Nausea and vomiting in pregnancy is a common condition that affects both the health of the pregnant woman and the fetus. It reduces the quality of life of pregnant women and significantly increases health care costs. Because “morning sickness in pregnancy” is common in early pregnancy, nausea and vomiting in pregnancy is highly underestimated by health care providers and pregnant women (1) and lacks treatment. One researcher found that less than 50% of pregnant women who subsequently terminated their pregnancies without any antiemetic treatment for severe nausea and vomiting called a pregnancy nausea and vomiting helpline (2,3). It is also unlikely that the regimen offered to 90% of the pregnant women who received treatment was effective. In addition, some pregnant women do not seek treatment because of safety concerns (4). However, once nausea and vomiting of pregnancy progresses, treatment becomes more difficult, so early treatment can prevent more serious complications, including hospitalization (5). Mild cases of pregnancy nausea and vomiting can be relieved by lifestyle and dietary changes, and safe and effective treatment is effective for more severe cases. Pregnant women’s awareness of the severity of their symptoms plays a decisive role in determining whether, when, and how to treat nausea and vomiting of pregnancy. More importantly, nausea and vomiting of pregnancy should be differentiated from other causes of nausea and vomiting. The purpose of this article is to review the best evidence in the diagnosis and management of nausea and vomiting of pregnancy.
Definition and prevalence
It is a common symptom affecting 70-85% of pregnant women (6). Among pregnant women, 50% have both nausea and vomiting, 25% have nausea only, and 25% have no discomfort such as nausea and vomiting (7,8). One study classified the severity of nausea and vomiting in pregnancy based on the assessment of the duration of nausea and vomiting per day (less than 1 hour as mild and more than 6 hours as severe) and the number of episodes of vomiting and dry heaving (up to 2 as mild and moderate and more than 5 as severe) (1). Although these classifications confirm a continuum of symptomatic delineation of nausea and vomiting in pregnancy, this classification may not be useful for clinical management. Patients’ perception of the severity of their symptoms and their willingness to treat may be more influential in clinical treatment decisions.
From an epidemiological point of view, severe pregnancy vomiting seems to represent a critical level of the nausea and vomiting symptom series of pregnancy (9). The incidence of severe pregnancy vomiting is approximately 0.5%-2%. The reported incidence varies depending on the diagnostic criteria and the ethnicity of the study population. There is no simple accepted definition of hyperemesis gravidarum; it is an exclusionary clinical diagnosis based on a typical clinical presentation that cannot be explained by other diseases (10). The most commonly cited diagnostic criteria are: persistent vomiting unrelated to other causes, measurable acute hunger (usually with large amounts of urinary ketone bodies), and some intermittent weight loss, usually at least 5% of pre-pregnancy weight (11). It may also be accompanied by abnormalities in electrolytes, thyroid, and liver function. Hyperemesis gravidarum is the most common disorder leading to hospitalization in early pregnancy and is the most common cause of hospitalization during pregnancy after preterm delivery (12,13).
Differential diagnosis
The timing of the onset of nausea and vomiting is important: almost all affected women experience nausea and vomiting before 9 weeks of gestation. When a patient first develops nausea and vomiting after 9 weeks of pregnancy, careful consideration should be given to differentiating it from the following conditions (see table below) Look for a history of chronic medical conditions associated with nausea and vomiting prior to pregnancy (e.g., cholelithiasis, vegetative dysfunction in diabetics). Rare cases of severe pregnancy vomiting associated with Mendelian diseases of hormone-receptor interactions (14) as well as mitochondrial disease (15) suggest that at least some of the vomiting is due to exposure to or worsening of individual disease states during pregnancy ……
Differential diagnosis of nausea and vomiting during pregnancy
Gastrointestinal disorders
Gastroenteritis
Gastroparesis
pancreatic dyschondria
Biliary tract disorders
Hepatitis
Intestinal obstruction
Peptic ulcer
Pancreatitis
Appendicitis
Genitourinary tract diseases
Pyelonephritis
Uremia
Ovarian torsion
Kidney stone
Uterine smooth muscle tumor degeneration
Metabolic diseases
Diabetic ketoacidosis
Porphyria
Addison’s disease
Hyperthyroidism
Neurological disorders
Pseudotumor cerebri
Vestibular lesions
Migraine
Central nervous system tumor
Other
Drug toxicity or allergic reaction
Psychogenic
Pregnancy-related diseases
Acute fatty liver during pregnancy
Pre-eclampsia
Some laboratory results may reveal symptoms of nausea and vomiting of pregnancy caused by other diseases. Abdominal pain is not the main feature of nausea and vomiting in pregnancy; it is not associated with pain or pressure in the abdomen, except for mild epigastric discomfort following dry heaving. It is a symptom of many other disorders associated with nausea and vomiting. Headache is not a characteristic feature of nausea and vomiting in pregnancy. An abnormal neurologic examination suggests a primary neurologic disorder as the cause of nausea and vomiting, although this may rarely be encountered as a result of severe pregnancy nausea and vomiting (e.g., thiamine deficiency encephalopathy or central pontine myelinolysis). Although severe pregnancy vomiting may present with biochemical indicators suggestive of hyperthyroidism, no goiter has ever been found in pregnancy nausea and vomiting. Primary thyroid disease should be suspected if a goiter is present.
Etiology and high-risk factors
The etiology of nausea and vomiting of pregnancy is unknown. Various theories including psychological predisposition (16), evolutionary adaptation (17) and hormonal stimulation have been proposed. The question of whether certain personality types or specific psychological disorders predispose to severe pregnancy vomiting has been mentioned in the literature for many years. Two of the more prevalent hypotheses have suggested that pregnancy nausea and vomiting is a neuropathological manifestation: 1) the psychoanalytic theory that pregnancy vomiting is a conversion or somatization disorder, and 2) that women are unable to cope with excessive life stress. There are no controlled studies to support these hypotheses.
A recent review of psychological theories explaining the etiology of pregnancy nausea and vomiting concluded that the evidence that pregnancy nausea and vomiting is due to a conversion disorder or an abnormal response to stress is “questionable” (18). The notion that nausea and vomiting in pregnancy is a psychological disorder is likely to have hindered further understanding of its true etiology (19).
It has also been hypothesized that nausea and vomiting in pregnancy is caused by an evolutionary adaptation to protect the pregnant woman and her fetus from potentially dangerous foods (20). This theory could explain the brief experience of taste and smell revulsion in pregnant women. Proponents of the adaptation theory consider nausea and vomiting of pregnancy as a protective response beneficial to the health of pregnancy. However, clinical application of this theory may lead to inadequate treatment of women whose quality of life is diminished by nausea and vomiting of pregnancy.
Hormones
Human chorionic gonadotropin
Because of the close temporal relationship between the peak concentration of human chorionic gonadotropin (hCG) and the peak time of onset of nausea in pregnancy, hCG has been recognized as an emesis-producing stimulant from the placenta. The fact that almost all thyroid hormone studies during pregnancy have shown that transient hyperthyroidism is associated with nausea and vomiting of pregnancy suggests another role for hCG. It has been shown that hCG is a stimulant of the thyroid gland during pregnancy (21); because hyperthyroidism itself rarely causes vomiting, this finding returns attention to hCG and its association with nausea and vomiting of pregnancy. In many studies comparing non-thyroid hormones in women with and without vomiting, only hCG and estradiol have been found to be associated. The failure of some studies demonstrating the association of pregnancy nausea and vomiting with hCG may be related to the corresponding biological activity of different hCG subtypes and the different sensitivity of women to emetogenic stimuli. hCG stimulation can be altered by the placental state that elevates its concentration (e.g., multiple pregnancy, gravida) and by the action of hormone receptors that influence the hormonal effect.
Estrogen
Another hormone known to affect nausea and vomiting of pregnancy is estrogen. Pregnancy nausea and vomiting is common with elevated levels of estradiol and less common with decreased levels of estradiol (22,23). Smoking is associated with lower levels of both hCG and estradiol (24), and many studies have shown that smokers are less likely to experience severe pregnancy nausea and vomiting. Estrogen in the combined contraceptive pill has been shown to induce nausea and vomiting in a one-dose dependent manner (25). Women who experience nausea and vomiting after estrogen exposure are more likely to experience pregnancy nausea and vomiting than those who have not been shown to be so sensitive to estrogen (26). Women who are sensitive to estrogen therapy are more likely to experience nausea and vomiting after pregnancy than women who are not sensitive to estrogen therapy.
High-risk factors
Women with increased placental mass (e.g., late gravida, multiple pregnancies) are at risk for severe pregnancy vomiting. Other risk factors include a family history (genetics) or a history of severe pregnancy vomiting in previous pregnancies. One study found that about 2/3 of women who described severe vomiting in a previous pregnancy would have similar symptoms in the next pregnancy; half of the women described mild symptoms in a previous pregnancy that worsened in the next pregnancy (7). Daughters or sisters of women with severe pregnancy vomiting are more likely to have the same problem as women carrying a female fetus (27). Additional risk factors include a history of motion sickness or migraine (26).
Effects of pregnancy nausea and vomiting on the mother
Until 60 years ago, nausea and vomiting of pregnancy was an important cause of maternal death, and in the 1930s, 7 of 85 women with severe vomiting were reported to have died in the United States (28). Although deaths from nausea and vomiting of pregnancy are now rarely reported, serious complications such as encephalopathy, splenic laceration, esophageal rupture, pneumothorax, and acute tubular necrosis have been reported in recent years (29-36). Thirty-three cases of Wernicke’s encephalopathy (caused by vitamin B1 deficiency) have been reported in the last 20 years in association with severe pregnancy vomiting. It is often accompanied by maternal death or permanent neurological deficits (29-31). In addition to an increased chance of hospitalization (37,38), some women experience severe psychosocial disorders caused by nausea and vomiting of pregnancy and eventually terminate their pregnancy.
Several subacute disorders that can produce nausea and vomiting symptoms of pregnancy have been described that produce reversible nausea and vomiting symptoms, including depression, somatization, and hypochondria (16). Of the women who called the pregnancy nausea and vomiting assistance line, 85% reported a lack of spousal support (3).
Effects of pregnancy nausea and vomiting on the fetus
The effects of maternal vomiting on the embryo and fetus depend on the severity of the illness. Mild or moderate vomiting has little to no significant effect on pregnancy outcomes. The most frequently detected outcome is low birth weight infants. 7 studies have shown that nausea and vomiting of pregnancy do not increase the incidence of low birth weight infants (9,10,39-43). However, three studies found a higher incidence of low birth weight in women without nausea and vomiting (41-43). In any case, a higher incidence of low birth weight babies has been reported in women with severe pregnancy vomiting (44-49).
Many studies have demonstrated a lower rate of miscarriage in women with nausea and vomiting of pregnancy and hyperemesis gravidarum compared to controls. This result is thought to be related to the formation of a strong placenta in healthy pregnancies rather than the protective effect of vomiting. Vigorous pregnancy vomiting is not necessarily associated with a significant increase in the risk of malformations in the offspring (50). Few reports have been seen on the long-term health status of children and women after pregnancies complicated by hyperemesis gravidarum. Although some fetal deaths have been reported, they are rare and usually limited to isolated cases of hyperemesis gravidarum. Therefore, it is also a great comfort to the pregnant woman that nausea and vomiting of pregnancy and even hyperemesis gravidarum most often predict a good pregnancy outcome.
Clinical considerations and recommendations
Many studies have confused patients with severe pregnancy vomiting and other varying degrees of pregnancy nausea and vomiting. Because gestational hyperemesis may be part of the continuum of nausea and vomiting in pregnancy, and because evidence suggests that treatment failure for early gestational nausea and vomiting increases the likelihood of hospitalization for gestational hyperemesis (37,38), the following discussion is devoted to the treatment of nausea and vomiting at all stages of pregnancy.
Is nonpharmacologic treatment of nausea and vomiting of pregnancy effective?
The treatment of nausea and vomiting in pregnancy begins with prevention. Two studies found that women who took multivitamin tablets at the time of conception were less likely to need medical treatment for vomiting (51,52). Therefore, it is reasonable to recommend that women with a history of nausea and vomiting or severe pregnancy vomiting in a previous pregnancy take a multivitamin at the time of the next conception.
A woman’s perception of the severity of her symptoms and her willingness to treat them can influence clinical decisions. Rest and avoidance of symptom-causing sensory stimuli are often recommended to relieve the initial manifestations of nausea and vomiting of pregnancy. Small and frequent meals are often recommended. Obstetricians and gynecologists often recommend avoiding spicy and high-fat foods, disabling iron-containing pills, and consuming light or dry foods, high-protein snacks, and crackers before waking up in the morning (53).
However, there is little published evidence that dietary changes are effective in preventing or treating nausea and vomiting in pregnancy. A small study showed that protein diets were more likely to reduce nausea and vomiting of pregnancy than carbohydrate and high-fat diets (54).
A comparative study of 250 mg ginger powder capsules and placebo in 27 women with severe pregnancy vomiting found that ginger reduced vomiting episodes (55). Another study of 70 women suffering from varying degrees of pregnancy nausea and vomiting using a similar ginger regimen found significant improvement in nausea and vomiting (56).
Pressing or electrically stimulating P6 (or Neguian) points within the wrist has been used in studies of nausea and vomiting of pregnancy, yielding conflicting results. The vast majority of the literature suggests benefit, but many studies have obvious methodological flaws, and the 2 largest and best-designed studies have shown no benefit from sham stimulation (57). Interestingly, the results of these 2 studies are consistent with a substantial placebo effect. A randomized controlled trial of acupuncture and a commercial transcutaneous electrical stimulator for varying degrees of pregnancy nausea and vomiting symptoms found that acupuncture improved nausea and vomiting symptoms in early pregnancy (58).
Are medications effective in treating nausea and vomiting of pregnancy?
Effective pharmacotherapy is available, but the consistency of appropriately timed antiemetic therapy has changed in recent years. Two randomized controlled studies evaluated pyridoxine (i.e., vitamin B6) for the treatment of nausea and vomiting in pregnancy of varying severity. One of 25 mg every 8 hours compared with placebo was found to significantly reduce severe vomiting but had minimal effect on mild vomiting (59). A large sample study (n=342) comparing pyridoxine (10 mg every 8 hours) with placebo found that pyridoxine reduced both nausea and vomiting (60). From 1958 to 1983, when the 10 mg vitamin B6 and 10 mg antimineral complex was available in the United States, it was estimated that 25-30% of pregnant women used this preparation. Analysis of hospitalizations during this period showed that the use of vitamin B6 and antimineral for nausea and vomiting of pregnancy, which was readily available, was associated with fewer hospitalizations for severe pregnancy vomiting (38). Since this compound was withdrawn from the U.S. market in 1983, the use of antiemetics for the treatment of nausea and vomiting of pregnancy has relatively decreased, whereupon hospitalizations for nausea and vomiting of pregnancy have increased (38).
Figure 1 depicts therapeutic interventions that balance the hierarchy of safety and efficacy. Despite the fact that a combination of antimineral and vitamin B6 is no longer available in the U.S. market, it is in the first-line therapeutic approach. Many community-based personal dispensing pharmacies will make a 10 mg combination of antimicrobial and 10 mg pyridoxine upon request. The only randomized controlled trial with placebo found a 70% reduction in pregnancy nausea and vomiting (61-63). Several case-control and cohort studies involving more than 170,000 participants found no effect of the complex on fetal health (64).
Many other traditional antiemetics are mentioned in the literature for the treatment of nausea and vomiting of pregnancy (Table 1). Several of these drug classes have data showing their safety and efficacy. The safety of antihistamine H1 receptor antagonists (e.g., antimineral) has been supported by a retrospective analysis of more than 200,000 cases taken during early pregnancy (65). One study considered phenothiazines as a possible cause of teratogenicity (66), but overall studies proved it to be safe (67). Three studies demonstrated the safety of trimethoprim (68-70).
Some drugs, including anticholinergics and gastrodiazepines, are quite safe, but there is no conclusive evidence for their effectiveness. In addition, there is limited evidence for the safety and efficacy of 5hydroxytryptamine 3 antagonists for nausea and vomiting in pregnancy; however, there is a trend toward increased use due to their effectiveness in reducing chemotherapy-induced vomiting. Although evidence is insufficient, haloperidol doses greater than 25 mg have been associated with prolonged Q-T intervals such that potentially lethal ventricular arrhythmias have occurred in some cases. This drug must be used with caution ……
This approach assumes that other causes of nausea and vomiting have been ruled out. At any step, if dehydration or persistent weight loss is noted, parenteral nutrition should be considered. Alternative therapies may be added for any subsequent period, depending on patient acceptance and clinician familiarity; there are wristband P6 pin compressions or pinpricks or 250 mg ginger capsules four times daily.
In the United States, antimineral is used as the active ingredient in some over-the-counter sleeping medications. Half of a 25mg tablet will provide 12.5mg of Anti-Allergy B.
Intravenous supplementation with vitamin B at 100 mg daily for 2-3 days (followed by intravenous multivitamin supplementation) is recommended for every woman who requires intravenous rehydration and vomiting for more than 3 weeks. There are no comparative studies of different fluids for nausea and vomiting in pregnancy.
In the first 10 weeks of pregnancy, corticosteroids increase the risk of cleft lip and palate.
Safety has not been established, especially in the first trimester; the effect on nausea is even less.
Figure 1: Pharmacological treatment of nausea and vomiting in pregnancy. (
)
Table 1: Summary of medications used to treat nausea and vomiting in pregnancy
Pharmacological agents
Randomized controlled studies
Efficacy evaluation
Safety evaluation
Antagonist
Anti-allergy
Diphenhydramine chlorophylline
Cetirizine
Chlorpheniramine
Buclizine
Hydroxyzine
Diphenhydramine
Anticholinergics
Scopolamine
Dopamine receptor antagonists
Benzamide
Triamcinolone acetonide
Gastroflucan
Butyrylbenzene
Haloperidol
Haloperidol
Phenothiazines
Isopropazine
Prochlorazine
Chlorpromazine
Hydroperazine
Benzodiazepines
Valium
Serotonin 3 receptor agonists
Endanserone
Steroids
Adrenocorticotropic hormone
Corticosteroids
Effective in reducing nausea and vomiting of pregnancy
No effectiveness trials for nausea and vomiting of pregnancy
Effective in reducing nausea and vomiting of pregnancy
No trials on effectiveness
Effective in reducing nausea and vomiting of pregnancy
One trial found the same effect as promethazine
Pooled results did not show benefit in reducing nausea and vomiting in pregnancy
No increase in teratogenic risk
No increased teratogenic risk
No known malformations
No known malformations
One limited power study confirmed no known malformations
Risk of prolonging Q-T interval in pregnant women
Substantial evidence of no teratogenicity (case reports were # ignored in the meta-analysis)
No malformations recorded
Slightly increased risk of cleft lip and palate
The drug was evaluated by at least one randomized controlled trial.
Several case series over the past decade have demonstrated the benefit of hormonal treatment of dramatic pregnancy vomiting. A study randomized to compare oral metholone (16 mg 3/day for 3 days, followed by 2-week decrements) with iproniazid in hospitalized patients showed the same rate of improvement.
However, those taking the hormone had a significantly lower incidence of readmission within 2 weeks of discharge (71). In contrast, in a subsequent randomized controlled study of women hospitalized for hyperemesis gravidarum using intravenous methylprednisolone followed by tapering of oral prednisone found that glucocorticoid use did not reduce the need for readmission to hospital (72).
Three recent studies have confirmed the association of cleft lip and palate with the use of methylprednisolone in early pregnancy (73-75). The teratogenic effect is weak, probably accounting for less than 1-2 cases per 1000 treated pregnancies (76). Nevertheless, because of this possible association, corticosteroids should be used with caution in severe pregnancy vomiting and avoided during the 10th week of gestation.
For those patients who require enteral or parenteral nutrition due to weight loss, corticosteroids may be considered as a last resort. The most commonly described regimen is methylprednisolone, 48 mg/day for 3 three days, administered orally or intravenously. Patients who do not see an effect within 3 days are unlikely to have an effect and treatment should be discontinued. For those that do have an effect, the dose may be tapered over a period of more than two weeks. For recurrent vomiting, dose reduction should be stopped and the patient maintained at the effective dose until 6 weeks. To limit severe side effects in pregnant women, the duration of corticosteroid therapy for severe pregnancy vomiting should not exceed this time frame (77).
Is laboratory or imaging evaluation useful in the diagnosis of pregnancy vomiting?
Most cases of nausea and vomiting of pregnancy do not require laboratory evaluation, but for those with severe, prolonged or progressive nausea and vomiting of pregnancy, laboratory evaluation can be useful in the differential diagnosis of hyperemesis gravidarum and to assess the severity of the disease. Common laboratory abnormalities in pregnancy vomiting include liver enzymes (typically <300 U/L), serum bilirubin (<4 mg/dL), and serum amylase or lipase concentrations (which can be 5 times higher than normal). Primary hepatitis is a cause of nausea and vomiting in pregnancy resulting in elevated liver enzyme levels, often in the thousands; bilirubin concentrations are often substantially elevated at the same time. Acute pancreatitis can cause vomiting and elevated amylase concentrations, but serum amylase concentrations are often 5-10 times greater than those elevated by nausea and vomiting of pregnancy.
Hypochloremic metabolic alkalosis can be seen in severe vomiting from any cause. Serum hCG concentrations are not helpful in determining whether vomiting is due to severe pregnancy vomiting. Urine tests may show elevated urine specific gravity or ketone bodies or both. Ulcers may be present in patients with persistent hyperemesis gravidarum who do not respond to standard therapy; treatment with antimicrobials and H2 receptor antagonists is safe (78, 79) and has been reported to be beneficial in cases (80).
Nearly 70% of patients with hyperemesis gravidarum will present with suppressed thyrotropin levels or elevated free thyroid hormone concentrations (81). In patients with no pre-pregnancy history of hyperthyroidism and no goiter, hyperthyroidism due to pregnancy vomiting can be expected to resolve spontaneously within 20 weeks of gestation and does not require specific antithyroid therapy. Hyperthyroidism itself is rarely likely to present with severe vomiting (82), but in patients without goiter, routine thyroid function tests are not necessary to clarify the differential diagnosis. To confirm the diagnosis of hyperthyroidism in nausea and vomiting of pregnancy, free thyroid hormone and free T3 concentrations should be measured.
Ultrasound may be effective in assessing severe cases of nausea and vomiting of pregnancy. It can identify predisposing factors, such as multiple pregnancies or hyperemesis gravidarum.
When is enteral or parenteral nutrition recommended?
The main criterion for the use of additional nutritional strategies is sustained weight loss. In women who are unable to maintain their weight even with antiemetic treatment, severe complications of hyperemesis gravidarum can occur in both the woman and the fetus. Intravenous rehydration should be used in patients who cannot tolerate prolonged oral rehydration or who present with clinical signs of dehydration. Attention should be focused on correcting ketosis and vitamin deficiencies. Glucose and vitamins, especially vitamin B1, should be included in the treatment of patients presenting with prolonged vomiting.
There have been no randomized trials comparing enteral and parenteral nutrition in women with nausea and vomiting of pregnancy who have been treated with antiemetic therapy but still have persistent weight loss. Several case reports and a small series of studies (83) have shown that the use of enteral tube feeding during pregnancy is well tolerated. Because life-threatening complications of parenteral nutrition have been reported (35,36,84), it is reasonable to try enteral tube feeding first. Use a high-fat formula for secondary parenteral nutrition for those patients with modest caloric needs and treatment duration not expected to exceed a few days. Case reports of severe pregnancy-related vomiting and 2 small series of studies suggest the use of complete parenteral nutrition for those patients who require long-term support and cannot tolerate enteral tube feeding (35,85). The use of peripheral central venous cannulation may avoid some of the complications of central catheters (86), but it is still associated with significant morbidity (87).
When is hospitalization indicated?
There are no controlled trials comparing inpatient versus outpatient treatment for hyperemesis gravidarum. Inpatient evaluation and treatment is recommended when the patient is unable to tolerate fluids without vomiting and does not respond to outpatient treatment. After admitting patients to the hospital once and examining the cause of their severe vomiting, revision of intravenous rehydration, nutritional support, and antiemetic therapy can often be accomplished at home. However, patients with changes in vital signs or mood, as well as persistent weight loss, should still be considered for hospitalization for observation and further evaluation.
Is psychotherapy effective?
There is little evidence of the effectiveness of traditional psychotherapy for hyperemesis gravidarum. No controlled studies have evaluated behavioral treatments for nausea and vomiting in pregnancy, but there are data suggesting that delayed or anticipated nausea and vomiting after chemotherapy is reduced with systematic desensitization (88) and relaxation therapy (89).
At least one controlled study supports the hypothesis (90) that hypnotized women with severe pregnancy nausea and vomiting are more susceptible to suggestion than controls. The few uncontrolled studies have shown (91,92) that hypnosis reduces the number of vomits in chemotherapy patients and in patients with severe pregnancy vomiting (93,94).
Summary recommendations
The following recommendations are based on good and consistent scientific evidence (A).
Administration of multivitamin agents during conception reduces the severity of nausea and vomiting in pregnancy.
The application of vitamin B6 or vitamin B6-doxylamine combination is safe and effective in the treatment of nausea and vomiting of pregnancy and should be considered as a first-line agent.
Patients with severe pregnancy vomiting combined with suppressed thyrotropin levels, without evidence of thyroid disease per se (e.g., goiter and/or thyroid autoantibodies), should not be treated for hyperthyroidism.
The following recommendations are based on limited or inconsistent scientific evidence (B).
Treatment of nausea and vomiting of pregnancy with ginger has shown beneficial effects and may be considered as a non-pharmacologic treatment option.
In refractory cases of nausea and vomiting of pregnancy, the following medications are considered safe and effective during pregnancy: antihistamine H1 receptor antagonists, phenothiazines, and benzamides.
Early treatment of nausea and vomiting of pregnancy is recommended to prevent progression to hyperemesis gravidarum.
Treatment of refractory cases of severe nausea and vomiting of pregnancy or severe vomiting of pregnancy with methylprednisolone may be effective; however, the risk profile of methylprednisolone suggests that it should be the last resort for treatment.
The following recommendations are based on preliminary consensus and expert opinion (C).
Intravenous rehydration should be used in patients who cannot tolerate oral rehydration for a prolonged period of time or who present with clinical signs of dehydration. Attention should be focused on correcting ketosis and vitamin deficiencies. Glucose and vitamins, especially vitamin B1, should be included in the treatment of patients presenting with prolonged vomiting.
Enteral or parenteral nutrition should be used in any patient who is unable to maintain weight because of vomiting.