Dr Samantha Robinson explores how primary care clinicians can advocate for and treat women experiencing nausea and vomiting in pregnancy

ROBINSON_Samantha

Dr Samantha Robinson

Read this article to learn more about:

  • the significant effect that nausea and vomiting in pregnancy can have on quality of life
  • non-pharmacological and pharmacological treatment options
  • when to refer to secondary care.

Nausea and vomiting in pregnancy (NVP) affects approximately 80% of all women.1 Those who experience NVP may have mild, moderate, or severe symptoms, with hyperemesis gravidarum (HG) being the most severe. HG occurs in 0.3–3.6% of pregnancies,2 but one prospective study found that up to 35% of women experienced symptoms of NVP that required them to take time off work.1

Despite being common, NVP is often under-recognised and under-treated. It has a significant effect on women, their families, and the wider community. It can be a difficult topic to negotiate, but this article includes top tips to help healthcare practitioners feel more confident to advocate for and treat these patients.

1. Be aware that ‘morning sickness’ is a misnomer

Nausea and vomiting in pregnancy typically starts before the 11th week of pregnancy and usually peaks around the ninth week.1 Sickness can occur at any time of day, with peaks in the morning and evening.1,3 There is no consensus on the definition of HG,4 but the Royal College of Obstetricians and Gynaecologists (RCOG) states that HG can be diagnosed when there is severe NVP associated with more than 5% weight loss, dehydration, and electrolyte imbalance.5

When a patient presents with symptoms, take a full history including the onset and frequency of symptoms, identify any risk factors for NVP and HG (see Box 1),6 and enquire about the effect on the patient’s life. Consider a different diagnosis if the symptoms begin at 11 weeks of gestation or later, or the patient complains of abdominal pain, fever, headache, or neck swelling (goitre),7,8 and examine the patient if necessary. If the history is straightforward, then NVP can usually be diagnosed clinically and no further investigations are needed.

Box 1: Risk factors for nausea and vomiting in pregnancy6

  • Increased placental mass (e.g. advanced molar gestation, multiple gestation)
  • History of HG in previous pregnancies
  • History of motion sickness
  • History of migraines
  • Family history (first-degree relatives) of NVP
  • History of nausea with oestrogen-containing oral contraceptives
  • First pregnancy
  • Obesity
  • Stress
  • Being seropositive for H. pylori; this is associated with an increased risk of HG.

NVP=nausea and vomiting in pregnancy; HG=hyperemesis gravidarum; H. pylori=Helicobacter pylori

2. Recognise that ketonuria is not diagnostic of HG

After history taking and examination, it is important to assess the severity of the symptoms. The 24-hour pregnancy-unique quantification of emesis (PUQE–24)9–11 score can be a useful tool for initial and ongoing assessments (see Table 1).5

Table 1: Pregnancy-unique quantification of emesis–24 score5
 
QuestionScore
 

1

2

3

4

5

In the last 24 hours, for how long have you felt nauseated or sick to your stomach?

Not at all

1 hour or less

2–3 hours

4–6 hours

More than 6 hours

In the last 24 hours have you vomited or thrown up?

I did not throw up

1–2 times

3–4 times

5–6 times

7 or more times

In the last 24 hours how many times have you had retching or dry heaves without bringing anything up?

None

1–2 times

3–4 times

5–6 times

7 or more times

Total score is sum of replies to each three questions.

PUQE-24 score: mild≤6; moderate=7–12; severe=13–15

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=pregnancy-unique quantification of emesis

Adapted from Royal College of Obstetricians and Gynaecologists. The management of nausea and vomiting of pregnancy and hyperemesis gravidarum (green-top guideline no. 69). London: RCOG, 2016. Available at: www.rcog.org.uk/globalassets/documents/guidelines/green-top-guidelines/gtg69-hyperemesis.pdf

Ketonuria is a contentious issue when it comes to NVP and HG. In any other illness, if a patient attended a GP with symptoms and signs of dehydration (hypotension, tachycardia, and dry mucous membranes), they would likely be admitted to hospital for intravenous (IV) rehydration, without a urine dip being checked for ketones. However, women with NVP and HG report being sent home from both primary and secondary care despite presenting with symptoms and signs of dehydration, because they had no ketones in their urine.12 A systematic review conducted in 20144 concluded that there was no support for the use of ketonuria in the diagnosis of HG, yet it remains as a diagnostic indicator in many trust guidelines. Urine dipsticks are important to rule out urinary tract infections (UTIs), but do not allow the absence of ketones to overrule your clinical judgement. (Note that many patients with NVP experience ptyalism in the first trimester, which may mask the typical dry mucous membranes seen in dehydration.)13

3. Think of other potential causes including Helicobacter pylori

If symptoms begin after the 10th week of pregnancy or are accompanied by abdominal pain or tenderness, headache, or fever, then other causes should be considered.14 It is important to examine the patient based on their symptoms, but specifically for abdominal tenderness and a thyroid goitre.9 Abdominal tenderness could herald gallstones, pancreatitis, or gastritis, and a goitre may indicate thyroiditis. Thyroid stimulating hormone (TSH) can be low, and free T4 can be raised in pregnancy due to the similarity between human chorionic gonadotrophin and TSH. However, the patient would not have a goitre or autoimmune thyroid antibodies present.

Be aware of women who have undergone weight loss surgery and then develop HG. This can be an emergency and admission should be considered to rule out herniation.15,16 Table 2 shows possible differential diagnoses and the investigations needed. Most of these investigations would be carried out in secondary care; however, a urine dipstick and midstream urine to rule out UTI, and blood glucose monitoring to exclude diabetic ketoacidosis should be done in primary care for these women.5 A meta-analysis has suggested a link between HG and H. pylori infection,18 and although further research is required, it is reasonable to consider investigation in secondary care.

Table 2: Differential diagnoses and investigations5,8,14,17
Differential diagnosisInvestigation

Hypothyroid/hyperthyroid

TFTs, thyroid antibodies

Gallstones/pancreatitis/hepatitis

LFTs, amylase

H. pylori

H. pylori antibodies

Infection, check for anaemia

FBC/MSU

Multiple pregnancy/trophoblastic disease

Abdominal USS

Herniation following weight-loss surgery

MRI/CT abdomen

Neurological causes e.g. space-occupying lesion

MRI/CT head

Monitor severity of symptoms

ABG/U&Es

TFTs=thyroid function tests; LFTs=liver function tests; H. pylori=Helicobacter pylori; FBC=full blood count; MSU=midstream specimen of urine; USS=ultrasound scan; MRI=magnetic resonance imaging; CT=computed tomography; ABG=arterial blood gas; U&Es=urea and electrolytes

4. Offer support and dietary advice

Once it has been established that the symptoms are pregnancy related, the PUQE–249–11 score and clinical judgement can be used to classify NVP as mild, moderate, or severe. This will help guide management. Women with mild symptoms can be managed in the community with support, rest,17,19 reassurance, rehydration, dietary advice, and antiemetics.5,20 Although reassurance that NVP can be normal is helpful, it is important not to trivialise or dismiss symptoms. The fact that the patient is seeking professional help suggests that it is beyond the typical mild symptoms of ‘morning sickness’, which most women self-manage without GP input. NVP symptoms can have an enormous effect on the patient’s life, including difficulty with working, caring for children, and their mental health.21

Dietary advice can include eating little and often, having a plain biscuit before getting out of bed in the morning, and avoiding smells that can trigger nausea (often cooking smells). Many women find the only foods they can tolerate are salty or sweet items, but worry about being judged for their ‘unhealthy food choices’.22 Consider avoiding the use of iron-containing products, such as some brands of pregnancy vitamins, as these can exacerbate symptoms.5,17

Some useful resources for further information and advice about NVP and HG are listed in Box 2.

Box 2: Useful resources

  • Pregnancy Sickness Support: information for women with NVP/HG and useful for GPs and other clinicians (www.pregnancysicknesssupport.org.uk)
  • Bumps—best use of medicines in pregnancy (run by UK Teratology Information Service): provides further information about medications in pregnancy (www.medicinesinpregnancy.org)
  • UK Teratology Information Service: a national service for information on toxicity of drugs and chemicals in pregnancy (www.uktis.org)
  • Breastfeeding Network: provides information about medication in breastfeeding, as some pregnant women may also currently be breastfeeding (www.breastfeedingnetwork.org.uk)
  • Hyperemesis Education and Research (HER) Foundation: provides information about HG and also has information for clinicians (www.hyperemesis.org)
  • Sick—the battle against HG: a 30-minute video that tells the story of women experiencing HG (www.amazon.co.uk/dp/B08GL4FLR5).

NVP=nausea and vomiting in pregnancy; HG=hyperemesis gravidarum

5. Do not suggest ginger!

The RCOG advises that women who wish to avoid antiemetics can try ginger and acustimulation.5 The heading of this tip is a little tongue in cheek—most women attending primary care for NVP have already researched online and tried several over-the-counter options before approaching their GP. To be told to ‘try ginger’ can be demoralising and dismissive of their significant, life-affecting symptoms. If you feel ginger needs to be suggested, then approaching the subject in a sensitive, thoughtful way is important.

Acustimulation, such as acupressure and acupuncture, is safe during pregnancy23 and may have some benefit for NVP.24 There is some evidence to suggest beneficial effects of the use of motion sickness bands on NVP; they should be used to apply pressure to the pericardium 6 point on the wrist.5

6. Prescribe antiemetics

NICE17 and the RCOG5 recommend first- and second-line medications for the management of NVP and HG (Table 3). Antiemetics have been shown to be safe and effective in pregnancy5 and can be prescribed in primary care, although local guidelines may vary. Doxylamine/pyridoxine was licensed in 2018 for the treatment of NVP when conservative measures have failed.25 Although the RCOG and NICE recommendations have not been updated since their release, it is thought that doxylamine/pyridoxine would likely fit in first-line treatments, especially if a patient wanted a medication that was specifically licensed for use in pregnancy.25 Doxylamine/pyridoxine is relatively expensive and may not be available to prescribe in some areas. The Medicines and Healthcare products Regulatory Agency advised in February 201925 that although the first-line antiemetics are not specifically licensed in pregnancy, they are not classed as being prescribed off label.

Table 3: Recommended antiemetic therapies and dosages5
Treatment stageTherapies and dosage

First line

  • Cyclizine 50 mg PO, IM, or IV 8 hourly
  • Prochlorperazine 5–10 mg 6–8 hourly PO; 12.5 mg 8 hourly IM/IV; 25 mg PR daily
  • Promethazine 12.5–25 mg 4–8 hourly PO, IM, IV, or PR
  • Chlorpromazine 10–25 mg 4–6 hourly PO, IV, or IM; or 50–100 mg 6–8 hourly PR

Second line

  • Metoclopramide 5–10 mg 8 hourly PO, IV, or IM (maximum 5 days’ duration)
  • Domperidone 10 mg 8 hourly PO; 30–60 mg 8 hourly PR
  • Ondansetron 4–8 mg 6–8 hourly PO; 8 mg over 15 minutes 12 hourly IV

Third line

  • Corticosteroids: hydrocortisone 100 mg twice daily IV and once clinical improvement occurs, convert to prednisolone 40–50 mg daily PO, with the dose gradually tapered until the lowest maintenance dose that controls the symptoms is reached.

IM=intramuscular; IV=intravenous; PO=by mouth; PR=by rectum

Adapted from Royal College of Obstetricians and Gynaecologists. The management of nausea and vomiting of pregnancy and hyperemesis gravidarum (green-top guideline no. 69). London: RCOG, 2016. Available at: www.rcog.org.uk/globalassets/documents/guidelines/green-top-guidelines/gtg69-hyperemesis.pdf

For some women, such as those who have undergone bariatric surgery, it may be necessary to consider other administration routes for medication due to malabsorption issues.

Stopping antiemetics is a process of trial and error. Some women may find that they can gradually taper off them after 16 weeks, whereas others may need to continue using them until the birth.

As well as prescribing antiemetics, consider using a proton pump inhibitor (PPI).11 Many women find that heartburn can make the nausea worse and a trial of a PPI may be beneficial.5,26

7. Prescribe ondansetron as a second-line antiemetic

Ondansetron is a drug used for the treatment of nausea and vomiting in patients receiving chemotherapy.27 However, it is commonly used as a second-line treatment in NVP and HG, and anecdotally many women find it very effective.

In 2019, the European Medicines Agency (EMA) stated that epidemiological studies had shown an increase in orofacial malformations in babies who had been exposed to ondansetron in the first trimester. It advised that not only should ondansetron not be used in the first trimester of pregnancy, but also that women of child-bearing potential who need to take it should be told to use effective contraception.28 The main study quoted by the EMA showed an increased risk of cleft palate from a background risk of 11 in 10,000 births to 14 in 10,000 births: an extra 3 in 10,000 risk of cleft palate.29

An editorial published in March 2020 in Obstetric Medicine, co-authored by the head of the UK Teratology Information Service (UKTIS), found several issues with the way the main study had been interpreted by the EMA30 and argued that the recommendations were disproportionate to the evidence. The UKTIS issued a joint statement with the European Network of Teratology Information Services in September 2019 to advise that ondansetron should remain a second-line antiemetic in the treatment of women with NVP and can be prescribed with counselling about the small increased risk of cleft palate.31

8. Write a fit note when needed

Rest is a mainstay of treatment for women with NVP or HG.5,17,19 Women may need time off work to rest properly and going back to work too soon is associated with relapse.32

9. Try all available treatment options before considering termination

Women with NVP that does not respond to treatment in the community and where the PUQE–24 score is less than 13 should be referred for ambulatory day care.5 Women can receive IV fluids, IV multi and B-complex vitamins, and antiemetics. Day care reduces inpatient stays and is usually acceptable to patients.33

Women with a PUQE–24 score of more than 13, recurrent symptoms despite antiemetics, 5% or more weight loss, and those with co-morbidities such as UTI and inability to tolerate oral antibiotics, should be admitted as an inpatient.5

While they are an inpatient, IV rehydration, regular antiemetics, and monitoring of electrolytes should be undertaken.5 There is a risk of Wernicke’s encephalopathy due to thiamine (vitamin B1) deficiency, which is potentially fatal but also preventable.5,34 Therefore, thiamine supplementation is important in these women. Corticosteroids can be used for inpatients when other interventions have failed.20 Parenteral or enteral nutrition may need to be considered in extreme circumstances.5

Of pregnancies complicated by HG, 10% end in unwanted termination.5 Sadly, many of these women were not offered all the treatment options available.35 One study found that a large proportion of women with HG felt that they were unable to care for themselves or their families and so termination was the only option.36

10. Consider the wider effect on the woman and her family

Severe NVP and HG are associated with an increased rate of pre-term delivery and low birth weight babies.5,37 There is an increased risk of HG in subsequent pregnancies and early management with lifestyle changes and antiemetics (the same antiemetic that was found to work in the initial HG pregnancy)11 before the development of symptoms may reduce the severity of NVP.5,11,38

Hyperemesis gravidarum has a significant effect on a woman’s life, which can range from the woman being unable to do activities of daily living, to affecting relationships with her family (see Box 3).5 Persistent nausea has the greatest adverse effect on a patient’s quality of life.5 Studies have found that anxiety and depression were associated with NVP and HG but resulted from the disease and were not the cause of NVP and HG.5 A recent study39 found that 49% of pregnant women with HG had probable depression compared with 6% of pregnant women without HG, and this trend continued after the birth. Therefore, a multidisciplinary approach is needed involving obstetricians, GPs, midwives, health visitors, and psychological support.

Box 3: Adverse effects of hyperemesis gravidarum5

  • Activities of daily living
  • Family relationships
  • Low quality of life
  • Lack of understanding and support
  • Inability to eat healthily
  • Grief for loss of normal pregnancy
  • Absence from work
  • Financial pressures
  • Isolation
  • Inability to care for family
  • Others’ belief that it is psychosomatic
  • Healthcare professionals’ reluctance to treat the condition.

Believing the patient is one of the most important aspects of management. In one study, a large proportion of women with HG reported that their healthcare providers were dismissive, unsympathetic, and reluctant to treat their symptoms. This increased the likelihood of these women developing depression and anxiety.5,40

Summary

Nausea and vomiting in pregnancy is a common condition, with HG at the extreme end of the spectrum. It has a profound effect on women, contributing to isolation, depression, time off work, and even unwanted terminations. Healthcare professionals have a duty to believe in, support, and advocate for these patients. We can make a significant difference to their, and their families’, lives.

Dr Samantha Robinson

GP, Worcestershire

References

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