A practical approach to hyperemesis gravidarum

VOMITING DURING PREGNANCY A practical approach to hyperemesis gravidarum By T. Murphy Goodwin, MD Delay in aggressively treating out-of-control, unremitting vomiting in pregnancy can dehydrate, deplete, and nearly starve a woman and her fetus. This expert's approach tells you how to quickly distinguish developing hyperemesis gravidarum from something more benign. Because mild nausea and vomiting of pregnancy (NVP) significantly diminish quality of life for up to 35% of pregnant women, clinicians need to identify and treat it early on. Untreated, some cases of NVP will progress to hyperemesis gravidarum (HG), which can lead to esophageal tearsand even Wernicke's encephalopathy. This condition, which affects up to 20 of every 1,000 pregnancies, is defined as persistent, otherwise unexplained NVP that leads to weight loss (usually of 5% or more) with or without electrolyte disturbances. Since the weight loss criterion can be hard to pin down, women who require hospital admission for hydration are more likely to be diagnosed. My goal here is to review the differential diagnosis of HG, emphasizing the need to quickly identify and treat it aggressively, and to share the treatment approach we use at our institution, which balances safety and efficacy. Puzzling out HG's etiology We don't know what causes HG. It's likely that for most patients the disorder represents the far end of the spectrum of NVP, which affects up to 90% of pregnant women. It is clear that some substance produced by the placenta triggers NVP, given that conditions with large placental mass, like advanced molar gestation and multiple gestation, are linked with higher rates of HG. Of the many hormonal products of the placenta studied for their association with HG, only hCG and estradiol have been found to have a link, although even for these hormones, there are conflicting data. Although the correlation between symptoms of NVP and total hCG concentration is weak, the correlation with various isoforms of hCG may be stronger. Between 50% and 70% of women with hyperemesis will have biochemical hyperthyroidism, which is due to hCG.1 The degree of thyroid stimulation varies directly with the severity of vomiting, suggesting that isoforms of hCG with a greater thyrotropic effect have a stronger relationship to HG.2 We know that estrogen can induce vomiting. Several studies show greater concentrations of estradiol in women with HG versus controls, and isoforms of hCG (which have a stronger gonadotropic effect) correlate with estradiol levels in hyperemesis.2 Some investigators suggest a role for cytokines in HG, while still others have found greater serum concentrations of TNF- in women with hyperemesis.3 Interestingly, TNF- , Il-1 and I1-6 are all involved in regulating hCG production in the placenta. Several studies have also linked Helicobacter pylori and HG, but the data are conflicting. Of four that showed an association, roughly 50% of women without HG and 80% with HG were H pylori positive on serum assays. In other words, the vast majority of women seropositive for H pylori do not develop the condition. Women with HG are no more likely to test positive for H pylori on a biopsy or breath test (which would indicate active disease), casting further doubt on a direct association. While unproven, several case reports of apparent response to standard H pylori treatment have prompted some physicians to take that approach as a last resort for intractable HG. Migraineurs and other women are more susceptible Many factors can predispose a pregnant woman's response to the aforementioned placental stimuli. Women with a history of motion sickness, migraine headache, oral contraceptive sickness, or a family or personal history of HG are more likely to develop the disorder. Research also points to differences in sensitivity to taste and smell. Some women seem to have a lower threshold to vomiting by the classic pathwayslike vestibular or gastrointestinalwhich could make them more susceptible to the new, emetogenic stimulus of pregnancy. In this sense, there are many distinct pathways leading to the syndrome of NVPwhich may partially explain why no single therapeutic approach to HG succeeds.4 Debunking untenable theories and myths Other researchers have promoted the theory that NVP is one way that the body avoids teratogen exposure in early pregnancy. In this view, NVP is generally not something to be treated but actually improves pregnancy outcome.5 Key problems with this theory are an incomplete understanding of environmental teratogenesis and a controversial interpretation of cause and effect from the data that show better outcomes in NVP pregnancies. It's unclear whether this putative adaptive process benefits the woman at this point in the course of evolution. This theory can deter clinicians from treating the roughly 35% of pregnant women for whom NVP significantly diminishes quality of life. As I've mentioned, the weight of evidence suggests NVP and HG are part of a continuumand there's also evidence that early treatment of NVP reduces the incidence of HG. A second theory centers on the body's adaptation to the reduced nutrient intake that occurs as a result of NVP, suggesting that it stimulates the expression of growth factors; this is thought to affect placentation and metabolism in a way that favors fetal growth, once NVP resolves.6 One of the most enduring myths about hyperemesis is that underlying psychiatric or personality disorders predispose some women to the condition. Recent studies, however, have found that a variety of abnormal personality features including anxiety, depression, and somatization may occur as a response to HG. Women with a history of HG, examined in the nonpregnant state, do not differ from women who were pregnant without HG.7 Onset of symptoms and complications About two thirds of women with severe NVP in one pregnancy will suffer just as much in a subsequent pregnancy. Some 13% of patients with NVP report the onset of symptoms at around the time of their missed period (4 weeks' gestation) and virtually all women who develop NVP or HG experience at least some symptoms by 9 weeks. Typically, symptoms cease for 30% of women by 10 weeks, for another 30% by 12 weeks, and a further 30% by 16 weeks. The daily variation in symptoms in NVP is less pronounced in HG but there is still a tendency for lesser symptoms in the late evening and night.8 Be prepared for the most dire complication Among the many complications of hyperemesis are Mallory Weiss tears of the esophagus, esophageal rupture, pneumomediastinum, splenic avulsion, and central pontine myelinolysis. Between 30% and 40% of women with vomiting of pregnancy salivate excessively. But by far the most serious direct complication is Wernicke's encephalopathy. This condition, which involves the classic triad of ataxia, nystagmus, and dementia in women with hyperemesis, can be tricky to recognize, given its more subtle presentation. Of the more than 30 known cases during pregnancy over the last 20 years, almost 70% of women presented with only confusion or blunted affect as the primary neurologic sign. The dementia most often surfaces as memory loss, which may go undetected during routine admission assessment. Importantly, most women diagnosed with this condition due to HG who survive will experience long-term ataxia or memory loss.9 An infusion of dextrose given to a woman whose stores of thiamine (vitamin B1) have been depleted by HG is typically what precipi-tates Wernicke's encephalopathy. Because every reported case of Wernicke's has occurred in patients who had been vomiting for at least 3 weeks, we're assuming that clinicians don't have to be too concerned about this complication before that cutoff. In a patient with persistent vomiting, it's essential to replace the presumed thiamine deficit. A common regimen is 100 mg of thiamine IV daily for 3 days, but be sure to give the first dose before giving the dextrose. The average multivitamin preparation (oral or IV) for daily administration contains only 3 mg of thiamine, not sufficient for replacement. Fetal effects include low birthweight Women who suffer from HG are significantly less likely to spontaneously abort. Birth defects (especially cardiac defects) are also less common according to most reports, although patients with Down syndrome are overrepresented among women with HG compared to controls. The principal adverse fetal effect of HG is a higher rate (about 30%) of low birthweight infants among mothers with HG who lose weight in early pregnancy.10 The long-term effects of HG on the fetus are unknown. Long-term follow up of children whose mothers suffered severe caloric restrictioneven those whose insult was limited to the first trimestershows significant increases in adult diseases like cardiovascular, pulmonary, and affective disorders, as well as higher rates of obesity.11-13 Since HG can cause a similar state of starvation, we recommend aggressive nutritional support for mothers with persistent weight loss. One of HG's most tragic consequences is the termination of a previously desired pregnancy. Surveys show that under-treatment and misinformation often affect a woman's decision. Women with HG may consider abortion, for example, because they think the condition or treatment is harming the fetus. In one study, most women contemplating abortion had received no specific medical therapy for HG by the time they were deciding whether to proceed with abortion.14 Differential diagnosis and lab abnormalities While NVP is the most likely reason for persistent nausea and vomiting during pregnancy, you'll first want to rule out the other causes (Table 1). Symptoms of NVP will begin by 9 weeks' gestation; therefore, nausea and vomiting that starts any later is rarely due to NVP. Other important points in the patient's history are maternal conditions that can involve vomiting like diabetes, porphyria, cholelithiasis, or migraine headaches. TABLE 1 What else besides hyperemesis gravidarum can cause nausea and vomiting? Gastrointestinal Gastroenteritis Gastroparesis Achalasia Biliary tract disease Hepatitis Intestinal obstruction Peptic ulcer disease Pancreatitis Appendicitis Genitourinary tract Pyelonephritis Uremia Ovarian torsion Kidney stones Degenerating uterine leiomyoma Metabolic Diabetic ketoacidosis Porphyria Addison's disease Hyperthyroidism Neurologic disorders Pseudotumor cerebri Vestibular lesions Migraine headaches CNS tumors Pregnancy-related conditions Acute fatty liver of pregnancy Preeclampsia Miscellaneous Drug toxicity or intolerance Psychologic factors Source: Adapted with permission from Goodwin TM. Hyperemesis gravidarum. Clin Obstet Gynecol. 1998;41:597-605. Although no findings on physical examination are unique to HG, several may clarify the differential diagnosis. With HG, you won't see abdominal tendernessother than mild epigastric discomfort after retching. Pain that precedes or is out of proportion to the vomiting suggests an intra-abdominal or retroperitoneal cause. Fever is not present in HG, but is characteristic of many other diseases associated with nausea and vomiting. Nor is headache characteristic of HG. An abnormal neurologic exam suggests a primary neurologic disorder as the cause of the nausea and vomiting. In rare cases, however, it may be encountered as a consequence of HG (for example, Wernicke's encephalopathy or central pontine myelinolysis). Finally, although you may see biochemical hyperthyroidism with HG, don't expect to find a goiter. The presence of a goiter suggests primary thyroid disease. Lab values. From 20% to 30% of women will have mildly elevated liver enzymes (usually <300 U/L) and serum bilirubin (<4 mg/dL); between 10% and 15% will have serum concentrations of amylase and lipase that are up to five times normal levels. Rarely, you'll see significant cholestasis and even liver dysfunction (with a prolonged prothrombin time). Liver enzyme elevations are much higher with primary hepatitis, often in the thousands, and the bilirubin concentration is usually much higher as well. Acute pancreatitis may cause vomiting and hyperamylasemia, but serum amylase is usually five to 10 times higher than elevations associated with NVP. Electrolyte abnormalitiesmost commonly hypokalemia, hyponatremia, and hypochloremic metabolic alkalosisare found in 15% to 25% of cases. With severe volume contraction, a metabolic acidemia may be seen. All abnormalities have been reported to regress with adequate volume and nutritional support. Transient hyperthyroidism. From 50% to 70% of women with hyperemesis will have transient hyperthyroidism. Three findings that usually distinguish it from intrinsic thyroid disease are: no history of hyperthyroid symptoms before pregnancy, the absence of goiter and thyroid antibodies, and the fact that triiodothyronine (T3) is much less commonly elevated than thyroxine (T4). Rarely are there symptoms of hyperthyroidism, except for occasional tachycardia. The self-limited condition, which is due to the effect of hCG on the TSH receptor, does not require antithyroid therapy.15 Because the severity of NVP and the TSH concentration are inversely related, a nonsuppressed TSH level suggests that the nausea and vomiting is due to something other than NVP. A TSH level greater than 2.0 mIU/L is rare with severe NVP, unless the patient has preexisting hypothyroidism. Initial evaluation When the diagnosis of HG is considered for the first time, an ultrasound should be performed to identify conditions known to be associated with HG such as molar gestation or multiple gestation. The laboratory workup should include a urinalysis for ketones and serum electrolytes. Since liver injury or dysfunction, or both, appear to identify a group of patients with a more complicated course, it is our practice to check transaminases and bilirubin when admission is required. Amylase and lipase should be ordered if epigastric abdominal pain is a prominent symptom. Thyroid tests, although often abnormal, are not generally helpful in managing HG except as described above. Unless findings suspicious for complete or partial molar gestation are noted on U/S, a serum hCG concentration is not helpful. Dietary and antiemetic treatment No dietary recommendations for HG have been studied systematically. Management usually begins with a recommendation for small, frequent high-carbohydrate, low-fat meals; frequent fluid intake is also important. However, in the lone analytic study, protein-rich meals alleviated nausea and associated gastric dysrhythmias more than high-fat or high-carbohydrate meals.16 Antiemetic therapy. A rational approach to treatment should balance safety (lack of teratogenesis) and efficacy. Because preconceptional multivitamin therapy has been linked with fewer hospital admissions for HG, we recommend it to patients who've suffered from HG in previous pregnancies, since about two thirds of them will have similar symp-toms in subsequent pregnancies.17 As hyperemesis is part of the spectrum of NVP, it's difficult to know when to move on to specific antiemetic therapy. From 1957 to 1983, approximately one third of all pregnant women received Bendectin for NVP. (Bendectin originally consisted of doxylamine 10 mg, pyridoxine 10 mg, and the anticholinergic dicyclomine. Later the third ingredient was dropped from the formulation when it failed to increase effectiveness.) This number corresponds to the 35% of pregnant women who say they suffer from some degree of disability due to NVP. With the withdrawal of Bendectin from the market and the fear of litigation over teratogens, clinicians tended to avoid specific treatment. But there is evidence that failure to treat NVP early on leads to a greater risk of subsequent hospitalization.18 Our treatment approach In our institution, we use a treatment algorithm modified from one proposed by Levichek.19 We assume, of course, that clinicians who use this approach will have first ruled out other causes of NVP and will consider parenteral nutrition if dehydration or persistent weight loss is noted at any step. Step 1: vitamins. Our first step is to give 10 to 25 mg pyridoxine (vitamin B6 ), three times daily, the effectiveness of which is supported by two randomized controlled trials. (Pyridoxine can also be given four times daily, but do not exceed 100 mg daily.) There is no concern for fetal effects. There have been some reports of peripheral neuropathy due to pyridoxine toxicity with low doses but the US National Academy of Sciences concluded that a dose of up to 100 to 200 mg daily is safe. Step 2: antihistamine. If patients don't get relief within 2 days, you may addthree or four times daily depending on severity of symptoms12.5 mg of doxylamine, an antihistamine with H-1 receptor antagonist properties. Currently, doxylamine is available in the United States over the counter as Unisom SleepTabs, 25 mg (note that the active ingredient in Unisom SleepGels is diphenhydramine, not doxylamine). To create a combination similar to Bendectin, divide the doxylamine tablet in half. One half tab can be taken with the pyridoxine morning, noon, and evening and a whole tab taken at bedtime. The effectiveness of this combination in the form of Bendectin is well-known, and paradoxically, we know more about its safety than almost any other medication used in pregnancy. Another alternative is to seek out a local compounding pharmacy that will formulate the pyridoxine/doxylamine combination. Plans are underway to re-introduce this combination into the US in the form of Diclectin, which is currently available in Canada. Alternative therapies at any time. Add alternative therapies at any time during treatment if your patient is willing and you're familiar with them. You can try acupressure for patients who do not benefit from steps 1 and 2, or even at the outset, as a first-line alternative before therapy with B6. Several studies support its effectiveness for NVP.20 Although there are conflicting data, it's clearly safe and need not be expensive. Acupressure bands (e.g., Sea Bands) can be purchased over the counter for around $10. Recently, transcutaneous electrical stimulation of the P6 acupressure point (ReliefBand) has been shown to reduce nausea and vomiting and promote weight gain in NVP.21 The device used in the study costs around $200. Another possible option is to give ginger capsules, at a suggested dose of 250 mg, four times daily. Two randomized trials support the efficacy of ginger in treating NVP, and it appears to be safe. Reports of possible mutagenic effects in vitro are balanced by reports of antimutagenic properties. Another recent study with an infant follow-up report of 187 fetuses exposed to ginger in utero found no increase in birth defects noted at birth.22 Drugs vs. hydration. Drugs in each major class of antiemetic have been used to treat NVP but few have been subjected to RCTs. (Those that have been include the antihistamines dimenhydrinate and doxylamine; the benzamide trimethobenzamide, the phenothiazine promethazine, the 5-HT-receptor antagonist ondansetron, and miscellaneous corticosteroids.) While there are no data suggesting that commonly used antiemetics are teratogenic, we also don't have the level of safety data for them that we do for first-generation antihistamines and Bendectin. Because safety and efficacy data are mixed, we'll discuss these drugs in no particular order . If your patient is not dehydrated and can tolerate the medicine by mouth, we recommend one of the following drugs: Metoclopramide (Reglan), 5 to 10 mg every 8 hours orally, or Promethazine, 12.5 to 25 mg every 4 hours, IM, orally, or rectally, or Trimethobenzamide (Tigan), 200 mg every 6 to 8 hours rectally. Therapy differs for the dehydrated patient who does not tolerate drugs by mouth, beginning with IV fluid replacement. In addition, for every woman who requires IV hydration and has been vomiting for more than 3 weeks, we recommend 100 mg thiamin IV daily for 2 to 3 days. Next, prescribe one of three drugs (listed in alphabetical order): Dimenhydrinate (Dramamine injection), 50 mg (in 50 mL saline, over 20 minutes) every 4 to 6 hours IV, or Metoclopramide (Reglan), 5 to 10 mg every 8 hours IV, or Promethazine (Phenergan), 12.5 to 25 mg every 4 hours IV. At this point, add either one of the following: Methylprednisolone (Medrol), 16 mg every 8 hours either orally or IV for 3 days. Taper over 2 weeks to the lowest effective dose and do not use for more than 6 weeks (bearing in mind that steroids appear to increase the risk for oral clefts in the first 10 weeks of pregnancy), or Ondansetron (Zofran), 8 mg, over 15 minutes every 12 hours IV. (Note that its safety, particularly in the first trimester, has not yet been determined. It also has less effect on nausea.) Other regimens One regimen that deserves special mention is continuous droperidol infusion.23 In December, 2001, the FDA issued a "Black Box Warning" for this drug because of a reported link with a potentially fatal arrhythmia: torsades de pointes. The agency's recommendation that continuous cardiac monitoring be in place whenever droperidol is used by continuous infusion is impractical for the treatment of hyperemesis. The basis for this recommendation has been debated and may exaggerate the risk based on a few cases not applicable to all patient populations. Anticholinergic agents like trihexyphenidyl or amitriptyline, have been used to treat nonpregnant patients with drug-induced hypersalivation, but there are no data on their use in HG patients with hypersalivation. Some researchers recommend corticosteroids for women who have failed other antiemetic regimens and especially those with persistent weight loss who will require nutritional support. Small series and one RCT suggest some benefit, but there are conflicting data.24 It's possible that the reason patient response to drug therapy varies so widely is related to the different pathways that mediate susceptibility to vomiting. Perhaps women with a history of motion sickness differ from those with a history of migraine or those who are easily hypnotized. It's also possible that women with hyperemesis vomit in part because of a conditioned response to various olfactory, visual, or other stimuli in the home or hospital environments. Many studies of chemotherapy-induced vomiting describe this phenomenon of "anticipatory NV."25 Interestingly, anticipatory NV by a woman under-going chemotherapy doesn't respond to antiemetic drugs but does improve with behavioral approaches. A similar phenomenon may explain a portion of HG symptoms, which may account for the reported success of hypnosis by several researchers.26 Continued weight loss requires nutritional support When vomiting cannot be sufficiently controlled to allow the pregnant mother to maintain her weight, we strongly recommend considering nutritional support. A few small series have examined enteral nutrition in HG. Of these, the most common regimens used a weighted tube that's allowed to migrate beyond the pylorus, which usually prevents regurgitation of the supplements placed in the stomach. There are no data on how well patients accept the technique and it's still possible for a postpyloric tube to be expelled in a paroxysm of retching. Nevertheless, it's a safe means of adding calories and can be used indefinitely with few reported complications The peripheral IV may be used for caloric supplementation. To achieve the highest number of calories with the least stress on the vein, a relatively high percentage of the calories must be from fat. A common formulation of D5, 3% protein, and 50 g of fat will yield 790 calories per liter. This is recommended as a bridge to definitive supplementation or in cases where you can reliably anticipate that this intervention won't be needed for more than a few days Peripheral IV won't suffice, though, and you must obtain central access when a patient requires complete caloric replacement indefinitely. It's the rare patient who needs this kind of last-resort approach. While studies show it's clearly an effective way to provide calories, many complications may arise. In the only series to examine a substantial number of consecutive cases of central venous access in pregnancy, three of 16 women developed central line sepsis and two others developed thrombosis and line dislodgment.27 Maternal deaths have been reported from complications of central venous access for caloric supplementation in HG. Serious complications are reported, even with the use of the peripherally inserted central catheter (PICC), but the latter technique does appear to be less morbid than direct central access.28 For this reason, we favor a PICC line if central access is needed in pregnancy.27 REFERENCES 1. Goodwin TM, Hershman JM. Hyperthyroidism due to inappropriate production of human chorionic gonadotropin. Clin Obstet Gynecol. 1997;40:32-44. 2. Jordan V, Grebe SK, Cooke RR, et al. Acidic isoforms of chorionic gonadotropin in European and Samoan women are associated with hyperemesis gravidarum and may be thyrotrophic. Clin Endo Crinol (Oxf). 1999;50:619-627. 3. Kaplan PB, Gucer F, Sayin NC, et al. Maternal serum cytokine levels in women with hyperemesis gravidarum in the first trimester of pregnancy. Fertil Steril. 2003;79:498-502. 4. Goodwin TM. Nausea and vomiting of pregnancy: an obstetric syndrome. Am J Obstet Gynecol. 2002; 186:S184-S189. 5. Flaxman SM, Sherman PW. Morning sickness: a mechanism for protecting mother and embryo. Q Rev Biol. 2000;75(2):113-148. 6. Huxley RR. Nausea and vomiting in early pregnancy: its role in placental development. Obstet Gynecol. 2000;95:779-782. 7. Buckwalter JG, Simpson SW. Psychological factor in the etiology and treatment of severe nausea and vomiting in pregnancy. Am J Obstet Gynecol. 2002;186:S210-S214. 8. Gadsby R, Barnie-Adshead AM, Jagger C. A prospective study of nausea and vomiting during pregnancy. Br J Gen Pract. 1993;43:245-248. 9. Spruill SC, Kuller JA. Hyperemesis gravidarum complicated by Wernicke's encephalopathy. Obstet Gynecol. 2002;99:875-877. 10. Gross S, Librach C, Cecutti A. Maternal weight loss associated with hyperemesis gravidarum: a predictor of fetal outcome. Am J Obstet Gynecol. 1989;160:906-909. 11. Ravelli AC, van der Meulen JH, Osmond C, et al. Obesity at the age of 50 y in men and women exposed to famine prenatally. Am J Clin Nutr. 1999;70:811-816. 12. Lopuhaa CE, Roseboom TJ, Osmond C, et al. Atopy, lung function, and obstructive airways disease after prenatal exposure to famine. Thorax. 2000;55:555-561. 13. Hoek HW, Brown AS, Susser E. The Dutch famine and schizophrenia spectrum disorders. Soc Psychiatry Psychiatr Epidemiol. 1998;33:373-379. 14. Mazzota P, Magee L, Koren G. Therapeutic abortions due to severe morning sickness. Unacceptable combination. Can Fam Physician. 1997;43:1055-1057. 15. Goodwin TM, Montoro M, Mestman JH. Transient hyperthyroidism and hyperemesis gravidarum: clinical aspects. Am J Obstet Gynecol. 1992;167:648-652. 16. Jednak MA, Shadigian EM, Kim MS, et al. Protein meals reduce nausea and gastric slow wave dysrhythmic activity in first trimester pregnancy. Am J Physiol. 1999;277(4 Pt 1):G855-G861. 17. Magee LA, Mazzotta P, Koren G. Evidence-based view of safety and effectiveness of pharmacologic therapy for nausea and vomiting of pregnancy (NVP). Am J Obstet Gynecol. 2002;186:S256-S261. 18. Neutel CI. Variation in rates of hospitalization for excessive vomiting in pregnancy by Bendectin/Diclectin use in Canada. In: Koren G, Bishai R, eds. Nausea and Vomiting of Pregnancy: State of the Art 2000. Toronto: Motherisk; 2000:54-59. 19. Levichek Z, Atanackovic G, Oepkes D, et al. Nausea and vomiting of pregnancy. Evidence-based treatment algorithm. Can Fam Physician. 2002;48:267-277. 20. Roscoe JA, Matteson SE. Acupressure and acustimulation bands for control of nausea: a brief review. Am J Obstet Gynecol. 2002;186:S244-S247. 21. Rosen T, deVeciana M, Miller HS, et al. A randomized controlled trial of nerve stimulation for relief of nausea and vomiting in pregnancy. Obstet Gynecol. 2003;02:129-135. 22. Portnoi G, Chng L, Karimi-Tabesh L, et al. Prospective comparative study of the safety and effectiveness of ginger for the treatment of nausea and vomiting in pregnancy. Am J Obstet Gynecol. 2003;189:1374-1377. 23. Nageotte MP, Briggs GG, Towers CV, et al. Droperidol and diphenhydramine in the management of hyperemesis gravidarum. Am J Obstet Gynecol.1996;174:1801-1806. 24. Safari HR, Fassett MJ, Souter IC, et al. The efficacy of methylprednisolone in the treatment of hyperemesis gravidarum: a randomized, double-blind, controlled study. Am J Obstet Gynecol. 1998;179:921-924. 25. Matteson S, Roscoe J, Hickok J, et al. The role of behavioral conditioning in the development of nausea. Am J Obstet Gynecol. 2002;186:S239-S243. 26. Simon EP, Schwartz J. Medical hypnosis for hyperemesis gravidarum. Birth. 1999;26:248-254. 27. Russo-Stieglitz KE, Levine AB, Wagner BA, et al. Pregnancy outcome in patients requiring parenteral nutrition. J Matern Fetal Med. 1999;8:164-167. 28. Ogura JM, Francois KE, Perlow JH. Complications associated with peripherally inserted central catheter use during pregnancy. Am J Obstet Gynecol. 2003;188:1223-1225. DR. GOODWIN is Associate Professor of Ob/Gyn, and Chief, Division of Maternal-Fetal Medicine, University of Southern California, Los Angeles, Calif. He is a coauthor of Management of Common Problems in Obstetrics & Gynecology and author of that textbook's chapter on Hyperemesis Gravidarum. He also assisted the ACOG Committee on Practice Bulletins in developing the newly published guidelines on this topic (Nausea and vomiting of pregnancy. ACOG Practice Bulletin No. 52. American College of Obstetricians and Gynecologists. Obstet Gynecol. 2004;103:803-815). Take-home messages While we don't know what causes HG, women with a history of motion sickness, migraine headache, oral contraceptive sickness, or a family or personal history of HG are more likely to develop it. Untreated nausea and vomiting of pregnancy can progress to hyperemesis gravidarum, which can lead to esophageal tearsand even Wernicke's encephalopathy. Most survivors of the latter condition usually experience long-term ataxia or memory loss. Treatment should balance safety (lack of teratogenicity) and efficacy. In patients who've had HG in past pregnancies, start with preconceptional multivitamin therapy, acupressure, and vitamin B6 therapy. Virtually all women who develop NVP or HG experience some symptoms by 9 weeks. Although no physical exam findings are unique to HG, several may clarify the differential diagnosis. Strongly consider nutritional support when vomiting cannot be sufficiently controlled to allow the pregnant mother to maintain her weight. Coding for hyperemesis gravidarum By Emily H. Hill, PA-C Patients with hyperemesis gravidarum (HG) likely will be seen for visits in addition to the scheduled routine prenatal visits. These services can be reported in addition to the global maternity package. In some instances, patients are admitted to the hospital or monitored in an observation care setting. Therefore, the CPT codes used and the method of reporting the services will depend on the circumstances. The evaluation of pregnancy-related complaints is considered part of routine obstetrical care when the issue is addressed at the time of a regularly scheduled prenatal visit. If you see the patient for additional visits to assess or treat the condition, you may bill these visits in addition to the global maternity care code. According to CPT, the maternity care package includes 13 prenatal visits. However, if a patient exceeds that number due to pregnancy complications, then you can report the extra visits. Since you can't know in advance if you'll be providing more than 13 visits, these additional services are tracked and billed once that number is exceeded. The date of service reported should match the date you saw the patient and the diagnosis should reflect the reason for the encounter. For a patient with HG, ICD-9 codes 643.0-643.9 are used, with the specific code determined by the initial onset of symptoms and the severity of the problem. Since HG generally presents early in pregnancy, codes 643.0 (mild hyperemesis gravidarum) or 643.1 (hyperemesis gravidarum with metabolic disturbance) are reported, since both describe HG starting before 22 weeks gestation. Code 643.2 describes late vomiting in pregnancy that begins after 22 weeks. These codes require a fifth digit to indicate the episode of care. The fifth-digit "3" describes an antepartum condition or complication and is the likely choice. Patients with severe HG might be observed in the hospital or admitted to an inpatient facility. If the patient is monitored in an observation area, then codes 9921899220 are reported for the initial assessment and periodic reassessments of the patient. Codes 9923499236 are used when patients are admitted and discharged on the same date of service during either observation or inpatient care. Report initial inpatient care using codes 9922199223 and daily care using codes 9923199233. For all categories of codes, the level of service depends on the extent of the history, exam, and medical decision-making required to evaluate and treat the patient. Report discharge services provided on a day other than admission using either the discharge code for observation services (99217) or an inpatient discharge day code (9923899239). Report observation and inpatient care at the time they are provided since the global package includes only routine inpatient care surrounding delivery. Ms. Hill is President of Hill & Associates, Inc., a consulting firm specializing in coding and compliance. She teaches coding seminars for the American College of Obstetricians and Gynecologists and serves as a representative on the American Medical Association's (AMA) Correct Coding Policy Committee and the Health Care Professionals Advisory Committee Review Board for the Relative Value Update Committee (RUC) and the National Uniform Claim Committee. She has also served on the AMA's CPT-5 Project and on a Clinical Practice Expert Panel for the Centers for Medicare and Medicaid Services (formerly HCFA) Practice Expense Study. Thomas Goodwin. A practical approach to hyperemesis gravidarum. Contemporary Ob/Gyn Jun. 1, 2004;49:47-62.