Samer Saouma OBGYN May 2013

Nausea and vomiting of moderate intensity are

especially common until about 12 to 14 weeks ; This is termed morning sickness. When severe and unresponsive to simple therapy such as reassurance and dietary changes, the condition is termed hyperemesis gravidarum.

 Hyperemesis gravidarum is a severe and intractable

form of nausea and vomiting in pregnancy, sufficient enough to produce weight loss, nutritional deficiencies, and abnormalities in fluids, electrolyte levels, and acid-base balance.

 The peak incidence is at 8-12 weeks of pregnancy, and

symptoms usually resolve by week 20 in all but 10% of patients where HG goes on to last for the whole pregnancy. If vomiting begins after 9 weeks gestation, accompanied with fever and abdominal pain (which are usually not characteristic of HG), other causes should be investigated, such as: - Acute appendicitis -Cholecystitis or cholelithiasis -Diabetic ketoacidosis -Gastritis -Gastroenteritis -Small bowel obstruction -Ovarian torsion -Pancreatitis -UTI -Preeclampsia

 Hyperemesis gravidarum occurs in 0.5-2% of

pregnancies, especially in patients younger than 30 years old. Hyperemesis is the second leading cause of hospitalization in pregnancy, second only to preterm labor.

 Severe nausea and vomiting Loss of 5% or more of pre-pregnancy body weight Dehydration, causing decreased skin turgor, decrease in urination,

hypotension, tachycardia, orthostatic hypotension, ketosis and constipation Headache, confusion and fainting Extreme fatigue Nutritional deficiencies (including hypokalemia, hyponatremia, vitamins) Acidosis from starvation Hypokalemic hypochloremic meabolic alkalosis from loss of HCL in vomitus Subconjuctival hemorrhage Hyperolfaction Secondary anxiety/depression

 Previous pregnancies with HEG Nulliparity Greater body weight Multiple gestations Trophoblastic disease Patients mother or sister suffered from HEG during their

pregnancies Pre-existing liver disease

 The physiologic basis of hyperemesis gravidarum is

controversial. HEG appears to occur as a complex interaction of biological, psychological, and sociocultural factors.
The following theories have been proposed:

Women with hyperemesis gravidarum often have higher hCG levels that cause transient hyperthyroidism. At a molecular level, there is a similarity of the pregnancy hormone hCG to the thyroid hormone. They both have an identical component-the "alpha chain molecule. Unfortunately, the rise in hCG that comes with pregnancy, and with it a rise in an alpha-chain molecule, makes the body react like there is too much thyroid hormone, therefore stimulating the thyroid gland, suppressing TSH and elevating the free thyroxine levels (T4) causing transient hyperthyroidism. 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.

 Some studies link high estradiol and progesterone levels

to the severity of nausea and vomiting in patients who are pregnant. Previous intolerance to oral contraceptives is associated with nausea and vomiting in pregnancy.

 Gastric dysrhythmias including tachygastrias and

bradygastrias have been associated with severe morning sickness. 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 during pregnancy. These pathophysiologic factors appear to be more severe or the gastrointestinal tract more sensitive in those who develop hyperemesis gravidarum.

 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 shown to play a role in the pathogenesis of maternal liver disease associated with hyperemesis gravidarum, due to the accumulation of fatty acids in the placenta and the generation of reactive oxygen species. What happens is 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, will cause hyperemesis gravidarum and liver injury.

 Studies have found conflicting evidence of the role of

H pylori in hyperemesis gravidarum. Some show that H pylori may aggravate nausea and vomiting during pregnancy; others show no correlation. However, persistent nausea and vomiting beyond the second trimester may be due to an active peptic ulcer caused by H pylori infection.

 Hyperemesis gravidarum is associated with overactivation

of sympathetic nerves and enhanced production of tumor necrosis factor (TNF)-alpha. Increased adenosine levels have also been noted, since adenosine is a suppressor of excessive sympathetic nerves activation. 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.

 Many studies suggest that a genetic predisposition may

play a role in the development of hyperemesis gravidarium. Daughters born from a pregnancy complicated by hyperemesis had a 3% risk of having hyperemesis in their own pregnancy while women who were born after an unaffected pregnancy had a risk of 1.1%. In surveys administered to mothers who had pregnancies complicated by hyperemesis, higher rates of hyperemesis were reported among their relatives.

Lab studies for HEG should include the following:

CBC Urinalysis for ketones and specific gravity: Ketones are a sign of

starvation and may be harmful to fetal development. High specific gravity occurs with volume depletion. Serum electrolytes to evaluate for low potassium or sodium and identify acidosis from starvation or alkalosis from loss of HCL in vomitus. Liver enzymes because elevated transaminase levels may occur in as many as 50% of patients with hyperemesis gravidarum. TSH, T4 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.

Imaging studies:
An U/S is usually warranted in patients with HEG to

evaluate for multiple gestations or trophoblastic disease.

 Outpatient or home intravenous hydration should be

considered. If medications and outpatient hydration fail or if severe electrolyte disturbances persist, inpatient admission for intravenous hydration may be necessary. Treatment may be initiated using vitamin B-6, 10-25 mg daily, 3-4 times daily. If hypokalemia is severe or symptomatic, potassium (40 mEq/L) should be replaced parenterally. Before administering intravenous potassium, renal function should be evaluated. An infusion rate of 10 mEq of potassium per hour should be safe as long as urine output is adequate. Some studies also show that ginger may be an effective treatment for HEG.

 Metoclopramide, 5-10 mg taken orally q8h may be used next.

Promethazine (Phenergan), 12.5 mg orally or rectally q4h, or dimenhydrinate 50-100 mg orally q4-6h, may be added as well. Ondansetron (a serotonin receptor antagonist) 4-8 mg orally or IV q8h can be used for further refractory cases. Methylprednisolone, 16 mg orally or IV q8h for 3 days, with a taper to lowest effective dose, can be used if persistent vomiting occurs despite the above therapy. Antihistamines such as Meclizine and Diphenhydramine can be used to decrease GERD and relieve N&V.

 If persistent dehydration, electrolyte loss, and/or weight

loss occur despite above therapy, nutrition supplementation by either the parenteral or enteral (by nasogastric tube) route is indicated.

Prognosis
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.