Between 50% and 80% of pregnant patients experience nausea and vomiting beginning at about the 4th week and ending at about the 12th week of gestation [1,2]. In fact, nausea and vomiting are considered a presumptive sign of pregnancy, and for 10% to 20% of pregnant patients, these symptoms may persist throughout the whole pregnancy. While nausea and vomiting are common occurrences, hyperemesis gravidarum is rare, occurring in 0.2% to 3.6% of all pregnancies [1,2,127].

There is some variation in the literature as to the exact definition of hyperemesis gravidarum. It has been described as intractable nausea and vomiting during pregnancy severe enough to require hospitalization [4,115]. The condition appears during the first trimester and is unassociated with other medical conditions, such as cholestasis, hepatitis, pre-eclampsia, viral syndromes, Ménière disease, or influenza.

The most commonly accepted definition of hyperemesis gravidarum is a severe form of nausea and vomiting with weight loss greater than 5% of prepregnancy body weight, dehydration, acidosis from starvation, alkalosis from loss of hydrochloric acid, hypokalemia, ketosis, acetonuria, and ptyalism (excessive salivation) [4]. Many patients require hospitalization in order to control the symptoms [5,115]. In most cases, the onset of symptoms is between 4 and 10 weeks' gestation and the symptoms usually subside by 20 weeks' gestation. Clinically, practitioners commonly treat nausea and vomiting in early pregnancy, regardless of whether the patient fits all the criteria of a diagnosis of hyperemesis gravidarum.

It has been suggested that hyperemesis gravidarum may be associated with low infant birth weight, likely related to maternal nutritional (i.e., weight) maintenance [6,7,8]. Researchers have found a modest association between severe nausea and vomiting in pregnancy and intrauterine growth restriction and low infant birth weight [6]. A maternal weight loss of greater than 5% seems to be the critical factor in fetal growth restriction. However, even insufficient weight gain can have negative repercussions. A weight gain of less than 7 kg (15.4 pounds) during the duration of pregnancy is associated with low birth weight and preterm births [5,7,115,119].

There also appears to be a correlation between severe hyperemesis during pregnancy and impaired insulin sensitivity in offspring [9]. In one study of healthy children (4 to 11 years of age) who were born at term to mothers who were admitted to hospital with severe hyperemesis gravidarum during their pregnancy, the offspring of the patients with hyperemesis had 20% lower insulin sensitivity compared to children of healthy individuals. Longer term follow-up studies are necessary to determine if this difference persists into adulthood.

One study found an increased risk for psychological and behavioral problems in adult offspring of pregnancies affected by hyperemesis [10]. Adult offspring exposed to hyperemesis in utero reported higher likelihood of depression, anxiety, and bipolar disorder diagnoses.

Various studies have linked a greater risk for birth defects, developmental delays, and serious health problems (e.g., type 2 diabetes, hypertension, high cholesterol, and cardiovascular disease) with maternal hyperemesis gravidarum [8,11]. One small Japanese study found impaired fetal head growth was associated with lower maternal weight gain from the lowest body weight to weight at 20 weeks' gestation [129]. The authors hypothesize that this could affect fetal brain growth and development. Other potential fetal complications include [12]:

Shorter length

Undescended testes

Testicular cancer

Behavioral/emotional problems

Integumentary abnormalities

Neurodevelopmental sequelae

Congenital heart disease

Neural tube defects

Hip dysplasia

Perinatal death

Although it is clear that hyperemesis gravidarum is associated with adverse fetal effects, the exact causation is the subject of debate. Poor maternal health and fetal exposure to stress hormones are thought to play a role, but some have suggested that the fetal complications seen with hyperemesis gravidarum may be the result of maternal risk factors, not the condition itself. In one study, the researchers assert that individuals who develop hyperemesis gravidarum tend to have pre-existing conditions that could predispose their infants to complications, including younger age, lower socioeconomic status, primiparity, use of assisted reproductive technologies, substance abuse, non-Western decent, and chronic health conditions (e.g., diabetes, hypertension, mental illness) [13]. It is possible that the factors that place patients at risk for developing hyperemesis gravidarum are responsible for low infant birth weight and other negative fetal effects associated with the condition.

Despite the fact that hyperemesis gravidarum may be associated with poor fetal growth and outcome, a large, epidemiologic study found that the likelihood of miscarriage was 70% lower in those who experienced normal nausea and vomiting early in pregnancy [14]. More severe sickness was associated with a greater decrease in the risk of miscarriage. This finding supports the belief that normal nausea and vomiting in the first trimester of pregnancy may be protective against miscarriage [14,15]. This may be a result of robust placental synthesis in a healthy pregnancy [92].

Wernicke encephalopathy results from a deficiency of thiamine (vitamin B1) and is manifested by confusion, gait ataxia, ophthalmoplegia (paralysis of the eye muscles), or convulsions. Typically, thiamine is initially lost by prolonged vomiting. When intravenous fluid replacement containing dextrose is given, the body's metabolism of the dextrose quickly consumes the remaining thiamine. Therefore, the cause is usually not the hyperemesis itself but is instead due to fluid replacement without thiamine supplementation. Although the condition is very rare, it is associated with a high mortality rate (20%) [16,130].

Human chorionic gonadotropin has been suspected as the cause of hyperemesis gravidarum based chiefly on the observation that its peak concentration in pregnancy coincides with the peak of nausea and vomiting [32]. Another suggestion for the causative role of hCG in persistent nausea and vomiting is the association between increased hCG concentrations and hyperemesis gravidarum in cases of twin and molar pregnancies.

Infection with Helicobacter pylori, a gram-negative spiral bacterium strongly associated with peptic ulcers, has been investigated as a cause of hyperemesis gravidarum. In one study, the investigators found that 89% of pregnant patients with hyperemesis gravidarum were seropositive for H. pylori, compared to 30% of the control group [44]. A 2010 study reached a similar conclusion, finding that 87% of women with hyperemesis gravidarum were infected with H. pylori, compared to 32% without the condition [45]. A meta-analysis of 38 cross-sectional and case-control studies, involving 10,289 patients, revealed a significant association between H. pylori infection and hyperemesis gravidarum [121]. As such, screening of H. pylori infection should be added to the investigation of hyperemesis gravidarum cases. IgG antibody testing may detect H. pylori infection in patients presenting with hyperemesis; post-eradication monitoring may be carried out by stool antigen testing. Eradication of H. pylori in pregnant patients can significantly improve symptoms. Treatment options include the utilization of triple therapy, consisting of a proton-pump inhibitor and two antibiotics (e.g., amoxicillin or erythromycin and metronidazole) for two weeks [121]. Several case reports have suggested that eliminating H. pylori infection may cure hyperemesis gravidarum or at least modify its course [44,46,47].

High prepregnancy body weight and nulliparity (having not given birth to a child) have been cited as risk factors for hyperemesis, and as discussed, a high-fat diet has been found to greatly increase the odds [4,63]. Maternal age younger than 20 years and twin gestation are also noted as risk factors [4]. The condition can repeat itself in subsequent pregnancies and is more common in patients with a history of spontaneous abortions [13]. Trogstad et al. found that if an individual experienced hyperemesis in her first pregnancy, there was a 15.2% risk that she would experience it in subsequent pregnancies [64]. Those never having suffered from the condition have a 0.7% risk in later pregnancies.

There are limited demographic data relating to hyperemesis gravidarum, but some (also limited) evidence suggests a higher rate among certain racial/ethnic minority groups [67]. One study did note an increased risk among Pacific Islander patients [68]. Inuit and Native American populations tend to have a lower incidence of hyperemesis gravidarum [10]. In a study of 67 women with hyperemesis presenting at Los Angeles Women's Hospital, 94% were Hispanic [23]. However, the authors did not evaluate the racial mix of the general population served by this facility. Several studies have shown no clear racial predominance for hyperemesis gravidarum [10]. A large study of 417,028 pregnancies in England showed a statistical predominance in Asian and Black patients [118,119].

Nausea and vomiting of pregnancy is usually initially treated conservatively with diet in the hopes that the problem will not progress to hyperemesis gravidarum. General recommendations include choosing a bland diet, increasing carbohydrate intake, decreasing fat intake, avoiding offensive food odors, and avoiding iron supplementation, if possible. Omitting prenatal vitamins containing iron until the nausea resolves may also be helpful.

Specific suggestions are to eat bread or crackers before getting out of bed in the morning, when nauseated, and before retiring for the night. Experts also recommend eating small meals every two to three hours; drinking liquids between meals rather than with meals to avoid gastric distention; eating low-fat, high-protein foods; avoiding fried foods; and salting food to taste.

Intractable cases may require total parenteral nutrition (TPN) via a central venous catheter or parenteral nutrition via a percutaneous endoscopic gastrostomy (PEG) tube. This may be continued as long as oral feeding is not tolerated.

While treatment strategies to this point have focused on symptomatic management of patients already experiencing hyperemesis gravidarum, one study shows promise for pre-emptive treatment for those who experienced hyperemesis in a previous pregnancy [69]. In this study, women who had hyperemesis in a previous pregnancy were assigned to either the treatment group or the control group. Women in the treatment group received a standard form of antiemetic pharmacologic therapy prior to the onset of symptoms, while those in the control group received treatment only after the onset of symptoms. The authors found that there was a substantial decrease in the symptoms of hyperemesis in the treatment group versus the control group [69]. In a subsequent randomized controlled trial, the authors again found pre-emptive treatment to be superior in decreasing the risk of hyperemesis when compared with treatment that begins after the onset of symptoms [70].

Nausea and vomiting of pregnancy is usually initially treated conservatively with diet in the hopes that the problem will not progress to hyperemesis gravidarum. General recommendations include choosing a bland diet, increasing carbohydrate intake, decreasing fat intake, avoiding offensive food odors, and avoiding iron supplementation, if possible. Omitting prenatal vitamins containing iron until the nausea resolves may also be helpful.

Specific suggestions are to eat bread or crackers before getting out of bed in the morning, when nauseated, and before retiring for the night. Experts also recommend eating small meals every two to three hours; drinking liquids between meals rather than with meals to avoid gastric distention; eating low-fat, high-protein foods; avoiding fried foods; and salting food to taste.

One controversial approach involves feeding patients with hyperemesis potato chips and lemonade [71]. The study found that potato chips were superior to the commonly prescribed saltine crackers in that they supplied more folic acid, vitamin C, and potassium. Potato chips also drive thirst, particularly for cold, tart, or sweet liquids. Researchers found that lemonade was better tolerated by patients than either ginger ale or plain water.

Because of the electrolytes lost in vomiting, consuming foods high in potassium and magnesium is recommended, as well as salting food, as tolerated, to replace chloride. Chewing one milk of magnesia tablet two to three times per day may help to settle the stomach and replace magnesium stores. Other frequently recommended foods are legumes, dairy products, nuts, oral nutrition supplements, and electrolyte-replacement drinks to preserve the body's electrolyte balance [46].

Behavioral changes recommended for patients with hyperemesis gravidarum are to take frequent rests, get plenty of fresh air, avoid sudden movements, avoid brushing teeth immediately after eating, and sit upright for some time after meals to reduce the frequency of gastric reflux. Acupressure wristbands, which are sometimes used by passengers on boats to prevent seasickness, have been found to be helpful for some patients with nausea in pregnancy [72].

Avoiding offensive odors is of special importance. An overly sensitive sense of smell is common in pregnancy, possibly due to increased estrogen levels. Offensive odors commonly are food odors but can also be perfumes or chemicals. Minimizing odors and increasing fresh air are key ways to avoid nausea.

Patients with hyperemesis should also have psychological support, including reassurance, perhaps family and individual counseling, and a reduction in demands of daily living and environmental stimulation. Because the smell of hot or cooking food often induces nausea, it may be helpful for a partner, spouse, friend, or other person to prepare meals [32]. If eating hot foods cause patients to feel ill, it is recommended they stick with cold foods, such as sandwiches [73].

It is important that healthcare professionals accept patients' complaints of nausea and vomiting as a real physical problem and not necessarily psychological in origin. Patients who think their providers do not believe their complaints of nausea and vomiting may feel anger, diminished self-esteem, and confusion [54]. Acceptance of the patient's complaint and the assurance that it is not all in her head are paramount to establishing a therapeutic relationship.

A nursing assessment should first evaluate the frequency of vomiting episodes. Next, the nurse should determine any patterns to the nausea and vomiting episodes, such as what time of day or night they occur. It should also be determined which conditions lead to vomiting, such as an empty stomach or certain smells. Assessment must also include which, if any, foods seem to make the situation worse or better. Finally, the nurse must determine which measures the patient has already tried to alleviate the symptoms.

A dietary plan may be created using most of the discussed strategies (e.g., eating small meals every two to three hours, avoiding an empty stomach, avoiding fried or highly seasoned foods, and maintaining adequate hydration). The nurse can suggest that the patient keep a log of the type and amount of food consumed, as well as any episodes of nausea and vomiting. This may help both the patient and the nurse find patterns and dietary solutions to the problem.

Evaluation of a dietary plan should be ongoing at every prenatal visit. The goal is normal weight gain, fewer episodes of nausea and vomiting, normal vital signs, and no ketonuria. The dietary plan is also an important adjunct to pharmacologic therapy for hyperemesis.

PHARMACOLOGIC MANAGEMENT

If diet and lifestyle changes do not resolve the problem of nausea and vomiting, drug therapy may be indicated (Table 1). Approximately 10% of patients with hyperemesis require pharmacologic treatment [74].

The dilemma in treating hyperemesis gravidarum pharmacologically is the fear of possible teratogenic effects; both providers and pregnant patients are reluctant to use pharmacologic agents with possible fetal effects, especially in the first trimester of pregnancy. This is complicated by the fact that only one drug (Diclegis) is approved by the U.S. Food and Drug Administration (FDA) for the treatment of nausea and vomiting of pregnancy [83].

The antiemetic medications used to treat nausea and vomiting in pregnancy fall into two broad classes: antihistamines and phenothiazines. Despite evidence of safety to the fetus, most antiemetics are contraindicated in pregnancy.

Among the antihistamines used by patients for nausea and vomiting during pregnancy is doxylamine in combination with pyridoxine hydrochloride (vitamin B₆). It carries an FDA pregnancy Category B, which indicates that human fetal risk is relatively unlikely [76]. The FDA approved the combination of 10 mg doxylamine and 10 mg pyridoxine (marketed as Diclegis) in 2013 for the treatment of hyperemesis gravidarum. It is the only drug specifically approved for this indication and has become a first-line therapy [83,92]. A version of this combination that also included dicyclomine hydrochloride (marketed as Bendectin) was originally introduced in 1956 and was taken off the market in 1983 [86]. Despite the fact that controlled studies found no increased risk of birth defects, highly publicized lawsuits in the 1970s, involving neonates with severe malformations whose mothers had taken Bendectin, were judged unfavorably against the manufacturer. It is interesting to note that after Bendectin was removed from the market, the incidence of the type of limb deformities and congenital heart disease attributed to the medication did not decrease [86].

The individual components of Bendectin have been available in both over-the-counter and prescription forms and have not demonstrated to be teratogenic [87]. Moreover, a form of Bendectin has remained available in the United Kingdom and in Canada. This, along with the fact that Bendectin has not been conclusively shown to be teratogenic, initiated the move to reintroduce combination doxylamine/pyridoxine [86].

Thiamine stores must be restored before intravenous therapy begins, as the dextrose in the solution causes the body to metabolize thiamine. As previously mentioned, thiamine deficiency can lead to Wernicke encephalopathy. Signs and symptoms of Wernicke encephalopathy include visual disturbances, such as diplopia or nystagmus, as well as disorientation, delusion, and gait ataxia. While there is no specific treatment regimen, some experts recommend parenteral thiamine 100–500 mg daily for three days and 2–3 mg per day thereafter [100].

Nursing assessments should include starting and maintaining the patency of the intravenous infusion, maintaining the infusion rate, and assessing the IV site for infection or infiltration. Venipuncture can be difficult in dehydrated patients, but placing the site in a dependent position and warming the area with warm compresses may cause enough vasodilatation to enable an easy insertion. Warming the first liter of fluid may prevent the feeling of coldness that dehydrated patients experience.

Assessments might also include intake and output, as well as assessing for episodes of vomiting. Vital signs are one marker of hydration status and should be monitored per protocol. Antiemetic therapy is often initiated as well as IV hydration; therefore, ongoing assessments for side effects should be included.

Shortly after IV therapy is initiated, oral feeding may be resumed. The diet is usually initiated with clear liquids and proceeds to small, frequent meals. Nurses should monitor dietary intake and advance the diet as tolerated. If the diet is not tolerated, enteral feeding may be an option [99].

Discharge planning should be initiated on admission. The goal is to discharge the patient to home as soon as dehydration is treated, vomiting has subsided, and the patient is able to keep food down. Discharge planning should include counseling regarding diet, as well as educating the patient regarding her medications, side effects, and warning signs.

Acupressure has been used for the treatment of morning sickness, as well as motion sickness and post-chemotherapy nausea and vomiting. As such, it is the best-studied alternative therapy. Treatment includes wearing wristbands that apply pressure to the inner forearm approximately three finger breadths proximal to the wrist (e.g., Sea-Bands). A 2014 Cochrane review did not find P6 acupuncture or acupressure wristbands significantly more effective than placebo for the treatment of nausea and vomiting in early pregnancy, but it is unclear if the approach would be more effective for patients with hyperemesis gravidarum [106]. While many clinical trials show statistically significant improvement in nausea, fewer studies show improvement in vomiting [90]. However, many of the studies are flawed, having small sample sizes, inadequate control groups, and little if any blinding [90].

On physical examination, the patient may appear weak, pale, and with dry mucous membranes. A ketotic breath smell may be noted. Infrequently, jaundice might be noted. A weight check may reveal weight loss, as much as 5 pounds in a week. Blood pressure may manifest orthostatic changes, and pulse may be elevated secondary to dehydration.

A urine dipstick analysis should be performed, with particular attention to the presence of ketones. Specific gravity will be increased [109].

Nausea is defined as "a subjective unpleasant, wave-like sensation in the back of the throat, epigastrium, or abdomen that may lead to the urge or need to vomit" [111]. Olfactory stimulation can sometimes trigger nausea. Interventions include avoiding unpleasant odors and food smells, particularly those that trigger the nausea. The patient should avoid fried or greasy meals because these also promote nausea. The patient should attempt small, frequent meals and drink fluids in between meals to help reduce the amount of food in the stomach and avoid the feeling of fullness that can aggravate nausea. The patient should avoid lying supine for at least 30 minutes after eating, because this position applies pressure on the diaphragm and digestion is improved by gravity.

Dehydration is a state in which an individual is at risk for or experiencing fluid depletion. The nursing assessment may reveal dry mucous membranes, decreased skin turgor, tachycardia, hypotension, increased body temperature, and ketonuria. The hemoglobin and hematocrit may be elevated, but sodium, potassium, and chloride may be reduced due to vomiting.

This nursing diagnosis includes impaired oral mucous membrane integrity, due to both dehydration and vomiting. Nursing assessments might reveal a complaint of dry mouth, bad taste, or even excessive salivation. Inspection may reveal dry or cracked mucous membranes, pallor, ulcerations, edema, coated tongue, or hemangiomas (a network of small blood-filled capillaries near the surface of the skin).