Hyperemesis Gravidarum

Overview

Please see the locally developed BNSSG wide Nausea and Vomiting in Pregnancy pathway produced by Dr Yusra Khan (GP and Chair of the Medical Advisory Board of Pregnancy Sickness Support) and reviewed by Dr Cressida Bond (NBT Gynaecology Consultant) and Dr Abigail Oliver (Consultant Obstetrician and Gynaecologist St Michael’s Hill Hospital, Bristol). 

There are also CKS guidelines on management of Nausea and vomiting in pregnancy (revised Feb 2020). The guidelines include advice on non-pharmacological measures as well as recommended medication and thresholds for referral for secondary care assessment.

Nausea and vomiting in pregnancy (NVP) occurs across a spectrum ranging from mild to severe. Hyperemesis Gravidarum (HG) is at the very extreme end of the spectrum and represents a complication of pregnancy. NVP affects 70% of pregnancies whereas HG affects 0.3-1% of pregnancies.¹ 

It is important to differentiate between NVP and HG. The Royal College of Obstetricians and Gynaecologists (RCOG) guidelines on NVP² advise diagnosing HG when there is protracted NVP with a triad of: 

1. More than 5% pre-pregnancy weight loss
2. Dehydration
3. Electrolyte imbalance

Assessment

Please see the full BNSSG Nausea and Vomiting in Pregnancy pathway

Consider using a validated questionnaire to assess the severity of NVP and monitor progress (for example the Pregnancy-Unique Quantification of Emesis [PUQE] score). This tool can help identify patients with HG but is not validated to assess the severity of HG.³ This is described in more detail in Appendix II of the guideline from the Royal College of Obstetricians and Gynaecologists and reproduced below.

Motherisk PUQE-24 Scoring system

PUQE-24 score: Mild ≤ 6, Moderate = 7-12, Severe = 13-15 

Please also note the following:

Ketones should not be used to diagnose or guide management of NVP or HG.  Ketones reflect the catabolism of adipose tissue stores secondary to prolonged starvation rather than dehydration. A systematic review and meta-analysis found no correlation between the grade of ketonuria and the severity of HG.³ Only a minority of patients with HG will actually have ketones. The diagnosis of dehydration should be based on history and examination not a urine dipstick test. A urine dipstick test should only be used if a UTI, DKA or pre-eclampsia is suspected.

Bloods do not need to be performed in primary care to guide need for admission.

Who to refer

Assess and treat in primary care initially, following local guidelines on management in the Before Referral section below.

Consider discussion with your local on call gynaecology team regarding need for further assessment and IV fluids and parenteral anti-emetics in any of the following circumstances: 

• PUQE score ≥13 with complications (eg dehydration)
• Unable to tolerate/keep down oral antiemetics
• Further blood tests required to assess clinical condition
• Suspicion of alternative diagnosis/complication requiring specialist management

See Referrals section below for details.

If concerns that NVP/HG is having adverse consequences on the woman's mental health, consider discussion with or referral to Perinatal mental health services. 

Red Flags

Consider admission to hospital via gynaecology on call team (NBT) or Gynae registrar (St Michael's) if:

• Continued N&V and inability to keep down oral antiemetics and clinical dehydration
• Continued N&V associated with weight loss (>5% body weight), despite oral antiemetics
• Confirmed or suspected comorbidity
• Unsuccessful ambulatory care

Advise all women with nausea and vomiting in pregnancy to seek urgent medical advice if they experience:

• Very dark urine, or no urination for more than 8 hours
• Abdominal pain or fever
• Severe weakness or feeling faint
• Vomiting blood
• Repeated, unstoppable vomiting
• Inability to keep down food or fluids for 24 hours despite oral antiemetics
• Severe headache, visual problems, severe epigastric pain, sudden swelling of the face, hands, or feet (symptoms of pre-eclampsia). 

Before referral

Management 

Women with mild to moderate nausea and vomiting in pregnancy (PUQE score 3-12) who are able to tolerate anti-emetics and maintain hydration should be managed in primary care. These cases are not associated with physical risks for the mother or fetus in the first trimester and often drug treatment is not required; advice on lifestyle measures can suffice. GPs should not offer lifestyle advice as the mainstay of HG or severe NVP treatment, but rather as a means of preventing exacerbation of symptoms.

Lifestyle measures:

Rest: A survey of 114 women found that rest was noted by most respondents to be the only effective management strategy apart from antiemetic medications.⁵ A structured daily diary can be useful in identifying periods of reduced nausea so eating and drinking can be planned for these times.

Ginger: Encouraging patients with HG to use a ‘morning sickness’ cure, such as crackers or ginger, is inappropriate. Ginger is a therapeutic option for women with mild-to-moderate NVP, which is commonly improved by dietary changes; however, HG requires medical treatment including medications and intravenous fluids. A self-selected internet-based survey of 512 women hospitalised with HG within a one-year period and collectively experiencing 965 HG pregnancies, concluded that ginger was unhelpful in controlling HG symptoms. It also caused unpleasant side-effects, worsening of mood, breakdown of the doctor–patient relationship and a delay in receiving effective management with worsening and longer duration of symptoms.⁶

Acupressure and electrical stimulation: a systematic review comprising 14 studies and meta-analysis showed that acupressure and electrical stimulation at the pericardium 6 point may have some benefit in alleviating nausea but less so vomiting.⁷

There is no evidence of benefit from complementary therapies such as acupuncture or hypnosis in HG.²

Pharmacological:

Anti-emetic medications

• Anti-emetic treatment is required for severe NVP and HG. It does not cure the symptoms but palliates them until natural improvement occurs.
• After prescribing an anti-emetic, a review of symptoms is required after 48-72 hours. A pragmatic stepwise approach should be followed adding in a further anti-emetic if symptoms remain uncontrolled; co-existent use of up to 3 anti-emetics may be required (eg Cyclizine+Prochlorperazine+Ondansetron) at which point specialist advice may be sought.
• The symptoms peak between 7 and 9 weeks from the last menstrual period⁸ hence additional anti-emetics are likely to be required.
• 90% of mild to moderate NVP cases resolve by 20 weeks⁸; the majority of HG patients continue to have symptoms after 16 weeks⁹ with 1 to 2% of patients enduring symptoms until delivery.¹⁰
• If a woman feels her symptoms have been controlled for a reasonable period of time (eg 2-3 weeks) and she is now able to function at a pre-pregnancy level, a gradual reduction in anti-emetics can be trialled.

Tell the patient that anti-emetics are generally safe to use in pregnancy. Use the Anti-emetic medications document to guide your choice of treatment.

If necessary give this specific information about: 

1. Dopamine agonists (eg Metoclopramide) are safe and effective but can be associated with extrapyramidal disorders and tardive dyskinesia particularly in younger patients. These drugs can be used as a second line agent at a maximum dose of 30mg per 24 hours for a maximum period of 5 days.² A further course may be considered to manage an acute exacerbation of symptoms at a later stage if required.
2. Ondansetron: In 2019, the European Medicines Agency (EMA) released a Pharmacovigilance Risk Assessment Committee (PRAC) update¹² claiming that Ondansetron is suspected to cause orofacial malformations hence it should not be used in the first trimester and women of child-bearing age who are taking ondansetron should consider using contraception. UKTIS, in collaboration with the European Network of Teratology Information Services (ENTIS) issued a joint statement in response concluding that the absolute risk of orofacial cleft posed by using ondansetron in pregnancy is low. The background risk for orofacial cleft is 11 per 10,000 pregnancies; the risk of orofacial cleft is 14 per 10,000 pregnancies following ondansetron use in the first trimester. This equates to an additional 3 cases of orofacial cleft per 10,000 pregnancies, which is clearly a small increase.¹³ Ondansetron should continue to be used as a second line agent where first line anti-emetics have failed. Women should be counselled regarding the small risk of oral facial cleft that may exist against the risks associated with untreated HG.

The following patient information leaflets can be sent to patients about safety of anti-emetics in pregnancy:

https://www.pregnancysicknesssupport.org.uk/get-help/treatments/

https://www.medicinesinpregnancy.org/Medicine--pregnancy/Morning-Sickness/

 Consider the need for: 

• Omeprazole/H2 receptor antagonists
• Laxatives: patients commonly suffer from constipation with anti-emetics such as Ondansetron.
• Thiamine 100mg daily to prevent Wernicke’s encephalopathy in all women with prolonged vomiting > 3 weeks.

Think about discussing steroid treatment with the patient’s antenatal team if symptoms are not controlled on maximal anti-emetics and they remain dehydrated or there is continued weight loss.

In hospital, patients are started on intravenous hydrocortisone 100mg BD converting to oral prednisolone 40-50mg OD tapering by 5mg per week to the lowest maintenance dose that controls symptoms.² One should aim to stop steroids at the gestational age at which HG usually improves (16-24 weeks). For patients taking steroids, consider BP and glucose monitoring and be aware of adrenal suppression. Omeprazole and Vitamin D should also be prescribed with steroids.

Psychological Support

NVP and HG can have profound psychosocial effects on women and their families. Some women become suicidal or can consider termination. Evidence shows that consequences may persist beyond pregnancy, with reports of post-traumatic stress symptoms in up to 20% of women with HG.¹⁴

A depression and anxiety screen should be performed (the PHQ-9 and HAD questionnaires can be useful here) and the following avenues of support should be considered:

• Support via the GP and midwife: holistic approach, facilitation of fit notes. Note, the intractable nausea can be markedly more debilitating than vomiting.
• Referral to the Pregnancy Sickness Support charity (helpline coordinator, online forum, volunteer support).pregnancysicknesssupport.org.uk
• Referral to AWP Primary Care Liaison Service (PCLS)
• https://www.nhs.uk/mental-health/nhs-voluntary-charity-services/charity-and-voluntary-services/get-help-from-mental-health-helplines/
• Books: “Hyperemesis Gravidarum – The Definitive Guide” and “How to be an HG Hero!”
• Maternity Action
• helpher.org: The Hyperemesis Education and Research Foundation- based in the United States, collaborates internationally.

Referral

St Michael's Hospital and Weston General Hospital

Please discuss need for admission with the gynae registrar at St Michael's.

UHBW do run a hyperemesis clinic but referral to this is via the Gynae registrar. ICE referrals have been suspended.

NBT

Patients requiring referral to the ambulatory day care unit or consideration for inpatient admission should be referred via the Gynaecology SHO.

Recurrence in subsequent pregnancy

The recurrence rate of HG in subsequent pregnancy is very high at 70–80%: 26% report more severe symptoms, 44% less severe symptoms and 30% experience the same degree of severity.⁶ The patient and GP should agree a pre-emptive care plan focusing on:

• Starting an anti-emetic as soon as the woman has a positive pregnancy test as this reduces the severity and duration of symptoms. This should be a first line anti-emetic that the patient found useful in her last pregnancy. A Canadian study where women took anti-emetics pre-emptively was associated with lower recurrence rates of HG, significant improvement in PUQE score of NVP severity compared to the previous pregnancy.
• The criteria and route for admission should be agreed.
• Aim for a healthy body mass index (BMI) aiming for the higher end of normal as weight loss is likely to occur with severe NVP/HG. A low BMI is associated with a greater number of admissions and a high BMI is associated with increased symptoms of NVP.
• Financial, employment and domestic concerns should be discussed and resolved, where possible, prior to conceiving.⁷

Resources

Further reading

1. RCOG (2016) The management of nausea and vomiting of pregnancy and hyperemesis gravidarum. Green-top guideline No.69. Available at: www.rcog.org.uk/globalassets/documents/guidelines/green-top-guidelines/gtg69-hyperemesis.pdf (accessed 25 April 2019).
2. Dean C R, Shemar M, Ostrowski G A U, Painter R C. Management of severe pregnancy sickness and hyperemesis gravidarumBMJ  2018; 363:k5000 doi:10.1136/bmj.k5000
3. Khan Y. Hyperemesis gravidarum. InnovAiT. 2019;12(8):434-441. doi:10.1177/1755738019850848

References

1. Niebyl JR. Clinical practice. Nausea and vomiting in pregnancy. N Engl J Med. Oct 14 2010;363(16):1544-1550.
2. RCOG (2016) The management of nausea and vomiting of pregnancy and hyperemesis gravidarum. Green-top guideline No.69. Available at:
3. Birkeland E, Stokke G, Tangvik RJ, etal . Norwegian PUQE (Pregnancy-Unique Quantification of Emesis and nausea) identifies patients with hyperemesis gravidarum and poor nutritional intake: a prospective cohort validation study. PLoS One 2015;10:e0119962. 10.1371/journal.pone.0119962 25830549
4. Niemeijer MN, Grooten IJ, Vos N, et al. Diagnostic markers for hyperemesis gravidarum: a systematic review and metaanalysis. Am J Obstet Gynecol 2012;211:150 e1-e15.
5. O’Hara M (2013) Women’s experience of hyperemesis gravidarum: Results of self-reported online surveys. Available at: www.preg- nancysicknesssupport.org.uk/documents/ HCPconferenceslides/womens-experience-2013-MOH.pdf (accessed 1 September 2018).
6. Dean, C, O'Hara, M (2015) Ginger is ineffective for hyperemesis gravidarum, and causes harm: An internet-based survey of sufferers. MIDIRS Midwifery Digest 25: 6. 
7. Helmreich RJ, Shiao SY, Dune LS. Meta-analysis of acustimulation effects on nausea and vomiting in pregnant women. Explore (NY). 2006 Sep-Oct;2(5):412-21. doi: 10.1016/j.explore.2006.06.002. Erratum in: Explore (NY). 2007 Mar-Apr;3(2):94. PMID: 16979105.
8. Gadsby R, Barnie-Adshead A and Jagger C (1993) A prospective study of nausea and vomiting during pregnancy. British Journal of General Practice 43(371): 245–248.
9. Lacroix R, Eason E, Melzack R. Nausea and vomiting during pregnancy: A prospective study of its frequency, intensity, and patterns of change. Am J Obstet Gynecol 2000;182:931-7. 10.1016/S0002-9378(00)70349-8 10764476
10. Goodwin TM (2008) Hyperemesis gravidarum. Obstetrics Gynecology Clinics of North America 35(3): 401–417. DOI: 10.1016/j.ogc.2008.04.002.
11. Saleh A and Sykes C (2014) The impact of online information on health related quality of life amongst women with nausea and vomiting in pregnancy and hyperemesis gravidarum. MIDIRS Midwifery Digest 24(2): 179–185
12. https://www.ema.europa.eu/en/documents/prac-recommendation/prac-recommendations-signals-adopted-8-11-july-2019-prac-meeting_en.pdf
13. Zambelli-Weiner A, Via C, Yuen M, Weiner DJ, Kirby RS. First trimester ondansetron exposure and risk of structural birth defects. Reprod Toxicol. 2019 Jan;83:14-20. doi: 10.1016/j.reprotox.2018.10.010. Epub 2018 Oct 29. PMID: 30385129.
14. Christodoulou-Smith J, Gold JI, Romero R, etal . Posttraumatic stress symptoms following pregnancy complicated by hyperemesis gravidarum. J Matern Fetal Neonatal Med 2011;24:1307-11. 10.3109/14767058.2011.582904 21635201
15. Brecht-Doscher A and Jones S (2010) Preparation for the hyperem- esis pregnancy. Available at: www.pregnancysicknesssuppor- t.org.uk/documents/conference_papers/ Preparation_for_the_hyperemesis_pregnancy.pdf (accessed 12 September 2018).
16. Dean C (2014) Helping women prepare for hyperemesis gravi- darum. British Journal of Midwifery 22(12): 847–852. DOI: 10.12968/BJOM.2014.22.12.847.

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