Treatments for pregnancy sickness and hyperemesis gravidarum

Treatments

None of the information provided by PSS is meant to suggest any medical course of action. Instead the information is intended to inform and to raise awareness so that these issues can be discussed by / with qualified Health Care Professionals. The responsibility for any medical treatment rests with the prescriber.

Contrary to popular belief, there are a number of effective anti-emetic (anti-sickness) medications that can be taken in the first trimester of pregnancy. Hyperemesis Gravidarum (HG) is typically at it's worst in the first trimester and it is important that treatment is begun without delay. Research indicates that anti-emetics are more effective the sooner they are begun, and the most recent treatment protocols recommend quick intervention. There is a tendency for GPs to leave women without help until they have lost weight and require IV fluids for dehydration. This is not considered to be best practice. HG can be managed so that no in-patient treatment is required. Weight loss and IV fluid therapy should not be a pre-requisite for either diagnosis or treatment.

Unfortunately many GPs in the UK are unaware of modern treatment protocols for the management of HG. If your GP is unable to or unwilling to give you medication and you want to pursue this treatment option please contact us for information. If you want to avoid taking prescription medication, or want to try additional treatments, see our information about Alternative Therapies on the FAQ's page.

Most effective medications for nausea and vomiting are not licensed in pregnancy because pharmaceutical companies usually exclude pregnant women from drug trials. This is not a situation which is likely to change as drug companies do not want to risk lawsuits which may arise if a woman in a trial gives birth to a baby with a birth defect. This is not to say that these drugs are harmful in pregnancy, it's to say that while safety has not been definitively proven, no evidence of harm has been found either. In order to assess their safety in pregnancy, other sources of information are required such as cases where women have taken them not knowing they were pregnant, or where their sickness has been so severe that they took them as the benefit outweighed the possible risk. 

That said, there are a number of drugs which are considered safe to take in pregnancy.

Many of the medications work in different ways and can compliment each other; for example, cyclizine is an anti-histamine and works on the vomit centre in the brain whereas domperidone works on the stomach to speed up the emptying process as well as in the brain.

As with treatment for most conditions it is sensible to start on the 'first rung of the ladder' and work upwards if relief is not achieved. There is excellent evidence for using cyclizine (50mg, 1 tablet 3 x a day) or promethazine (Avomine 25mg 1 tablet 4 x a day), which are very similar, both being anti-histamines or prochloperazine (Stemetil 10mg 3 x a day). If this treatment is started early enough then further treatment may not be needed. In second and subsequent pregnancies this treatment should be used as a prophylactic (taken before hand to prevent you getting ill), pre-empting the severity experienced previously. It is most effective when used as early as possible but unfortunately with many first pregnancies it is often a number of weeks before treatment is started and therefore too late for the 'first step' medications to have much impact, meaning that women need to move on to stronger medication to obtain adequate symptom control.

If you are not managing to take medications orally or are throwing them up after taking them then many of the drugs can be taken in suppository form (put inside your back passage and absorbed into your blood stream that way). Some can be given first off as an injection by your doctor in the hope you would then keep the next dose down orally. Some medications such as Ondansetron have 'oro-dispersal' versions, i.e. it melts on your tongue, which some women find easier to manage. 

For a basic introduction about the medications above please click on the relevant drug name. However, if you would like further information and to read the research about the various treatments then please refer to our resources section and our information for health care professionals.

If you are currently breastfeeding and suffering with NVP / HG please click here for more information on safe medications you can take.This information is provided by Wendy Jones, PhD MRPharmS, Breastfeeding and Medication.

Typically, the most common anti-emetic drugs used for HG are:

 

Antihistamines - Cyclizine and Promethazine

Brand names for these antihistamines are:

  • Valoid (cyclizine)
  • Avomine (promethazine)

A wide body of evidence suggests that H1 receptor antagonist antihistamines have no human teratogenic potential (teratogenic means harmful defects in the foetus). Pooled data from 7 randomised controlled trials indicate that these antihistamines are effective in the treatment of nausea and vomiting in pregnancy. These antihistamines can cause drowsiness and should not be taken without medical advice, although they are available over the counter. It can take a couple of weeks to become accustomed to the drowsy effect.

By using either cyclizine or promethazine in combination with pyridoxone (B6) it is very similar to the Canadian drug Diclectin which can be very effective if used as a prophylactic for women who have previously had hyperemesis gravidarum. This is the basic first line treatment in the UK.

Prochlorperazine (Stemetil)

Prochlorperazine or 'Stemetil' is one of a number of drugs called phenothiazine. Prospective and retrospective cohort studies, case-control, and record linkage studies of patients with exposure to various and multiple phenothiazines have failed to demonstrate an increased risk of major malformations. It was found to be effective for nausea and vomiting in pregnancy in 3 randomised controlled trials in severe nausea and vomiting in pregnancy (Hyperemesis Gravidarum). Side effects include drowsiness, restlessness and occasional extra pyramidal effects (Such as tremor, slurred speech, anxiety, distress and others). This medication is also available as Buccastem which you allow to melt in between your gum and lip. These are prescription only medications.

Metoclopramide (Maxolon)

There is only limited information on its safety in pregnancy, although the little that has been published is reassuring. There are a very limited number of studies that indicate the effectiveness of metoclopramide in the treatment of nausea and vomiting in pregnancy. Side effects include drowsiness, restlessness and occasionally extra pyramidal effects (such as tremor, slurred speech, anxiety, distress and others). This is a prescription only medication.

In 2015 the European Medicines Agency recommended that maxolon/metoclopramide should only be given for 5 days. This is because it is felt that longer courses are more likely to produce side effects in the person taking this therapy, although this mostly relates to children and older patients. Specifically, there is concern that beyond 5 days there is more chance of oculogyric crisis and dystonia developing, which put into more understandable terms is facial and skeletal muscle spasms and dizziness.

Please note, there is no new concern about foetal problems this recommendation refers only to side effects for the mother.

Ondansetron (Zofran)

If your nausea and vomiting is so severe that the first and second line treatments have not suppressed symptoms to an adequate level then your doctor may prescribe Ondansetron (known also as Zofran). It is a relatively new medication which was originally used to treat nausea and vomiting caused by chemotherapy for cancer patients but is increasingly used for hyperemesis gravidarum and you are likely to read about it on internet forums and websites.

Research regarding the safety of this drug is increasing. A study in Canada by the Motherisk program looked at foetal outcomes for mothers who had taken Ondansetron as well as mothers who had taken other anti emetics and compared them to the baseline rate of birth defects. It was found that there was no increase in the rate of birth defects for mothers who had taken Ondansetron. The HelpHer site also has further information.

A more recent study in Denmark by Pasternak et al (2013) looked at 1,233 women exposed to ondansetron between weeks 7-12 of pregnancy (from LMP) and compared the birth defect rate with that of 4,932 women not exposed to ondansetron. They found that the birth defect rate was 2.9%, at birth, for both groups. The literature review found the baseline risk of 1-3% for a major congenital birth defect at birth for all pregnancies which is in line with this research. This is very encouraging research.

It is a prescription only medication and side effects include constipation and headaches. It can be taken orally, as an injection, as a suppository (inside your rectum) or as an 'oro-dispersal' tablet (melted on the tongue).

 

 

Domperidone (Motilium)

Domperidone works by speeding up the passage of food through the stomach into the intestine, which then prevents nausea and vomiting. It also prevents food from flowing the wrong way through the stomach and so can prevent reflux. Domperidone blocks dopamine receptors found in an area of the brain known as the chemoreceptor trigger zone (CTZ). The CTZ is activated by nerve messages from the stomach when an irritant is present or when certain chemicals are in the blood stream, such as pregnancy hormones. Once activated, messages are sent to the vomiting centre which sends messages to the gut and triggers vomiting. By blocking the dopamine receptors in the CTZ, domperidone prevents nausea messages from being sent to the vomiting centre and in turn reduces the nausea and vomiting.

As with many of the treatments mentioned here, the safety of Domperidone has not been established in proper medical trials. It has, however, been used for a number of years in pregnancy and as yet no adverse effect on the foetus has been reported. As with all these treatments, their use should be restricted to cases where first line treatment has failed to suppress symptoms and the benefits of further treatment would outweigh the risks to the foetus.

Like with metoclopramide, domperidone may only be suitable for short term use due to European Medicines Agency guidance regarding prolonged use and an association with heart problems, however this advice mostly relates to people over 60 or those already taking certain heart medications. 

Domperidone can be given as a suppository (in your rectum) which some women may find easier then swallowing orally. 

 

Corticosteroids (Prednisolone)

There is increasing evidence for the use of Steroids for the treatment of the more severe end of the Nausea and Vomiting spectrum, know as Hyperemesis Gravidarum. Steroids have been used for a number of years in pregnancy for conditions such as acute asthma and Crohns disease. There may be a small increased risk of oral clefting associated with the use of corticosteroids and many authorities say that they should not be used to treat nausea and vomiting in pregnancy in the first 12 weeks of pregnancy, however, recent more recent studies are questioning this and theoretical risks should be weighted against the risks of malnutrition and dehydration. There is emerging data on the effectiveness of corticosteroids to treat severe and persistent nausea and vomiting in pregnancy and hyperemesis gravidarum. Corticosteroids need to be given under medical supervision and assessment. They are normally started in hospital Intravenously at a high dose and then tapered off over a number of weeks.

Long term use of steroids can have side effects for mums as they can in any person taking them for a prolonged period and these risks should be discussed with your doctor if you need to take them for more than a few weeks.

If your hyperemesis is so severe that you are considering termination of the pregnancy then your doctor should be willing to try steroids first.

 

 

Therapeutic Termination

Sadly, many women who experience hyperemesis gravidarum, at some point in their pregnancy will consider termination as a treatment and the Hyperemesis Research Foundation in America found that over 10% of pregnancies complicated by Hyperemesis Gravidarum were terminated. Here in the UK a large scale survey we conducted found 9% of women had terminated. More often than not this is due to inadequate treatment of symptoms and a lack of support and understanding from Health Care Professionals, employers and the general public. If you are considering termination as an option please contact us first to explore all your treatment options first.

There are a number of women in our support network who have themselves terminated due to hyperemesis and and there is also a section on our forum to help women who have lost babies to hyperemesis gravidarum. You can also read our report on women's experiences of terminating for hyperemesis gravidarum here.

Intravenous Fluids

Intravenous (IV, meaning directly into the vein) fluids are given to correct dehydration, and medication can be given through the IV port when oral medication is unable to be tolerated.

Unfortunately, a lot of doctors and hospitals rely on assessing ketones in urine to decide the need of IV fluids. However, ketones have been shown by systematic review to not correlate with the severity of HG and they are not an indicator of dehydration. Signs and symptoms of dehydration should be assessed as they would for any non-pregnant or pregnant patient with any other condition. For example, assessing fluid intake and urine output, skin turgor, dry mucous membranes, dizziness, tachycardia, reduced blood pressure and so on. Women with HG who are showing signs of dehydration are unlikely to be able to rehydrate themselves sufficiently due to the ongoing and constant nature of the condition, therefore the threshold for IV fluid rehydration should be low. 

Although IV therapy is common and some doctors would prefer to repeatedly prescribe IV fluids rather than medication for pregnant women, they are not without risk. The main risk associated with IV therapy lies at the site of cannulation. Blood and fluids can leak in to surrounding tissues causing damage and pain. Repeated cannulations can lead to destruction of the vein by scar tissue making future cannulations impossible. Infection is a risk, and in the days of antibiotic-resistant strains of bacteria such as MRSA, treating infection can be difficult. Therefore, women who require IV rehydration should also be treated with appropriate anti sickness medication to reduce the need for repeated IVs.

However, IV fluid replacement does remain an effective treatment for dehydration, which actually can cause nausea and vomiting. Women often feel temporary but effective relief from a few bags of IV fluids.

Recently, in rural areas around the United Kingdom, there is an increasing service provision for IV fluids to be administered at home which is an exciting development for HG sufferers who can find the trip to and from hospital and the ward environment quite distressing and exacerbating of symptoms. In particular, a pioneering service led by community nurse Emma Moxham, near Bath in the south west of England, has been successfully providing IV at home for women with HG for about 3 years now and interest in the service is increasing in other areas too. Click here for more information.

In inner city areas there is an increasing move towards IV day clinics where hyperemesis patients can be rapidly rehydrated during the day and go home in the evening. For more information click here.

 

Non-pharmacological remedies - Ginger

The conclusion from 6 randomised controlled trials with a total of 675 participants was that ginger extract at 1000 mgs per day may be effective treatment for NVP. However the small number of patients in these studies allocated to receive ginger (n=303) may have been insufficient to properly test the safety of ginger with regards to pregnancy outcome. Ginger is a non regulated food product and most preparations available are of variable purity and composition so dose is uncertain. Side effects include heartburn and thromboxane synthetase inhibition i.e. inhibits platelet aggregation.

Survey work conducted via our charity of over 500 women's experience of being offered and taking ginger for hyperemesis gravidarum found that it was ineffective and could cause harm. Not only did ginger produce unpleasant side effects which could exacerbate symptoms but the psychological impact of being told to take ginger repeatedly was very detrimental to well-being. Where healthcare professionals recommended ginger to women with HG trust and confidence in the professional was eroded and women were left feeling dismissed and not believed.

 

Acupuncture and Acupressure

Stimulation of the P6 point, located three fingers breadth above the wrist, has been used for many years to treat nausea from a variety of causes. Trials of a non-blinded randomised nature have shown a decrease of persisting nausea by at least 50%. Bands worn at the wrist (e.g. Sea Bands) that apply pressure may be a simple way of stimulating the P6 point. There are no theoretical concerns about the safety of acupressure in pregnancy. Long term use throughout pregnancy may cause minor scaring on the wrists.

 

 

Understanding risk

The risk of a baby being born with a congenital abnormality - the difference between relative and absolute risk

Have you been scared when you have read something that says “Taking drug X to help manage severe pregnancy sickness symptoms increases the risk of your baby having a congenital abnormality by 50%”? This is an increase in “relative risk”

It helps to understand that a 50% relative risk increase in a small absolute risk is still a small “absolute" risk.

The risk of a baby being born with ANY congenital abnormality is quoted as being around 5% or 50 per 1000 births Some of these abnormalities are minor , for example skin blemishes, abnormalities of fingers and toes etc. Major congenital abnormality rates are quoted as 2-3% or 20 – 30 per 1000 births.

The quoted rates for severe congenital abnormalities are around:-

  • Heart problems 6 per 1000
  • Limb defects 4 per 1000
  • Central Nervous system (CNS) problems 2 per 1000
  • Cleft lip & palate 2 per 1000

Let us use these figures to illustrate 1000 women taking Drug X to manage their severe pregnancy symptoms where taking drug X is thought to give a 50% increased risk of having a baby born with cleft lip and palate. The major organ systems of the foetus develop in the first 12 weeks from Last Menstrual Period (LMP) of pregnancy. So it is taking drug X in the first 12 weeks from LMP that could cause foetal abnormalities. Medications taken after 12 weeks cannot usually cause major congenital abnormalities in any major organ system because these are already fully developed.

Among these 1000 women taking drug X compared with 1000 women not taking drug X

 

Taking Drug X

Not Taking Drug X

Babies born with heart problems

6

6

Limb defects

4

4

CNS Problems

2

2

Cleft Lip & Palate

3

2

 

So drug X which is thought to cause a 50% increased risk of cleft lip and palate would result in 1 extra baby to be born with a cleft for every 1000 women taking it to control their severe pregnancy sickness symptoms before 12 weeks of pregnancy. If drug X does help to manage their symptoms we might expect to prevent a number of women from having to terminate the pregnancy as well as making the pregnancies of many more manageable. Additionally, because severe NVP and HG are not without their own risks, where women are extremely malnourished or dehydrated in pregnancy, or exposed to high levels of stress, the risks of taking drug X must be balanced with the risks of being seriously unwell.

Did you know?

KETONES ARE NOT AN INDICATOR OF DEHYDRATION

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