Hyperemesis Gravidarum Nursing CE Course

ng delivery or pregnancy loss. Monitoring the decline of hCG levels is essential following the termination of a pregnancy, especially if molar or ectopic, to ensure that the intervention was successful (Betz & Fane, 2021; Lowdermilk et al., 2016).  

HCG is necessary to maintain a pregnancy because it promotes progesterone production for approximately 3 to 4 weeks following pregnancy implantation. HCG interacts with the lutropin-choriogonadotropin hormone (LHCG) receptors on the ovaries and helps maintain the corpus luteum during the beginning of pregnancy. The corpus luteum helps produce the hormone progesterone during early pregnancy. Progesterone enriches the uterus with a thick lining of blood vessels and capillaries to sustain the fetus. The corpus luteum will continue to produce progesterone until the placenta produces adequate levels to maintain the pregnancy, which happens between 7 and 9 weeks. Although hCG is responsible for nausea and vomiting associated with early pregnancy, the pregnancy would not be successful without it (Betz & Fane, 2021; Lowdermilk et al., 2016). 

Pathophysiology 

HG has a complex interaction of biological, psychological, and sociocultural factors supported by many theories. The exact cause of HG is not entirely understood, which is why so many theories have been suggested to explain this disorder. In the early 1900s, theories for hyperemesis were ruled by psychological themes such as rejection of pregnancy due to embarrassment about sexual relations or fears of childbirth and motherhood. Today, the psychological and social effects of hyperemesis are likely underestimated. Pregnant individuals with HG, particularly severe HG, are at risk for psychological stress. The severity of vomiting is linked with social dysfunction, anxiety, sleep disorders, and severe depression (Dean et al., 2018; National Organization for Rare Disorders [NORD], 2020; Gabra, 2018).  

Theories used to explain the etiology of HG are genetic predisposition, the effects of increased hormone levels (i.e., estrogen and hCG), and vitamin B deficiencies. Some believe that HG evolved as a protective factor to remove dangerous substances that may cause harm to the fetus (such as pathogenic microorganisms in meat products and toxins in plants). Other possible causes of HG include hyperthyroidism, gastroesophageal reflux (GERD) associated with gastric dysrhythmias, Helicobacter pylori infections of the stomach, disturbances in carbohydrate metabolism, gall bladder dysfunction, vestibular sensitivity, dehydration, malnutrition, stress, and fatigue. Many of these theories are based on symptoms that HG itself might cause. For example, individuals diagnosed with HG often cannot tolerate food and fluid intake in pregnancy and may develop vitamin deficiencies, a thyroid imbalance, and other metabolic disturbances. This rationale makes diagnosing HG more difficult when the HCP cannot discern whether the HG or the imbalances came first (Agmon et al., 2019; NORD, 2020; Hyperemesis Education & Research [HER] Foundation, n.d.; Jennings & Mahdy, 2022; Lowdermilk et al., 2016). 

Thyroid function is altered during normal pregnancy. The rise in thyroxine-binding globulin (TBG), induced by estrogens, leads to decreased free thyroxine concentration. This negative feedback on the pituitary incites an increase in thyroid-stimulating hormone (TSH) secretion and hyperstimulation of the thyroid. Thyrotoxic crisis during pregnancy is rare, but the physiological processes described above place the mother and fetus in danger, especially in patients with pre-existing hyperthyroidism. Additionally, individuals with HG often have high hCG levels that cause brief increased activity in the thyroid gland due to activation of the TSH receptors on the thyroid gland. This thyroid gland stimulation can lead to symptoms of hyperthyroidism, such as palpitations, shortness of breath, nausea, vomiting, and diarrhea due to the increased metabolic rate. Another mechanism present is an increase in iodine clearance; this leads to hyperstimulation of the thyroid gland to compensate for a perceived deficiency. HCG levels usually peak in the first trimester, and thyroid function normalizes by the 18th week with no further intervention. HCG may not cause HG alone, but it may be indirectly involved due to thyroid stimulation (Zimmerman et al., 2022). 

Newer studies have focused on a genetic predisposition to HG. As described below, a family history of HG increases the risk of HG. A study of more than 53,000 participants using 23andMe identified an association between HG and variants in the placenta and appetite genes GDF15 and IGFBP7. Fejzo and colleagues (2019) replicated these results in a second cohort study. This second study also found that HG included variants in the GDR15 receptor gene, GFRAL, located in the brain's vomiting center. These studies determined that hyperthyroidism, malnutrition, long-term fasting, hypokalemia, and infection increased the levels of GDF15, causing a cyclical effect (Fejzo et al., 2019; NORD, 2020).  

Risk Factors 

Family history is a significant risk factor for HG since genetic predisposition in developing severe nausea and vomiting during pregnancy has been documented. Family history also significantly increases the risk to children and siblings of a person with a history of HG. Children and siblings of an individual affected by HG have a 30% higher risk of experiencing HG than the general population. Researchers also report that a history of HG in a previous pregnancy increases the risk of developing or increasing the duration of HG by 15% to 80%. Admission to the hospital due to HG during a previous pregnancy increases the risk of hospitalization during subsequent pregnancies by 29%. Evidence also supports a genetic predisposition to HG when multiple fetuses are present during pregnancy or the individual has had no previous completed pregnancies (nulliparity, during a first-time pregnancy; Dean et al., 2017; Dinberu et al., 2019; NORD, 2020; Ioannidou et al., 2019).  

Other risk factors for developing HG include a subsequent pregnancy with a current or previous molar pregnancy. Young maternal age, ethnicity, smoking status, pre-existing diabetes, body mass index (BMI) greater than 30, asthma or allergies, carrying a female fetus, history of urinary tract infections (UTIs), dysmenorrhea, or peptic ulceration also increase the risk of developing HG (NORD, 2020).  

Signs and Symptoms  

HG can develop rapidly or slowly over several weeks with a gradual increase in the severity of symptoms. Individuals with HG experience severe and persistent nausea and vomiting. Due to the inability to tolerate oral intake, HG can cause tachycardia, hypotension, weight loss, decreased skin turgor, ptyalism (excessive salivation), dehydration, dizziness, and dry mucous membranes. Some individuals may also have ketone (i.e., fruity) breath due to metabolic changes. When symptoms are severe, many individuals cannot complete activities of daily living (ADLs). Also, many affected individuals experience extreme fatigue due to a lack of caloric intake (HER Foundation, n.d.; NORD, 2020).  

Diagnosis 

The HCP should ask about symptoms, take a medical history, and perform a physical exam to assess for HG's most common signs and symptoms. The patient will be asked about the onset, duration, and frequency of nausea, a loss of appetite, feeling light-headed or dizzy, with weight loss due to the inability to keep food down. There is no single accepted definition of HG. It is generally accepted that a diagnosis of HG indicates severe nausea and vomiting during pregnancy that causes significant dehydration and weight loss not attributed to another underlying cause. Ketonuria or serum electrolyte imbalances support significant dehydration. Weight loss due to HG involves the loss of 5% of the individual's pre-pregnancy weight (Jennings & Mahdy, 2022). 

If HG is suspected, urine ketones, TSH, complete metabolic panel (CMP), complete blood count (CBC), and liver function tests should be performed. An ultrasound should also be completed to rule out a hydatidiform mole or multifetal pregnancy. Diagnosis can be difficult due to the cyclic nature and waxing and waning of symptoms of HG. Some individuals may not produce ketones, and others may not lose weight but still suffer from HG. Due to the variability and complexity of symptoms and patient presentation, the HER Foundation created the hyperemesis level prediction (HELP) score assessment. The HELP assessment requires the patient to self-report symptoms using a Likert scale. Also included is the percentage of overall body weight lost since the last visit and the number of prescriptions the patient takes to manage symptoms. Patient response trends can help detect symptom changes. A HELP score greater than 32 indicates a need for more aggressive interventions (Dulay, 2020; HER Foundation, n.d.). 

Treatment 

The goal of treatment is to reduce symptoms and improve the patient's quality of life through dietary and lifestyle modifications followed by pharmacologic therapy if needed. It is important to initiate treatment before serious complications occur to minimize the effects on the pregnant individual and the fetus (Smith et al., 2022).  

Dietary Management 

The first intervention recommended for patients suffering from nausea and vomiting during pregnancy is to switch prenatal vitamins due to the nauseating effects of iron in most. The pregnant patient should continue to take folic acid supplementation (Lowdermilk et al., 2016). Other interventions for self-management of HG include: 

• avoid an empty stomach and eat small frequent meals every 2-3 hours 

• eat a high-protein snack before going to bed and getting out of bed in the morning 

• consume cold food instead of hot food  

• eat dry, bland, low-fat, high-protein foods 

• eat what sounds good and can be tolerated instead of focusing on a balanced diet 

• eat protein after eating sweets 

• drink liquids from a cup with a lid or use a straw  

• suck on a popsicle or peppermint candies if vomiting occurs on an empty stomach  

• drink ginger ale (without artificial sweetener), ginger tea, or water with lemon  

• eliminate coffee and foods that are spicy, high-fat, acidic, odorous, and very sweet  

• consume fluids at least 30 minutes before or after meals to minimize the feeling of a full stomach; cold, clear, carbonated, or sour liquids are most likely to be tolerated (Lowdermilk et al., 2016; Smith et al., 2022) 

Ginger has been studied as a therapy to treat hyperemesis. The effectiveness of ginger is dependent on its aromatic, anti-flatulent, and absorbent characteristics. It acts on the gastrointestinal tract to increase motility, and its absorbent property may decrease stimuli to chemoreceptors in the medulla that send impulses to the emetic center of the brain stem. Ginger may also block nausea feedback and has been successfully described as an adjunct treatment for nausea and vomiting (Marx et al., 2017).  

If dietary modifications and other interventions are ineffective, the patient may need to start enteral or parental supplementations. Enteral therapy is the first choice; however, if the patient does not respond to enteral nutrition, then parenteral nutrition is used as a last resort (HER Foundation, n.d.; Lowdermilk et al., 2016).  

Lifestyle Changes  

It is important to change certain routines and avoid situations that may exacerbate the symptoms of HG. Once trigger foods are identified, avoiding these foods, even if not consuming them, is essential. For example, being in the same room while these foods are prepared can cause nausea and vomiting. Other triggers to be avoided include being in a stuffy room with minimal airflow; strong odors from perfume, candles, air fresheners, chemicals, or smoke; heat; high humidity; excessive noise or visual stimulation; or physical motion such as driving or riding in a car. Keeping upright after eating can promote gastric emptying, decreasing fullness and nausea. Brushing teeth after eating or changing toothpaste to one with less flavor can also help reduce nausea. It is also important to rest and get adequate sleep, as being tired or sleep-deprived can aggravate symptoms (Smith et al., 2022).  

Alternative Medicine 

Preventive measures may include a pericardium 6 (P6) acupressure wristband. The P6 pressure point is located on the palmar side of the wrist 5 cm proximal to the wrist crease. Compared to placebo groups, research has shown that applying pressure to this point can help patients cope with nausea and vomiting from pregnancy and anesthesia. Acupuncture may also be offered as an adjunct therapy to conventional treatment. Acupuncture therapy has no documented teratogenic side effects, and patients may appreciate the avoidance of medications. Some patients have found hypnosis to help reduce pregnancy-induced nausea and vomiting. Psychotherapy can also be effective for individuals with anxiety-related nausea and vomiting. If nausea and vomiting persist despite these strategies, antiemetic drug therapy may be the next step (Karim et al., 2019; Smith et al., 2022).  

Pharmacologic Management 

Medications to prevent nausea are used when persistent vomiting poses possible risks to the pregnant individual or baby, and other interventions have been unsuccessful. Taking medications during pregnancy may be distressing. The patient's concerns about hurting their baby may need to be addressed to avoid compliance issues. When patients avoid pharmacological intervention when indicated, it may worsen their condition. Patients must understand the risks of untreated HG on themselves and their unborn child, including dehydration, malnutrition, metabolic abnormalities, electrolyte imbalances, emotional stress, and reduced mobility. Several medications are used to control nausea and vomiting during pregnancy. The safety and benefits of any medication prescribed should be weighed carefully and collaboratively with the HCP. The inherent risks of leaving the condition untreated should be weighed against the risks of the treatment. In 2014, the US Food and Drug Administration (FDA) removed the older system of ranking medications for pregnant persons (Category A, B, C, D, and X) and now requires detailed specific information about pregnancy safety (including during labor and delivery), safety while breastfeeding, and protection for individuals of reproductive potential (HER Foundation, n.d.; US FDA Center for Drug Evaluation and Research, 2022).  

Initial treatment for HG without hypovolemia involves pyridoxine (Vitamin B6) and doxylamine (Unisom), which may be administered separately or as a combination drug (pyridoxine/doxylamine succinate [Diclegis, Bonjesta]).Doxylamine is an antihistamine, used to relieve symptoms of allergy, hay fever, and the common cold. This medication works by blocking certain natural substances (histamine, acetylcholine) that your body makes. This effect helps to relieve allergy/cold symptoms such as watery eyes, runny nose, and sneezing. Doxylamine is an antihistamine, used to relieve symptoms of allergy, hay fever, and the common cold. This medication works by blocking certain natural substances (histamine, acetylcholine) that your body makes. This effect helps to relieve allergy/cold symptoms such as watery eyes, runny nose, and sneezing. Pyridoxine safely improves nausea with minimal side effects, which is why it is considered a first-line treatment. Doxylamine succinate (Unisom) is an over-the-counter antihistamine often sold as a sleep aid that is also used to help with nausea and vomiting in pregnancy. Both medications were previously categorized under pregnancy category A by the FDA, meaning they are considered safe to use in pregnancy. The primary mechanism of antihistamines in treating nausea and vomiting during pregnancy is direct inhibition of histamine at the H1 receptor. The secondary mechanism indirectly affects the vestibular system by decreasing the stimulation of the vomiting center. Doxylamine succinate (Unisom) can cause drowsiness, and patients are cautioned to avoid driving after taking this medication. Antihistamines can also cause dry mouth and dry nasal passages. Additionally, antihistamines should be avoided in people taking ondansetron (Zofran) or other medications that prolong the QT interval. If symptoms do not resolve, pyridoxine/doxylamine succinate (Diclegis, Bonjesta) should be discontinued, and a different antihistamine such as dimenhydrinate (Dramamine), diphenhydramine (Benadryl), or meclizine (Antivert) should be initiated (Jennings & Mahdy, 2022; Smith et al., 2022). 

Second-line medications include dopamine antagonists. Several classes of dopamine receptor antagonists can be used for nausea and vomiting, but the most common include benzamides (metoclopramide [Reglan]), phenothiazines (promethazine [Phenergan], prochlorperazine [Compazine]), and butyrophenones (droperidol [Marinol]). These medications are thought to stimulate gastric motility and emptying, resulting in antiemetic effects. Blockage of dopamine 2 receptors is also believed to block emetic signaling. Metoclopramide (Reglan) is one of the most commonly prescribed medications for nausea and vomiting. It was previously an FDA pregnancy category B, meaning it is likely safe and is not associated with any congenital fetal malformations. Prochlorperazine (Compazine) and promethazine (Phenergan) were previously category C drugs, meaning that risk to the fetus cannot be ruled out. Common side effects of these medications include drowsiness, dizziness, headaches, and urinary retention (Smith et al., 2022).  

If symptoms continue despite treatment, a serotonin antagonist can be added. Ondansetron [Zofran] is a selective antagonist at the 5-hydroxytryptamine-3 (5-HT3) serotonin receptor. Although commonly used in nonpregnant individuals, the use of ondansetron [Zofran] during pregnancy is controversial. Some organizations recommend not initiating ondansetron [Zofran] until the second trimester due to an increased risk of oral palate and ventricular septal defects. Common side effects include headache, fatigue, constipation, and drowsiness (HER Foundation, n.d.; Smith et al., 2022).  

Ranitidine (Zantac) and famotidine (Pepcid) are histamine H2 -receptor antagonists developed for treating GERD. Both were previously category B medications indicating they are likely safe to use during pregnancy. These medications will sometimes work for the pregnant patient experiencing nausea and vomiting if the nausea is triggered by stomach or intestinal problems (HER Foundation, n.d.).  Doxylamine is an antihistamine, used to relieve symptoms of allergy, hay fever, and the common cold. This medication works by blocking certain natural substances (histamine, acetylcholine) that your body makes. This effect helps to relieve allergy/cold symptoms such as watery eyes, runny nose, and sneezing. 

If all other measures fail, corticosteroids are used as a last resort for severe nausea and vomiting. Although the symptoms improve dramatically with corticosteroids, this therapy should not be initiated before 10 weeks of gestation secondary to associated congenital malformations like cleft palate in neonates. Prednisone (Deltasone) was previously a category D drug indicating some risk to the fetus, and methylprednisolone (Medrol) was a category C meaning that risk cannot be ruled out (HER Foundation, n.d.; Lowdermilk et al., 2016). 

An alternate administration route should be used if the individual cannot take medications by mouth due to severe HG. Medications may need to be administered intravenously, intramuscularly, rectally, or vaginally (Lowdermilk et al., 2016). 

Restoring Homeostasis 

Fiaschi and colleagues (2019) described four main categories for treatment based on the care setting and severity of HG:  

1. primary care diagnosis only 

2. treatment in primary care 

3. early hospital admissions (before 20 weeks' gestation) 

4. late hospital admissions 

A pregnant person needs to maintain fluid intake. Pregnancy increases the demand for hydration to form amniotic fluid, increase blood volume, build new tissues, transport nutrients, improve digestion, and eliminate wastes or toxins. For those individuals diagnosed with HG and demonstrating compromised physical functioning, immediate hospitalization to restore fluids and replace electrolytes by infusing intravenous (IV) medication and fluids is the treatment of choice. Food should not be given orally until vomiting stops and dehydration has been corrected. Instead, nutrition may be provided by enteral or parenteral routes (Fiaschi et al., 2019; Jennings & Mahdy, 2022).  

The type of treatment required depends on patient presentation and laboratory results. IV fluid resuscitation is indicated when vomiting cannot be controlled, and correction of fluid and electrolyte imbalances is needed. In the past, patients would need to be admitted to the hospital for IV fluid administration; however, this can now be managed in the patient's home. In severe cases requiring close monitoring of laboratory values, hospitalization is indicated. Fluid resuscitation and the replacement of electrolytes are crucial in treating hyperemesis. Normal saline or lactated ringers are suitable solutions; potassium chloride can be added as needed to correct hypokalemia common in HG. After prolonged and persistent vomiting, vitamins and minerals may also deplete and require replacement. The optimum fluid replacement protocol has not been established; however, IV fluids with dextrose should be avoided without first administering 100 mg of thiamine IV due to the risk of inducing encephalopathy. Wernicke's encephalopathy is a degenerative brain disease affecting the thalamus and hypothalamus caused by a lack of thiamine. IV fluids may be discontinued once the patient tolerates oral intake (Dulay, 2020; Smith et al., 2022). 

Enteral feedings via nasogastric tube can provide needed fluids and nutrients to patients experiencing HG, but the literature is mixed regarding overall efficacy. For example, Grooten and colleagues (2017) found that early enteral tube feeding in pregnant individuals diagnosed with HG did not improve birth weight or overall fetal outcomes. Many individuals requested that tube feedings be discontinued due to discomfort, indicating that it was poorly tolerated as an early treatment of HG. Van Vliet and colleagues (2018) discussed perceptions of patients treated with tube feedings. They shared that it might have been beneficial to prevent weight loss, ensure essential nutrition to the fetus, and reduce vomiting due to an empty stomach. However, no definitive information was found to support the benefits outweighing the risks or inconvenience of enteral feedings, and it remains a treatment option for individuals experiencing HG (van Vliet et al., 2018). 

The most severe cases of HG might require total parenteral nutrition (TPN), a complex, balanced solution of nutrients to be given via IV throughout pregnancy. This treatment is indicated in prolonged cases of HG when there is a concern for long-term outcomes due to hypovolemia and nutritional deficits. Researchers found that TPN support during early pregnancy was associated with a decreased risk for perinatal morbidity in patients experiencing HG. Vitamin supplementation (particularly vitamins B6, C, and thiamine) is also recommended. Thiamine supplementation is critical; 100 mg IV should be administered daily until laboratory values are stable and dietary intake returns to baseline (HER Foundation, n.d.; NORD, 2020). 

Nursing Implications 

Trovik and Vikanes (2019) recommend that improved treatment for patients suffering from nausea and vomiting in pregnancy is needed. Strategies include better awareness of the impact this condition has on a pregnant person's quality of life and educating care providers regarding medication best practices to relieve symptoms earlier. It is important to decide on the correct regimen and ensure the medication is tolerated and taken correctly for optimal effectiveness. Early pregnancy symptoms are challenging to manage as symptoms generally increase until the end of the first trimester. Many variables affect responsiveness to medications, such as hydration and nutritional status, duration of symptoms, and medication interactions. These must be considered when assessing a pregnant individual's response. Additionally, minimizing changes to doses and regimens when symptoms improve can prevent relapse, especially during initial recovery (Trovik & Vikanes, 2019). 

Van Vliet and colleagues (2018) interviewed individuals affected by HG. Interviewees emphasized the importance of early recognition of the severity of HG, increasing caregivers' knowledge of HG, early medical intervention, and nasogastric tube feeding (when appropriate). Participants also valued a private room in the hospital to avoid exposure to environmental stimuli, which increased symptoms (odors, noise, stress). Additionally, discussion of treatment options, more possibilities of home-based treatment, psychological support during HG and after childbirth, and more uniform information and policies regarding HG treatment were identified during qualitative interviews to improve evidence-based practice (van Vliet et al., 2018). 

Future Research  

More effective antiemetic drugs approved for nausea and vomiting in pregnancy would assist the pregnant individual in maintaining adequate hydration and nutrition throughout their pregnancy. More effective and safe medications are needed to improve patient outcomes. The association between HG and adverse pregnancy outcomes remains an issue of considerable controversy. These adverse outcomes include maternal complications and neonatal adverse effects such as placental dysfunction disorders (e.g., intrauterine growth restriction, preeclampsia, and stillbirth). Given this lack of clarity, the association between HG and adverse pregnancy outcomes should be further researched. The degree of severity associated with HG diagnosis has not been consistently described in the literature, and no clear definitions exist. Investigating whether the severity of the disorder is clinically significant and related to outcomes with consistent guidelines to document patient cases would be an essential step (Agmon et al., 2019; Trovik & Vikanes, 2019). 

References  

Agmon, N., Sade, S., Pariente, G., Rotem, R., & Weintraub, A. Y. (2019).  Hyperemesis gravidarum and adverse pregnancy outcomes. Archives of Gynecology & Obstetrics, 300(2), 347-353. https://doi.org/10.1007/s00404-019-05192-y 

Betz, D., & Fane, K. (2021). Human chorionic gonadotropin. StatPearls [Internet]. https://www.ncbi.nlm.nih.gov/books/NBK532950/ 

Dean, C., Bannigan, K., O'Hara, M., Painter, R., & Marsden, J. (2017). Recurrence rates of hyperemesis gravidarum in pregnancy: A systematic review protocol. JBI Database of Systematic Reviews and Implementation Reports, 15(11), 2659-2665. https://doi.org/10.11124/JBISRIR-2016-003271 

Dean, C., Bannigan, K., & Marsden, J. (2018). Reviewing the effect of hyperemesis gravidarum on women's lives and mental health. British Journal of Midwifery, 26(2), 109-119. https://doi.org/10.12968/bjom.2018.26.2.109 

Dinberu, M. T., Mohammed, M. A., Tekelab, T., Yimer, N. B., Desta, M., & Habtewold, T. D. (2019). Burden, risk factors and outcomes of hyperemesis gravidarum in low-income and middle-income countries (LMICS): Systematic review and meta-analysis protocol. BMJ Open, 9, e025847. https://doi.org/10.1136/bmjopen-2018-025841 

Dulay, A. T. (2020). Hyperemesis gravidarum. Merck Manual Professional Version. https://www.merckmanuals.com/professional/gynecology-and-obstetrics/abnormalities-of-pregnancy/hyperemesis-gravidarum 

Fejzo, M. S., Trovik, J., Grooten, I. J., Sridharan, K., Roseboom, T. J., Vikanes, A., Painter, R. C., & Mullin, P. M. (2019). Nausea and vomiting of pregnancy and hyperemesis gravidarum. Nature Reviews Disease Primers, 5(62). https://doi.org/10.1038/s41572-019-0110-3 

Fiaschi, L., Nelson, P. C., Deb, S., King, R., & Tata, L. (2019). Clinical management of nausea and vomiting in pregnancy and hyperemesis gravidarum across primary and secondary care:  A population-based study. British Journal of Obstetrics & Gynaecology, 126(10), 1201-1211. https://doi.org/10.111/1471-0528.15662 

Gabra, A. (2018). Complications of hyperemesis gravidarum: A disease of both mother and fetus, review article. Critical Care Obstetrics and Gynecology, 5(1). https://doi.org/10.21767/2471-9803.1000168 

Grooten, I. J., Koot, M. H., van der Post, J. A., Baise, J. M., Ris-Stalpers, C., Naaktgeboren, C., Bremer, H. A., van der Ham, D. P., Heidema, W. M., Huisjes, A., Kleiverda, G., Kuppens, S., van Laar, J. O., Langenveld, J., vander Made, F., van Pampus, M. G., Papatsonis, D., Pelinck, M.-J., Pernet, P. J., . . . Painter, R. C. (2017). Early enteral tube feeding in optimizing treatment of hyperemesis gravidarum: The maternal and offspring outcomes after treatment of hyperemesis by refeeding (MOTHER) randomized controlled trial. The American Journal of Clinical Nutrition, 106(3), 812-820. https://doi.org/10.3945/ajcn.117.158931  

HER Foundation. (n.d.). About HG. Retrieved July 5, 2022, from https://www.hyperemesis.org/who-we-help/healthcare-providers/about-hg-for-pros/ 

Ioannidou, P., Papanikolaou, D., Mikos, T., Mastorakos, G., & Goulis, D. G. (2019). Predictive factors of hyperemesis gravidarum: A systematic review. European Journal of Obstetrics & Gynecology & Reproductive Biology, 238, 178-187. https://doi.org/10.1016/j/ejogrb.2019.04.043 

Jennings, L. K., & Mahdy, H. (2022). Hyperemesis gravidarum. StatPearls [Internet]. https://www.ncbi.nlm.nih.gov/books/NBK532917/ 

Karim, F., Dilley, J., & Cheung, E. (2019). A review of acupuncture in obstetrics and gynecology. Obstetrician & Gynaecologist, 21(3), 209-214. https://doi.org/10.1111/tog.12574 

Lowdermilk, D. L., Perry, S. E., Cashion, K., & Olshansky, E. F. (2016). Maternity & women's health care (11th ed.). Elsevier.  

Marx, W., Ried, K., McCarthy, A. L., Vitetta, L., Sali, A., McKavanagh, D., & Isenring, L. (2017). Ginger - Mechanism of action in chemotherapy-induced nausea and vomiting: A review. Critical Reviews in Food Science and Nutrition, 57(1), 141-146. https://doi.org/10.1080/10408398.2013.865590 

National Organization for Rare Disorders. (2020). Hyperemesis gravidarum. https://rarediseases.org/rare-diseases/hyperemesis-gravidarum/ 

Smith, J. A., Fox, K. A., & Clark, S. M. (2022). Nausea and vomiting of pregnancy: Treatment and outcome. UpToDate. Retrieved July 5, 2022, from https://www.uptodate.com/contents/nausea-and-vomiting-of-pregnancy-treatment-and-outcome?search=hyperemesis-gravidarum 

Trovik, J., & Vikanes, A. V. (2019). Antiemetics in hyperemesis gravidarum: Unawareness or negligence? British Journal of Obstetrics & Gynaecology, 126(10), 1201-1211. https://doi.org/10.111/1471-0528.15824  

US Food and Drug Administration Center for Drug Evaluation and Research. (2022). Drug safety and availability - Medication guides. https://www.fda.gov/Drugs/DrugSafety/ucm085729.htm 

van Vliet, R., Bink, M., Polman, J., Suntharan, A., Grooten, I., Zwolsman, S. E., Roseboom, T. J., & Painter, R. C. (2018). Patient preferences and experiences in hyperemesis gravidarum treatment: A qualitative study. Journal of Pregnancy, 5378502. https://doi.org/10.1155/2018/5378502 

Zimmerman, C. F., Ilstad-Minnihan, A. B., Bruggeman, B. S., Bruggeman, B. J., Dayton, K. J., Joseph, N., Moas, D. I., & Rohrs, H. J. (2022). Thyroid storm caused by hyperemesis gravidarum. AACE Clinical Case Reports, 8(3), 124-127. https://doi.org/10.1016/j.aace.2021.12.005