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This common condition of pregnancy has potential for costly medical management and significant psychosocial and medical morbidity.
COMMITTEE ON PRACTICE BULLETINS-OBSTETRICS
Practice Bulletin No. 153: Nausea and vomiting of pregnancy. September 2015. American College of Obstet Gynecol 2015;126:e12-24. Full text of ACOG Practice Bulletins is available to ACOG members at www.acog.org/Resources-and-Publications/Practice-Bulletins/Committee-in-Practice-Bulletins-Obstetrics/Nausea-and-Vomiting-of-Pregnancy
NAUSEA AND VOMITING OF PREGNANCY Nausea and vomiting of pregnancy is a common condition that affects the health of the pregnant woman and her fetus. It can diminish the woman’s quality of life and also significantly contributes to health care costs and time lost from work (1,2). Because “morning sickness” is common in early pregnancy, the presence of nausea and vomiting of pregnancy may be minimized by obstetricians, other obstetric providers, and pregnant women and, thus, undertreated (1). Furthermore, some women do not seek treatment because of concerns about safety of medications (3). Once nausea and vomiting of pregnancy progresses, it can become more difficult to control symptoms; treatment in the early stages may prevent more serious complications, including hospitalization (4). Mild cases of nausea and vomiting of pregnancy may be resolved with lifestyle and dietary changes, and safe and effective treatments are available for more severe cases. The woman’s perception of the severity of her symptoms plays a critical role in the decision of whether, when, and how to treat nausea and vomiting of pregnancy. The purpose of this document is to review the best available evidence about the diagnosis and management of nausea and vomiting of pregnancy.
A common condition of pregnancy with potential for costly medical management and significant psychosocial and medical morbidity
By Haywood L Brown, MD
Haywood L Brown, MD, is F. Bayard Carter Professor and Chair, Obstetrics and Gynecology, Duke University, Durham, North Carolina. He is also a member of the editorial board of Contemporary OB/GYN.
Nausea and vomiting is an expectation for the majority of women during the first trimester of pregnancy. In fact, only 25% of pregnancies are unaffected by nausea with or without vomiting. Among affected woman, subsequent pregnancies have a recurrence of 15.2% to 81%.1 The etiology is unknown but there are various theories including: psychologic predisposition, evolutionary adaptation to protect the woman and fetus from potentially dangerous foods, and the hormonal stimulus of high human chorionic gonadotropin (HCG) and estradiol levels in early pregnancy. Conditions with increased placental mass such as molar pregnancy and multiple gestations are associated with a higher risk for nausea and vomiting.
The severity of symptoms is variable from patient to patient and they typically peak by 9 weeks. With early treatment and dietary counseling, the severity of symptoms diminishes as gestation advances; for most women, symptoms abate or resolve by the end of the first trimester. However, for some women, the condition is severe and progresses to hyperemesis gravidarum, which occurs in 0.3 to 3% of pregnancies.2 Certain clinical criteria should be met in to define this extreme form of nausea and vomiting. These include persistent nausea and vomiting not caused by other underlying medical conditions, ketonuria as a measure of acute starvation, and at least a 5% weight loss from the pre-pregnancy weight. Hyperemesis is the most common reason for obstetrical triage visits and hospital admission in the first half of pregnancy and significantly impacts psychosocial well-being, loss of productivity, and quality of life.
Differential diagnosis is extensive for women who first experience nausea and vomiting after 9 weeks’ gestation, as seen in Table 1 of Practice Bulletin 153.3 History predating the pregnancy is important especially for the gastrointestinal conditions cholelithiasis or peptic ulcer disease, or metabolic endocrine conditions involving the thyroid or parathyroid, or diabetes. Symptoms of fever or abdominal pain should also prompt an investigation for other causes in the differential because neither are typical features of hyperemesis. Abnormal laboratory findings in hyperemesis can include mildly elevated liver transaminase and bilirubin, elevated amylase, and suppressed thyroid stimulating hormone (TSH) levels.
While death due to hyperemesis is rare, morbidity can be significant if the condition is not properly managed, not to mention the psychological impact that prompts some women to consider termination of pregnancy. Wernicke encephalopathy is caused by vitamin B1 deficiency as a result of persistent vomiting leading to nutrition deprivation and has resulted in permanent neurological disability and death. As such, it is important that treatment, particularly on admission, include hydration and replacement of the B vitamin, thiamine and attention to electrolyte balance. When replacing fluid care to be taken in overcorrection of severe and prolonged hyponatremia (< 120 meg/L) which could lead to osmotic demyelination syndrome.
A systematic review and meta-analysis of women with hyperemesis gravidarum showed a higher incidence of low birthweight and small for gestational age infants at birth, and premature infants.4 Otherwise, a lower rate of first-trimester pregnancy loss has been reported in women with nausea and vomiting and no increased risk of birth defects.
Treatment of nausea and vomiting depends on the perception of severity. Basic recommendations include avoidance of stimuli that provoke nausea and vomiting such as sensory stimuli to strong odors, and other sensory stimuli such as heat and noises that trigger the labyrinthine areas. Dietary counseling about frequent small meals and avoidance of spicy or fatty foods is appropriate even though the evidence for such recommendation is lacking.
Ginger has been recommended and shown, in some randomized trials, to improve symptoms for some women.5 Studies of other treatments such as acupressure, acupuncture, or electrical nerve stimulation at the P6 point on the inside of the wrist have produced conflicting results on benefit. A systematic review of randomized trials found no difference for P6 acupuncture and acupressure wristbands compared to placebo.2
For many decades pyridoxine (vitamin B6) has been the primary recommendation for pharmacotherapy for nausea and vomiting of pregnancy. Doxylamine (10 mg) and vitamin B6 (10 mg) was available for use in the United States from 1958 to 1983 as Bendectin until removed from the market. Many clinicians continued to prescribe vitamin B6 and doxylamine as first line as an over-the-counter regimen for nausea and vomiting. In 2013 the US Food and Drug Administration has approved the release of a new product containing doxylamine-vitamin B6, marketed as Diclectin, which was proven effective in significantly improving nausea and vomiting symptoms compared to placebo.6 The medication should be prescribed before bedtime as a prophylaxis against “morning sickness.”
Various phenothiazines have been prescribed and are effective as treatment for more significant nausea and vomiting. Over the last decade drugs that reduce chemotherapy-induced emesis (the 5-hydroxytryptamine 3 inhibitor, ondansetron, and metoclopramide) have gained favor as a treatment for women with hyperemesis. In various trials both have been found to have similar efficacy when given orally, subcutaneously and intravenously (IV). Continuous subcutaneous pump therapy, while not widely used, has limited evidence of efficacy beyond oral therapy and it is associated with complications in 25% to 31% of patients.7 While there have been reports of an association between ondansetron use in early pregnancy and birth defects of the heart and oral clefts, a prospective cohort and a retrospective cohort study showed no increased risk of congenital anomalies over the background risk for such congenital defects.8
For hyperemesis resistant to traditional antiemetic regimens, corticosteroids have been studied in randomized trials to reduce readmission with IV dosing followed by oral tapering.9 Patients who do not respond in 3 days are not likely to respond. Treatment with methylprednisolone should be reserved for refractory cases of hyperemesis as a last-resort treatment.
Prolonged and persistent nausea and vomiting can lead to dehydration, ketosis, and electrolyte imbalance. As such, judicious IV hydration, including electrolytes, dextrose and thiamine-containing vitamins, should be administered to women who cannot tolerate oral liquids or feeding.
Enteral or parenteral nutrition is occasionally required for women with persistent hyperemesis who are not responsive to medical management and unable to stabilize their weight. If necessary, total parenteral nutrition through a peripherally inserted central catheter (PICC) can be used as a last resort. However, PICC parenteral nutrition is not without the potential for maternal infectious morbidities.
Nausea and vomiting of pregnancy is common, impacts quality of life, and is costly. Hyperemesis is a serious form of the conditions and has the potential for serious morbidity if not managed appropriately.
Prenatal vitamins in the preconception period may reduce the severity of nausea and vomiting in early pregnancy. Early treatment with vitamin B6 and B6 plus doxylamine as a first-line therapy is safe and effective.
Hyperemesis or refractory cases lead to dehydration, vitamin deficiency, and weight loss, therefore, attention to hydration, vitamin replacement, nutrition, and antiemetic therapy is critical to avoid maternal morbidity.
ACOG Abstract References
Attard CL, Kohli MA, Colemans S. Bradley C, Hux M, Atanackovic G, et al. The burden of illness of severe nausea and vomiting of pregnancy in the United States. Am J Obstet Gynecol 2002;186:S220-7.
Piwko C, Koren G, Babshov V, Vicente C, Einarson TR. Economic burden of nausea and vomiting of pregnancy in the USA. J Popul Ther Clin Pharmacol 2013;20:e149-60.
O’Brien B, Naber S. Nausea and vomiting during pregnancy: effects on the quality of women’s lives. Birth 1992;19:138-43.
Brent R. Medical, social, and legal implications of treating nausea and vomiting of pregnancy. Am J Obstet Gynecol 2002;186:S262-6.
Trogstad LI, Stoltenberg C, Magnus P, Skjaerven R, Irtens LM. Recurrence risk in hyperemesis gravidarum. BJOG 2005;112:1641-5.
Matthews A, Haas DM, O’Mathuna DP, Dowswell T, Doyle M. Interventions for nausea and vomiting in early pregnancy. Cochrane Database of systematic Reviews 2014, Issue 3. Art. No: CD007575. DOI: 10.1002/14651858. CD007575.pub3.
Nausea and Vomiting of Pregnancy. American College of Obstetricians and Gynecologists. Practice Bulletin Number 153, September 2014.
Veenendaal MV, van Abeelen AF, Painter RC, van der Post JA, Roseboom TJ. Consequences of hyperemesis gravidarum for offspring: a systematic review and meta-analysis. BJOG 2011;118:1302-13.
Vutyavanich T, Kraisarin T, Ruangsri R. ginger for nausea and vomiting in pregnancy: randomized, double masked, placebo-controlled trial. Obstet Gynecol 2001;97:577-82.
6. Slaughter SR, Hearns-Stokes R, van der Vlugt T, Joffe HV. FDA approval of doxylamine-pyridoxine therapy for use in pregnancy. N Engl J Med 2014;370:1081-3.
Reichmann JP, Kirkbride MS. Reviewing the evidence for using continuous subcutaneous metoclopramide and ondansetron to treat nausea and vomiting during pregnancy. Manag Care 2012;21:4407.
Einarson A, Maltepe C, Navioz Y, Kennedy D, Tan MP, Koren G. The safety of ondansetron for nausea and vomiting of pregnancy: a prospective comparative study. BJOG 2004;111:940-3.
Safari HR, Fassett MJ, Souter IC, Alsulyman OM, Goodwin TM. The efficacy of methyprednisone in the treatment of hyperemesis gravidarum: A randomized double-blind, controlled study. Am J Obstet Gynecol 1998;179:921-4.