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Journey into the world of hyperemesis gravidarum...

Journey into the world of hyperemesis gravidarum

 - Written by Dr Margaret O'Hara

Sometimes in science, two separate discoveries happen at the same time and combine to make more than the sum of their parts. This is the case with a discovery published in late 2017, and another in March 2018, both of them in the Nature group of journals.

These discoveries have huge implications and are extremely hopeful for women with Hyperemesis Gravidarum.

The first one was seemingly nothing to do with pregnancy, in a field of biology relevant for obesity and diabetes. It concerns a protein called GDF15, which has been the subject of research for several years and is known to be associated with various conditions – for example cardiovascular disease, tissue injury, chronic kidney disease and cancer. It is also known to be higher in people who have a condition called cancer cachexia, this causes loss of appetite which makes these people waste away as they are unable to eat. Pharmaceutical companies are interested in GDF15 as a possible target for anti-obesity drugs due to its ability to cause loss of appetite.

The breakthrough on GDF15 came in publications in Nature Medicine in October 2017. Finally, after years of searching, the receptor for this protein had been discovered. It is located in the brainstem in a part of the brain which is responsible for producing the sensation of nausea. This is where things get interesting for women with HG, because it is known that GDF15 is also higher in pregnancy. It increases in the blood of pregnant women early in pregnancy, increasing tenfold within a short space of time.

The cause of pregnancy sickness has never been identified. Partly because not a great deal of scientific attention has been paid to it, compared with other disorders. Various causes have been suggested, but none has ever really been tied to a very good reason why that would make you feel sick. Also none of them have ever been able to explain why hyperemesis gravidarum exists. For example, hormones have been implicated because they rise in early pregnancy, particularly human chorionic gonadotropin. But hCG peaks early and drops at the end of the first trimester. This may explain regular pregnancy sickness, but it can’t explain HG, which continues well into the second and, often, the third trimesters.

GDF15 on the other hand has a lot going for it as an explanation – it rises in early pregnancy, it causes loss of appetite in people with cancer who have cachexia; mice who are given drugs which cause GDF15 to rise in their blood eat less and lose weight; mice who are genetically engineered to not have the receptors for GDF15 suffer no such effects from this drug and carry on eating as normal; and the receptors for GDF15 are in a part of the brain that causes nausea.

This is already incredibly encouraging, but then in March 2018, a paper is published in Nature Communications which really seals the deal. Marlena Fejzo, a scientist at UCLA and USC and partly funded by the HER (Hyperemesis Education and Research) foundation in the USA has been working on the genetics of HG for some time. Marlena had HG herself, and the rationale for investigating genetics is that it has long been known that HG can run in families. You may not always see it in your family because, for example, it may be inherited from your father. She obtained genome data from women who had completed a questionnaire about pregnancy sickness from the genomics company 23andMe. This showed that two genes are associated with HG. One of these is GDF15. She then confirmed the link between GDF15 and HG in the DNA from her separate collection of 100s of HG patients, validating the genetic findings.

To explore whether the HG gene might result in higher GDF15 levels in the blood of women with HG, she then analysed GDF15 in patients hospitalized for HG. This work, presented in October 2017 at the ICGH ( revealed that women with HG did indeed have abnormally high levels of GDF15 compared to women with normal NVP. In addition to all this, Stephen O’Rahilly, a clinical academic at Cambridge University has done some recent work showing that GDF15 is higher in the blood of pregnant women who have taken antiemetics compared with pregnant women who haven’t. Generally speaking, the only women who take antiemetics in pregnancy are those who have HG or, at least, severe pregnancy sickness. So this is another way of saying that pregnant women with severe nausea and vomiting have more GDF15 in their blood than pregnant women who don’t.

Further work will have to be done before we can say definitively that GDF15 causes HG, but the evidence so far is compelling. It’s certainly the most promising theory yet.

If it does prove to be the case, then it opens up the possibility that a drug treatment could be developed that would treat the root cause of HG. This would be a huge improvement on current treatment with antiemetics that just attempt to treat the symptoms, often ineffectively. There are no guarantees, and in any case, it would take years for a drug to pass through all the stages of development. So not on a timescale to help all the women with HG now, but hopefully in time for our daughters.

Even if they can’t develop a treatment, then just the existence of a known biochemical pathway to explain HG will mean that healthcare professionals will have to stop telling women that it is all in their heads, or that it’s normal. For women who are dismissed by their doctors or told to go away and just get on with it, this will be the most immediate benefit of all of these developments.

This sort of research is incredibly expensive and there is very little interest worldwide from funding bodies, Most of this research to date has been funded through donations to the HER Foundation. If you would like to support the ongoing research by Marlena Fejzo please consider donating.

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For those of us working entirely immersed in the hyperemesis gravidarum world, (namely myself and Karen Lodge in the Pregnancy Sickness Support office working alongside each other, her answering the helpline and my engaging in research activity and education for healthcare professions) there can be periods of time where we really feel the impact of the work we are doing and we go home at the end of the day knowing that so many women in the UK are getting really great care and support for their HG, in part thanks to the work that we’re doing from our little office in Cornwall.

We are not in one of those periods at the moment.

It feels like we took a huge step forward with developments like the Greentop Guidelines and now we’re at least ten steps backwards.

The calls to the helpline recently have been increasingly frustrating. From most hospitals having a 3+ ketone criteria on their local guidelines to perinatal mental health teams being “anti anti-depressants” and doctors who don’t “believe” in using medication in pregnancy. We haven’t practiced “belief based medicine” in the UK for at least 100 years now… SHOW ME THE EVIDENCE!

We’ve had two women who were so dehydrated that they couldn’t produce a urine sample were sent home because the staff can’t test for ketones. That is insane and frankly, it’s a death waiting to happen!

We’ve had doctors tell a woman with an unplanned but wanted pregnancies tell them they should have been more careful not to get pregnant if they didn’t want HG.

We’ve had a women with an IVF pregnancy thinking she had no choice but to terminate because she’d been told there was no treatments for nausea and vomiting.

We’ve had staff in a day unit adamant that is a women doesn’t have 3+ ketones then her HG is in fact a totally normal part of pregnancy.

We’ve had a perinatal mental health crisis team debating that wanting to die and commit suicide isn’t suicidal ideation because she hadn’t come up with a way to do it yet (mainly because lifting her head off a pillow was too hard let alone getting to a train station or pharmacy!)

We’ve had a woman whose partner is “normally so sweet and caring but is just horrible about this.” He thinks she’s being weak and pathetic and needs to get a grip.

So you see, while we appreciate all the excellent care going on out there and increasing support and understanding for women with HG, right now it still feels like we have an almighty mountain in front of us yet to climb.

Couple that with yet another lottery rejection and BT screwing up our internet access and some days it can feel like we don’t have the resources to even aim for the top of that mountain.

So on this International Women's Day 2018 feel free to cheer us up by posting about your GOOD experiences of HG care and treatment in recent years to let us know our goals are still achievable…

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Our lovely granddaughters are now 6 and 3 and I had intended to write this a very long time ago. However, one thing about HG is that memories do not fade very quickly, if at all. I may have forgotten some of the small details but the rest of it is as clear in my mind as if it had only happened yesterday. It may sound dramatic to say that at times I feared that my daughter might just fade away out of her life in front of my eyes, and in modern times I don't think this would happen.....but I'm sure I am not alone in struggling to believe during those years that life would ever be normal again.

It was my sister who first mentioned the H word! Our whole family had been overjoyed to hear the news that my daughter Fiona and her husband, were expecting their first child, and I could barely contain my excitement at the thought of being a grandmother!

Then it all started.

Fi was suffering from 'morning sickness' but from the outset it seemed to be something rather more. Was it really normal to be so relentlessly sick all day, for her to be climbing up stairs on hands and knees because she was so weak, to be unable to keep even water down, and to be barely able to communicate with us? 

Her job as a physio became a daily nightmare, and then impossible to maintain. I drove her to the GP and she was told that she was just unlucky. Some women are more sick than others. So we carried on and then the phone call came from my sister who had been surfing the internet for information and found out about HG.

She said 'Fi has got hyperemesis'...and it was such a defining moment.

All of a sudden there was a reason for what was happening - it had a name and maybe there was a cure. Unfortunately, this was not of course, the case! I will not forget the day Fi saw a different GP in her practice after she had been many times seeking help and been dismissed. A lovely lady who listened to her, tested her urine sample sky high with ketones, and told her she needed to go to hospital. Fi cried, and I cried with her. Relief that someone was listening at last. T

his was just the beginning of endless visits to hospital, always through A and E, which we weren't allowed to bypass, even though we knew what was wrong and where we would end up. Hours sitting with what Fi's brother crudely called 'the vom kit'!!....the cardboard hat, a plastic bag, wet wipes and a pile of kitchen towel. Other patients gave us a wide berth, clearly thinking she had some terrible gastric disease. It was so difficult for Fi to wait for for long periods to be seen...very much a low priority in the triage system..... either feeling desperately sick or actually throwing up.  I used to feel so utterly desperate and powerless as she either tried to lie down or put her head on her knees, saying nothing. The end result was always 48 hours in a ward on a drip, at which point she was able to manage a little to eat and looked very much better. 24 hours after leaving hospital we were back where we started.

My son in law is a surgeon and was very keen to keep her out of hospital! I had decided that the best thing was for the two of them to move in with us, so I could look after both, and I would often come home to find a drip rigged up from a curtain rail in our makeshift hospital!! I would serve Fi food  in egg cups, coffee cups and saucers in teeny weeny quantities.  She even struggled to eat these. Most of the time she was unable to cope with the light and lay in a dark room, only getting out of bed to crawl to the bathroom. Smells of all kinds were a nightmare for her, as I subsequently discovered is common among HG sufferers. We had to abandon cooking and live on cold food, and I wasn't allowed to wear perfume or have flowers in the house! Even the smell of water could start the' vom' process!! Amazingly the result of this terrible ordeal was Charlotte - weighing a little under 7lbs and in perfect working order. Truly a miracle!

Pregnancy number 2 was a leap of faith, in the hope that things might not be as bad the second time.

Sadly they were worse! I had never felt that Fi regained her strength fully after the first pregnancy, and there seems to be very little mentioned about the physical and mental health of new Mums who have gone through HG. Once the baby is born they seem to be viewed in the same way as any other woman who has given birth. The baby has arrived, the sickness is gone, all is well. The reality as I saw it very clearly, was a young woman with a body very weakened by her long ordeal, and a mind traumatised to a degree by it as well.

Had someone been that ill for so long with a disease not connected with pregnancy, it would have been considered necessary for that person to spend time recuperating and regaining strength. HG sufferers do not have that consideration, although perhaps six years on things have improved?

Of course pregnancy 2 brought another dimension to the problem in the form of a two year old child needing care, and a Mother too ill to give it! I found myself in the role of both mother and grandmother for the greater part of the pregnancy....on the one hand a joy and on the other absolutely exhausting!  Between us we got through again, and Lucy was born safe and sound in March 2014. Unfortunately we were unaware that Fi had become osteopenic, and she  suffered a stress fracture of her pelvis. This gave her months of great pain following the birth and she was on crutches, again unable to care fully for her children. I felt upset yet again about the lack of care for these women before they embark on another pregnancy, and also post partum. This is not the case everywhere I know, and there are some marvelous GPs around who are doing great work for their HG patients.

Throughout these difficult years the PSS was a shining light of hope and support for us!

Caitlin, with her huge work load, was never too busy to chat, and to offer wonderful advice on both a professional and personal basis. With her medical knowledge as well as having gone through three HG pregnancies herself there can be no better person to have on the end of the phone!! She is still working tirelessly for the 'cause' and we can't thank her enough! I've been pleased to take part in the first two rounds of the Definition and Core Outcomes research project for HG which is being carried out currently, and very much look forward to reading the conclusions.

There will be no more babies for my daughter (!) but we will continue to support where we can, and hope that there is a better future ahead for all women who find themselves unexpectedly facing the longest nine months of their lives! 


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You’re making a list and checking it twice… but what do you get for the HG sufferer in your life who can’t leave the house, is triggered by smells and cant eat much apart from a tiny bit of toast?

Thanks to all of the wonderful ideas from Spewing Mummy followers on Facebook and Instagram I have compiled a list with some links that might be helpful in finding that perfect gift!

Pyjamas; as comfortable and soft as you can find to make those hours lying in bed a tiny bit more tolerable.

Dressing Gown; to wrap up in if she does manage to get downstairs


New bed linen; to ensure a healthy bedroom environment and to enjoy that clean bed sheet feeling for just a minute.


Lip balm; not only helps lips to recover from dehydration but some sufferers like a scented lip balm to help cover up trigger smells (check triggers before you buy!)

Scent free lip balm

Peppermint lip balm


A cosy pillow; to make sure she's as comfy as possible when bed or sofa bound


Unscented candles; to help create a relaxing atmosphere.


Audio book app; to help pass the time


DVD Box set; to help pass the time


Detangle brush; bushing her hair everyday can be a challenge, when she is able to a detangling one can help.


Mediation / hypnobirthing cd or podcast; can aid relaxation


Bubble bath; can help relaxation when a bath is possible (make sure there is someone to call if she needs to get out)


A pregnancy massage; can help relaxation if she has some respite from your symptoms


A scrapbook of memories; so she can enjoy reminiscing and be reminded that this won’t last forever.


A bump to birth photo shoot; to remind her of the HG Hero she is


A 2018 diary; planning ahead could help remind her that HG will not last forever.


A soft knitted cotton blanket; to snuggle up in and keep her at just the right temperature


Netflix; to help pass the time


A favourite magazine subscription; to help those hours pass by a little quicker


Hyperemesis Gravidarum The Definitive Guide: to help her feel informed and empowered


Spewing Mummy Pregnancy Calendar; To help tick off those long days


Maybe book a hairdresser to do a home visit.

Something to look forward too after the baby

A paid night out for the couple after the baby is born as relationships can suffer during hg

A cleaner!


And for the HG survivors...

Spend as much time together as a family as you can and make new memories... and possibly a spa day!


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29Nov 17


Here is a question for doctors and nurses:

You have a patient (not a pregnant women) who is being sick, perhaps post-operatively or due to chemotherapy or an acute condition like appendicitis, viral meningitis or so on. You suspect they may be getting dehydrated and are deciding if you should give them IV fluids. What criteria would you use to assess for dehydration?

Answer: You would probably look at their skin to see if it was dry (does it stay up on the hand when pinched), is their mouth dry, is their urine output down and does their urine appear concentrated. They would be initial signs that would make you think perhaps IV fluids would be good if they are unable to rehydrate themselves orally, for example due to nausea and/or vomiting.

For patients who are starting to get dizzy, confused and drowsy, who aren’t producing tears if they’re crying and have symptoms such as a headache, increased pulse rate and/or low blood pressure you’d be likely to get those fluids up pretty pronto as they’ll likely feel better quickly and even if they could manage sips of fluids orally they’d struggle to rehydrate themselves sufficiently on sips of water.

Additionally, if you happened to dip the urine of someone, say with a Urinary Tract Infection (UTI) and noticed their urine was concentrated with increased specific gravity you would hopefully think “dehydration”.

In my time nursing on wards I never once came across a doctor or nurse use ketones as a test for dehydration or a criteria for prescribing IV fluid rehydration. With the sole exception of hyperemesis gravidarum.

That is because KETONES ARE NOT AN INDICATOR OF DEYDRATION and because nurses and doctors are more than capable of knowing if a patient is dehydrated from their clinical experience without dip tests. And because, with the exception of pregnant women, we generally believe a patient, for example a chemo patient, who says “I can’t stop throwing up and therefore am dehydrated because I’m not keeping fluid down”.

So why are ketones such a barrier to treatment for women with HG? Why do the vast majority of hospital guidelines for treating HG in the UK have “ketones in urine” (often it will specify 3+ or 4+) as a criteria for prescribing IV fluids?

Why do highly skilled doctors and nurses ignore all of their clinical judgment and experience and turn seriously dehydrated pregnant women away from hospital without IV fluids simply because she doesn’t have ketones in her urine? Often these women are showing every other clinical sign of dehydration such as dry skin, mouth and eyes, dramatically reduced urine output and concentrated dark urine, headache, lethargy, dizziness and even confusion. Yet that lack of ketones means she is denied fluid and sent home.

Is it because, ultimately, the doctors and nurses deep down believe that really she could correct the dehydration herself by simply drinking more and not throwing up? Is it because their commitment to following guidelines means that they are unable to trust their own clinical judgement? Is it because they ultimately believe that these women are just making a fuss?

And how do we change this situation?

Well I think really the only way to change it is to challenge it. If you are a doctor or nurse reading this then I implore you… find your hospital guidelines and request that they (ie. Those in charge) take out the line about ketonurina, replace it with “signs of dehydration” (simply that). Need an evidence base for that? Here you go… Click here for the systematic review which has shown that ketones are NOT an indicator of severity for hyperemesis gravidarum. Systematic Reviews are our highest level of evidence and what guidelines should be based on.

Furthermore, ketones shouldn’t be a barrier to discharge either, again because they are not an indicator of dehydration but also because a lot of pregnant women will simply have ketones throughout pregnancy! (for further information on that check out Prof Catherine Nelson-Piercy’s presentation from the ICHG conference this year).

What I would really love to see is a move towards trust by healthcare professionals, not just trust of the pregnant woman who is saying she can’t keep fluid down and therefore maintain her own hydration, but trust of one’s own ability to spot the signs of dehydration and know how to treat it, like you would for every other dehydration inducing condition. Even if a woman has early signs of dehydration sat there in A&E… if send her home she’ll be right back, because guess what… She’s puking up!! Rehydrate her while you wait for the antiemetic script to send her home and perhaps she’ll keep those oral meds down and manage to drink enough to not come back. That early bag or two of fluids could prevent days of admission next week, or even a termination of a wanted pregnancy. 

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The Book

Hyperemesis Gravidarum - The Definitive Guide by Caitlin Dean

The Kids Book

Hoe to be an HG Hero by Caitlin Dean

About Me

I am mother of three beautiful children and wife to a fantastic and supportive husband. I am a nurse, a farmer and a trustee for Pregnancy Sickness Support. I love working hard and spending time with my kids.

About this blog

Information and support for pregnancy sickness and hyperemesis gravidarum. Views are my own and do not represent those of any other organisation. Information provided here should not be a substitute for medical advice. My aim is to raise awareness and encourage sufferers to know they are not alone.

Previous award nominations

MAD Blog Awards UK 2015