. © Copyright 1995-2016 The Cleveland Clinic Foundation. All rights reserved.

This information is provided by the Cleveland Clinic and is not intended to replace the medical advice of your doctor or health care provider. Please consult your health care provider for advice about a specific medical condition.This document was last reviewed on: 11/4/2016...#12232 index#12232 Hyperemesis Gravidarum: Causes, Symptoms & Diagnosis Read This Next What Is Hyperemesis Gravidarum? Many women experience morning sickness, or nausea, during pregnancy. This condition is generally harmless. While morning sickness can be quite uncomfortable, it typically goes away within 12 weeks. Hyperemesis gravidarum (HG) is an extreme form of morning sickness that causes severe nausea and vomiting during pregnancy. Morning sickness and HG are very different conditions. They have different complications and side effects for pregnant women. It’s important to distinguish between these two conditions to properly treat symptoms. Morning sickness typically includes nausea that’s sometimes accompanied by vomiting. These two symptoms typically disappear after 12 to 14 weeks, and the vomiting doesn’t cause severe hydration. HG typically includes nausea that doesn’t go away and severe vomiting that causes severe hydration and doesn’t allow you to keep any food or fluids down.

Morning sickness typically begins in the first month of pregnancy. It usually goes away by the third or fourth month. Pregnant women with morning sickness can get fatigue and a slight loss of appetite. They may have difficulty performing daily activities The symptoms of HG begin within the first six weeks of pregnancy, and nausea often doesn’t go away. HG can be extremely debilitating and cause fatigue that lasts for weeks or months. According to the HER Foundation , women with HG may experience a complete loss of appetite and may not be able to work or perform daily activities. HG can lead to dehydration and poor weight gain during pregnancy. There’s no known way to prevent morning sickness or HG, but there are ways to manage the symptoms. What Are the Symptoms of Hyperemesis Gravidarum? HG usually starts during the first trimester of your pregnancy. Less than half of women with HG experience symptoms their entire pregnancy. Some of the most common symptoms of HG are: vomiting more than three or four times per day becoming dehydrated losing more than 10 pounds or 5 percent of your body weight due to vomiting feeling nearly constant nausea What Causes Hyperemesis Gravidarum? Almost all women experience some degree of morning sickness during their pregnancy.

Morning sickness is nausea and vomiting during pregnancy. Despite the name, morning sickness isn’t confined to the morning and can occur at any time. Morning sickness and HG seem to have a connection to human chorionic gonadotropin (hCG). This is a hormone created during pregnancy by the placenta. Your body produces a large amount of this hormone at a rapid rate early in pregnancy. The American Pregnancy Association states that hCG levels typically double every 48 to 72 hours. These levels can continue to rise throughout your pregnancy. Who Is at Risk for Hyperemesis Gravidarum? Some factors that could increase your risk of getting HG are: having a history of HG being pregnant with more than one baby being overweight being a first-time mother Trophoblastic disease can also cause HG. Trophoblastic disease occurs when there’s an abnormal growth of cells inside the uterus. How Is Hyperemesis Gravidarum Diagnosed? Your doctor will ask you about your medical history and your symptoms. A standard physical exam is enough to diagnose most cases. Your doctor will look for common signs of HG, such as abnormally low blood pressure or a fast pulse. Blood and urine samples may also be necessary to check for signs of dehydration.

Your doctor might also order additional tests to rule out gastrointestinal problems as a cause of your vomiting. An ultrasound, which uses sound waves to create an image of the inside of your body, might be necessary to find out if you’re pregnant with twins or if there’s a mass in your uterus from trophoblastic disease. How Is Hyperemesis Gravidarum Treated? Treatment for HG depends on the severity of your symptoms. Your doctor may recommend natural nausea prevention methods such as vitamin B-6 or ginger. Try eating smaller, more frequent meals and dry foods such as crackers. You should drink plenty of fluids to stay hydrated. Severe cases may require hospitalization. Pregnant women who are unable to keep fluids or food down due to constant vomiting will need to get them intravenously, or through an IV. Medication is necessary when vomiting is a threat to the mother or child. The most commonly used anti-nausea drugs are promethazine and meclizine. You can’t take medication orally. You can receive it through an IV or as a suppository. Taking medication while pregnant can cause potential health problems for your baby, but in severe cases of HG, maternal dehydration is a more concerning problem.

Talk to your doctor about the risks associated with any method of treatment. What Is the Long-Term Outlook? The good news is that symptoms of HG will disappear after giving birth. However, the HER Foundation finds that postpartum recovery is often longer for women with HG. Talking with your doctor and pursuing education and support groups can help you and your family deal with the repercussions of HG. The psychological and emotional stress of HG can impact your quality of life, so be sure to communicate your feelings to your doctor and personal support system. Hyperemesis gravidarum - the extreme form of morning sickness in pregnancy Hyperemesis gravidarum Medically Reviewed by Dr Rob Hicks What is hyperemesis gravidarum? Hyperemesis gravidarum, or HG, is an uncommon condition that is much more severe than normal pregnancy sickness. It is a severe form of nausea and vomiting in pregnancy (NVP). It can be so severe that a woman becomes dehydrated , loses weight and may have to be admitted to hospital and treated with intravenous fluids under specialist care. Hyperemesis gravidarum affects around 1 to 3 in every 100 pregnant women. What are the symptoms of hyperemesis gravidarum?

The symptoms of hyperemesis gravidarum go far beyond the discomfort of morning sickness and require urgent medical attention. They include: Prolonged and severe nausea and vomiting Dehydration caused by the vomiting Ketosis - raised levels of toxic acidic chemicals in the blood called ketones Losing weight due to inability to keep food down Low blood pressure , known as hypotension, especially on standing up Risk of DVT - deep vein thrombosis (blood clots in a vein) - due to dehydration. In terms of the quality of life, HG can affect a woman’s work, home life and her ability to care for her family due to frequent vomiting - or trying to vomit because there’s nothing in the stomach so she can’t vomit, and retches instead. It’s been described by some women as like having your stomach turned inside out, it’s so severe. It can last for many weeks, sometimes throughout pregnancy. Although support from family and friends can help, the Royal College of Obstetricians and Gynaecologists (RCOG) recognises that symptoms can sometimes be so severe that women may become depressed and need extra support, such as counselling.

It recommends that a pregnant woman who persistently 'feels down' should speak to their healthcare professional. Is there any risk that hyperemesis gravidarum can cause a woman to lose her baby? Experts at the RCOG say hyperemesis gravidarum is unlikely to cause harm to an unborn baby. In fact, you may have a slightly lower risk of miscarriage than women who do not have the condition. However, left untreated, weight loss during pregnancy may lead to a baby having a low birth weight and you may be offered extra scans to monitor the growth of your baby. Is there anything that pregnant women can do themselves to lessen the symptoms? Experts suggest trying to move less, avoiding tasks such as cleaning the house may help, as any movement may make the feeling of nausea worse. Rest and relaxation may be recommended as well as avoiding some smells, including food or cooking odours. Further advice is to eat small amounts often. Meals that are high in carbohydrate and low in fat, such as potato, rice and pasta, are easier to tolerate. Biscuits or crackers may also be easier to digest. Some women find that eating or drinking ginger products helps. However, be aware that these may sometimes irritate your stomach.

Complementary therapies such as acupressure or acupuncture may also be helpful. What if my symptoms don't resolve themselves? If your symptoms do not settle or if they prevent you doing your day-to-day activities, you should make an appointment to see your GP . He or she may prescribe anti-sickness medication which is safe to take in pregnancy. Your GP or midwife may arrange for you to be seen in the assessment unit at your hospital. Next Article: Morning sickness: MedlinePlus Medical Encyclopedia URL of this page: //medlineplus.gov/ency/patientinstructions/000604.htm Morning sickness The term "morning sickness" is used to describe nausea and vomiting during pregnancy. Some women also have the symptoms of dizziness and headaches. More About Morning Sickness Morning sickness often begins 4 to 6 weeks after conception and may continue until the 4th month of pregnancy. Some women have morning sickness during their entire pregnancy. This happens most often for women who are carrying more than 1 baby. It is called morning sickness because the symptoms are more likely to occur early in the day, but they can occur at any time. For some women, morning sickness lasts all day. The exact cause of morning sickness is not known.

Most experts think changes in the woman's hormone levels during pregnancy cause it. Other factors that can make the nausea worse include a pregnant woman's enhanced sense of smell and gastric reflux . Morning sickness that is not severe does not hurt your baby in any way. In fact: It may even be a sign that all is well with you and your baby. Morning sickness may be associated with a lower risk of miscarriage. Your symptoms probably show that the placenta is making all the right hormones for your growing baby. When nausea and vomiting are severe, a condition known as hyperemesis gravidarum may be diagnosed. Eating and Drinking Changing what you eat may help. Try these tips: Eat a lot of protein and carbohydrates. Try peanut butter on apple slices or celery; nuts; cheese and crackers; and low-fat dairy products like milk, cottage cheese, and yogurt. Bland foods, such as gelatin, frozen desserts, broth, ginger ale, and saltine crackers, also soothe the stomach. Avoid eating foods that are high in fat and salt. Try to eat before you get hungry and before nausea occurs. Eat a few soda crackers or dry toast when you get up at night to go to the bathroom or before you get out of bed in the morning.

Avoid large meals. Instead, have a snack as often as every 1 to 2 hours during the day. DO NOT let yourself get too hungry or too full. Drink plenty of liquids. Try to drink between meals rather than with meals so that your stomach does not get too full. Seltzer, ginger ale, or other sparkling waters may help control symptoms. Foods that contain ginger may also help. Some of these are ginger tea and ginger candy, along with ginger ale. Check to see that they have ginger in them rather than just ginger flavoring. What Else Can I Try? Try changing how you take your prenatal vitamins. Take them at night, since the iron they contain may irritate your stomach. At night, you might be able to sleep through this. Also take them with a little food, not on an empty stomach. You may have to try several different brands of prenatal vitamins before finding one you can tolerate. You can also try cutting your prenatal vitamins in half. Take half in the morning and the other half at night.

Some other tips are: Hyperemesis Gravidarum Hyperemesis Gravidarum Author: Dotun A Ogunyemi, MD Chief Editor: Christine Isaacs, MD Prognosis Practice Essentials Hyperemesis gravidarum is the most severe form of nausea and vomiting in pregnancy, characterized by persistent nausea and vomiting associated with ketosis and weight loss (>5% of prepregnancy weight). This condition may cause volume depletion, electrolytes and acid-base imbalances, nutritional deficiencies, and even death. Severe hyperemesis requiring hospital admission occurs in 0.3-2% of pregnancies.[1] Signs and symptoms The defining symptoms of hyperemesis gravidarum are gastrointestinal in nature and include nausea and vomiting. Other common symptoms include ptyalism (excessive salivation), fatigue, weakness, and dizziness. Patients may also experience the following: Sleep disturbance See Clinical Presentation for more detail. Diagnosis Physical examination in women with suspected hyperemesis gravidarum is usually unremarkable. Findings may be more helpful if the patient has unusual complaints suggestive of other disorders (eg, bleeding, abdominal pain).

Examination includes the following: Vital signs, including standing and lying blood pressure and pulse Volume status (eg, mucous membrane condition, skin turgor, neck veins, mental status) General appearance (eg, nutrition, weight) Thyroid evaluation Neurologic evaluation Laboratory tests Initial laboratory studies used in the evaluation of women with hyperemesis gravidarum should include the following: Urinalysis for ketones and specific gravity Serum levels of electrolytes and ketones Liver enzymes and bilirubin levels[2] Amylase/lipase levels Thyroid stimulating hormone, free thyroxine levels[3] Urine culture The following imaging studies may be used to assess women with hyperemesis gravidarum: Obstetric ultrasonography: Usually warranted to evaluate for multiple gestations or trophoblastic disease Upper abdominal ultrasonography: If clinically indicated, to evaluate the pancreas and/or biliary tree Abdominal computed tomography scanning or magnetic resonance imaging: If appendicitis is suspected as a cause of nausea and vomiting in pregnancy Additional imaging studies may be warranted if the patient’s clinical presentation is atypical (eg, nausea and/or vomiting beginning after 9-10 wk of gestation, nausea and/or vomiting persisting after 20

-22 wk, acute severe exacerbation) or if another disorder is suggested based on the history or physical examination findings.

Procedures In patients with abdominal pain or upper gastrointestinal bleeding, upper gastrointestinal endoscopy appears to be safe in pregnancy, although careful monitoring is suggested. See Workup for more detail. Management Initial management in pregnant women with hyperemesis gravidarum should be conservative and may include reassurance, dietary recommendations, and support. Alternative therapies may include acupressure and hypnosis.[4] Pharmacotherapy The only FDA-approved drug for treating nausea and vomiting in pregnancy is doxylamine/pyridoxine. However, antihistamines, antiemetics of the phenothiazine class, and promotility agents (eg, metoclopramide) have also been used to manage nausea and vomiting during pregnancy. In cases refractory to standard therapy, ondansetron and steroids may be considered.

The following medications may be used in women with hyperemesis gravidarum: Vitamins (eg, pyridoxine) Antihistamines (eg, meclizine, diphenhydramine) Surgery In some refractory severe cases of hyperemesis gravidarum, if maternal survival is threatened, or if hyperemesis gravidarum is causing severe physical and psychological burden, termination of the pregnancy should be considered.[5] See Treatment and Medication for more detail. References Background Nausea and vomiting in pregnancy is extremely common. Hyperemesis gravidarum (HEG) is the most severe form of nausea and vomiting in pregnancy. A continuous spectrum of the severity of nausea and vomiting ranges from the nausea and vomiting that occurs in most pregnancies to the severe disorder of hyperemesis gravidarum. Studies estimate that nausea and vomiting occurs in 50-90% of pregnancies. The nausea and vomiting associated with pregnancy usually begins by 9-10 weeks of gestation, peaks at 11-13 weeks, and resolves in most cases by 12-14 weeks.

In 1-10% of pregnancies, symptoms may continue beyond 20-22 weeks.[6, 7] Normal nausea and vomiting may be an evolutionary protective mechanism—it may protect the pregnant woman and her embryo from harmful substances in food, such as pathogenic microorganisms in meat products and toxins in plants, with the effect being maximal during embryogenesis (the most vulnerable period of pregnancy). This is supported by studies showing that women who had nausea and vomiting were less likely to have miscarriages and stillbirth.[8, 9] Hyperemesis gravidarum is characterized by persistent nausea and vomiting associated with ketosis and weight loss (>5% of prepregnancy weight). Hyperemesis gravidarum may cause volume depletion, electrolytes and acid-base imbalances, nutritional deficiencies, and even death. Severe hyperemesis requiring hospital admission occurs in 0.3-2% of pregnancies.[1] References Pathophysiology The physiologic basis of hyperemesis gravidarum is controversial. Hyperemesis gravidarum appears to occur as a complex interaction of biological, psychological, and sociocultural factors.

The following theories have been proposed: Hormonal changes Women with hyperemesis gravidarum often have high hCG levels that cause transient hyperthyroidism. hCG can physiologically stimulate the thyroid gland thyroid-stimulating hormone (TSH) receptor. hCG levels peak in the first trimester. Some women with hyperemesis gravidarum appear to have clinical hyperthyroidism. However, in a larger portion (50-70%), TSH is transiently suppressed and the free thyroxine (T4) index is elevated (40-73%) with no clinical signs of hyperthyroidism, circulating thyroid antibodies, or enlargement of the thyroid. In transient hyperthyroidism of hyperemesis gravidarum, thyroid function normalizes by the middle of the second trimester without antithyroid treatment. Clinically overt hyperthyroidism and thyroid antibodies are usually absent.[9, 10, 11, 1] A report on a unique family with recurrent gestational hyperthyroidism associated with hyperemesis gravidarum showed a mutation in the extracellular domain of the TSH receptor that made it responsive to normal levels of hCG.

Thus, cases of hyperemesis gravidarum with a normal hCG may be due to varying hCG isotypes.[12, 13] A positive correlation between the serum hCG elevation level and free T4 levels has been found, and the severity of nausea appears to be related to the degree of thyroid stimulation. hCG may not be independently involved in the etiology of hyperemesis gravidarum but may be indirectly involved by its ability to stimulate the thyroid. For these patients, hCG levels were linked to increased levels of immunoglobulin M, complement, and lymphocytes. Thus, an immune process may be responsible for increased circulating hCG or isoforms of hCG with a higher activity for the thyroid.

Critics of this theory note that (1) nausea and vomiting are not usual symptoms of hyperthyroidism, (2) signs of biochemical hyperthyroidism are not universal in cases of hyperemesis gravidarum, and (3) some studies have failed to correlate the severity of symptoms with biochemical abnormalities.[14, 15, 16] Some studies link high estradiol levels to the severity of nausea and vomiting in patients who are pregnant, while others find no correlation between estrogen levels and the severity of nausea and vomiting in pregnant women. Previous intolerance to oral contraceptives is associated with nausea and vomiting in pregnancy. Progesterone also peaks in the first trimester and decreases smooth muscle activity; however, studies have failed to show any connection between progesterone levels and symptoms of nausea and vomiting in pregnant women.

Lagiou et al studied prospectively 209 women with nausea and vomiting who showed that estradiol levels were positively correlated while prolactin levels were inversely associated with nausea and vomiting in pregnancy and no correlation existed with estriol, progesterone, or sex-hormone binding globulin.[17] Gastrointestinal dysfunction The stomach pacemaker causes rhythmic peristaltic contractions of the stomach. Abnormal myoelectric activity may cause a variety of gastric dysrhythmias, including tachygastrias and bradygastrias. Gastric dysrhythmias have been associated with morning sickness. The presence of dysrhythmias was associated with nausea while normal myoelectrical activity was present in the absence of nausea. Mechanisms that cause gastric dysrhythmias include elevated estrogen or progesterone levels, thyroid disorders, abnormalities in vagal and sympathetic tone, and vasopressin secretion in response to intravascular volume perturbation. Many of these factors are present in early pregnancy.

These pathophysiologic factors are hypothesized to be more severe or the gastrointestinal tract more sensitive to the neural/humoral changes in those who develop hyperemesis gravidarum.[18] Hepatic dysfunction Liver disease, usually consisting of mild serum transaminase elevation, occurs in almost 50% of patients with hyperemesis gravidarum. Impairment of mitochondrial fatty acid oxidation (FAO) has been hypothesized to play a role in the pathogenesis of maternal liver disease associated with hyperemesis gravidarum. It has been suggested that women heterozygous for FAO defects develop hyperemesis gravidarum associated with liver disease while carrying fetuses with FAO defects due to accumulation of fatty acids in the placenta and subsequent generation of reactive oxygen species. Alternatively, it is possible that starvation leading to peripheral lipolysis and increased load of fatty acids in maternal-fetal circulation, combined with reduced capacity of the mitochondria to oxidize fatty acids in mothers heterozygous for FAO defects, can also cause hyperemesis gravidarum and liver injury while carrying nonaffected fetuses.

Lipid alterations Jarnfelt-Samsioe et al found higher levels of triglycerides, total cholesterol, and phospholipids in women with hyperemesis gravidarum compared with matched, nonvomiting, pregnant and nonpregnant controls. This may be related to the abnormalities in hepatic function in pregnant women. However, Ustun et al found decreased levels of total cholesterol, LDL cholesterol, apoA and apoB in women with hyperemesis gravidarum compared with controls.[19, 20] Infection Helicobacter pylori is a bacterium found in the stomach that may aggravate nausea and vomiting in pregnancy. Studies have found conflicting evidence of the role of H pylori in hyperemesis gravidarum. Recent studies in the United States have not shown association with hyperemesis gravidarum. However, persistent nausea and vomiting beyond the second trimester may be due to an active peptic ulcer caused by H pylori infection.[21, 22] Vestibular and olfaction Hyperacuity of the olfactory system may be a contributing factor to nausea and vomiting during pregnancy. Many pregnant women report the smell of cooking food, particularly meats, as triggers to nausea.

Striking similarities between hyperemesis gravidarum and motion sickness suggest that unmasking of subclinical vestibular disorders may account for some cases of hyperemesis gravidarum.[23, 24] Genetic In studies examining the familial link of hyperemesis gravidarum, research suggests a possible genetic aspect to hyperemesis. A study was performed looking at 544,087 pregnancies from Norway’s mandatory birth registry from 1967-2005. This study demonstrated that daughters born from a pregnancy complicated by hyperemesis had a 3% risk of having hyperemesis in their own pregnancy. Women who were born after an unaffected pregnancy had a risk of 1.1%.[25] In surveys administered to mothers who had pregnancies complicated by hyperemesis, higher rates of hyperemesis were reported among their relatives. This was particularly so in their sisters.[26] Overall, the data suggest that a genetic predisposition may play a role in the development of hyperemesis gravidarium.

Biochemical research Hyperemesis gravidarum is associated with overactivation of sympathetic nerves and enhanced production of tumor necrosis factor (TNF)-alpha.[27] Increased adenosine levels have also been noted; since adenosine is an established suppressor of excessive sympathetic nerves activation and cytokine production, the increase in plasma adenosine in hyperemesis gravidarum may be modulatory.[28] Trophoblast-derived cytokines have been reported to induce secretion of hCG. Immunoglobulins C3 and C4 and lymphocyte counts are significantly higher in women with hyperemesis gravidarum. T-helper 1/T-helper 2 balance is decreased in women with hyperemesis gravidarum, which results in increased humoral immunity. Increased fetal DNA has been found in the maternal plasma of women with hyperemesis gravidarum, and the increased DNA is speculated to be derived from trophoblasts that have been destroyed by the hyperactive maternal immune system.

Thus, hyperemesis gravidarum may be mediated by immunologic aberrations in pregnancy.[29, 30, 31, 32] Psychological issues Physiological changes associated with pregnancy interact with each woman's psychologic state and cultural values. Psychologic responses may interact with and exacerbate the physiology of nausea and vomiting during pregnancy. Nonetheless, hyperemesis gravidarum is typically the cause of, as opposed to the result of, psychologic stress. In very unusual instances, cases of hyperemesis gravidarum could represent psychiatric illness, including conversion or somatization disorder or major depression.[33, 34, 35] Of all pregnancies, 0.3-2% are affected by hyperemesis gravidarum (approximately 5 per 1000 pregnancies). International Hyperemesis gravidarum appears to be more common in westernized industrialized societies and urban areas than rural areas. References Mortality/Morbidity Hyperemesis gravidarum was a significant cause of maternal death before 1940.

In Great Britain, mortality decreased from 159 deaths per million births from 1931-1940 to 3 deaths per million births from 1951-1960. Charlotte Brontë is thought to have died of hyperemesis gravidarum in 1855. In the United States, 7 deaths from hyperemesis gravidarum were reported in the 1930s. Today, although hyperemesis gravidarum is still associated with significant morbidity, it is still a rare cause of maternal mortality. Many hours of productive work are lost because of nausea and vomiting during pregnancy. Nearly 50% of employed women believe that their work is affected, and up to 25% require time off from work. Hyperemesis gravidarum is a debilitating illness that can cause severe suffering, which profoundly affects both patients and their families. In about half of the women there is an adverse effect on spousal relationships, and 55% have feelings of depression. In one study of 140 women with hyperemesis gravidarum, 27% required multiple hospitalizations.

The financial burden of hyperemesis gravidarum on the American health system has been estimated as approximately $130 million dollars per year, excluding physician fees. Women with hyperemesis gravidarum who have a low pregnancy weight gain (< 15.4 lb or 7 kg) have increased risk for delivering neonates of low birth weight, delivering neonates who are small for gestational age, preterm delivery, and a 5-minute Apgar score of less than 7. Race No clear racial predominance is noted for hyperemesis gravidarum. Hyperemesis gravidarum is less common in American Indian and Eskimo populations. Hyperemesis gravidarum is less common in African and some Asian populations (but not industrialized Japan). Sex Physical The physical examination is usually unremarkable in patients with hyperemesis gravidarum. The physical examination findings may be more helpful if the patient has unusual complaints suggestive of other disorders (eg, bleeding, abdominal pain).

Pay attention to the vital signs, including standing and lying blood pressure and pulse, volume status (eg, mucous membrane condition, skin turgor, neck veins, mental status), general appearance (eg, nutrition, weight), thyroid examination findings, abdominal examination findings, cardiac examination findings, and neurologic examination findings. References Causes In a review of 1,301 cases of hyperemesis gravidarum from Canada, Fell et al showed that medical complications of hyperthyroid disorders, psychiatric illness, previous molar disease, gastrointestinal disorders, pregestational diabetes, and asthma were significantly independent risk factors for hyperemesis gravidarum, whereas maternal smoking and maternal age older than 30 years decreased the risk. Pregnancies with female fetuses and multiple fetuses were also at increased risk.[36, 37] In some studies, women from low to middle socioeconomic class, women with lower levels of education, women with previous pregnancies with nausea and vomiting, women in their first pregnancy, and women with previous intolerance to oral contraceptives more commonly experience nausea and vomiting during pregnancy. Nausea and vomiting during pregnancy is also more common with multiple-gestation pregnancies.

Other factors that have been proposed include ethnicity, occupational status, fetal anomalies, increased body weight, nausea and vomiting in a prior pregnancy, history of infertility, interpregnancy interval, corpus luteum in right ovary, and prior intolerance to oral contraceptives. Risk factors for hyperemesis gravidarum may include the following: Previous pregnancies with hyperemesis gravidarum Greater body weight Laboratory Studies Initial lab studies for hyperemesis gravidarum should include the following: Urinalysis for ketones and specific gravity: A sign of starvation, ketones may be harmful to fetal development. High specific gravity occurs with volume depletion. Serum electrolytes and ketones: Assess electrolyte status to evaluate for low potassium or sodium, identify hyperchloremic metabolic alkalosis or acidosis, and evaluate renal function and volume status. Liver enzymes and bilirubin: Elevated transaminase levels may occur in as many as 50% of patients with hyperemesis gravidarum. Mild transaminitis often resolves once the nausea has resolved.

Significantly elevated liver enzymes, however, may be a sign of another underlying liver condition, such as hepatitis (viral, ischemic, autoimmune), or some other etiology of liver injury.[2] Amylase/lipase: Amylase level is elevated in approximately 10% of patients with hyperemesis gravidarum. Lipase, when combined with amylase, can increase the specificity in diagnosing pancreatitis as an etiology. TSH, free thyroxine: Hyperemesis gravidarum is often associated with a transient hyperthyroidism and suppressed TSH levels in 50-60% of cases. However, an elevated free thyroxine may suggest that overt hyperthyroidism is present, thus necessitating further workup and treatment.[3] Urine culture: This may be indicated because urinary tract infection is common in pregnancy and can be associated with nausea and vomiting. Calcium level: Consider measuring Ca++ levels. Some rare cases have been reported of hypercalcemia being associated with hyperemesis gravidarum, resulting from hyperparathyroidism. Hematocrit: This may be elevated because of volume contraction.

Hepatitis panel: If clinically indicated, hepatitis A, B, or C may be confused with hyperemesis gravidarum.[1] Imaging Studies Obstetric ultrasonography is usually warranted in patients with HEG to evaluate for multiple gestations or trophoblastic disease. Additional imaging studies generally are not needed unless the clinical presentation is atypical (eg, nausea and/or vomiting beginning after 9-10 wk of gestation, nausea and/or vomiting persisting after 20-22 wk, acute severe exacerbation) or another disorder is suggested based on history or physical examination findings. If indicated clinically, performing upper abdominal ultrasonography to evaluate the pancreas and/or biliary tree appears to be a low-risk study. In rare cases, abdominal CT scan or even MRI may be indicated if appendicitis is under consideration as a cause of nausea and vomiting in pregnancy. References Procedures In patients with abdominal pain or upper gastrointestinal bleeding, upper gastrointestinal endoscopy appears to be safe in pregnancy, although careful monitoring is suggested. References Medical Care Initial management should be conservative and may include reassurance, dietary recommendations, and support.

Alternative therapies may include acupressure and hypnosis.[4] Studies have not shown a clear benefit of acupressure in patients with hyperemesis gravidarum. However, a randomized study by Rosen et al using pressure or electrical stimulation at the P6 (or Neguian) point on the inside of the wrist showed some efficacy in reducing nausea and vomiting and promoting weight gain in women with hyperemesis gravidarum.[38] More controversy surrounds the benefit of hypnosis, but it has been studied in some cases of hyperemesis gravidarum and has been shown to be beneficial. Psychological counseling may be considered.[4] Outpatient or home intravenous (IV) hydration should be considered. If medications and outpatient hydration fail or if severe electrolyte disturbances persist, inpatient admission for IV hydration may be necessary. Pharmacologic therapy If pharmacologic therapy is necessary, treatment may be initiated by giving vitamin B-6 10-25 mg 3-4 times daily; doxylamine 12.5 mg 3-4 times daily can be used in addition.

Ginger capsules 250 mg 4 times daily can be added at this point if the patient is still vomiting; this has been shown to be effective in randomized trials.[39] Metoclopramide 5-10 mg orally every 8 hours may be used next. Promethazine 12.5 mg orally or rectally q4h or dimenhydrinate 50-100 mg orally q4-6h may be added as well. Ondansetron 4-8 mg orally or IV q8h can be used for further refractory cases. Methylprednisolone 16 mg orally or IV q8h for 3 days, tapered to the lowest effective dose, can be used if persistent vomiting occurs despite the above therapy.

Steroids seem to increase risk for oral clefts in first 10 weeks of gestation.[40, 1] The only FDA-approved drug for treating nausea and vomiting in pregnancy is doxylamine-pyridoxine (Diclegis).[41, 42] Originally sold between 1956 and 1983 under a different brand name, it was pulled from the market because of safety concerns, which have since been disproved. The new dosage form approved in April 2013 is a delayed-release tablet that, when taken at bedtime, is at its peak serum concentrations in the morning, when nausea and vomiting may be worse. Approval of the new formulation of doxylamine-pyridoxine was based on a study of pregnant women between 7 and 14 weeks' gestation who were suffering from nausea and vomiting.

Compared with placebo, doxylamine-pyridoxine significantly improved both the Pregnancy-Unique Quantiﬁcation of Emesis and Nausea (PUQE) scores and quality of life of the trial participants.[43] Doxylamine-pyridoxine’s approval did not include hyperemesis gravidarum, but a study by Koren and Maltepe showed that the drug may work best when administered before the onset of symptoms. A greater reduction in the recurrence of hyperemesis gravidarum was observed in those who used the doxylamine-pyridoxine combination preemptively compared to those who took the drug at symptom onset (43% vs 17%).[44] Metoclopramide is widely used for nausea and vomiting during pregnancy, but information regarding human teratogenicity has been lacking. Matok et al found no increased risk for major congenital malformations, low birth weight, preterm delivery, Apgar scores, or perinatal death between infants of mothers who took metoclopramide within the first trimester compared with infants’ mothers who did not take metoclopramide.

The retrospective cohort study included a total of 81,703 infants who were born to women registered in a single health system with computerized maternal and infant hospital records. Of these, 3458 (4.2%) had first trimester exposure to metoclopramide.[45] Since confirmation of adherence was unavailable, a secondary analysis was performed on infants of mothers who refilled their prescription for metoclopramide at least once (n=758), and no increased risk was found in this subpopulation exposed to metoclopramide compared with infants not exposed. Additionally, the results of the study were unchanged when therapeutic abortions of exposed and unexposed fetuses were included in the analysis. The study provides clinicians reassurance that metoclopramide does not cause congenital malformations; although, dopamine antagonists can cause maternal extrapyramidal symptoms (ie, acute dystonic reactions, tardive dyskinesia). If hypokalemia is severe or symptomatic, potassium should be replaced parenterally. Before administering IV potassium, renal function should be evaluated.

Potassium is usually added to intravenous fluid to achieve a concentration of 40 mEq/L (and not >80 mEq/L). An infusion rate of 10 mEq of potassium per hour should be safe as long as urine output is adequate. When administrating intravenous hydration to a patient who has severe volume depletion in an effort to prevent the development of Wernicke encephalopathy, avoid intravenous glucose until intravenous thiamine has been administered. If persistent dehydration, electrolyte loss, and/or weight loss occur despite above therapy, nutrition supplementation by either the parenteral or enteral route is indicated. The standard method has been via total parenteral nutrition (TPN). However, documented risks of bacteremia, sepsis, and thrombosis have been associated with the PICC lines required for TPN supplementation.

Nasogastric tube placement and subsequent enteral feeding has been shown in small series and reports to be a valid alternative, with less complication risks, similar efficacy, and similar outcomes in regard to neonatal outcome when compared with TPN.[46] References Surgical Care In some refractory severe cases of hyperemesis gravidarum, if maternal survival is threatened, or if hyperemesis gravidarum is causing severe physical and psychological burden, termination of the pregnancy should be considered.[5] Consultations Patients with HEG should be under the care of an obstetrician who is familiar with this disorder. Consultation with a psychiatrist or psychologist may be warranted because psychological assessment may be needed. In some cases, even supportive or focal psychotherapy or psychiatric medications may be indicated. Behavioral therapy may be beneficial early in the course of HEG. When certain disorders are considered the cause of nausea and vomiting (see Differentials), referral to a gastroenterologist or surgeon may be necessary. Diet Initial suggestions for dietary modification in patients with nausea and vomiting associated with pregnancy include the following: Eat when hungry, regardless of normal meal times. Eat frequent small meals. Avoid fatty and spicy foods and emetogenic foods or smells.

Increase intake of bland or dry foods. Eliminate pills with iron. Antihistamines Medication Summary Antihistamines, antiemetics of the phenothiazine class, and promotility agents (eg, metoclopramide) have been used in the treatment of nausea and vomiting during pregnancy. Vitamin B-6 (pyridoxine) has also been studied in the treatment of nausea and vomiting during pregnancy and reduced nausea and vomiting when compared with placebo. Ondansetron (Zofran), a serotonin-receptor antagonist, showed no benefit over the antiemetic promethazine (Phenergan), at much greater cost. It may be reserved for refractory cases. A meta-analysis of 6 randomized, double-blind trials showed that ginger was an effective treatment for HEG. Steroids may be used in patient's refractory to standard therapy. Promethazine (Phenergan) was compared with methylprednisolone in a randomized, double-blind, controlled trial. Methylprednisolone appeared to decrease the rate of readmission for hyperemesis gravidarum; however, the patients randomized to promethazine had a significantly longer duration of symptoms prior to treatment.

However, concerns exist about association between oral clefts and methylprednisolone use in the first trimester; thus, it should be used with caution before 10 weeks of gestation. References Prognosis Hyperemesis gravidarum is self-limited and, in most cases, improves by the end of the first trimester. However, symptoms may persist through 20-22 weeks of gestation and, in some cases, until delivery. References Author Dotun A Ogunyemi, MD, Associate Professor of Obstetrics and Gynecology, David Geffen School of Medicine at UCLA; Residency Program Director, Clerkship Director, Department of Obstetrics and Gynecology, Cedars Sinai Medical Center Disclosure: Nothing to disclose. Alex Fong, MD, Staff Physician, Obstetrics and Gynecology Department, Cedars-Sinai Medical Center Disclosure: Nothing to disclose. Tiffany Chen Herrero, MD, Resident Physician, Department of Obstetrics and Gynecology, Cedars Sinai Medical Center Disclosure: Nothing to disclose.

Specialty Editors Suzanne R Trupin, MD, FACOG, Clinical Professor, Department of Obstetrics and Gynecology, University of Illinois College of Medicine at Urbana-Champaign; CEO and Owner, Women's Health Practice; CEO and Owner, Hada Cosmetic Medicine and Midwest Surgical Center Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference Disclosure: Medscape Salary Employment Richard S Legro, MD, Professor, Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology, Pennsylvania State University College of Medicine; Consulting Staff, Milton S Hershey Medical Center Disclosure: Korea National Institute of Health and National Institute of Health (Bethesda, MD) Honoraria Speaking and teaching; Greater Toronto Area Reproductive Medicine Society (Toronto, ON, CA) Honoraria Speaking and teaching; American College of Obstetrics and Gynecologists (Washington, DC) Honoraria Speaking and teaching; National Institute of Child Health and Human Development Pediatric and Adolescent Gynecology Research Think Tank Panel (Bethesda, MD) Honoraria Speaking and teaching; University of Illinois (Chicago, IL) Honoraria Speaking and teaching; Georgetown University Hospital (Washington, DC) Honoraria Speaking and teaching; Heilongjiang University (Harbin, China) Speaking and teaching; New England Fertility Society (Nashua, NJ) Honoraria Speaking and teaching; William Beaumont Hospital Division of Reproductive Endocrinology and Infertility (Detroit

, MI) Honoraria Speaking and teaching; Wayne State University School of Medicine (Detroit MI) Honoraria Speaking and teaching Frederick B Gaupp, MD, Consulting Staff, Department of Family Practice, Hancock Medical Center Disclosure: Nothing to disclose.

Chief Editor Christine Isaacs, MD, Associate Professor, Department of Obstetrics and Gynecology, Division Head, General Obstetrics and Gynecology, Medical Director of Midwifery Services, Virginia Commonwealth University School of Medicine Disclosure: Nothing to disclose. Additional Contributors The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous author Giulia A Michelini, MD to the development and writing of this article. References Hyperemesis Gravidarum Hyperemesis Gravidarum What is hyperemesis gravidarum? The majority of all pregnant women experience nausea and sometimes vomiting in the first trimester--a condition often called morning sickness, as these symptoms are often more severe in the morning. Some women may have nausea and vomiting throughout the pregnancy. The cause of morning sickness may be due to the changes in hormone levels during pregnancy. A smaller percentage of women develop a severe form of nausea and vomiting of pregnancy called hyperemesis gravidarum. With this condition, nausea and vomiting may be constant, and women often have weight loss, dehydration, and changes in their metabolic state. What causes hyperemesis gravidarum? The cause of hyperemesis gravidarum is unknown but may be hormone-related.

It is more common in multiple pregnancies (twins or more) and in women with migraines. Women with a family history of hyperemesis gravidarum or who had the condition in a previous pregnancy are much more likely to have it with future pregnancies. Why is hyperemesis gravidarum a concern? Hyperemesis gravidarum can lead to fluid and electrolyte imbalances and nutritional deficiencies. Liver damage and jaundice (yellowing of the skin, eyes, and mucous membranes) may occur with severe hyperemesis gravidarum. Thiamine deficiency may occur. Excessive weight loss and poor nutrition in the mother may affect fetal growth. What are the symptoms of hyperemesis gravidarum? The following are the most common symptoms of hyperemesis gravidarum. However, each woman may experience symptoms differently. Symptoms may include: Constant nausea, especially during the first trimester Vomiting after eating or drinking Vomiting not related to eating Weight loss (especially 5% or more of a woman's weight before pregnancy) Dehydration The symptoms of hyperemesis gravidarum may resemble other medical conditions. Always consult your doctor for a diagnosis. How is hyperemesis gravidarum diagnosed?

In addition to a complete medical history and physical examination, weight loss and electrolyte imbalances (detected by blood tests) often aid in the diagnosis of hyperemesis gravidarum. Treatment for hyperemesis gravidarum Specific treatment for hyperemesis gravidarum will be determined by your doctor based on: Your pregnancy, overall health, and medical history Extent of the condition Your tolerance for specific medications, procedures, or therapies Expectations for the course of the condition Your opinion or preference

Question: Hyperemesis Gravidarum is severe what in females?
Answer: ‘Morning’ sickness