Although each woman with NVP can present differently, the symptoms predominantly include any combination of the following: nausea, gagging, retching, dry heaving, vomiting, and odor and/or food aversion [11
]. Each woman usually has a certain precipitating factor that triggers the nausea and vomiting, that is, movement-induced, heartburn, food and/or odor triggers [14
]. During initial history taking, questioning on the onset, timing, severity, and aggravating and alleviating factors may point to another cause for the nausea and vomiting. This information is also helpful when formulating a treatment plan. One of the most important aspects of the history is the duration of vomiting in order to assess the potential risk for Wernicke's encephalopathy due to thiamine deficiency.
If the diagnosis of HG is made, the patient should be evaluated for urinary ketones, BUN, creatinine, aspartate aminotransferase (AST) and alanine aminotransferase (ALT), amylase, and electrolytes [15
]. Thyroid stimulating hormone (TSH) and free T4 (FT4) should also be checked as human chorionic gonadotropin (hCG) cross-reacts with thyrotropin and stimulates the thyroid gland [15
]. As a result, thyrotropin is typically lower in these patients. In fact, the values of TSH and FT4 in patients with HG may be similar to that seen in Graves' disease, but without the clinical symptoms and findings of Graves' disease or thyroid antibodies [16
]. This form of hyperthyroidism usually resolves without treatment by 20 weeks gestational age, and management of nausea and vomiting until then is as indicated.
The vomiting observed with NVP and HG can be quantified with a scoring system, the Pregnancy-Unique Quantification of Emesis scale (PUQE) [17
]. Similar to the Rhodes Scale used for the assessment for nausea and vomiting in patients receiving chemotherapy, the PUQE scoring system was designed to focus on nausea and vomiting of pregnancy [17
]. The 12 hour PUQE scoring system assesses the severity of NVP by focusing on the number of hours of nausea and the number of episodes of retching and vomiting, as well as an overall well-being score in the 12 hours immediately before assessment [19
]. The 24 hour PUQE scoring system, validated in 2009, was subsequently developed to account for global nausea and vomiting, including the time spent sleeping and the severity of symptoms throughout the first trimester [20
]. The PUQE scoring system has a minimum score of 3 and maximum score of 15 with a score of <6 suggesting mild HG, 7–12 moderate, and >13 severe NVP. This scoring system has been validated and shown to correlate with clinical outcomes such as rates of hospitalization and women's subjective feelings of well-being [19
]. There is also a well-being score of 0 (the worst possible) to 10 (the best possible), which is a general self-perception score of physical and psychological health and a question on the amount of sleep including naps in a 24 hour period of time [17
]. The PUQE scoring system is helpful not only to qualify and quantify the nausea and vomiting, but to follow the response to treatment and improvement over time.
Regardless of when the patient presents, it cannot be assumed that nausea and vomiting is due to NVP. It is more appropriate to take the pregnancy-related versus nonpregnancy-related approach when determining the etiology. More often than not, if the patient initially presents before 10 weeks, it is likely NVP. However, a thorough history and physical exam is still required to elicit any potential contributing or confounding factors at any gestational age. If the diagnosis of NVP or HG is made, but there is poor response to initial interventions, an atypical presentation, or initial presentation after 9–10 weeks, other causes must be explored [3
]. lists other potential causes of nausea and vomiting in pregnancy. If there is fever, a source of infection should be sought or if the history suggests a CNS abnormality, check for signs of raised intracranial pressure [11
]. Specific signs such as peritoneal signs, RUQ pain, or jaundice should raise the suspicion for acute abdomen, preeclampsia, and acute fatty liver of pregnancy, respectively [11
]. In addition, headache with nausea and vomiting can occur with dehydration, but preeclampsia should still be ruled out, especially if there is elevated blood pressure. Although epigastric pain and hematemesis is rare, if this is observed, a Mallory Weiss tear from prolonged vomiting or gastrointestinal ulcer may be the cause. Finally, heartburn and gastric reflux occurs in a significant number of pregnant women, and appropriate recognition and treatment of this particular condition may improve symptoms quite rapidly.
Differential diagnosis of NVP.
Prolonged nausea and vomiting in the setting of NVP or HG can lead to maternal vitamin deficiencies. As mentioned above, Wernicke's encephalopathy is a potential serious or fatal maternal complication and is due to severe vitamin B1 (thiamine) deficiency. Approximately 47% of patients with this condition will present with a history of prolonged nausea and vomiting along with the triad of abnormal ocular movements, ataxia, and confusion; an additional percentage will also have diplopia [22
]. Symptoms can also be more variable and include memory loss, apathy, decreased level of consciousness, or blurred vision [22
]. Although this condition is reversible with prompt treatment, 60% of women will have residual impairment and there is a 37% fetal loss rate [22
]. Because maternal serum thiamine levels are not useful in making the diagnosis, any pregnant woman who presents with prolonged nausea and vomiting and neurologic abnormalities should be empirically treated with intravenous thiamine. Deficiencies in vitamins B6 and B12 are rare and not as potentially serious, but can cause anemia and peripheral neuropathy associated with hematemesis, malnutrition, and psychological effects [23
]. Vitamin K deficiency and coagulopathy can also occur, leading to an abnormal coagulation profile and bleeding [24
One consequence of NVP and HG that is commonly neglected, especially when the focus is on treatment, is the psychosocial impact of this disorder. NVP can adversely affect family and social life, physical and mental health, employment, and can impose an economic hardship [25
]. This can range from missing days of work to termination of the pregnancy due to severe symptoms. Up to 25% of pregnant women have to change their normal daily activities due to symptoms [14
]. In addition, these women have lower physical and social functioning and miss more days of work [27
]. Furthermore, depression and anxiety can develop, which can make management of the patient more complicated. Koken et al. investigated the association between depression and anxiety in early pregnancy, and nausea and vomiting in a cross-sectional study of 230 women using the Hospital Anxiety and Depression Scale as a measure of anxiety and depression, and the Rhode's System for nausea and vomiting [28
]. A significant correlation between Rhode's score and both anxiety and depression scores was found. Gestational age showed an inverse correlation with anxiety scores. They also found an association between anxiety and depression in early pregnancy and severity of NVP. They concluded that recognizing depression in the early stages of pregnancy might be a key step in assisting the mother. As a result, health care providers should assess the severity of NVP and address the psychological situations of the patient [28
]. Depression and anxiety can contribute to and confound the symptoms of NVP and render treatment more challenging.