PRACTICE UPDATE: NAUSEA AND VOMITING

JACQUI ANDERSON MIDWIFERY ADVISOR

nausea and vomiting in pregnancy: it’s enough to make you sick

Nausea and vomiting during pregnancy (NVP) is one of the most common pregnancy-related conditions that midwives support women through. NVP has been shown to greatly impact a woman’s life, negatively affecting daily activities, relationship with partner, parenting, occupation and social functioning. Women have also identified feeling isolated, deeply tired, depressed, and a sense of helplessness due to nausea (Heitmann et al., 2015; Lowe et al., 2020; Tan, Lowe & Henry, 2017).

Approximately seven out of 10 women experience nausea during pregnancy and 50% experience both nausea and vomiting (Heitmann et al., 2015). NVP is generally defined as symptoms of nausea, vomiting and/or dry-retching, commencing in the first trimester of pregnancy without any pathophysiological cause (Lowe et al., 2020).

For most women, symptoms appear around the sixth week of pregnancy, often peaking around 8-12 weeks and gradually resolving by about 16-20 weeks. Approximately 10% of women will still experience symptoms after 20-22 weeks of pregnancy (London, Grube & Sherer, 2017). While persistent nausea and vomiting in early pregnancy can be particularly debilitating for some women, it is not usually associated with any adverse pregnancy outcomes. However, because NVP is viewed as a normal and expected part of pregnancy, some women tolerate significant symptoms, both physical and psychological (Lowe et al., 2020; Tan, Lowe & Henry, 2017).

The most severe form of NVP, hyperemesis gravidarum (HG), affects about 1% of pregnant women and requires referral for a management plan, including ascertaining physiological and psychological wellbeing and the need for rehydration and antiemetics. Signs of dehydration include: decreased skin turgor; dry mucous membranes; decreased urine output; concentrated urine and postural drop in blood pressure. The most commonly cited criteria for diagnosis of HG include: persistent vomiting with weight loss not related to other causes, along with an objective measure of acute starvation such as carbohydrate depletion, electrolyte abnormalities and/or acid-base disturbance (London, Grube & Sherer, 2017).

Women with diabetes or other pre-existing conditions (e.g. epilepsy, thyroid disease) who may be adversely affected by nausea and vomiting, especially in relation to timing and absorption of medications, need early support to manage NVP. Women with diabetes need to be monitored carefully, as dehydration increases the risk of diabetic ketoacidosis, along with the usual effects of early pregnancy on blood sugar stability.

ASSESSMENT OF THE DEGREE OF NVP

Asking women to keep a diary of when they are affected by nausea and/or vomiting can help to identify the degree to which they are affected and the potential for dehydration. This can also help women to identify triggers and therefore consider ways to avoid or mitigate these where possible.

One validated assessment tool used to try to determine the severity of NVP is the PUQE (Pregnancy Unique Quantification of Emesis and Nausea) scoring index (Ebrahimi et al., 2009) (see p.28). This tool can be used to assist the diagnosis of HG, but can also help midwives and women gauge the degree of their particular experience.

While women with a mild score may not require medical management, they still need support and affirmation that this will eventually improve, and to be given strategies to try and manage their symptoms. Acknowledgement that NVP is wearying and very unpleasant can be supportive for women and their families.

MANAGING NVP

A 2015 Cochrane systematic review identified that there is insufficient strong evidence to support any one treatment or management regime (Matthews et al., 2015). There is limited evidence from clinical trials about the effectiveness of dietary and lifestyle interventions, but it is generally agreed that making adjustments in these areas should be the initial approach to managing NVP.

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NVP symptoms and management

• NVP symptoms are very common in early pregnancy and usually resolve between 12-20 weeks gestation. • In most cases these symptoms can be managed with diet and lifestyle advice.

• NVP does not usually have any adverse effects on the wellbeing of the fetus.

• NVP can significantly negatively affect women’s daily lives, physical and psychological wellbeing, and general functioning. • Women with more severe symptoms may require treatment with medication, and in severe cases, referral to hospital for IV fluids and antiemetics.

PUQE-24 SCORING SYSTEM

Mild = 4-6 Moderate = 7-12 Severe = ≥ 13

1. IN THE LAST 24 HOURS, FOR HOW LONG HAVE YOU FELT NAUSEATED OR SICK TO YOUR STOMACH?

Not at all (1) 1 hour or less (2) 2-3 hours (3)

2. IN THE LAST 24 HOURS, HAVE YOU VOMITED OR THROWN UP?

4-6 hours (4) More than 6 hours (5)

I did not throw up (1) 1-2 times (2) 3-4 times (3) 5-6 times (4) 7 or more times (5)

3. IN THE LAST 24 HOURS, HOW MANY TIMES HAVE YOU HAD RETCHING OR DRY HEAVES WITHOUT THROWING UP?

None (1) 1-2 times (2) 3-4 times (3) 5-6 times (4) 7 or more times (5)

Midwives have a variety of suggestions to offer women regarding lifestyle and diet, including:

1 / Drink small amounts often - dehydration can exacerbate nausea so it is important to maintain hydration by drinking adequate fluids. Try a variety of fluids. 2 / Avoid having an empty stomach, as this can increase nausea - eat a light snack every one to two hours between meals.

3 / Avoid very large meals - small amounts of food more often are usually better tolerated.

4 / Early morning nausea may be helped by eating a dry biscuit, or cracker, before getting out of bed.

5 / Frequent, small, carbohydrate-rich meals with a low fat content may be helpful.

Consider flavours, temperature and textures that appeal:

1 / Sweet, salty, bitter, or sour

2 / Hot, warm, or cold

3 / Crunchy, dry or soft

4 / Thin, wafer-like slices or small cubes

5 / If the smell of hot food worsens nausea, try cold food instead. Avoid cooking if possible, or cook in well ventilated areas so that odours do not accumulate.

Other suggestions that may help:

• Eat well when feeling the best, or whenever feeling hungry.

• Delay brushing your teeth in the morning if you find it makes you sick. Instead, wait to brush until your stomach feels more settled.

• Lie down when nauseated. • Tiredness in early pregnancy is usual, but it can increase NVP - try to rest as much as possible. Consider reducing work hours if at all possible.

• Take pregnancy vitamins (including folic acid) at a good time of the day when feeling well.

• Avoid iron-containing supplements on an empty stomach in early pregnancy, as they can exacerbate nausea.

• Ginger has been shown in some studies to improve nausea and vomiting compared to placebo (Matthews et al., 2015). Products containing ginger such as tea, biscuits or confectionery, may help. Ginger can cause reflux and heartburn in some people, so peppermint may be more helpful for some women.

• Pyridoxine (vitamin B6) is also used as a low level support. Studies have shown that pyridoxine improves mild to moderate nausea but does not significantly reduce vomiting (Matthews et al., 2015). The recommended dose in pregnant women is 25mg, up to three times per day. There are some products combining B6 and ginger on the market, but there is no strong evidence to support the efficacy of these products in reducing NVP.

• Acu-stimulation, such as acupressure and acupuncture, is safe during pregnancy and may have some benefit for NVP. 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 inside of the wrist, or alternatively apply pressure for at least a minute at a time. • Heartburn/gastro-oesophageal reflux (GORD/

GERD) has been associated with increased severity of nausea and vomiting in pregnancy.

Managing GORD/GERD by making dietary changes or using medications may improve symptoms.

As midwives, you will also have a variety of suggestions from your own practice to add to the above list. It is common for a combination of suggestions to be needed to help women manage NVP to the point where it naturally reduces and/or subsides.

PHARMACOLOGICAL TREATMENT OF NVP

Many women and their health practitioners are cautious about the use of medications due to concerns about teratogenicity, especially in early pregnancy. This can lead to women feeling that they have to manage regardless, and therefore they don’t seek the support that is available. This does not mean that we should ignore the teratogenic potential in the use of medications, especially in the first trimester when organogenesis is in process.

In general, antiemetic medication use in pregnancy is considered to be off-label, as there is little or no specific data relating to safety in pregnancy. However, the Christchurch Medicines Information Service NVP bulletin (2016) identifies that first-line treatments are usually well tolerated and have a large body of data to support their use. These medications include the sedating antihistamine cyclizine, and the dopamine antagonists: metoclopramide, promethazine and prochlorperazine (Christchurch Medicines Information Service, 2016).

First-line pharmacological treatment for mild to moderate NVP is recommended as follows:

• Start with ginger +/- B6

• Add oral antihistamine or dopamine antagonist if needed.

Second-line treatment is usually reserved for women with severe NVP who have not responded to other therapies. If this level of treatment is needed, then this would require a medical assessment. Ondansetron is generally considered a second-line therapy, even though it is increasingly being used as a first-line treatment. The approved indications for the use of ondansetron are the management of nausea and vomiting caused by cytotoxic chemotherapy and radiotherapy, and for the prevention of postoperative nausea and vomiting. However, it is also prescribed off-label for nausea and vomiting due to other causes, including for women in the early stages of pregnancy (BPACNZ, 2020).

There is concern at the increasing use of ondansetron as a first-line treatment for NVP (Lowe et al., 2020; Huybrechts et al., 2018; Zambelli-Weiner, 2019; Medsafe, 2020; Christchurch Medicines Information Service, 2016). This concern relates to findings of the most recent studies, which suggest an approximate 25% increase in the risk of oral cleft defects with first trimester use of ondansetron, amounting to an additional three cases per 10,000 exposed pregnancies (Huybrechts et al., 2018; Zambelli-Weiner, 2019). Even though the research findings lack consistency and in some cases are conflicting, it appears that ondansetron exposure may also be associated with a small increased risk of heart defects, as well as orofacial defects (Zambelli-Weiner, 2019).

Some guidelines recommend that ondansetron should be limited to second-line treatment and preferably used after the first trimester of pregnancy (Lowe et al., 2020; Christchurch Medicines Information Service, 2016). Although the absolute increased risk of oral cleft and heart defects is small, essentially it is recommended that ondansetron should only be prescribed in severe cases (i.e. HG) during the first trimester if the benefits of use clearly outweigh the risks of harm to the woman and fetus, and other non-pharmacological and pharmacological methods have not worked (Medsafe, 2020; Christchurch Medicines Information Service, 2016). Due to the fact that there is growing concern surrounding the use of ondansetron and given its use is only recommended as a second-line treatment, together with its off-label use in pregnancy, midwives are advised to refer for medical assessment rather than prescribe this medication themselves.

Generally, where an antiemetic is not effective at the maximum recommended dose, the advice is to discontinue that medication before commencing an alternate agent. When NVP does not improve with initial medication, investigation of other causes should be considered and would require a medical assessment. This is also important when nausea and/or vomiting begin after the first trimester, as the cause is less likely to be related to normal NVP.

Intravenous (IV) fluids have been shown to reduce vomiting and are therefore valuable for management of the symptoms of HG and severe NVP, as well as associated dehydration and electrolyte disorders. The prescription of IV fluids needs to take into account the degree of dehydration and any electrolyte and/or acid-base disturbances. Depending on how the woman is affected, IV therapy may be administered as an inpatient, or as an outpatient in GP and after-hour clinics, primary and/or rural units, depending on the DHB pathway for management of this condition. Some women with HG require multidisciplinary support in addition to midwifery care including obstetric, dietetic and social work input. square

References available on request.

TABLE: MEDICATIONS FOR TREATMENT OF NVP

First-line treatments

MEDICATION

Cyclizine (Nausene)

(oral histamine)

Prochlorperazine (Stemetil,

Nausafix) (dopamine antagonist)

Promethazine (Phenergan)

(dopamine antagonist)

Metaclopramide (Maxalon)

(dopamine antagonist)

Second-line treatments Ondansetron (Zofran)

(selective serotonin receptor antagonist)

DOSE

25-50mg orally up to three times daily

5-10mg orally two to three times daily

10-25mg at bedtime or 4-6 hrly orally (max 100mg daily)

10mg three times daily

4-8mg twice daily

SIDE EFFECTS

Sedation/dry mouth

Sedation/skin sunlight sensitive/ dry mouth/dizziness

Sedation/dry mouth

Restlessness/drowsiness/extra pyramidal symptoms (abnormal motor function), drug-induced movement disorders especially if longer than 12 weeks. Do not use for women with epilepsy.

Headache, constipation, fatigue (see discussion on concerns re: oral cleft and heart defects)