The Management of Nausea and Vomiting in Pregnancy and Hyperemesis Gravidarum (Green-top Guideline No. 69).

An objective and validated index of nausea and vomiting such as the Pregnancy-Unique Quantification of Emesis (PUQE) and HyperEmesis Level Prediction (HELP) tools can be used to classify the severity of NVP and HG. [Grade C] Ketonuria is not an indicator of dehydration and should not be used to assess severity. [Grade A] There are safety and efficacy data for first line antiemetics such as anti (H1) histamines, phenothiazines and doxylamine/pyridoxine (Xonvea®) and they should be prescribed initially when required for NVP and HG (Appendix III). [Grade A] There is evidence that ondansetron is safe and effective. Its use as a second line antiemetic should not be discouraged if first line antiemetics are ineffective. Women can be reassured regarding a very small increase in the absolute risk of orofacial clefting with ondansetron use in the first trimester, which should be balanced with the risks of poorly managed HG. [Grade B] Metoclopramide is safe and effective and can be used alone or in combination with other antiemetics. [Grade B] Because of the risk of extrapyramidal effects metoclopramide should be used as second-line therapy. Intravenous doses should be administered by slow bolus injection over at least 3 minutes to help minimise these. [Grade C] Women should be asked about previous adverse reactions to antiemetic therapies. If adverse reactions occur, there should be prompt cessation of the medications. [GPP] Normal saline (0.9% NaCl) with additional potassium chloride in each bag, with administration guided by daily monitoring of electrolytes, is the most appropriate intravenous hydration. [Grade C] Combinations of different drugs should be used in women who do not respond to a single antiemetic. Suggested antiemetics for UK use are given in Appendix III. [GPP] Thiamine supplementation (either oral 100 mg tds or intravenous as part of vitamin B complex (Pabrinex®)) should be given to all women admitted with vomiting, or severely reduced dietary intake, especially before administration of dextrose or parenteral nutrition. [Grade D] All therapeutic measures should have been tried before considering termination of pregnancy. [Grade C].

Fetal demise and Wernicke-Korsakoff syndrome in a patient with hyperemesis gravidarum: a case report.

BACKGROUND: Wernicke-Korsakoff syndrome is a neuropsychiatric disorder caused by thiamine deficiency composed of two related disorders accounting for an acute presentation and chronic progression. Hyperemesis gravidarum presents a significant risk factor for Wernicke-Korsakoff syndrome as symptoms may rapidly progress in the setting of pregnancy. We present the first-reported case of hyperemesis-gravidarum-associated Wernicke encephalopathy in a patient in the first half of pregnancy in which a missed diagnosis led to septic shock, fetal demise, and eventual profound Korsakoff syndrome. CASE PRESENTATION: We present the case of a 33-year-old primigravid African American woman at 15 weeks gestational age who initially presented at a community emergency department with nausea and vomiting that ultimately progressed to severe hyperemesis-gravidarum-associated Wernicke-Korsakoff syndrome, fetal demise, and septic shock. The patient received a total of 6 weeks of high-dose parenteral thiamine. Magnetic resonance imaging of the head and formal neuropsychological assessment following treatment plateau confirmed the diagnosis of Wernicke-Korsakoff syndrome. CONCLUSIONS: The multisystem complications seen in severe thiamine deficiency can delay timely administration of high-dose thiamine, particularly in pregnancy, in which the classic triad of Wernicke-Korsakoff syndrome may not raise clinical suspicion due to rapid progression of neurological sequelae in this population. We advise a low threshold for parenteral thiamine repletion in pregnant women with persistent vomiting as hyperemesis gravidarum-induced severe thiamine deficiency can result in Wernicke-Korsakoff syndrome, sepsis, and fetal demise.

[Expert consensus from the College of French Gynecologists and Obstetricians: Management of nausea and vomiting of pregnancy and hyperemesis gravidarum]. / Consensus formalisé d'experts du Collège national des gynécologues et obstétriciens français : prise en charge des nausées et vomissements gravidiques et de l'hyperémèse gravidique.

OBJECTIVE: To determine the management of patients with 1st trimester nausea and vomiting and hyperemesis gravidarum. METHODS: A panel of experts participated in a formal consensus process, including focus groups and two Delphi rounds. RESULTS: Hyperemesis gravidarum is distinguished from nausea and vomiting during pregnancy by weight loss≥5 % or signs of dehydration or a PUQE score≥7. Hospitalization is proposed when there is, at least, one of the following criteria: weight loss≥10%, one or more clinical signs of dehydration, PUQE (Pregnancy Unique Quantification of Emesis and nausea) score≥13, hypokalemia<3.0mmol/L, hyponatremia<120mmol/L, elevated serum creatinine>100µmol/L or resistance to treatment. Prenatal vitamins and iron supplementation should be stopped without stopping folic acid supplementation. Diet and lifestyle should be adjusted according to symptoms. Aromatherapy is not to be used. If the PUQE score is<6, even in the absence of proof of their benefit, ginger, pyridoxine (B6 vitamin), acupuncture or electrostimulation can be used, even in the absence of proof of benefit. It is proposed that drugs or combinations of drugs associated with the least severe and least frequent side effects should always be chosen for uses in 1st, 2nd or 3rd intention, taking into account the absence of superiority of a class over another to reduce the symptoms of nausea and vomiting of pregnancy and hypermesis gravidarum. To prevent Gayet Wernicke encephalopathy, Vitamin B1 must systematically be administered for hyperemesis gravidarum needing parenteral rehydration. Patients hospitalized for hyperemesis gravidarum should not be placed in isolation (put in the dark, confiscation of the mobile phone or ban on visits, etc.). Psychological support should be offered to all patients with hyperemesis gravidarum as well as information on patient' associations involved in supporting these women and their families. When returning home after hospitalization, care will be organized around a referring doctor. CONCLUSION: This work should contribute to improving the care of women with hyperemesis gravidarum. However, given the paucity in number and quality of the literature, researchers must invest in the field of nausea and vomiting in pregnancy, and HG to identify strategies to improve the quality of life of women with nausea and vomiting in pregnancy or hyperemesis gravidarum.

Adjuvant Hypnotherapy for Hyperemesis Gravidarum: A Randomized Pilot Study.

Hyperemesis gravidarum, which requires hospitalization in approximately 1% to 5% of patients, is characterized by severe nausea and vomiting in pregnancy. This study investigated the effects of hypnosis on nausea, vomiting, use of antiemetic medications, and hospital stay among patients diagnosed with hyperemesis gravidarum. Patients were randomized to receive either conventional therapy alone (control condition, n = 23) or adjuvant hypnotherapy plus conventional therapy (treatment group, n = 18). Sociodemographic data, severity of nausea, frequency of vomiting per day, rescue medications used, and length of hospital stay were recorded. Participants in the treatment group received 2 sessions of hypnosis and were instructed in daily self-hypnosis practice. Those in the control group received treatment as usual. Results from this study indicated that adjunctive use of hypnotherapy with patients diagnosed with hyperemesis gravidarum experienced significantly reduced severity of nausea and frequency of vomiting compared to treatment-as-usual alone. Also, hospital stay was found to be shorter in the treatment group as compared to the control group. These findings are encouraging and suggest it is feasible and potentially beneficial to include adjunctive hypnotherapy to treat hyperemesis gravidarum.

Efficacy of group biofeedback treatment on hyperemesis gravidarum with psychosomatic symptoms diagnosed with the revised version of Diagnostic Criteria for Psychosomatic Research (DCPR-R): study protocol for a randomised controlled trial.

INTRODUCTION: Hyperemesis gravidarum (HG) is a condition characterised by dehydration, electrolyte imbalance, lack of nutrition and at least 5% loss in body weight, occurring in the first half of pregnancy. The aim of this trial is to examine the efficacy of group biofeedback treatment on patients with HG with psychosomatic symptoms, which will be evaluated through the revised version of Diagnostic Criteria for Psychosomatic Research (DCPR-R). METHODS AND ANALYSIS: In this single-blinded randomised controlled clinical trial, 68 patients with HG diagnosed with at least one psychosomatic syndrome according to DCPR-R and aged 18-40 years, will be recruited in a Chinese Maternal and Child Health Hospital. The sample will be randomised (1:1) into two arms: experimental group, which will undergo group biofeedback treatment, psycho-education and treatment as usual (TAU); and control group, which will undergo psycho-education and TAU only. The primary outcomes will be reduction of the frequency of psychosomatic syndromes, severity of nausea/vomiting, quality of life and heart rate variability. The secondary outcomes will include days of hospitalisation, repeated hospitalisation and laboratory investigations. ETHICS AND DISSEMINATION: This study has received ethical approval from the Nanjing Medical University (No. 2019/491, granted 22 February 2019). All participants will be required to provide written informed consent. Study outcomes will be disseminated through peer-reviewed publications and academic conferences, and used to confirm a tailored biofeedback intervention for patients with HG with psychosomatic symptoms. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry (ChiCTR2000028754).

The association between quality of life and complementary and alternative medicine use in pregnant women with hyperemesis gravidarum.

AIM: This study investigated the association between quality of life and complementary and alternative medicine (CAM) use in pregnant women with hyperemesis gravidarum in Turkey. METHODS: This cross-sectional descriptive study was conducted between October 2017 and July 2018 in Turkey. The sample consisted of 240 pregnant women with hyperemesis gravidarum. Data were collected using a Demographic Information Form, the Index of Nausea, Vomiting, Retching, and the 36-item Short-Form Health Survey. RESULTS: The majority (84.2%) of participants stated that they used CAM, mostly "biologically based therapies" (97.5%). They were most satisfied with the "mental and physical treatments" (3.71 ± 1.74). Participants who did not use CAM had a higher quality of life "emotional role" than those who used CAM (p = 0.038). However, there were no statistically significant differences in the other quality of life subscale scores between the two groups. CONCLUSION: There is limited evidence for the association between quality of life and CAM use in pregnant women with hyperemesis gravidarum in Turkey. Therefore, more evidence-based research is warranted to evaluate the association between CAM use and quality of life in pregnant women with hyperemesis gravidarum.

A comparison of the efficacy and safety of traditional Chinese medicine external treatment for the hyperemesis gravidarum: A protocol for systematic review and network meta-analysis.

BACKGROUND: The symptoms of frequent nausea and vomiting, inability to eat, and fluid imbalance caused by hyperemesis gravidarum (HG) seriously impact the quality of life of pregnant women. In some serious cases, it is even necessary to terminate the pregnancy, and threatens the life of the pregnant woman. A great many of studies have proved that HG can be effectively treated by traditional Chinese medicine (TCM) external treatment. Nevertheless, its relative effectiveness and safety haven't yet been confirmed because of the variety of TCM external treatment. Therefore, we will use the method of network meta-analysis to verify the effectiveness and safety of different types of TCM external treatment for the HG. METHODS: In this study, English and Chinese literatures that meet the requirements will be searched in EMBASE, PubMed, Cochrane Library, Web of Science, CnKI, VIP, Wanfang, and CBM. Regardless of whether blinding is used or not, all randomized controlled trials (RCTs) using TCM external treatment for the HG will be included. Then, Stata 16.0 will be used to conduct a series of pairwise meta-analysis. WinBUGS 1.4.3 and Stata 16.0 will be used to conduct Bayesian network meta-analysis to evaluate the relative results of different TCM external treatments for the HG. The quality included in the study will be evaluated through the classification of Grading of Recommendations Assessment, Development and Evaluation (GRADE). RESULTS: This study will evaluate the effectiveness and safety of TCM external treatment for the HG according to the primary and secondary outcomes, and we rank different kinds of TCM external treatments in accordance with effectiveness. The primary outcomes are the intensity of nausea and vomiting. Secondary outcomes include quality of life, adverse outcome of pregnant women, adverse outcome of fetal, duration of hospitalization and so on. CONCLUSION: This study will provide more convincing and detailed information of TCM external treatment for the HG, and the reference value for clinical treatment. INPLASY REGISTRATION NUMBER: INPLASY 202090089.

Interventions for treating hyperemesis gravidarum: a network meta-analysis of randomized clinical trials.

Background: Several interventions were explored in clinical trials for treating hyperemesis gravidarum (HG). The present study is a network meta-analysis of such interventions.Methods: Electronic databases were searched for appropriate randomized clinical trials comparing interventions for treatment of patients with HG. Control of HG symptoms was the primary outcome and emetic episodes, hospital stay, nausea scores, patients requiring rescue antiemetics, hospital readmission, adverse events, and adverse pregnancy outcomes were the secondary outcome measures. Random-effects model was used and odds ratio (OR) [95% confidence interval (CI)] was the effect estimate for categorical outcomes and weighted mean difference (WMD) [95% confidence interval] for numerical outcomes.Results: Twenty studies were included in the systematic review and 18 in the meta-analysis. Acupuncture (OR: 18.9; 95% CI: 2.1, 168), acupressure (OR: 26.7; 95% CI: 2.5, 283.1) and methylprednisolone (OR: 6.7; 95% CI: 1.1, 38.8) were associated with better control of HG symptoms than standard of care. Acupressure decreases the requirement of rescue antiemetics (OR: 0.06; 95% CI: 0.01, 0.44); ondansetron with reduced hospital stay (WMD: -0.2; 95% CI: -0.31, -0.01) and diazepam with reduced risk of hospital admission (OR: 0.11; 95% CI: 0.01, 0.95). The quality of evidence is very low.Conclusion: Acupuncture, acupressure, and methylprednisolone were observed with better therapeutic benefits than other interventions for treating HG. However, the pooled estimates may change with the advent of results from future head-to-head clinical trials.

The Management of Nausea and Vomiting of Pregnancy: Synthesis of National Guidelines.

IMPORTANCE: Nausea and vomiting of pregnancy (NVP) affects a high proportion of the pregnant population. OBJECTIVE: The aim of this study was to compare and synthesize recommendations from national guidelines regarding the management of NVP. EVIDENCE ACQUISITION: A descriptive review of 3 recently published national guidelines on NVP was conducted: Royal College of Obstetricians and Gynaecologists on "The Management of Nausea and Vomiting of Pregnancy and Hyperemesis Gravidarum," American College of Obstetricians and Gynecologists on "Nausea and Vomiting of Pregnancy," and Society of Obstetricians and Gynaecologists of Canada on "The Management of Nausea and Vomiting of Pregnancy." These guidelines were summarized and compared in terms of the recommended management of pregnant women. The quality of evidence was also reviewed based on the method of reporting. RESULTS: Several differences were identified on the different guidelines regarding the management of NVP. Frequent small meals and avoidance of iron supplements are recommended for prevention. The consumption of ginger, acustimulations, antihistamines, phenothiazines, dopamine, and serotonin 5-hydroxytryptamine type 3 receptor antagonists is routinely recommended for use in the community as treatment. CONCLUSIONS: Evidence-based medicine may lead to the adoption of an international guideline for the management of NVP, which may lead to a more effective management of that entity.

Treatment of hyperemesis gravidarum with anthroposophic complex therapy in 3 case reports.

BACKGROUND: Hyperemesis gravidarum (HG) is generally characterized by intractable nausea and vomiting which interferes with daily life. As the cause of HG has not yet been clearly identified, conventional medicine therapies address only the symptoms. Conventional treatment is also effective for a comparatively short time and may have unfavorable side effects. Given that the condition affects more than 1% of pregnant women, there is a significant need for effective long-lasting treatments with limited side effects. CASE REPORTS: This paper is based on three case reports of pregnant women suffering from HG. They received inpatient treatment based exclusively on anthroposophic medical approaches at the Paracelsus Hospital Richterswil, Switzerland. Treatments were selected individually based on the specific patient profiles and included infusion therapy with Nux vomica, Solum uliginosum compositum and Bryophyllum pinnatum as well as art therapy (wet-on-wet painting), eurythmy therapy and rhythmical massage therapy. Anthroposophic complex therapies induced an improvement in symptoms of nausea and vomiting within one week in all three cases. CONCLUSION: Anthroposophic complex therapy is a valuable option in the treatment of HG. Well-tolerated and long-lasting, it represents a holistic and causal approach that does not only address symptoms.

Complete recovery in Wernicke's encephalopathy complicating hyperemesis gravidarum.

Wernicke's encephalopathy (WE) is an uncommon neurological complication in pregnancies complicated with hyperemesis due to thiamine deficiency. In women with hyperemesis, inadvertent glucose administration prior to thiamine supplementation triggers the development of neurological manifestations. Delay in the diagnosis can lead to maternal morbidity, and in one-third of cases may lead to persistence of some neurological deficit. With early recognition and thiamine supplementation, complete recovery is reported. We report a case of WE complicating a case of triplet pregnancy with hyperemesis gravidarum, which highlights the importance of early recognition and treatment, resulting in complete recovery as in the index case.

Interventions for treating nausea and vomiting in pregnancy: a network meta-analysis and trial sequential analysis of randomized clinical trials.

INTRODUCTION: Several drugs were explored for their utility in treating nausea and vomiting in pregnancy (NVP). The present study is a network meta-analysis of such drugs. METHODS: Electronic databases were searched for randomized clinical trials that have compared active interventions (with placebo or other active interventions) for treating NVP. Nausea scores were the primary outcome and changes in nausea scores, emetic episodes, adverse events, and vomiting control were the key secondary outcomes. Weighted mean difference was the effect estimate for continuous variable and odds ratio for the numerical variable. Random-effects model was used and the strength of the evidence was graded. RESULTS: Fifty studies were included in the systematic review and 42 in the meta-analysis. Acupuncture, chamomile, dimenhydrinate, doxylamine/vitamin B6, ginger, quince, metoclopramide, and vitamin B6 were associated with reduced nausea scores compared to placebo. Of these interventions, ginger and vitamin B6 were also associated with better vomiting control and less incidence of adverse events. Adequate evidence supporting the use exists only for ginger and the quality of evidence for this comparison is moderate. Strength of evidence for all other comparisons is very low. CONCLUSION: Present evidence is conclusive on the therapeutic benefits of ginger in treating NVP. Although favorable results were obtained for several other interventions, the strength of evidence is very low. The results of this network meta-analysis should be interpreted with extreme caution as it might change with the advent of data from future head-to-head clinical trials.

Interventions for treating hyperemesis gravidarum: a Cochrane systematic review and meta-analysis.

INTRODUCTION: While nausea and vomiting in early pregnancy are very common, affecting approximately 80% of the pregnancies, hyperemesis gravidarum is a severe form affecting 0.3-1.0% of the pregnancies. Although hyperemesis gravidarum is rarely a source of mortality, it is a significant source of morbidity. It is one of the most common indications for hospitalization in pregnancy. Beyond the maternal and fetal consequences of malnutrition, the severity of hyperemesis symptoms causes a major psychosocial burden leading to depression, anxiety, and even pregnancy termination. The aim of this meta-analysis was to examine all randomized controlled trials of interventions specifically for hyperemesis gravidarum and evaluate them based on both subjective and objective measures of efficacy, maternal and fetal/neonatal safety, and economic costs. MATERIAL AND METHODS: Randomized controlled trials were identified by searching electronic databases. We included all randomized controlled trials for the treatment of hyperemesis gravidarum. The primary outcome was intervention efficacy as defined by severity, reduction, or cessation in nausea/vomiting; number of episodes of emesis; and days of hospital admission. Secondary outcomes included other measures of intervention efficacy, adverse maternal/fetal/neonatal outcomes, quality of life measures, and economic costs. RESULTS: Twenty-five trials (2052 women) met the inclusion criteria but the majority of 18 different comparisons described in the review include data from single studies with small numbers of participants. Selected comparisons reported below: No primary outcome data were available when acupuncture was compared with placebo. There was insufficient evidence to identify clear differences between acupuncture and metoclopramide in a study with 81 participants regarding reduction/cessation in nausea or vomiting (risk ratio (RR) 1.40, 95% CI 0.79-2.49 and RR 1.51, 95% CI 0.92-2.48, respectively). Midwife-led outpatient care was associated with fewer hours of hospital admission than routine inpatient admission (mean difference (MD) - 33.20, 95% CI -46.91 to -19.49) with no difference in pregnancy-unique quantification of emesis and nausea (PUQE) score, decision to terminate the pregnancy, miscarriage, small-for-gestational age infants, or time off work when compared with routine care. Women taking vitamin B6 had a slightly longer hospital stay compared with placebo (MD 0.80 days, 95% CI 0.08-1.52). There was insufficient evidence to demonstrate a difference in other outcomes including mean number of episodes of emesis (MD 0.50, 95% CI -0.40-1.40) or side effects. A comparison between metoclopramide and ondansetron identified no clear difference in the severity of nausea or vomiting (MD 1.70, 95% CI -0.15-3.55, and MD -0.10, 95% CI -1.63-1.43; one study, 83 women, respectively). However, more women taking metoclopramide complained of drowsiness and dry mouth (RR 2.40, 95% CI 1.23-4.69, and RR 2.38, 95% CI 1.10-5.11, respectively). There were no clear differences between groups for other side effects. In a single study with 146 participants comparing metoclopramide with promethazine, more women taking promethazine reported drowsiness, dizziness, and dystonia (risk ratio (RR) 0.70, 95% CI 0.56-0.87, RR 0.48, 95% CI 0.34-0.69, and RR 0.31, 95% CI 0.11-0.90, respectively). There were no clear differences between groups for other important outcomes including quality of life and other side effects. In a single trial with 30 women, those receiving ondansetron had no difference in duration of hospital admission compared to those receiving promethazine (mean difference (MD) 0.00, 95% CI -1.39-1.39), although there was increased sedation with promethazine (RR 0.06, 95% CI 0.00-0.94). Regarding corticosteroids, in a study with 110 participants there was no difference in days of hospital admission compared to placebo (MD -0.30, 95% CI -0.70-0.10), but there was a decreased readmission rate (RR 0.69, 95% CI 0.50-0.94; 4 studies, 269 women). For hydrocortisone compared with metoclopramide, no data were available for primary outcomes and there was no difference in the readmission rate (RR 0.08, 95% CI 0.00-1.28; one study, 40 women). In a study with 80 women, compared to promethazine, those receiving prednisolone had increased nausea at 48 h (RR 2.00, 95% CI 1.08-3.72), but not at 17 days (RR 0.81, 95% CI 0.58-1.15). There was no clear difference in the number of episodes of emesis or subjective improvement in nausea/vomiting. CONCLUSIONS: While there were a wide range of interventions studied, both pharmaceutical and otherwise, there were a limited number of placebo controlled trials. In comparing the efficacy of the commonly used antiemetics, metoclopramide, ondansetron, and promethazine, the results of this review do not support the clear superiority of one over the other in symptomatic relief. Other factors such as side effect profile medication safety and healthcare costs should also be considered when selecting an intervention.

Treatments for Hyperemesis Gravidarum and Nausea and Vomiting in Pregnancy: A Systematic Review.

Importance: Nausea and vomiting affects approximately 85% of pregnant women. The most severe form, hyperemesis gravidarum, affects up to 3% of women and can have significant adverse physical and psychological sequelae. Objective: To summarize current evidence on effective treatments for nausea and vomiting in pregnancy and hyperemesis gravidarum. Evidence Review: Databases were searched to June 8, 2016. Relevant websites and bibliographies were also searched. Titles and abstracts were assessed independently by 2 reviewers. Results were narratively synthesized; planned meta-analysis was not possible because of heterogeneity and incomplete reporting of findings. Findings: Seventy-eight studies (n = 8930 participants) were included: 67 randomized clinical trials (RCTs) and 11 nonrandomized studies. Evidence from 35 RCTs at low risk of bias indicated that ginger, vitamin B6, antihistamines, metoclopramide (for mild symptoms), pyridoxine-doxylamine, and ondansetron (for moderate symptoms) were associated with improved symptoms compared with placebo. One RCT (n = 86) reported greater improvements in moderate symptoms following psychotherapy (change in Rhodes score [range, 0 {no symptoms} to 40 {worst possible symptoms}], 18.76 [SD, 5.48] to 7.06 [SD, 5.79] for intervention vs 19.18 [SD, 5.63] to 12.81 [SD, 6.88] for comparator [P < .001]). For moderate-severe symptoms, 1 RCT (n = 60) suggested that pyridoxine-doxylamine combination taken preemptively reduced risk of recurrence of moderate-severe symptoms compared with treatment once symptoms begin (15.4% vs 39.1% [P < .04]). One RCT (n = 83) found that ondansetron was associated with lower nausea scores on day 4 than metoclopramide (mean visual analog scale [VAS] score, 4.1 [SD, 2.9] for ondansetron vs 5.7 [SD, 2.3] for metoclopramide [P = .023]) but not episodes of emesis (5.0 [SD, 3.1] vs 3.3 [SD, 3], respectively [P = .013]). Although there was no difference in trend in nausea scores over the 14-day study period, trend in vomiting scores was better in the ondansetron group (P = .042). One RCT (n = 159) found no difference between metoclopramide and promethazine after 24 hours (episodes of vomiting, 1 [IQR, 0-5] for metoclopramide vs 2 [IQR, 0-3] for promethazine [P = .81], VAS [0-10 scale] for nausea, 2 [IQR, 1-5] vs 2 [IQR, 1-4], respectively [P = .99]). Three RCTs compared corticosteroids with placebo or promethazine or metoclopramide in women with severe symptoms. Improvements were seen in all corticosteroid groups, but only a significant difference between corticosteroids vs metoclopramide was reported (emesis reduction, 40.9% vs 16.5% at day 2; 71.6% vs 51.2% at day 3; 95.8% vs 76.6% at day 7 [n = 40, P < .001]). For other interventions, evidence was limited. Conclusions and Relevance: For mild symptoms of nausea and emesis of pregnancy, ginger, pyridoxine, antihistamines, and metoclopramide were associated with greater benefit than placebo. For moderate symptoms, pyridoxine-doxylamine, promethazine, and metoclopramide were associated with greater benefit than placebo. Ondansetron was associated with improvement for a range of symptom severity. Corticosteroids may be associated with benefit in severe cases. Overall the quality of evidence was low.

Treatments for hyperemesis gravidarum and nausea and vomiting in pregnancy: a systematic review and economic assessment.

BACKGROUND: Nausea and vomiting in pregnancy (NVP) affects up to 85% of all women during pregnancy, but for the majority self-management suffices. For the remainder, symptoms are more severe and the most severe form of NVP - hyperemesis gravidarum (HG) - affects 0.3-1.0% of pregnant women. There is no widely accepted point at which NVP becomes HG. OBJECTIVES: This study aimed to determine the relative clinical effectiveness and cost-effectiveness of treatments for NVP and HG. DATA SOURCES: MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature, Cochrane Central Register of Controlled Trials, PsycINFO, Commonwealth Agricultural Bureaux (CAB) Abstracts, Latin American and Caribbean Health Sciences Literature, Allied and Complementary Medicine Database, British Nursing Index, Science Citation Index, Social Sciences Citation Index, Scopus, Conference Proceedings Index, NHS Economic Evaluation Database, Health Economic Evaluations Database, China National Knowledge Infrastructure, Cochrane Database of Systematic Reviews and Database of Abstracts of Reviews of Effects were searched from inception to September 2014. References from studies and literature reviews identified were also examined. Obstetric Medicine was hand-searched, as were websites of relevant organisations. Costs came from NHS sources. REVIEW METHODS: A systematic review of randomised and non-randomised controlled trials (RCTs) for effectiveness, and population-based case series for adverse events and fetal outcomes. Treatments: vitamins B6 and B12, ginger, acupressure/acupuncture, hypnotherapy, antiemetics, dopamine antagonists, 5-hydroxytryptamine receptor antagonists, intravenous (i.v.) fluids, corticosteroids, enteral and parenteral feeding or other novel treatment. Two reviewers extracted data and quality assessed studies. Results were narratively synthesised; planned meta-analysis was not possible due to heterogeneity and incomplete reporting. A simple economic evaluation considered the implied values of treatments. RESULTS: Seventy-three studies (75 reports) met the inclusion criteria. For RCTs, 33 and 11 studies had a low and high risk of bias respectively. For the remainder (n = 20) it was unclear. The non-randomised studies (n = 9) were low quality. There were 33 separate comparators. The most common were acupressure versus placebo (n = 12); steroid versus usual treatment (n = 7); ginger versus placebo (n = 6); ginger versus vitamin B6 (n = 6); and vitamin B6 versus placebo (n = 4). There was evidence that ginger, antihistamines, metoclopramide (mild disease) and vitamin B6 (mild to severe disease) are better than placebo. Diclectin® [Duchesnay Inc.; doxylamine succinate (10 mg) plus pyridoxine hydrochloride (10 mg) slow release tablet] is more effective than placebo and ondansetron is more effective at reducing nausea than pyridoxine plus doxylamine. Diclectin before symptoms of NVP begin for women at high risk of severe NVP recurrence reduces risk of moderate/severe NVP compared with taking Diclectin once symptoms begin. Promethazine is as, and ondansetron is more, effective than metoclopramide for severe NVP/HG. I.v. fluids help correct dehydration and improve symptoms. Dextrose saline may be more effective at reducing nausea than normal saline. Transdermal clonidine patches may be effective for severe HG. Enteral feeding is effective but extreme method treatment for very severe symptoms. Day case management for moderate/severe symptoms is feasible, acceptable and as effective as inpatient care. For all other interventions and comparisons, evidence is unclear. The economic analysis was limited by lack of effectiveness data, but comparison of costs between treatments highlights the implications of different choices. LIMITATIONS: The main limitations were the quantity and quality of the data available. CONCLUSION: There was evidence of some improvement in symptoms for some treatments, but these data may not be transferable across disease severities. Methodologically sound and larger trials of the main therapies considered within the UK NHS are needed. STUDY REGISTRATION: This study is registered as PROSPERO CRD42013006642. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Interventions for treating hyperemesis gravidarum.

BACKGROUND: Hyperemesis gravidarum is a severe form of nausea and vomiting in pregnancy affecting 0.3% to 1.0% of pregnancies, and is one of the most common indications for hospitalization during pregnancy. While a previous Cochrane review examined interventions for nausea and vomiting in pregnancy, there has not yet been a review examining the interventions for the more severe condition of hyperemesis gravidarum. OBJECTIVES: To assess the effectiveness and safety, of all interventions for hyperemesis gravidarum in pregnancy up to 20 weeks' gestation. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register and the Cochrane Complementary Medicine Field's Trials Register (20 December 2015) and reference lists of retrieved studies. SELECTION CRITERIA: Randomized controlled trials of any intervention for hyperemesis gravidarum. Quasi-randomized trials and trials using a cross-over design were not eligible for inclusion.We excluded trials on nausea and vomiting of pregnancy that were not specifically studying the more severe condition of hyperemesis gravidarum. DATA COLLECTION AND ANALYSIS: Two review authors independently reviewed the eligibility of trials, extracted data and evaluated the risk of bias. Data were checked for accuracy. MAIN RESULTS: Twenty-five trials (involving 2052 women) met the inclusion criteria but the majority of 18 different comparisons described in the review include data from single studies with small numbers of participants. The comparisons covered a range of interventions including acupressure/acupuncture, outpatient care, intravenous fluids, and various pharmaceutical interventions. The methodological quality of included studies was mixed. For selected important comparisons and outcomes, we graded the quality of the evidence and created 'Summary of findings' tables. For most outcomes the evidence was graded as low or very low quality mainly due to the imprecision of effect estimates. Comparisons included in the 'Summary of findings' tables are described below, the remaining comparisons are described in detail in the main text.No primary outcome data were available when acupuncture was compared with placebo, There was no clear evidence of differences between groups for anxiodepressive symptoms (risk ratio (RR) 1.01, 95% confidence interval (CI) 0.73 to 1.40; one study, 36 women, very low-quality evidence), spontaneous abortion (RR 0.48, 95% CI 0.05 to 5.03; one study, 57 women, low-quality evidence), preterm birth (RR 0.12, 95% CI 0.01 to 2.26; one study, 36 women, low-quality evidence), or perinatal death (RR 0.57, 95% CI 0.04 to 8.30; one study, 36 women, low-quality evidence).There was insufficient evidence to identify clear differences between acupuncture and metoclopramide in a study with 81 participants regarding reduction/cessation in nausea or vomiting (RR 1.40, 95% CI 0.79 to 2.49 and RR 1.51, 95% CI 0.92 to 2.48, respectively; very low-quality evidence).In a study with 92 participants, women taking vitamin B6 had a slightly longer hospital stay compared with placebo (mean difference (MD) 0.80 days, 95% CI 0.08 to 1.52, moderate-quality evidence). There was insufficient evidence to demonstrate a difference in other outcomes including mean number of episodes of emesis (MD 0.50, 95% CI -0.40 to 1.40, low-quality evidence) or side effects.A comparison between metoclopramide and ondansetron identified no clear difference in the severity of nausea or vomiting (MD 1.70, 95% CI -0.15 to 3.55, and MD -0.10, 95% CI -1.63 to 1.43; one study, 83 women, respectively, very low-quality evidence). However, more women taking metoclopramide complained of drowsiness and dry mouth (RR 2.40, 95% CI 1.23 to 4.69, and RR 2.38, 95% CI 1.10 to 5.11, respectively; moderate-quality evidence). There were no clear differences between groups for other side effects.In a single study with 146 participants comparing metoclopramide with promethazine, more women taking promethazine reported drowsiness, dizziness, and dystonia (RR 0.70, 95% CI 0.56 to 0.87, RR 0.48, 95% CI 0.34 to 0.69, and RR 0.31, 95% CI 0.11 to 0.90, respectively, moderate-quality evidence). There were no clear differences between groups for other important outcomes including quality of life and other side effects.In a single trial with 30 women, those receiving ondansetron had no difference in duration of hospital admission compared to those receiving promethazine (MD 0.00, 95% CI -1.39 to 1.39, very low-quality evidence), although there was increased sedation with promethazine (RR 0.06, 95% CI 0.00 to 0.94, low-quality evidence) .Regarding corticosteroids, in a study with 110 participants there was no difference in days of hospital admission compared to placebo (MD -0.30, 95% CI -0.70 to 0.10; very low-quality evidence), but there was a decreased readmission rate (RR 0.69, 95% CI 0.50 to 0.94; four studies, 269 women). For other important outcomes including pregnancy complications, spontaneous abortion, stillbirth and congenital abnormalities, there was insufficient evidence to identify differences between groups (very low-quality evidence for all outcomes). In other single studies there were no clear differences between groups for preterm birth or side effects (very low-quality evidence).For hydrocortisone compared with metoclopramide, no data were available for primary outcomes and there was no difference in the readmission rate (RR 0.08, 95% CI 0.00 to 1.28;one study, 40 women).In a study with 80 women, compared to promethazine, those receiving prednisolone had increased nausea at 48 hours (RR 2.00, 95% CI 1.08 to 3.72; low-quality evidence), but not at 17 days (RR 0.81, 95% CI 0.58 to 1.15, very low-quality evidence). There was no clear difference in the number of episodes of emesis or subjective improvement in nausea/vomiting. There was insufficient evidence to identify differences between groups for stillbirth and neonatal death and preterm birth. AUTHORS' CONCLUSIONS: On the basis of this review, there is little high-quality and consistent evidence supporting any one intervention, which should be taken into account when making management decisions. There was also very limited reporting on the economic impact of hyperemesis gravidarum and the impact that interventions may have.The limitations in interpreting the results of the included studies highlights the importance of consistency in the definition of hyperemesis gravidarum, the use of validated outcome measures, and the need for larger placebo-controlled trials.

Hyperemesis in Pregnancy Study: a pilot randomised controlled trial of midwife-led outpatient care.

OBJECTIVE: To assess the feasibility of implementing a complex intervention involving rapid intravenous rehydration and ongoing midwifery support as compared to routine in-patient care for women suffering from severe nausea and vomiting in pregnancy, (NVP)/hyperemesis gravidarum (HG). STUDY DESIGN: 53 pregnant women attending the Maternity Assessment Unit (MAU), Newcastle upon Tyne NHS Foundation Trust, Newcastle, UK with moderate-severe NVP, (as determined by a Pregnancy Unique Quantification of Emesis and Vomiting [PUQE] score ≥nine), consented to participate in this pilot randomised controlled trial (RCT). Subsequently 27 were randomised to the intervention group, 26 to the control group. Women in the intervention group received rapid rehydration (three litres Hartman's solution over 6h) and symptom relief on the MAU followed by ongoing midwifery telephone support. The control group were admitted to the antenatal ward for routine in-patient care. Quality of life (QoL) determined by SF36.V2 score and PUQE score were measured 7 days following randomisation. Completion rates, readmission rate, length of hospital stay and pregnancy outcomes data were collected. RESULTS: Groups were comparable at baseline. Questionnaire two return rate was disappointing, only 18 women in the control group (69%) and 13 women in the intervention groups (44%). Nonetheless there were no differences between groups on Day 7 in terms of QoL, mean PUQE score, satisfaction with care, obstetric and neonatal outcomes or readmission rates. However, total combined admission time was higher in the control group (94h versus 27h, p=0.001). CONCLUSIONS: This study suggests that day-case management plus ongoing midwifery support may be an effective alternative for treating women with severe NVP/HG. A larger trial is needed to determine if this intervention affects women's QoL.

Effect of acustimulation on nausea and vomiting and on hyperemesis in pregnancy: a systematic review of Western and Chinese literature.

BACKGROUND: Nausea and vomiting in pregnancy (NVP) and hyperemesis gravidarum (HG) have a significant impact on quality of life. Medication to relieve symptoms of NVP and HG are available but pregnant women and their caregivers have been concerned about the teratogenic effect, side effects and poor efficacy. The aim of this review was to investigate if there is any clinical evidence for the efficacy of acustimulation in the treatment of NVP or HG. METHODS: A systematic review of randomized controlled trials (RCTs), including both English and Chinese databases was conducted to assess the efficacy of various techniques of acustimulation for NVP and HG. The methodological quality of the studies was assessed using the Cochrane's risks of bias tool. Revised STRICTA (2010) criteria were used to appraise acustimulation procedures. Pooled relative risks (RRp) and standard mean deviations (SMD) with 95% confidence intervals (CI) were calculated from the data provided by the investigators of the original trials. RESULTS: Twenty-nine trials including 3519 patients met the inclusion criteria. Twenty trials could be included in statistical pooling. The overall effect of different acustimulation techniques shows a significant reduction for the combined outcome for NVP or HG in pregnancy as a dichotomous variable (RRp 1.73, 95% CI 1.43 to 2.08). Studies with continuous outcome measures for nausea, vomiting and the combined outcome did not show any evidence for relieving symptoms of NVP and HG (SMD -0.12, 95% CI -0.35 to 0.12). CONCLUSIONS: Although there is some evidence for an effect of acustimulation on nausea and vomiting or hyperemesis in pregnancy, results are not conclusive. Future clinical trials with a rigorous design and large sample sizes should be conducted to evaluate the efficacy and safety of these interventions for NVP and HG.

Successful Treatment of Ptyalism Gravidarum With Concomitant Hyperemesis Using Hypnosis.

Ptyalism gravidarum, or sialorrhea, is the excessive secretion of saliva during pregnancy. Treatment of ptyalism gravidarum is often challenging due to its unknown etiologies. This article discusses a case of ptyalism gravidarum with concomitant hyperemesis in which the condition was successfully treated with hypnosis. A 28-year-old woman presented with ptyalism 2 months into her pregnancy and hyperemesis 3 months into pregnancy with associated vomiting that occurred following every meal. Hypnosis was administered at week 16 of pregnancy to eliminate ptyalism and hyperemesis, to prepare for childbirth, and to increase overall psychological well-being. Ptyalism resolved by week 36, concurrent with the final hypnosis session.