Hyperemesis Gravidarum DRAFT

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). 

The RCOG Green-top No.69 guideline on Nausea and Vomiting in pregnancy and Hyperemesis Gravidarum should be referred to for further information.

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 90% of pregnancies¹ whereas HG affects 0.3 - 3.6% of pregnancies².

It is important to differentiate between NVP and HG. NVP is defined as the symptom of nausea and/or vomiting during pregnancy when onset is prior to 16 weeks of gestation and where there are no other causes. Symptoms typically start between week 4 and 7. HG should be diagnosed when the nausea and vomiting is severe, begins before 16 weeks gestation, there is an inability to eat and drink normally and daily living activities are significantly limited³. Signs of dehydration are considered contributory to diagnosis. This definition represents a shift from a historic reliance on objective measures such as weight loss and electrolyte imbalance, and towards subjective patient focused criteria with the aim of achieving an improved recognition and diagnosis of HG.

Assessment

Please see the full BNSSG Nausea and Vomiting in Pregnancy pathway

The  Pregnancy-Unique Quantification of Emesis [PUQE] score can be used to determine whether the NVP is mild, moderate or severe⁴. The PUQE score can also be used to assess the response to treatment for mild to moderate NVP but is not valid for severe NVP and HG^5.

Motherisk PUQE-24 Scoring system⁴

How many hours have you slept out of 24 hours? Why?

On a scale of 0 to 10, how would you rate your wellbeing?0 (worst possible) 10 (The best you felt before pregnancy)

Can you tell me what causes you to feel that way?

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

The HELP (HyperEmesis Level Prediction) score can be used to quantify HG symptoms into a score that can be trended over time to monitor progress and response to treatment. It is available as an online calculator (https://www. hyperemesis.org/tools/help-score/) and in app form.⁶

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 HG⁷. 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 eg UTI or diabetes mellitus
• Comorbidity and unable to take medication eg epilepsy, diabetes mellitus, HIV, psychiatric disorders, hypoadrenalism.
• Unsuccessful ambulatory care
• Any PUQE score and complications

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 medications⁸. 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.⁹

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.¹⁰

There is no evidence of benefit from complementary therapies such as acupuncture or hypnosis in HG.¹¹

Pharmacological:

Anti-emetic medications

• Anti-emetic treatment is definitely required for severe NVP and HG. Anti-emetics may not cure the symptoms but can palliate them until natural improvement occurs.

• A slow-release combination of doxylamine and pyridoxine (vitamin B6) called xonvea is the only licensed treatment of NVP in the UK¹². However, a Cochrane review¹³, systematic reviews^14,15 and birth registry¹⁶ data have all concluded the safety of anti-emetics such as H1 receptor antagonists (cyclizine, xonvea), phenothiazines (prochlorperazine) and dopamine agonists (metoclopramide).

• Metoclopramide should be used as a second line agent due to the risk of extrapyramidal side effects and tardive dyskinesia particularly in young people. Metoclopramide can be used for more than 5 days if symptomatic benefit is gained from its use. It should be noted that phenothiazines can also increase the risk of oculogyric crisis hence this should be discussed if Metoclopramide is prescribed alongside Prochlorperazine.¹⁷ 

• Ondansetron: The European Medicines Agency (EMA) issued a controversial warning that Ondansetron should not be used in the first trimester and should not be used in women of child-bearing age without contraception. This was based on two large epidemiological studies which showed a small increased risk of cardiac defects¹⁸ and orofacial clefting¹⁹. The MHRA did not endorse this and the UK Teratology Information Service (UKTIS) published a systematic review concluding that currently available data does not show that Ondansetron use in the first trimester is associated with an increased overall malformation rate.²⁰ In conclusion, Ondanstron use should not be discouraged if first-line anti-emetics are ineffective. Women can be reassured regarding the very small increase in the absolute risk of orofacial clefting with Ondansetron use in the first trimester which should be balanced against the risks of poorly managed HG (an additional three oral clefts per 10, 000 births (14 per 10,000 births with Ondansetron use versus 11 cases per 10, 000 birth in unexposed women).²¹

• 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/

• After prescribing an anti-emetic, a review of symptoms is required after 24-72 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 from first and second-line options (different drug classes) may be required at which point specialist advice may be sought. When uptitrating anti-emetics, add drugs as opposed to replacing them because they have not proved effective initially on lone use²².

• The symptoms peak between 7 and 9 weeks from the last menstrual period hence additional anti-emetics are likely to be required at this point

• 90% of mild to moderate NVP cases resolve by 20 weeks²³; the majority of HG patients continue to have symptoms after 16 weeks²⁴ with 1 to 2% of patients enduring symptoms until delivery²⁵ Symptoms of NVP and HG should resolve rapidly after the birth. Persistent nausea and vomiting post-delivery requires investigation.

• 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. It is important to note that a previous history of gastric reduction surgery may cause malabsorption of oral medication and increase the risk of nutrient and vitamin deficiency, particularly thiamine and vitamin K¹¹.

 Consider the need for: 

• Omeprazole/H2 receptor antagonists
• Laxatives: patients commonly suffer from constipation with anti-emetics particularly Ondansetron.
• Thiamine 100mg TDS daily to prevent Wernicke’s encephalopathy in all women with prolonged vomiting > 3 weeks/severely reduced dietary intake. Thiamine stores in a previously healthy individual can deplete rapidly and cause symptoms of tachycardia, weakness and decreased deep tendon reflexes within one week without intake.
• Oral nutritional supplements may supplement an inadequate food intake however may not be tolerated.

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. Corticosteroid use in the first trimester has not been associated with an increased risk of congenital malformations overall however data is limited to a maximum of approximately 35000 exposures hence is less well studied in comparison to anti-emetic medication²⁶.

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 symptoms¹¹. One should aim to stop steroids at the gestational age at which HG usually improves (16-24 weeks). For patients taking steroids, BP and glucose monitoring should be performed as there is an increased rate of hypertension and gestational diabetes respectively. There can also be a risk 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. A UK wide survey of 5071 participants found a quarter of those suffering HG occasionally reported suicidal ideation and 6.6% frequently considered suicide due to the severity of the condition,4.9% had a termination of pregnancy (TOP) due to HG and 52.1% considered TOP due to HG. Both of these awful outcomes were associated with perceived poor care from their healthcare providers²⁷. Around 10% of women with HG will terminate a wanted pregnancy²⁸ due to the condition. Pregnancy Sickness Support found that most of these women had not been offered the full range of treatments available with less than 10% being offered steroids.²⁹

Evidence shows that consequences may persist beyond pregnancy, with reports of post-traumatic stress symptoms in up to 20% of women with HG.³⁰

A depression and anxiety screen should be performed (the PHQ-9 and GAD-7questionnaires 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 (e.g more than a few weeks). 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.
• UK Teratology information service (UKTIS)
• Best use of medicines in pregnancy (BUMPS)

Referral

St Michael's Hospital and Weston General Hospital

Please discuss need for inpatient 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.

Ambulatory day care service is available. Referral ideally before midday is advised.

NBT

Patients requiring referral to the ambulatory day care unit or consideration for inpatient admission should be referred via the Gynaecology SHO. Referral ideally before midday is advised

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.⁹ 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.³¹
• 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.¹⁰

Resources

Further reading

1. RCOG 2024 Green-top guideline. The Management of Nausea and Vomiting in Pregnancy and Hyperemesis Gravidarum (Green‐top Guideline No. 69) (wiley.com)

2. For professionals: UKTIS. Treatment of nausea and vomiting in pregnancy https://uktis.org/monographs/treatment-of-nausea-and-vomiting-in-pregnancy/

References

Please see attached list of references

Efforts are made to ensure the accuracy and agreement of these guidelines, including any content uploaded, referred to or linked to from the system. However, BNSSG ICB cannot guarantee this. This guidance does not override the individual responsibility of healthcare professionals to make decisions appropriate to the circumstances of the individual patient, in consultation with the patient and/or guardian or carer, in accordance with the mental capacity act, and informed by the summary of product characteristics of any drugs they are considering. Practitioners are required to perform their duties in accordance with the law and their regulators and nothing in this guidance should be interpreted in a way that would be inconsistent with compliance with those duties.

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