Article Figures & Tables
Tables
Risk Management Short-term maternal outcomes Weight loss (21) Refer to a dietitian (preferably with experience in treating hyperemesis gravidarum) (21) Dehydration (21) Administer IV fluids in either an outpatient clinic or inpatient setting (22) Electrolyte imbalances (21) Hospital admission to correct electrolyte imbalances (21) Wernicke encephalopathy (23) Offer thiamine supplementation to patients admitted with prolonged lack of nutrient intake, especially before administration of dextrose or enteral or parenteral nutrition (22) Vitamin K deficiency (24) Consider vitamin K supplementation (150 μg IV) Thromboembolism (25) Consider thrombosis prophylaxis in patients admitted to hospital or in patients with other risk factors for thromboembolism (21) Depression, anxiety, or PTSD (2), (26), (27) Ask about depressive symptoms and offer psychosocial help (21) Suicidal ideation (28) Ask about suicidal ideation and refer if necessary Consideration of pregnancy termination (28) Ask if patient is considering pregnancy termination, talk about recurrence risks, expand antiemetic treatment, and refer if necessary Long-term maternal outcomes Changes to family planning (7) After a pregnancy affected by hyperemesis gravidarum, suggest follow-up to discuss future pregnancy and, if desired, make a plan for treatment of hyperemesis gravidarum in a next pregnancy (7) Depression, anxiety, or PTSD (2), (29) Offer psychosocial help (21) Perinatal outcomes Placental abruption (30) Birth weight < 1500 g (30) Offer ultrasonography to measure fetal growth in pregnancy if symptoms persist beyond second trimester Preterm delivery (30) Resuscitation or admission to NICU (30) Long-term outcomes to offspring Reduced insulin sensitivity (30) Anxiety disorders (31) Sleep problems (31) Attention-deficit/hyperactivity disorder (31) Autism spectrum disorder (31) Testicular cancer (31) Note: IV = intravenous, NICU = neonatal intensive care unit, PTSD = posttraumatic stress disorder.
- Table 2:
Evidence of the effectiveness and adverse effects of antiemetic treatments for hyperemesis gravidarum
Drug or therapy Dose* Effectiveness Safety in pregnancy Other comments Doxylamine– pyridoxine† 10 mg doxylamine + 10 mg pyridoxine every 6 h More effective than placebo in reducing nausea and vomiting scores. However, the clinical importance of this effect is uncertain because of its modest magnitude. (40)– (44) Doxylamine has been extensively studied in more than 60 000 pregnancies. The studies do not reveal a higher risk of congenital abnormalities or specific abnormalities. (21) Antihistamines can provide an additional anticholinergic benefit to those distressed by ptyalism. (45) Cyclizine†‡ 50 mg every 8 h Has not been shown to be more effective than placebo or other treatments. (22), (37) Almost 3500 pregnancies have been studied with cyclizine. No evidence indicates that this drug increases the risk of birth defects. (46) Antihistamines can provide an additional anticholinergic benefit to those distressed by ptyalism. (45) Promethazine† 25 mg every 8 h More effective than placebo in relief of nausea and vomiting. (21) Promethazine has been extensively studied in more than 25 000 pregnancies. The studies do not reveal a higher risk of congenital abnormalities or specific abnormalities. (21) Promethazine is a strong sedative. When used just before delivery, sedation and respiratory depression of the newborn is a theoretical risk. (21) Dimenhydrinate† 25–50 mg every 6 h More effective than placebo in relief of nausea and vomiting. (21) Dimenhydrinate is commonly used and safety data are generally reassuring that it is not a teratogen. (21) If the patient is taking doxylamine, the total dose of dimenhydrinate should not exceed 200 mg/d to reduce the risk of adverse effects, or doxylamine should be stopped. Metoclopramide 10 mg every 8 h More effective than placebo in reducing the intensity of nausea and vomiting. (21), (47) Metoclopramide has been extensively studied in more than 90 000 pregnancies. (48) Only 1 study (49) (n = 958 pregnancies) reported a small increase of genital organ defects; all other studies showed no increase in prevalence of congenital abnormalities. Metoclopramide may therefore be safely prescribed. Metoclopramide can give tardive dyskinesia, but this is uncommon in young patients. Early detection and discontinuation of metoclopramide is important. If metoclopramide is prescribed, clinicians should warn for this adverse effect. (21) Ondansetron 4 mg every 8 h In a small RCT, use of ondansetron resulted in clinically significant reductions in both nausea and vomiting compared with the combination of doxylamine and pyridoxine. (50) In another RCT, it was more effective than metoclopramide for reducing vomiting but not nausea. (51) Because the results of the studies are contradictory, whether ondansetron is associated with a slightly increased risk of cleft palate and heart defects, or whether the severity of the indication plays a role, is unclear. (21), (52), (53) Ondansetron should only be used in the first trimester if other antiemetics are insufficiently effective. Clinicians should weigh the risk of untreated severe hyperemesis gravidarum and small increased risk of congenital abnormalities, in consultation with the patient. Steroids IV hydrocortisone 100 mg every 12 h or methylprednisolone 125 mg; switch from IV to oral as soon as clinical improvement occurs: oral prednisolone 40 mg (day 1), 20 mg (day 2–3), 10 mg (day 4–6), 5 mg (day 7–14) More effective than placebo, the rate of hospital readmission is lower. (21), (37) No higher risk of congenital abnormalities has been clearly shown; therefore, corticosteroids can be used during pregnancy if necessary. Preference is given to prednisolone and hydrocortisone as these corticosteroids are least likely to reach the unborn child; these should be used for as short a time and dosed as low as possible. Long-term use of high doses of corticosteroids can slow the growth of the unborn child and inhibit the child’s adrenal cortex. As a result, the child may have low blood glucose levels, low blood pressure, and electrolyte disturbances in the first days after birth. - Table 3:
Evidence of the effectiveness and adverse effects of other treatments for hyperemesis gravidarum
Drug or therapy Dose Effectiveness Safety in pregnancy Other comments Cannabis Research has suggested that cannabis may provide an antinausea effect in adults with cancer receiving chemotherapy. (54) In pregnancy, prenatal cannabis is suggested to be associated with adverse neurocognitive outcomes in offspring. (55), (56) The use of cannabis is not advised Ginger May be helpful to patients with mild nausea and vomiting, but the evidence of effectiveness was limited and inconsistent for patients with hyperemesis gravidarum. (44), (57) Ginger is not known to cause any problems related to pregnancy. (57) Relevant adverse effects of ginger were reported in a large self-selected online survey of 512 patients hospitalized for hyperemesis gravidarum, namely unpleasant physical effects in around half of those who tried it and negative psychological effects in 82% of participants. (58) Acupressure and acupuncture Acupressure may be helpful in some patients and was associated with less need for additional antiemetics and a larger reduction in PUQE score than placebo. (43), (44) A systematic review showed adverse events were all mild–moderate in severity, with needling pain being the most frequent. (59) Psychotherapeutic treatment Few studies have evaluated psychotherapeutic treatment for hyperemesis gravidarum; most have been evaluated as being of poor methodological quality. Several report a positive effect of psychotherapeutic treatment on symptoms of hyperemesis gravidarum. (60) Eradication of Helicobacter pylori Triple drug therapy, 3 times daily for 7–10 d Whether eradication of H. pylori might improve or prevent symptoms of hyperemesis gravidarum remains unclear. (15) Eradication of H. pylori requires high doses, making this approach poorly feasible among patients with hyperemesis gravidarum. If H. pylori is present, treatment is typically deferred until after delivery. However, with the exception of bismuth, fluoroquinolones, and tetracycline, the other medications used for H. pylori eradication are low risk in pregnancy, especially after 14 weeks. H. pylori eradication before conception may be an attractive method of ameliorating risk of recurrent hyperemesis gravidarum in subsequent pregnancies, but its possible effectiveness in achieving this goal remains unproven. Laxatives Laxatives do not affect nausea or vomiting, but are prescribed for constipation, which can be an adverse effect of antiemetics or dehydration Laxatives are considered safe in pregnancy for treatment of constipation. Proton pump inhibitors Acid-reducing drugs resulted in significant decreases in PUQE and well-being scores. After intervention with acid-reducing pharmacotherapy, a reduction in acid symptoms correlated with significant reductions in nausea and vomiting of pregnancy. (21) Proton pump inhibitors are considered safe in pregnancy, especially omeprazole and lansoprazole. Studies have not shown an elevated risk of birth defects or other adverse effects in pregnancy. (61) Antidepressants Recent case reports suggest that mirtazapine could be considered in refractory hyperemesis gravidarum. The results of a recent double-blind placebo-controlled RCT investigating mirtazapine as a treatment for hyperemesis gravidarum have yet to be published. (62) SSRIs are generally considered an option during pregnancy. Potential complications include maternal weight changes and preterm birth. Most studies show that SSRIs are not associated with birth defects. (63) Antidepressants can be prescribed as an adjunct when nausea causes sleep disorders, or when sleep disorder worsens nausea. Note: PUQE = Pregnancy-Unique Quantification of Emesis and Nausea, RCT = randomized controlled trial, SSRI = selective serotonin reuptake inhibitor.