Nausea and Vomiting of Pregnancy

Stacey Chamberlain

Amina Basha

OVERVIEW

Nausea and vomiting of pregnancy (NVP) is a common complaint encountered by emergency providers, especially for women in their first trimester of pregnancy. Up to 85% of pregnant women will experience these symptoms, with 0.3% to 2% of patients presenting with the more severe condition of hyperemesis gravidarum (HG). There is no single accepted definition of HG, but it is considered to be a diagnosis of exclusion based on persistent nausea and vomiting associated with measures of acute starvation such as ketosis, more than 5% weight loss, or hospitalization in the absence of other diseases.¹^,² Although NVP is associated with a reduced risk for pregnancy loss, HG is the most common reason for hospitalization during the first half of pregnancy and is associated with increased risk of maternal morbidity and adverse birth outcomes such as anemia, preeclampsia, eclampsia, venous thromboembolism, preterm delivery, and delivery by cesarean section.³^,⁴ Severe untreated cases of HG can lead to Wernicke encephalopathy, central pontine myelinolysis, esophageal rupture, pneumothorax, as well as hepatic and renal impairment.⁵ The emergency department (ED) management of these patients focuses on evaluating for other causes of these symptoms and providing appropriate treatment modalities.

PATHOPHYSIOLOGY

The pathogenesis is believed to be multifactorial involving genetic, endocrine, and gastrointestinal factors, but the exact mechanism behind NVP is unclear. Multiple studies have linked human chorionic gonadotropin (hCG) to NVP, but other studies find no correlation between hCG levels and HG.⁶ It is theorized that different isomers of hCG account for the variability of findings linking hCG levels and severity of symptoms.⁶ Estrogen is known to influence nausea and vomiting and is implicated as a cause because NVP is more common with elevated levels of estradiol. There are no data to support the theory that psychological factors contribute to NVP or HG.¹^,⁷

EPIDEMIOLOGY AND RISK FACTORS

Symptoms of NVP are generally first noticed in the 4th week of pregnancy and resolve by the 20th week of pregnancy. However, up to 20% of women may experience symptoms throughout
pregnancy.⁸ Nausea and vomiting beginning prior to conception or starting after 9 weeks’ gestation suggest alternate diagnoses. HG is considered a more severe form of the NVP spectrum.

Risk factors for HG are young age, less socioeconomic deprivation, nulliparity, Asian or black ethnicity, female fetus, history of HG in a previous pregnancy, thyroid and parathyroid dysfunction, hypercholesterolemia, and type 1 diabetes.⁹ Both low and high body mass index increase risk for HG as well as maternal history of HG.¹⁰^,¹¹ In addition, allergies and a prepregnancy restrictive diet are associated with prolonged HG.⁵ Women with larger placental mass, such as with advanced molar pregnancy or multiple gestation, are at increased risk of HG. Although historically gestational trophoblastic disease (GTD) was related to higher rates of HG, earlier detection of GTD prior to development of symptoms is now more common.¹²

There is an association of Helicobacter pylori (H. pylori) and HG.¹³ Therefore, patients with HG found to have H. pylori infections are provided nonteratogenic treatment of H. pylori as part of their management of HG, particularly in intractable cases.

CLINICAL FEATURES

An evaluation of signs and symptoms should focus on assessing the patients’ hydration status. The Pregnancy-Unique Quantification of Emesis and Nausea (PUQE) index, a validated severity index, and related clinical decision tools (PUQE-24 and modified-PUQE) are useful adjuncts to determine the severity of illness and prognosis (Table 11.1).⁸ These tools generate a risk score based on symptoms of nausea and frequency of vomiting and retching; a moderate to severe score (≥7) prompts further evaluation of hydration and electrolyte status in addition to evaluating for traditional signs and symptoms including dry mucous membranes, loss of skin turgor, decreased urine output, and hypotension. Abdominal pain is usually absent and, if present, warrants further evaluation for alternate etiologies of the patient’s symptoms.

DIFFERENTIAL DIAGNOSIS

The potential etiologies for nonpregnancy-related vomiting are numerous (Table 11.2). The timing of the onset of symptoms is helpful in establishing alternative diagnoses as NVP manifests in all affected women before 9 weeks of gestation. The onset of symptoms after 9 weeks’ gestation and the presence of abdominal pain should warrant further investigation for nonpregnancy-related causes. Fever and headache are not present in NVP.

TABLE 11.1 Modified Pregnancy-Unique Quantification of Emesis and Nausea

Circle the answer that best suits your situation from the beginning of your pregnancy
1. On average in a day, for how long do you feel nauseated or sick to your stomach?
Not at all (1)	1 h or less (2)	2-3 h (3)	4-6 h (4)	>6 h (5)
2. On average in a day, how many times do you vomit or throw up?
7 or more times (5)	5-6 times (4)	3-4 times (3)	1-2 times (2)	I did not throw up (1)
3. On average in a day, how many times do you have retching or dry heaves without bringing anything up?
None (1)	1-2 times (2)	3-4 times (3)	5-6 times (4)	7 or more times (5)
Total score (sum of replies to 1, 2, and 3): mild NVP, ≤6; moderate NVP, 7-12; severe NVP, ≥13.
NVP, nausea or vomiting of pregnancy.
Reprinted from Lacasse A, Rey E, Ferreira E, Morin C, Bérard A. Validity of a modified Pregnancy-Unique Quantification of Emesis and Nausea (PUQE) scoring index to assess severity of nausea and vomiting of pregnancy. Am J Obstet Gynecol. 2008;198(1):71.e1-e7, with permission from Elsevier.

TABLE 11.2 Differential Diagnosis of Nausea and Vomiting of Pregnancy

Gastrointestinal Conditions

Gastroenteritis

Gastroparesis

Achalasia

Biliary tract disease

Hepatitis

Intestinal obstruction

Peptic ulcer disease

Pancreatitis

Appendicitis

Conditions of the Genitourinary Tract

Pyelonephritis

Uremia

Ovarian torsion

Kidney stones

Degenerating uterine leiomyoma

Metabolic Conditions

Diabetic ketoacidosis

Porphyria

Addison disease

Hyperthyroidism

Hyperparathyroidism

Neurologic Disorders

Pseudotumor cerebri

Vestibular lesions

Migraine headaches

Tumors of the central nervous system

Lymphocytic hypophysitis

Miscellaneous Conditions

Drug toxicity or intolerance

Psychological conditions

Pregnancy-Related Conditions

Acute fatty liver of pregnancy

Preeclampsia

Reprinted from Goodwin TM. Hyperemesis gravidarum. Obstet Gynecolog Clin Norm Am. 2008;35:401-417; viii, with permission from Elsevier.

Although acute appendicitis is rare during pregnancy, outcomes are worse in pregnant patients, so this diagnosis should be considered in the right clinical context.¹⁴ Acute pancreatitis is rare and more common in the third trimester, so late onset of symptoms and the presence of pain warrant further evaluation.¹⁵ Hiatal hernias and diaphragmatic tears are reported with delayed diagnoses, leading to life-threatening cardiorespiratory compromise; as with other conditions, the presence of abdominal pain, intractable symptoms, and late onset for HG requires further workup.¹⁶^,¹⁷

Preexisting conditions such as diabetes and Addison disease can be exacerbated during pregnancy. Patients with these conditions should be evaluated similar to the nonpregnant patient to exclude diabetic ketoacidosis or an adrenal crisis. Marijuana is the most frequently used illicit drug during pregnancy, and its use is increasing.¹⁸ Frequent marijuana use can lead to cannabis hyperemesis syndrome; therefore, practitioners should inquire about marijuana use and suspect this in cases where intractable nausea is relieved by hot bathing.

An evaluation for vomiting must also consider high-risk pregnancy-related conditions including GTD, liver disease in pregnancy, preeclampsia, and HELLP (hemolysis, elevated liver enzymes, and a low platelet count) syndrome. A complete history, physical examination, and review of systems should consider these pathologies. Earlier detection of GTD has resulted in fewer patients progressing to the point of developing symptoms of NVP and HG. In those with HG, GTD prevalence is not higher compared with control groups, so routine ultrasound is not recommended in the absence of other concerning symptoms such as vaginal bleeding.¹⁹

Most pregnancy-related liver diseases including intrahepatic cholestasis of pregnancy, acute fatty liver of pregnancy, preeclampsia, and HELLP syndrome are conditions that manifest in the third trimester and may be associated with additional signs and symptoms including pruritus, jaundice, abdominal pain, headache, edema, hypertension, and proteinuria.²⁰

DIAGNOSTIC TESTING

Diagnostic testing focuses on excluding other causes of NVP and assessing the patients’ hydration and electrolyte status. There are no biomarkers for making the diagnosis or to assess severity.² Common testing includes a complete blood count (CBC) to evaluate for anemia, electrolytes and renal function to evaluate for complications of prolonged vomiting (hypokalemia, hyponatremia, and acute renal failure), and urinalysis to exclude infection and assess hydration status. Ketonuria, although classically one of the hallmarks of HG, is not as helpful in the diagnosis as previously believed as a meta-analysis revealed that the severity of the ketonuria did not correlate with the severity of the HG.²

Many women with HG have abnormally high serum thyroxine (T4) levels and low thyroid-stimulating hormone (TSH) levels. However, this gestational transient hyperthyroidism is rarely symptomatic, does not benefit from treatment, and does not lead to adverse pregnancy outcomes.²¹^,⁵¹ Therefore, routine thyroid screening is not recommended for patients with HG. Routine liver function tests and lipase are not recommended. An elevated serum lipase has been found in some patients with HG in the absence of abdominal pain and should not be used exclusively to make the diagnosis of acute pancreatitis in patients with HG.²²

It is unclear if H. pylori eradication is useful in reducing HG symptoms; therefore, routine testing for H. pylori is not recommended, as many patients with H. pylori are asymptomatic. Testing and treatment are considered for refractory cases.¹³ In regard to imaging, routine ultrasound screening is not recommended for those with HG in the absence of vaginal bleeding or other concerning symptoms.¹⁹

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