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].

The Nutritional Online sUrvey for pRegnancy Induced Sickness & Hyperemesis (NOURISH) study: results from the first trimester.

BACKGROUND: Hyperemesis gravidarum (HG) is severe pregnancy sickness, often leading to dehydration, weight loss and electrolyte disturbances. Little is known about nutritional intake and its consequences in those affected. The aim of this study was to explore the first trimester nutritional intake and clinical characteristics in those with severe sickness. METHOD: Recruitment was via the social media accounts of national pregnancy charities. The eligibility criteria were as follows: between 6 and 11 weeks pregnant, age ≥18 years and residing in the UK. Participants completed a self-report online questionnaire including the Pregnancy Unique Quantification of Emesis 24 (PUQE24) score and a 3-day online diet diary. Groups were compared by PUQE24 categories. Nutritional intakes were compared to dietary reference values. RESULTS: One hundred sixty-six participants took part in the study: 36 categorised with mild, 109 with moderate and 21 with severe symptoms at a median gestation of 8.1 (interquartile range [IQR] 3) weeks. Those in the severe category had significantly higher weight loss (3.0 kg, IQR 3.5) than the mild category (0.0 kg, IQR 0.9). In those who completed the diet diary (n = 70), intakes of energy, carbohydrate, protein, fat, fibre, calcium, iron, zinc, thiamine, riboflavin, folate and vitamin C were all significantly lower in the severe category (p < 0.05). The severe group consumed only 39.5% and 41.6% of energy and protein needs, respectively, and were more likely to stop taking micronutrient supplements (p < 0.05). CONCLUSION: Nutritional and supplement intake in those with severe pregnancy sickness was poor; however, intake across all participants was suboptimal. Future research should investigate how to improve nutritional intake across all categories of pregnancy sickness.

Nutritional consequences and management of hyperemesis gravidarum: a narrative review.

Hyperemesis gravidarum (HG) is a condition at the extreme end of the pregnancy sickness spectrum, estimated to affect 1-2 % of pregnant women. This narrative review provides an overview of the current literature concerning the nutritional implications and management of HG. HG can persist throughout pregnancy, causing malnutrition, dehydration, electrolyte imbalance and unintended weight loss, requiring hospital admission in most cases. In addition to its negative effect on maternal, physical and psychological wellbeing, HG can negatively impact fetal growth and may have adverse consequences on the health of the offspring. HG care and research have been hampered in the past due to stigma, inconsistent diagnostic criteria, mismanagement and lack of investment. Little is known about the nutritional intake of women with HG and whether poor intake at critical stages of pregnancy is associated with perinatal outcomes. Effective treatment requires a combination of medical interventions, lifestyle changes, dietary changes, supportive care and patient education. There is, however, limited evidence-based research on the effectiveness of dietary approaches. Enteral tube feeding and parenteral nutrition are generally reserved for the most intractable cases, where other treatment modalities have failed. Wernicke encephalopathy is a rare but very serious and avoidable consequence of unmanaged HG. A recent priority-setting exercise involving patients, clinicians and researchers highlighted the importance of nutrition research to all. Future research should focus on these priorities to better understand the nutritional implications of HG. Ultimately improved recognition and management of malnutrition in HG is required to prevent complications and optimise nutritional care.

Recurrence, postponing pregnancy, and termination rates after hyperemesis gravidarum: Follow up of the MOTHER study.

INTRODUCTION: Hyperemesis gravidarum (HG) complicates 1% of pregnancies and has a major impact on maternal quality of life and well-being. We know very little about HG's long-term impact after an affected pregnancy, including recurrence rates in future pregnancies, which is essential information for women considering subsequent pregnancies. In this study, we aimed to prospectively measure the recurrence rate of HG and the number of postponed and terminated subsequent pregnancies due to HG. We also aimed to evaluate if there were predictive factors that could identify women at increased risk for HG recurrence, and postponing and terminating subsequent pregnancies. MATERIAL AND METHODS: We conducted a prospective cohort study. A total of 215 women admitted for HG to public hospitals in the Netherlands were enrolled in the original MOTHER randomized controlled trial and associated observational cohort. Seventy-three women were included in this follow-up study. Data were collected through an online questionnaire. Recurrent HG was defined as vomiting symptoms accompanied by any of the following: multiple medication use, weight loss, admission, tube feeding or if nausea and vomiting symptoms were severe enough to affect life and/or work. Outcome measures were recurrence, postponing, and termination rates due to HG. Univariable logistic regression analysis was used to identify predictive factors associated with HG recurrence, and postponing and terminating subsequent pregnancies. RESULTS: Thirty-five women (48%) became pregnant again of whom 40% had postponed their pregnancy due to HG. HG recurred in 89% of pregnancies. One woman terminated and eight women (23%) considered terminating their pregnancy because of recurrent HG. Twenty-four out of 38 women did not get pregnant again because of HG in the past. Univariable logistic regression analysis identifying possible predictive factors found that having a western background was associated with having weight loss due to recurrent HG in subsequent pregnancies (odds ratio 12.9, 95% CI 1.3-130.5, p = 0.03). CONCLUSIONS: High rates of HG recurrence and a high number of postponed pregnancies due to HG were observed. Women can be informed of a high chance of recurrence to enable informed family planning.

Women's experiences of over-the-counter and prescription medication during pregnancy in the UK: findings from survey free-text responses and narrative interviews.

OBJECTIVES: To explore women's experiences of over-the-counter and prescription medication advice and use during pregnancy. DESIGN: A study design consisting of an online survey and nested in-depth interviews with a subsample of participants. We analysed data from survey free-text responses and in-depth interviews using thematic analysis. Quantitative survey data is published elsewhere. SETTING: The UK. PARTICIPANTS: Women were eligible if living in the UK, aged 16-45 years, were pregnant or had been pregnant in the last 5 years regardless of pregnancy outcome. A total of 7090 women completed the survey, and 34 women who collectively had experienced 68 pregnancies were subsequently interviewed. RESULTS: Medication prescribing and use during pregnancy was common. The prescribing, dispensing and taking of some advised medications were restricted through women's or prescribers' fear of fetal harm. Lack of adherence to national prescribing guidance, conflicting professional opinion and poor communication resulted in maternal anxiety, avoidable morbidity and women negotiating complex and distressing pathways to obtain recommended medications. In contrast, some women felt overmedicated and that pharmacological treatments were used without exploring other options first. CONCLUSION: Increased translation of national guidance into practice and greater personalisation of antenatal care are needed to improve the safety, efficacy and personalisation of prescribing in pregnancy.

Termination of wanted pregnancy and suicidal ideation in hyperemesis gravidarum: A mixed methods study.

Background: Difficulty accessing medication and poor patient experience have been implicated as risk factors for termination of pregnancy and suicidal ideation in women with hyperemesis gravidarum. We aimed to gain further insight into these factors in order to further inform and improve patient care. Methods: We performed a sub-analysis on quantitative data generated through a UK-wide survey of 5071 participants. A qualitative analysis of free text comments was performed using an inductive thematic approach. Results: 41.2% % of women taking prescribed medications had to actively request them. 'Extremely poor' or 'poor' experiences were described in 39.4% and 30.0% of participants in primary and secondary care respectively. Protective factors for termination of pregnancy and suicidal ideation include holistic support from family, friends and healthcare providers. Conclusion: Optimal care in hyperemesis gravidarum should incorporate timely access to pharmacotherapy, assessment of mental health, consideration of referral to specialist services and care being delivered in a compassionate manner.

Systematic evidence map of evidence addressing the top 10 priority research questions for hyperemesis gravidarum.

OBJECTIVE: Knowledge gaps regarding hyperemesis gravidarum (HG) are substantial. We aimed to systematically identify and map recent evidence addressing the top 10 priority questions for HG, as published in 2021 in a James Lind Alliance Priority Setting Partnership. DESIGN: Systematic evidence map. METHODS: We searched MEDLINE and EMBASE on 12 January 2021 and CINAHL on 22 February 2021 with search terms hyperemesis gravidarum, pernicious vomiting in pregnancy and their synonyms. Results were limited to 2009 onwards. Two reviewers independently screened titles and abstracts to assess whether the studies addressed a top 10 priority questions for HG. Differences were discussed until consensus was reached. Publications were allocated to one or more top 10 research questions. Study design was noted, as was patient or public involvement. Two reviewers extracted data synchronously and both cross-checked 10%. Extracted data were imported into EPPI-Reviewer software to create an evidence map. OUTCOME MEASURES: The number and design of studies in the search yield, displayed per the published 10 priority questions. RESULTS: Searches returned 4338 results for screening; 406 publications were included in the evidence map. 136 publications addressed multiple questions. Numerous studies address the immediate and long-term outcomes or possible markers for HG (question 8 and 9, respectively 164 and 82 studies). Very few studies seek a possible cure for HG (question 1, 8 studies), preventative treatment (question 4, 2 studies) or how to achieve nutritional requirements of pregnancy (question 10, 17 studies). Case reports/series were most numerous with 125 (30.7%) included. Few qualitative studies (9, 2.2%) were identified. 25 (6.1%) systematic reviews addressed eight questions, or aspects of them. 31 (7.6%) studies included patient involvement. CONCLUSIONS: There are significant gaps and overlap in the current HG literature addressing priority questions. Researchers and funders should direct their efforts at addressing the gaps in the top 10 questions.

Depression, anxiety, and post-traumatic stress disorder symptoms after hyperemesis gravidarum: a prospective cohort study.

OBJECTIVE: To determine the prevalence of depression, anxiety, and posttraumatic stress disorder (PTSD) years after hyperemesis gravidarum (HG) and its association with HG severity. MATERIAL AND METHODS: This prospective cohort study consisted of a follow-up of 215 women admitted for HG, who were eligible to participate in a randomized controlled trial and either declined or agreed to be randomized between 2013 and 2016 in 19 hospitals in the Netherlands. Participants completed the Hospital Anxiety and Depression Scale (HADS) six weeks postpartum and during follow-up and the PTSD checklist for DSM-5 (PCL-5) during follow-up. An anxiety or depression score ≥8 is indicative of an anxiety or depression disorder and a PCL-5 ≥ 31 indicative of PTSD. Measures of HG severity were symptom severity (PUQE-24: Pregnancy Unique Quantification of Emesis), weight change, duration of admissions, readmissions, and admissions after the first trimester. RESULTS: About 54/215 participants completed the HADS six weeks postpartum and 73/215 participants completed the follow-up questionnaire, on average 4.5 years later. Six weeks postpartum, 13 participants (24.1%) had an anxiety score ≥8 and 11 participants (20.4%) a depression score ≥8. During follow-up, 29 participants (39.7%) had an anxiety score ≥8, 20 participants (27.4%) a depression score ≥8, and 16 participants (21.9%) a PCL-5 ≥ 31.Multivariable logistic regression analysis showed that for every additional point of the mean PUQE-24 three weeks after inclusion, the likelihood of having an anxiety score ≥8 and PCL-5 ≥ 31 at follow-up increased with OR 1.41 (95% CI: 1.10;1.79) and OR 1.49 (95% CI: 1.06;2.10) respectively. CONCLUSION: Depression, anxiety, and PTSD symptoms are common years after HG occurred.

What is known about the nutritional intake of women with Hyperemesis Gravidarum?: A scoping review.

Hyperemesis gravidarum (HG) is characterised by extreme nausea and vomiting of pregnancy, which can lead to dehydration, weight loss and electrolyte disturbances. Historically research has been challenging due to a lack of diagnostic criteria and objective outcome measures. Most studies in this population group have focused on medical management of symptoms, with little known about the effect of HG on nutritional intake and how this relates to perinatal outcomes. The aim of this study was to synthesise current knowledge of the dietary intake of women with HG. A systematic search of search engines was conducted in April 2020 using the following databases: MEDLINE, Embase, CINAHL, Cochrane database, Scopus, NHS Evidence, BNI, Emcare, ClinicalTrials.gov, PROSPERO, Ethos and Open Grey. Titles and abstracts were screened independently by two reviewers against predefined inclusion and exclusion criteria. Studies were included where the authors described severe pregnancy nausea and vomiting as HG, regardless of how HG was defined. After removal of duplicates, 4402 titles were identified, of which 3992 were initially excluded based on abstract and title. Following full text review, four of 10 articles were included. Three of the studies were hospital-based case control studies, one was an observational women's cohort study. Assessment of dietary intake was heterogeneous, with both retrospective and prospective self-report methods used, over different timeframes. In three of the studies, dietary intake was reported at one time point only. In total, across all four studies, data from only 314 women were included. Overall, despite data collected from four different countries, over 30 years, with various methods, women with HG had a significantly poorer dietary intake compared to non-affected pregnant women, consuming less than 50 % of recommended intakes for most nutrients. Nutritional intake worsened with increasing severity of symptoms. As this was a scoping review, study quality was not assessed. Overall, this review has identified a paucity of data about the dietary intake of women with HG; the limited available data indicates that women with HG are at risk of malnutrition. Future research quantifying nutritional intake in women with HG at several time points during pregnancy would provide valuable reference data, enabling nutritional status and outcomes to be monitored and interventions to be evaluated.

The Contribution of Registered Dietitians in the Management of Hyperemesis Gravidarum in the United Kingdom.

Hyperemesis Gravidarum (HG) is a condition at the extreme end of the pregnancy sickness spectrum, which can cause poor oral intake, malnutrition, dehydration and weight loss. The aim of this study is to explore the role of Registered Dietitians (RD) in the management of HG in the United Kingdom (UK). A survey was designed and distributed electronically to members of the British Dietetic Association. There were 45 respondents, 76% (n = 34) worked in secondary care hospitals, 11% (n = 5) were in maternal health specialist roles. The most commonly used referral criteria was the Malnutrition Universal Screening Tool (40%, n = 18), followed by second admission (36%, n = 16). However 36% (n = 16) reported no specific referral criteria. About 87% (n = 37) of respondents did not have specific clinical guidelines to follow. Oral nutrition supplements were used by 73% (n = 33) either 'sometimes' or 'most of the time'. Enteral and parenteral nutrition were less commonly used. There was an inconsistent use of referral criteria to dietetic services and a lack of specific clinical guidelines and patient resources. Further training for all clinicians and earlier recognition of malnutrition, alongside investment in the role of dietitians were recommended to improve the nutritional care of those with HG.

A patient-clinician James Lind Alliance partnership to identify research priorities for hyperemesis gravidarum.

OBJECTIVE: There are many uncertainties surrounding the aetiology, treatment and sequelae of hyperemesis gravidarum (HG). Prioritising research questions could reduce research waste, helping researchers and funders direct attention to those questions which most urgently need addressing. The HG priority setting partnership (PSP) was established to identify and rank the top 25 priority research questions important to both patients and clinicians. METHODS: Following the James Lind Alliance (JLA) methodology, an HG PSP steering group was established. Stakeholders representing patients, carers and multidisciplinary professionals completed an online survey to gather uncertainties. Eligible uncertainties related to HG. Uncertainties on nausea and vomiting of pregnancy and those on complementary treatments were not eligible. Questions were verified against the evidence. Two rounds of prioritisation included an online ranking survey and a 1-hour consensus workshop. RESULTS: 1009 participants (938 patients/carers, 118 professionals with overlap between categories) submitted 2899 questions. Questions originated from participants in 26 different countries, and people from 32 countries took part in the first prioritisation stage. 66 unique questions emerged, which were evidence checked according to the agreed protocol. 65 true uncertainties were narrowed via an online ranking survey to 26 unranked uncertainties. The consensus workshop was attended by 19 international patients and clinicians who reached consensus on the top 10 questions for international researchers to address. More patients than professionals took part in the surveys but were equally distributed during the consensus workshop. Participants from low-income and middle-income countries noted that the priorities may be different in their settings. CONCLUSIONS: By following the JLA method, a prioritised list of uncertainties relevant to both HG patients and their clinicians has been identified which can inform the international HG research agenda, funders and policy-makers. While it is possible to conduct an international PSP, results from developed countries may not be as relevant in low-income and middle-income countries.

The chance of recurrence of hyperemesis gravidarum: A systematic review.

Around 1 % of pregnancies develop Hyperemesis Gravidarum (HG), causing high physical and psychological morbidity. Reports on HG recurrence rate in subsequent pregnancies vary widely. An accurate rate of recurrence is needed for informed reproductive decision making. Our objective is to systematically review and aggregate reported rates for HG subsequent to index pregnancies affected by HG. We searched databases from inception as per the protocol registered on PROSPERO. No language restrictions were applied. Inclusion was not restricted based on how HG was defined; reports of severe NVP were included where authors defined the condition as HG. We included descriptive epidemiological, case control and cohort study designs. Eligibility screening was performed in duplo. We extracted data on populations, study methods and outcomes of significance. A panel of patients reviewed the results and provided discussion and feedback. Quality was assessed with the JBI (2017) critical appraisal tool independently by two reviewers. We performed the searches on 1st November 2019. Our search yielded 4454 unique studies, of which five (n = 40,350 HG cases) matched eligibility criteria; One longitudinal and four population-based cohort studies from five countries. Follow-up ranged from 2 to 31 years. Definition of HG and data collection methods in all the studies created heterogeneity. Quality was low; studies lacked valid and reliable exposure, and/or follow-up was insufficient. Meta-analysis was not possible due to clinical and statistical heterogeneity. This systematic review found five heterogeneous studies reporting recurrence rates from 15 to 81%. Defining HG as hospital cases may have introduced detection bias and contribute to clinical heterogeneity. A prospective longitudinal cohort study using an internationally agreed definition of HG and outcomes meaningful to patients is required to establish the true recurrence rate of HG.

Recurrence rates of hyperemesis gravidarum in pregnancy: a systematic review protocol.

REVIEW QUESTION/OBJECTIVE: The quantitative objective of this review is to identify the recurrence rate of hyperemesis gravidarum (HG) in subsequent pregnancies.