Nausea and vomiting of pregnancy (NVP) is a common condition experienced in the early first trimester of pregnancy, with symptoms on a varied continuum from mild nausea to severe hyperemesis gravidarum (HG).¹ Nearly three-quarters of women report nausea with or without vomiting in pregnancy, with mean onset of 5 weeks gestation, and with 90% of patients who will develop NVP experiencing symptom onset by 8 weeks gestation.^2,3 Resolution occurs for 50% of patients by 14 weeks gestation, with up to 90% experiencing relief from symptoms by 22 weeks gestation.² HG is the most severe form of NVP, with intractable nausea and vomiting, loss of more than 5% of prepregnancy weight, dehydration, and electrolyte imbalances.^4–6 HG occurs at a mean rate of 1.1% worldwide.^3,5

Both NVP and HG are diagnoses of exclusion, with other pathologic causes of nausea and vomiting, such as peptic ulcer disease, cholecystitis, gastroenteritis, appendicitis, hepatitis, and genito-urinary, metabolic, and neurologic disorders, should be evaluated and considered in the differential diagnosis.^5,7 Although instances are rare, women with NVP and HG are at risk for Wernicke’s encephalopathy, splenic avulsion, Mallory-Weiss tears, bleeding, esophageal rupture, diaphragmatic rupture, pneumothorax, pneumomediastinum, pneumopericardium, hypoprothrombinemia due to vitamin K deficiency, acute kidney injury, and significant psychosocial morbidity.^1,8 Of these complications, Wernicke’s encephalopathy due to vitamin B₁ deficiency is the most significant, as it is associated with permanent neurologic disability,¹ particularly if it is not recognized or if dextrose is given prior to thiamine administration in patients with NVP and HG.^1,6–9

Recurrence rates of hyperemesis vary significantly, with one study citing 15.2% recurrence¹⁰ and another, self-reported study noting a recurrence rate of 81%.¹¹ Taking a multivitamin for one month prior to conception can reduce the incidence and severity of NVP in a subsequent pregnancy.¹

The pathophysiology of NVP and HG is unknown and is likely to be multifactorial.^1,7,8 Currently, two hormones, human chorionic gonadotropin (hCG) and estrogen, are the only nonthyroidal hormones found to have an association with vomiting.^1,12 The symptoms of nausea and vomiting increase in correlation with rising hCG levels; therefore it is suspected that the hCG concentration itself or hormone-receptor interactions are a cause of NVP and HG.^1,12 Pregnancies with increased placental mass and hCG secretion, such as gestational trophoblastic disease or multiple gestation, are at higher risk of NVP and HG.^1,13 Estrogen has been implicated in symptoms of nausea and vomiting, as evidenced through dose-related symptoms in the combined oral contraceptive pill.¹ Conversely, smokers are less likely to have NVP and HG, with cigarette smoking associated with lower levels of hCG and estrogen.¹

RISK FACTORS

Pregnancies with increased placental mass and hCG levels, such as multiple gestation or gestational trophoblastic disease, have an increased risk of NVP and HG, as discussed previously. A personal or family history of NVP and HG increases the risk of these disorders in pregnancy.¹ Multiparity and the number of previous pregnancies have an associated increased risk of NVP and HG.¹³ Women carrying a female fetus are also at a slightly higher risk of developing HG.^13–15

MATERNAL COMPLICATIONS

Most pregnancies continue without significant maternal complications. In the setting of persistent and protracted nausea and vomiting, the most common immediate complications of NVP and HG include electrolyte imbalances such as hyponatremia and hypokalemia as well as nutritional deficiencies. A deficiency in vitamin B_1, or thiamine can cause Wernicke’s encephalopathy that, if untreated, can result in permanent neurologic disability.¹⁶ Other rare but significant complications of persistent nausea and vomiting include splenic avulsion, Mallory-Weiss tears, bleeding, esophageal rupture, diaphragmatic rupture, pneumothorax, pneumomediastinum, pneumopericardium, hypoprothrombinemia due to vitamin K deficiency, acute kidney injury, and significant psychosocial morbidity caused by NVP and HG.^1,6,8

FETAL COMPLICATIONS

Numerous studies have demonstrated a lower rate of miscarriage among women with NVP and HG, which is postulated to relate to robust placental synthesis in a healthy pregnancy.¹ Patients can be reassured that NVP and HG can be a sign of a healthy pregnancy.¹ Regarding pregnancy outcomes, there are studies with conflicting findings, with some investigators demonstrating no significant increase in the incidence of low birth weight or preterm delivery,^17,18 while others have noted an increase in rates of low birth weight and preterm delivery among women with HG and pregnancy weight gain <7 kg.¹⁹ Still other research has noted an increase in the incidence of low birth weight, small size for gestational age, and premature infants,²⁰ as well as an increased risk of preterm preeclampsia, placental abruption, and being small for gestational age when the first admission for HG occurred in the second trimester.²¹

NVP and HG are diagnosed when symptoms present prior to 9 weeks gestation and in the absence of other causes of nausea and vomiting. The differential diagnosis of nausea and vomiting includes gastrointestinal (GI) conditions, genitourinary tract conditions, metabolic conditions, neurologic disorders, pregnancy-related conditions, drug toxicity, and psychogenic disorders (see Fig. 30-1). The timing of symptoms, physical examination, and laboratory investigations can often differentiate these disorders.

Nausea and vomiting that started prior to pregnancy is not likely due to NVP or HG; it warrants investigation into chronic conditions such as biliary tract disease or cholelithiasis, peptic ulcer disease, diabetic gastroparesis, metabolic disorders, or migraine headaches. Symptoms of nausea and vomiting that commence after 9 weeks gestation are also suggestive of other nonpregnancy conditions, as >90% of women with NVP and HG see onset of symptoms prior to this time.¹ Other pregnancy-related conditions that can present with nausea and vomiting include preeclampsia and acute fatty liver of pregnancy; however, these typically present later in pregnancy, after at least 20 weeks gestation. Furthermore, symptoms of fever, headache, back pain, and abdominal pain are not present in NVP or HG and point to another underlying etiology.

For patients who have initiated treatment for NVP or HG and continue to have persistent symptoms that are unresponsive to treatment, the differential diagnosis should include peptic ulcer disease and Helicobacter pylori (H. pylori) infection.

Patients will often present to the Emergency Department (ED) or obstetric triage unit (OBTU) with nausea, vomiting, and inability to tolerate oral food or fluids. A comprehensive evaluation is essential in evaluating a patient and excluding other underlying causes of nausea and vomiting. A tool to quantify the severity of nausea and vomiting involves the Pregnancy–Unique Quantification of Emesis (PUQE) score,²² presented in Figure 30-2. The modified PUQE score can classify the patient’s symptoms as mild, moderate, or severe, and it also can be used to monitor symptoms and improvement after treatment initiation.⁶ Regardless of the symptom severity, the decision to treat should be based on the patient’s perception of the severity of her symptoms, desire for treatment, and potential effect of treatment on her fetus.¹

On physical examination, patients should be afebrile; the presence of fever suggests an underlying infectious or inflammatory etiology. Many patients will have tachycardia or low blood pressure due to dehydration. Some patients may have mild epigastric discomfort after retching; otherwise, the presence of abdominal pain on physical examination suggests a GI or genitourinary etiology underlying the nausea and vomiting. If a palpable goiter is present, this is indicative of primary thyroid disease, as a goiter is not caused by NVP or HG. A transvaginal ultrasound examination should be performed to document the presence of a viable intrauterine pregnancy, confirm gestational age, and assess for risk factors of NVP and HG, such as multiple pregnancy and gestational trophoblastic disease.

Care should be taken to evaluate the patient’s neurologic status, in particular assessing for developing or underlying Wernicke’s encephalopathy due to thiamine deficiency. Wernicke’s encephalopathy classically presents with a triad of ophthalmoplegia, ataxia, and global confusion; however, only one-third of patients present with all three classic symptoms.¹⁶ Most patients present with profound disorientation, indifference, or inattentiveness, and physical examination may reveal focal ophthalmologic deficits such as lateral gaze nystagmus, lateral rectus palsy, conjugate gaze palsies, or ophthalmoplegia, alongside cerebellar symptoms of gait ataxia or finger-to-nose ataxia.^6,16 Focal neurologic deficits prior to initiation of IV fluid hydration or other treatment is concerning for a primary neurologic disorder. However, neurologic symptoms that present after IV fluid hydration and treatment are concerning for iatrogenic Wernicke’s encephalopathy if thiamine was not given previously, or central pontine myelinolysis if the patient presented with severe hyponatremia.

Patients with suspected NVP or HG may have mildly elevated liver enzymes, amylase, or lipase values. Underlying hepatobiliary and pancreatic disorders should be considered in the differential; however, these often present with significant abdominal pain and markedly elevated laboratory values compared to NVP and HG, as discussed in the section “Diagnosis,” later in this chapter.

The comprehensive evaluation checklist shown in Figure 30-3 is adapted from the Royal College of Obstetrics and Gynecology Guideline on management of NVP and HG.

NVP is diagnosed when symptoms begin prior to 9 weeks gestation and other causes of nausea and vomiting have been excluded.^1,6 If symptoms of nausea and vomiting manifest after 9 weeks gestation, other diagnoses should be considered.¹ HG is diagnosed when there is protracted nausea and vomiting in the absence of other conditions, with loss of more than 5% of prepregnancy weight, dehydration, and electrolyte imbalances.^4–6 Electrolyte abnormalities include hyponatremia, hypokalemia, low serum urea, elevated hemoglobin and hematocrit, and ketonuria.⁶ Metabolic hypochloremic alkalosis may be present due to vomiting and loss of hydrogen protons, but it can progress to a metabolic acidosis if severe.⁶

Other laboratory abnormalities may exist in a patient with NVP and HG, and they must be differentiated from other pathologic causes. Elevated liver transaminases of up to 300 units/L and serum bilirubin of up to 4 mg/dL may be present. This is compared to acute hepatitis, where serum transaminases are >2000 units/L and serum bilirubin is 5–20 mg/dL.^1,23 HG also may cause elevated serum amylase and lipase concentrations up to five times greater than the normal levels.²³ In the patient with elevated liver function tests, amylase, or lipase, underlying hepatobiliary and pancreatic disorders should be evaluated.

Of note, up to 70% of patients will have decreased thyroid-stimulating hormone (TSH) levels or elevated free thyroxine concentrations; however, in the patient with nausea and vomiting or pregnancy or HG who has no goiter, true hyperthyroidism is rare and thyroid function tests are not routinely needed to clarify the differential diagnosis.¹ Treatment of hyperthyroidism should not be considered without evidence of primary thyroid disease, including goiter or thyroid autoantibodies.^1,6

For the OB/GYN hospitalist, the most likely encounter with a patient experiencing nausea and vomiting in pregnancy occurs in the ED or OBTU. The initial approach to management involves determining whether a patient can be treated in the same setting and discharged home or whether she requires admission and inpatient treatment. After evaluating the severity of the nausea and vomiting and ruling out other causes of severe vomiting, a patient who does not have a change in vital signs or a change in mental status and is observed to tolerate oral intake can be treated in an ambulatory setting and discharged home. A patient¹ with a PUQE score <13 can likely be managed in the ambulatory setting.⁶ IV hydration and modification of antiemetic therapy often can be accomplished at home, and these treatments decrease hospital inpatient stays with equal patient satisfaction with their care.²⁴