Episode 169 Hyperemesis

I am excited to bring you this episode on hyperemesis gravidarum. Joined by renowned experts Professor Catherine Nelson-Piercy, Dr. Melanie Nana, and Professor Catherine Williamson, we dissect the impact of this condition and the ground breaking RCOG guidelines that are transforming care for pregnant women. These leading figures pull back the curtain on shocking statistics like the 5% termination rate for wanted pregnancies due to severe nausea, emphasizing the urgency for healthcare providers to truly listen and validate the experiences of their patients.

Navigating through a maze of myths and half-truths can be daunting for anyone dealing with hyperemesis gravidarum. This episode dismantles the misplaced faith in ginger remedies and sheds a revealing light on the ineffective use of ketones as a dehydration marker. We also engage in a crucial discourse on the controversial use of ondansetron, weighing the systematic review findings against the necessity for evidence-based treatment. Our guests don't just talk facts; they advocate for a compassionate approach to care, urging clinicians to tune in to their patients' needs and foster a supportive healing environment.

Wrapping up this crucial conversation, we turn to the poignant, often hidden psychological repercussions of hyperemesis gravidarum. The episode shares heartening stories of how pre-pregnancy counselling and proactive treatments can dramatically improve women's pregnancy experiences. Furthermore, we delve into the potential that genetic studies on HG hold for future treatment avenues, as our guests offer a glimpse into the exciting possibilities on the horizon. This isn't just a discussion—it's a beacon of hope for standardized care and understanding for every woman braving the storm of hyperemesis gravidarum.

Want to know more?

https://www.rcog.org.uk/news/updated-rcog-green-top-guideline-on-the-management-of-nausea-and-vomiting-in-pregnancy-and-hyperemesis-gravidarum-published/
https://uktis.org/monographs/use-of-ondansetron-in-pregnancy/
https://www.medicinesinpregnancy.org/
https://pubmed.ncbi

Thank you all for listening, My name is Florence Wilcock I am an NHS doctor working as an obstetrician, specialising in the care of both mother and baby during pregnancy and birth. If you have enjoyed my podcast please do continue to subscribe, rate, review and recommend my podcast on your podcast provider.
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Transcript

Florence Wilcock: 0:00

Hello, my name's Florence. Welcome to the OBSpod. I'm an NHS obstetrician hoping to share some thoughts and experiences about my working life. Perhaps you enjoy Call the Midwife. Maybe birth fascinates you, or you're simply curious about what exactly an obstetrician is. You might be pregnant and preparing for birth. Perhaps you work in maternity and want to know what makes your obstetric colleagues tick, or you want some fresh ideas and inspiration. Whichever of these is the case and, for that matter, anyone else that's interested, the OBS pod is for you. Episode 169 hyperemesis.

Florence Wilcock: 0:57

So today I've got three fantastic guests on the podcast.

Florence Wilcock: 1:01

So I've got professor katherine nelson piercey and Dr Melanie Nanner, who have joined me before, to talk about obstetric medicine and maternal medicine networks, and in addition we have Professor Catherine Williamson, who is also doing a lot of work in maternal medicine networks, and all three of them are joining us today to talk about hyperemesis, in particular, the new nausea and vomiting in pregnancy and hyperemesis gravidarum.

Florence Wilcock: 1:38

Green top guideline from the RCOG, which has been written collaboratively by these three wonderful people, and also a bit about the implementation of that advice and guidance and also what the future holds, because there's lots of exciting developments going on in this area. So thank you very much for giving up your time to join us today. I wanted to start a little bit because last time we talked a bit about hyperemesis briefly we touched on it and, melanie, you were telling me a bit about some of the work you had done in what women's experiences were of nausea and vomiting and hyperemesis in pregnancy and some of the quite frankly horrific stories that you'd kind of unearthed. So can you tell us a bit about the problem and the sort of prevalence and how it's affecting women?

Dr Melanie Nana: 2:40

Thank you, florence. So, as all of the listeners on this podcast will know, nausea and vomiting of pregnancy is common it affects around 80% of patients who are pregnant but hyperemesis gravidarum is less common. It affects 2% to 3% of the pregnant population, and it's essentially a severe form of nausea and vomiting of pregnancy. There was a new definition in 2021, which described the disease as nausea and vomiting, one of which must be severe, which has started before 16 weeks of pregnancy, and it needs to be severe enough to affect the patient's daily life or their ability to eat and drink normally. So this form of the disease women can vomit 10, 20 or more times per day, and typically the symptoms will stop by sort of the second trimester, but one in five women who have hyperemesis gravidarum will vomit throughout their entire pregnancy.

Dr Melanie Nana: 3:35

So, um a few years ago, we undertook a study of patients in the uk and we asked them to give a description of their experience of suffering with hyperemesis gravidarum, and we were quite struck that just over 5,000 women across the UK replied to this survey, which asked them questions about how often did you vomit, had you vomited in previous pregnancy, had you had any hospital admissions, were you able to access care and I think the key findings from the study were that 5% of the women who replied had terminated a wanted pregnancy because the symptoms of nausea and vomiting were so severe that they felt this was their only option, and 6.6% experienced regular suicidal ideation because their symptoms were so bad.

Dr Melanie Nana: 4:23

We looked to try and understand a little bit about why these women were going and having these poor experiences and adverse outcomes, and some of the risk factors we identified was severe vomiting, so the more severe the disease was, which would make sense if they were bed bound, so they weren't able to go about their day-to-day activity, but also if they felt that the experience of care that they had from health practitioners was poor. So that sort of summarizes some of that work and I can talk a little bit more in detail a bit later, if you like, about some of the feedback we had specifically about those outcomes from the women yeah, I think those stats are really striking and I think for me this topic is quite a lot about.

Florence Wilcock: 5:14

Back to the thing we talked about before about not listening to women or not believing women. So I've certainly seen women come and people not really take seriously how bad their vomiting is or it's just a bit of vomiting. And I do recognize what you're saying about access to care and we've we've even had women say well, I'm only going to get pregnant if I know I can access care, pregnant if I now can access care. But for 5% of women to terminate a really wanted pregnancy, that's a really shocking statistic, isn't it?

Dr Melanie Nana: 5:52

Yeah, Cathy.

Professor Cathy Nelson-Piercy: 5:54

Well, I was just going to add that I think the reason for this, this lack of validation that women get, is historical and the fact that a little bit of nausea is viewed as a good thing in pregnancy, and so traditionally, women have just been sort of patted on the head and told to get on with it, it will pass, this is normal, don't make such a fuss. And I think it's difficult for the lay public and women themselves and their families to understand that in hyperemesis the extreme form this is not normal, and when they are told this is normal, it will get better. Women don't feel validated, they feel dismissed, and it's those sorts of attitudes that Melanie and Cath highlighted in that study. That feeling dismissed, feeling not listened to, not having their symptoms validated, contributes to their perception of poor care, and so, as healthcare professionals, we need to, first and foremost, understand that what women require is true empathy, which means validating the severity of their symptoms and how it's making them feel.

Professor Cath Williamson: 7:08

I think something else that healthcare professionals don't always realise is it is not just the vomiting that is so awful for women, but the nausea, which can be so debilitating and can result in people being effectively bed bound and not to go about activities of daily living, which can also mean not being able to go about activities of daily living, which can also mean not being able to go to work, potentially not being able to pay their rent, not being able to look after other children. So the effect on people's lives are so great in some cases and I think there isn't an appreciation of this massive impact the condition could have.

Florence Wilcock: 7:43

Yeah, when I was looking at the guidance I don't know, maybe I'm a bit ignorant because I'm obstetric so I don't do gynae so I don't necessarily see people that early in pregnancy but the idea of the scoring system to kind of monitor the severity and therefore be able to monitor the benefit or whether treatment is efficacious, that was kind of new to me yeah, I, I think the the scoring systems that the, particularly the puke score that is mentioned in in the guideline florence this is a way of objectively tracking women's symptoms, but but you will have noticed that there is a huge subjective element to the scoring.

Professor Cathy Nelson-Piercy: 8:27

So it's a way of saying look, it's about how the woman is feeling and how her symptoms are making her feel and whether she's able to function or not. That is part of the scoring system, not just how many times she vomits or how many hours she feels nauseous, for it's the effect on her life and the effect on her well-being. And actually the scoring system has, if you like, received some criticism because people say well, this is a subjective score, but that is a way of validating what the effect that we've just been discussing, the effect on the woman. And it's particularly useful for in the context of research, for tracking symptoms, for and and, as you said, florence, for assessing the response to treatment, because it allows you to put a numerical number onto the symptoms, including the subjective feeling of the woman yeah, and the subjective feeling is that's the kind of bottom line, really, isn't it?

Florence Wilcock: 9:25

That sort of brings me on to the ketones issue. So I don't know how we ended up in this situation where if you have ketones, you're dehydrated and if you don't have ketones you're not. I don't I don't really know where that came from. It's almost like a myth. But I was really glad to see that, because I've certainly looked after women that have had hyperemesis throughout their entire pregnancy and I've made arrangements to give them not only antiemetics you know, anti-sickness medication but also intravenous fluids. And people have said to me well, why is this woman attending for fluids? She hasn't got any ketones, so do you want to?

Professor Cath Williamson: 10:11

explode the ketones business. Cath, you do that bit. Yes, I think the important thing to remember, and all of us have studied basic biochemistry and physiology when we were students we produce ketones when we're breaking down fat, when we have insufficient glucose, and pregnant women have a tendency to produce more ketones anyway, particularly in the second half of pregnancy but they represent starvation. They are not a marker in any way of dehydration, and a poor woman with terrible hyperemesis, who is also very dehydrated, may have managed to just eat one biscuit for breakfast, which could bring her ketones back to normal, but she could be very, very sick. So, as you say, florence, it's the wrong marker and I applaud the guideline for bringing this out.

Florence Wilcock: 10:58

Yeah, to me that was a big stride, provided we can get that through to everyone you know. Back to what we're saying about implementation, actually, because to get into the mindset of all the midwives and doctors seeing women that ketones chuck it out the window, or you know, it's not not to do with dehydration people have to unlearn something that is deeply instilled and I take some responsibility, florence, because I was an author on the previous iteration of the guideline.

Professor Cathy Nelson-Piercy: 11:31

That and previous review articles that followed fell into the same trap. I mean, often the woman is starving as well as dehydrated. So often a woman with severe hyperemesis will have lots of ketones because she's unable to eat. But it becomes a very important differentiation when it's used as a marker for whether to admit or whether to discharge, and not letting women go home until they've cleared their ketones. That's as bad as not spitting her just because she doesn't have ketones. Yeah, because you know, ketones are very, very common actually in normal pregnancy. If you test women's urine in a morning antenatal clinic and they've missed breakfast, they will have ketoneuria almost always. But they have no nausea and no vomiting. They've just missed a meal.

Professor Cath Williamson: 12:22

As a small aside, I would encourage people listening do not ignore ketones in late pregnancy if somebody is vomiting, because that could be a marker of them being very sick, but it is the wrong marker to use for your women with hyperemesis in early pregnancy.

Florence Wilcock: 12:37

Yes, now that makes complete sense and I've definitely seen exactly what Cathy, you just described. Well, her ketones have gone gone now so she can go home. The other thing that was kind of stuck out to me it's a big no-no was the the ginger, the ginger biscuits and ginger and the fact that there's no evidence for that whatsoever. Melanie, you want to say something about that?

Dr Melanie Nana: 13:05

Yes, I just remember when, at the point that we were talking about taking this out of the guideline, and I looked through all of the literature and there is a small amount of evidence that if you have very, very mild disease that it may be a bit helpful for some patients. But in actual fact, the patients that had moderate or severe nausea and vomiting of pregnancy there was a lovely survey done of patients experience of being offered ginger and not only did it make them feel as if they weren't really being listened to because we wouldn't offer, for example, a ginger biscuit if someone had another cause of vomiting for any other reason but it actually contributed towards them having more reflux. So not only is it not helpful, it probably is doing some harm to some patients. So I absolutely agree we shouldn't be using it at all in patients that have moderate or severe disease.

Professor Cathy Nelson-Piercy: 13:51

The other thing that sufferers will say, florence, is that by the time they present to health care facilities, be it in primary care or secondary care, they've normally read on the Internet that ginger might work. If they're at their gp surgery or they're in the early pregnancy unit, they don't want to be told to go and eat a ginger biscuit, that they they want antiemetics, um, and you know that that needs to be remembered as well yeah, they do also say that it is horrendous to bring up if you're vomiting.

Professor Cath Williamson: 14:22

So if these poor women are told to take ginger and then they're vomiting, it's very unpleasant right.

Florence Wilcock: 14:29

So big no-no and possibly makes things even worse.

Dr Melanie Nana: 14:34

Adds insult to injury unanimous no from all of us that's really helpful that sort of brings me to.

Florence Wilcock: 14:45

So I really like appendix 3 because I'm a very simple person. I need very basic instructions. So Appendix 3 seemed to have a very, very clear plan of what treatment and then escalation in terms of what to try if the first kind of line doesn't work and what next. And I particularly wanted to ask a bit or ondansetron, because I maybe because I'm secondary care I tend to see the women that's already tried the first line agents and she's coming to me in antenatal clinic. Maybe by then she's 12 weeks or 16 weeks and it's not gone away. Or she's had some admissions to the early pregnancy unit for fluids and treatment. And there's always this issue about on dancetron whether it's safe or not in the first trimester. I don't know if you could expand a bit on on that ondansetron is a really effective antiemetic.

Professor Cathy Nelson-Piercy: 15:54

The reason it's second line and not first line is because there have been some safety signals published from some papers. But there have now been three large systematic reviews done and these systematic reviews of the literature have variably shown a very small increase in cardiac defects, a very small increase in oral facial clefting and no increase in either. Using the same literature which always makes me very interested, whether you take the same literature and you, you dice it up a different way and you get a different conclusion. But but those are the big published systematic reviews. When you look at the issue of oral facial clefting, which is what most people worry about, because there was a ema warning, which I'll come to in a minute but but that's, that's the sort of message that's got down that first trimester exposure to ondansetron can cause oral facial clefting, if you believe the one systematic review that suggests that's a risk.

Professor Cathy Nelson-Piercy: 16:55

The background risk of cleft lip and cleft palate in women in pregnancy is 11 per 10,000. And in this study the risk in women taking ondansetron in the first trimester was 14 per 10,000, which gives an attributable risk of the ondansetron of three per 10,000. Teeny tiny. So the point being is that, if those that one study is true, the attributable risk of ondansetron is very, very small and the argument is that not treating the hyperemesis and leaving the woman with first-line drugs that aren't working very well, the risk to her fetus from potential malnutrition and micronutrient deficiency is arguably greater than the 4 per 10,000 risk of taking the ondansetron. So that's what it's second line, not first line because of the query. It's second line use if you need to, because it's likely to be safer than not treating. But if you use ondansetron, which we all believe you should, then you must co-prescribe laxatives because it nearly always causes horrendous constipation.

Florence Wilcock: 18:10

Right, yes, and the other thing that maybe I'm a bit dim about was this issue that actually none of these, apart from the first line treatment, nothing else is actually licensed for use in pregnancy.

Professor Cathy Nelson-Piercy: 18:27

Correct.

Florence Wilcock: 18:28

And maybe I don't think about that because so many drugs I prescribe are probably not licensed for use in pregnancy. But I know, having been an obstetrician for quite a long time, what's safe and I know I can look things up. But that seemed, if I was a woman, I that might be bothering me.

Professor Cathy Nelson-Piercy: 18:51

It goes back to the history. The history relates to thalidomide, and thalidomide was a drug that was particularly marketed as an anti-emetic in the first trimester. So people subconsciously think that drugs for vomiting in the first trimester are more likely to be dangerous, because that's what thalidomide was. But actually the first line antihistamines, particularly doxilamine and pyridoxine, are some of the best research drugs. In pregnancy, over 30 million women have taken doxilamine and many, many women have taken antihistamines as part of research studies without any safety signals whatsoever. So it's just the sort of legacy, it's the thalidomide legacy, that leads people to feel anxious about prescribing antiemetics in the first trimester. But hopefully, as you said, florence, that the Appendix 3, this stepwise approach will, will help yeah, melanie.

Dr Melanie Nana: 19:57

I'm just thinking about what you're saying about.

Dr Melanie Nana: 19:59

You know, we think about the drugs and the safety and we can look them up and I think as clinicians or healthcare professionals we're used to weighing up the the risks and benefits of the drug and the risks and benefits of untreated disease.

Dr Melanie Nana: 20:12

And I think while we sort of really focus on these for example the EMA warning and these drugs get a reputation that we get asked these questions over and over again. I don't think necessarily the understanding of the risks of untreated hyperemesis gravidarum are that well understood and they're quite significant. So I think you know, as we learn more about this and more research is done to talk about the physical complications which in severe cases, can result in venicose encephalopathy from thiamine deficiency because people can't eat, women having a fatal heart rhythm because their potassium is too high or low. You know, I think that we need to be kind of educating both healthcare professionals and patients about the risks so that we can let them be involved in more informed decision making. So the way that we think about these things I think needs to have a bit of a change yeah, I think you're right.

Florence Wilcock: 21:01

There definitely needs to be a shift, and that's a conversation I often have in clinic with women. They're like I'm pregnant, I'm not taking anything, it's not safe. And it's like, well, you're not safe how you currently are with whatever it is the, the illness that I'm seeing them with. You know, I guess it perhaps with antibiotics when they've got a really bad chest infection or a urine infection and I'm trying to say you should be taking these because it's bad for you and bad for your baby, particularly urine infections. There's a risk of preterm birth as well and they're oh, but it's taking antibiotics. That must be bad.

Dr Melanie Nana: 21:40

So I think you're right, there needs to be a shift and I think when you talk to patients who are pregnant, rightly or wrongly, they worry about their baby and the traditional thinking was that hyperemesis was protective because you're vomiting, so that you must be having a healthy pregnancy. But some of the work that Cath and I are doing focuses on the long-term child outcomes for these women and there are very good data now to suggest that if a woman who has severe hyperemesis, their children are at threefold increased risk by the time they're teenagers of having a form of neurodevelopmental disorder, whether that's ADHD or autism spectrum disease. So again, I think as as we do more work, we'll be able to clearly delineate the risks of both treated and untreated disease. That hopefully will help.

Professor Cath Williamson: 22:28

I don't have much more to say except I totally concur with everything you're both saying, but thinking about the way we present it to women in clinic. As clinicians, something I'll often say to women with asthma who don't want to take their medicine is your lungs, are your baby's lungs. Having healthy lungs for you and taking the safe medicine means you can give your baby the oxygen they need. In the same way, the medicines that keep her gut functioning. Her gut is her baby's gut and is the way her baby's gut and it's the way her baby will get nutrients. So keeping her gut healthy with medicines we know are safe will help her have a healthier baby. And I think, as you both say, we have to shift the message to be an easy message that women understand, so they know that we're all aiming for the best outcome for them and their baby, using the best treatment.

Professor Cathy Nelson-Piercy: 23:14

I just want to come back to the EMA warning Florence just to make the point that the MHRA so the UK authority did not issue a similar warning. On the contrary, they have put out a statement with the UK Territology Information Service saying that Ondansetron should be used if indicated so to the healthcare practitioners listening, please don't deny womendansetron should be used if indicated so. To the healthcare practitioners listening, please don't deny women ondansetron in the first trimester if first-line antihistamines are not working. It's a very good drug. Co-prescribe laxatives.

Professor Cathy Nelson-Piercy: 23:46

And while we're on the subject of second-line drugs, metocopramide is also a good drug and also works well and you can prescribe it for more than five days and sometimes you have to play around a little bit. Some women will say, well, I feel a little bit better on the antihistamines and if that's the case, we don't take them away. We add in a second line drug. Some women will respond to metoclopramide with an antihistamine, some women respond to ondansetron, some women need all three and hopefully the. The new guideline makes it clear that, that you should give them what they need. If that's one drug, that's fine.

Florence Wilcock: 24:21

If that's two, if that's three, if that's four, you just have to control the symptoms and that's that's the important message and that just made me think about taking these medications regularly, because sometimes I have women that I prescribe stuff and they said, oh yeah, that made me better and then, because they were better, they then stopped stuff, whereas I'm suggesting to them maybe they need to continue, because it's taking it regularly. That's potentially having the benefit. I don't know if you've got a view about that.

Professor Cathy Nelson-Piercy: 24:57

Absolutely. I mean, I'm more and more convinced that you need to take whatever it is that's working until such time as the symptoms would have abated physiologically anyway, and in some women that can be until delivery. In most women it abates by 20 weeks. But what women can sometimes do is reduce the frequency as their symptoms improve. But you're right, florence, in those early days women need regular antiemetics, because once you break the cycle of therapeutic levels of antiemetics you then start vomiting again and then then the danger is that they vomit up the antiemetics and then they're in the early pregnancy unit again. So I totally agree with you counselling and clear instructions about taking these drugs regularly is really important. Equally important is giving them regularly on the gynecology wards.

Florence Wilcock: 25:53

Yes, and I really like, kath, your analogy about this is your baby's gut and this is your baby's lungs. I'm definitely going to use that. I really like that way of explaining it to people. Melanie, do you want to come in?

Dr Melanie Nana: 26:09

Yes, I was just going to go back to the study that we did with the lived experience of those patients, and I think that many patients have significant concerns about taking medication. So I was just going to read a couple of the comments that relate to that. The first was that one patient, for example, mentioned that she'd taken medications for sickness and her baby was born visually impaired and she didn't know whether it was coincidental, but she'll always blame herself. So we know that there are good data that these antiemetics that are suggested in the green top guidance do not increase the risk of visual impairment. But unless we empower women to understand the safety, the the risk, you know we, we accept that three percent of the background population will have some form of congenital malformation, and so you know, I think we've just got to be really clear about the safety evidence and we have a lot of data now.

Dr Melanie Nana: 26:57

But another lady mentioned that her family accused her of hurting a baby because she was taking medication. So I think it's not just educating the woman, it's educating those that are around her family, her friends, to understand that that's okay. So, and I often in clinical say, if someone's had severe disease or has severe disease, I'll start you on one medication, but it's very likely you're going to need two, three or four and that you're going to need them for a long period of time, so that you're not constantly adding another medication. They're becoming increasingly worried, but they kind of know what they're going in for.

Florence Wilcock: 27:28

No, that's definitely true. I've definitely been outside of work asked to speak to someone with hyperemesis by their parents as a kind of sort this person out type thing, and not in a prescription way but in a kind of yeah, this is normal. Back to back to your point, kathy, about what is and isn't normal, and we're talking about something quite extreme here. So I wanted to bring in here a bit about pregnancy sickness support, because I know kind of peer support and support from that for women may help sometimes. I think as healthcare professionals we change better when women come and ask us for stuff. So if we educate women and give them the information, then they can push us practitioners along a bit. So do you want to talk about that?

Professor Cathy Nelson-Piercy: 28:29

I think that again, it's down to validation. Women sometimes feel that that this is worse than any of their friends, worse than their family, and they feel out on a limb and they feel they often feel like a failure. And we sometimes in clinic Melanie and I have done this we'll sometimes introduce women with terrible hyperemesis to other women and that's a sort of buddy peer support mechanism. So I mean there is a very good charity called pregnancy sickness support that is run by women for women. That's about education and also has a fantastic helpline when women just feel desperate and they.

Professor Cathy Nelson-Piercy: 29:11

What this charity does in my experience, is it empowers the women to go back to the health care professional and say you know, I I need some drugs or I need more drugs or I can take this drug for longer. But also, some of these women have had recurrent, severe hyperemesis and speaking to women that have actually gone through it again with support is enormously powerful to women who might be in their first pregnancy. They sort of can see a way out and with all these you know, third sector, hearing it from another sufferer is often more powerful than hearing it from a healthcare professional. I think we as healthcare professionals think that we're the, you know, the oracle and that everyone's going to listen to us, but actually we're not, and getting peer support is phenomenally important in a condition such as this, I think.

Dr Melanie Nana: 30:07

Yeah, I agree, and the Pregnancy Sickness Support have a lot of volunteers who have suffered themselves who provide peer support. But I think that Pregnancy Sickness Support have a lot of volunteers who have suffered themselves who provide peer support. But I think that Pregnancy Sickness Support is the UK's largest Pregnancy Sickness Support charity, but there are a couple of others and I think we're becoming more clear that, depending on a woman's background cultural background depends on how acceptable it is to take medications and seek seek help. So I think there's a brilliant charity called HG Help which supports women from the Jewish community, and there's a charity called Mummy's Day Out which supports women of black ethnicity with medical complications. So there are increasing numbers of charities which serve different populations which I think we can be aware of.

Professor Cathy Nelson-Piercy: 30:57

I just want to make the point, florence, that if we as healthcare professionals had got this right, then we wouldn't need these charities, and I'm sort of embarrassed that women have to turn to the charitable sector. I'm not saying the charities are bad, that they're wonderful, but they have been born out of necessity because of the reluctance of healthcare professionals to help these women, take them seriously and, as I said at the beginning, to validate their symptoms and offer them. You know, the other thing that the Green Top Guideline now stresses is the need for mental health support and a mental health assessment as part of the, as Melanie explained at the beginning. You know a lot of these women.

Professor Cathy Nelson-Piercy: 31:44

When I was starting out, it was still written in articles that hyperemesis was because women had an unwanted pregnancy, they didn't want to be pregnant, they were rejecting the pregnancy, and to be told that by a woman who has no previous mental health disorder is very distressing and that, again, that's a mindset that needs to change. It is the severity of the symptoms, it is the desperation that women feel that causes the secondary mental health problems, and we are. We must know that, accept that and ask women okay, you know, we've prescribed this, we've prescribed that, but you know you're having a tough time. How are you feeling? What support do you have? And and ask about their mental health, because there are sadly cases of suicide related to this condition, uh, which is a tragedy, a preventable tragedy yeah, I.

Florence Wilcock: 32:43

I think that's partly why I tend to see some of these women, because I have a mental health clinic and because there is that overlap. But I think what you're saying about the mental health being a secondary effect of having had such severe hyperemesis is really important to kind of state clearly rather than I agree, early on in my career it was very much.

Professor Cathy Nelson-Piercy: 33:11

Well, this is psychological issue in the first place which really really needs kind of a line drawing through it now and you know, given that what we know about how mental health can affect the pregnancy and later bonding is another argument for early and aggressive treatment of hyperemesis. These women go on to have subsequent mental health problems. They have problems, fear of vomiting, they have eating problems, disorders of various sorts. So we must treat it properly and aggressively and any mental health issues that come out of it that may also need treating Just to come on partly of relevance to all the wonderful charities that support women.

Professor Cath Williamson: 33:57

They also they signpost women to where they can go if they're not managing to obtain the care that they may need, and they have also supported research and they're aiming to improve care through research as well, and PSS supported the work that Melanie and I did in collaboration with them with the survey and some shocking statistics that came out of that. Just under 7% of the women that we surveyed had regular suicidal thoughts and a third had occasional suicidal thoughts. So the impact of HG to cause severe mental health problems is massive and we all see in our clinics women with post-traumatic stress and where there are ongoing both physical and mental health problems as a consequence of having had the condition. So it really is very, very important and the charities helped us to identify this because they really are investing well thank you, I think that's really helpful and also I take, melanie, your point about the cultural issues that it's difficult.

Florence Wilcock: 35:08

You need to find the right, the right support for for that particular individual woman, because it's not going to suit everybody. So that's made me curious. So I have an assumption and I don't know if this is correct. So I'd like you to tell me Is there an ethnic difference in prevalence or not?

Professor Cath Williamson: 35:35

Yes, there is. A number of studies have shown that HG is commoner in women from non-white ethnic groups. Some have shown that it's commoner in women of both Asian ancestry and African or Black backgrounds. Melanie and I have been doing some work in South London where it is quite striking that HG seems to be commoner in women of African ancestry and yet we don't see considerably more women from these groups in our clinics. So this raises additional issues that we have to delve into further. Are we listening to women from different, different ethnic groups? Equally? Do they have the same access to secondary care? So I think there is an important piece of work to be done there. And then also thinking about susceptibility is there a biological reason for this? Is it more social communication being listened to?

Dr Melanie Nana: 36:33

maybe a bit of both there's so much to do in this area and I think it's just becoming more and more evident. But I think and Kathy might want to comment but we also do some pre-pregnancy counselling for patients who've had very severe disease Florence and they come back and we go through some of the options and ways that we can plan future pregnancies, which perhaps we can touch on in a moment. But I think, anecdotally, all of us would agree that we see women of white ethnicity typically and all patients who can advocate for themselves to be able to access what are quite rare pre-pregnancy counselling clinics. So I think you know, beyond the biological aspects there's there's a lot of work to be done in making sure that all women are accessing like equal care yeah, I think I'm picking that.

Florence Wilcock: 37:21

I mean, we're doing a lot of work about equality and equity and you know, it really strikes me that this is a general condition which has been not ignored but not properly dealt with, and then for it also to be more prevalent in a population that we know we're not serving. Well, it's, it's um, yeah, there's a lot of work to do, like you say. So we've talked a bit about kind of the negative impact on women's health and the baby, but I don't know if you want to expand a bit on that. So, within the guideline, it talks about things like preterm birth and birth weight and weight loss for women and their mental health. And, melanie, you touched on W when it goes in cephalopathy, but I think there's also that perhaps much longer term impact. You know even things like family size. I don't know if you want to talk a bit about the impact women have talked to you about or that you've observed in your research.

Dr Melanie Nana: 38:40

So essentially, when we did the study, we asked, we asked quantitative questions. So we said you know, how many times are you vomiting? How many of the pregnancies do you have this vomiting in? But we also had an open box, feedback comment at the bottom, where people could just describe, or patients could describe, their previous experience. And we were surprised that over 5 000 of the 5071 patients wrote about their experience and kath and I felt that, having had so many women share their experience, we only did them justice if we were to qualitatively analyze those, those data.

Dr Melanie Nana: 39:08

And so we went through and looked for common themes and this was um. One of the themes that came up was future pregnancy. 386 women mentioned specifically that they would um, had changed their plans for for future pregnancy but but even worse than that, had been sterilized because they couldn't have thought of a future pregnancy. And I think we do. We do hear this in our clinics. So I think, yes, family size is reduced, but patients going to clear efforts to make sure that that doesn't happen. And I think you know I feel enthusiastic and positive about how we can offer pre-pregnancy counselling to these patients and actually see patients having better pregnancies. So it seems very sad when women don't always know the options available to them in the future pregnancy.

Professor Cathy Nelson-Piercy: 40:05

I have an anecdotal story to follow on from that. Melanie, a lady who I gave pre-pregnancy counselling to, has recently got pregnant again, but with a sort of recipe for what to take, and I suggested that she take pre-emptive Zonvia, because that's the only drug, that for which there's data that pre-emptively the symptoms can be less severe if if you take it at the time for positive pregnancy tests instead of waiting for symptoms. And she's taking that and an antihistamine in addition. So she's taking effectively two antihistamines. But she messaged me today to say you know, I thank you so much because at this stage she's only six weeks, seven weeks, pregnant at this stage.

Professor Cathy Nelson-Piercy: 40:42

In my last pregnancy I was bed bound and now I can function by taking these two drugs. And so it does preemptive treatment and appropriate treatment. It works. It works to change the experience of women and I'm not saying she's completely asymptomatic, but she is able to manage her condition and she's able to, she's empowered now to advocate for herself, to to get more of the drugs, to to have second drug, to have different formulations of drug, because she's information is power right. So that's what all women deserve and you know it's like any aspect of medicine, we don't operate in a sort of patriarchal system. Take these tablets, you'll get better. It's educating women about what to do for themselves and this is just a nice recent example of because normally you counsel people and you don't often get to hear what happens. So it was just nice of her to email me and say you know, and she's only got you know, she's only just pregnant, but already she's having a very, very different pregnancy and she's not been admitted that's really, really lovely to have that.

Florence Wilcock: 41:56

Yeah, that feedback directly, which sort of brings me to kath. You talked briefly before we started recording about the implementation of guidance and I'm just listening to that, thinking how many women actually have access to that sort of pre-pregnancy counselling and advice that you're clearly offering women on on your patch. So is there some way that we can get a better standard of care or pre-pregnancy so that the woman knows from the get-go what she needs and how to get it?

Professor Cath Williamson: 42:38

from the get-go what she needs and how to get it. Well, in terms of implementation, I'll start with pre-pregnancy care, but I might move on to a bit more, if you'll allow me so, for pre-pregnancy counselling, kathy, melanie and I and a number of other colleagues around the country provide pre-pregnancy counselling and would welcome anyone who is referred to come for advice. But hopefully we can improve implementation of guidelines so we don't have to be providing this for everyone, and something we felt after the survey study that we'd put out and also Melanie then designed another study that was very important, where we studied the confidence of GPs and GP trainees in one country in Wales to prescribe guideline-recommended drugs for hyperemesis, and the results were quite striking. Many GPs were not confident using most of the drugs in the guidelines. The slight exception was cyclizine, but even thiamine some were worried about being harmful. But when we asked them about how much education they'd had and would they like more, the overwhelming answer was we would like more education about this. So they acknowledged they didn't know enough and on the back of this and our own experiences, cathy, melanie and I decided to run a policy lab.

Professor Cath Williamson: 43:57

We worked with King's Policy Institute and invited a lot of stakeholders to address the question why, when we have really good guidelines, are they not being followed and how can we progress implementation? It was a phenomenal day. It was a phenomenal day. Some very impactful people attended, including Dame Leslie Regan, lucy Chappell and many and we came up almost with a roadmap of what we felt we had to do to shift this.

Professor Cath Williamson: 44:28

Melanie has been amazing at working, at implementing a lot of it and we really hope we will make a difference with this. We're working with the different Royal Colleges having standardised guidance which is being circulated alongside the RCOG guideline and Cathy and Melanie may want to say more that is approved by, for example, the College of Emergency Medicine, so a simple flowchart for people to follow from different specialties. We're working with the Department of Health to have HG hopefully mentioned in the Women's Health Strategy. We're working with the Royal College to ensure there are questions about the condition in the exam, so everyone will be reading and up to date, and so on. Melanie or Cathy, would you like to say any more about the steps to implementation? Melanie or Cathy, would you like to say any?

Professor Cathy Nelson-Piercy: 45:15

more about the steps to implementation. Firstly, to congratulate Melanie for having the idea to have the different appendices focused on the different healthcare practitioner groups. So there's one for emergency gynae units, one for inpatients, one specifically aimed at GPs, one for emergency medicine. They're all subtly different based on the perspective of those healthcare practitioners. But I do think it's not a secret that the biggest barrier to accessing care, I think for hyperemesis, is primary care and the GPs, and that's not the GP's fault, it's because they follow a guideline that is wrong, and so we decided very early in the policy lab that everyone must follow the same guideline. So instead of writing a guideline under the auspices of the RCOG and then watching everyone else write another guideline, we thought, well, why don't we have it? Everyone else must follow this guideline, so that. Hence the appendices that Melanie developed.

Professor Cathy Nelson-Piercy: 46:21

But the Royal College of General Practitioners really rely on something called clinical knowledge summaries CKSs they're called which are synthesis of, or syntheses of, nice guidelines or Syntheses of NICE guidelines, and one of the aims of the Policy Lab is to engage with NICE to change that clinical knowledge summary and allow them to use either the appendix or write another clinical knowledge summary that says the same as the appendix, because when you read that clinical knowledge summary you realise why GPs are reluctant to prescribe on Danstron, prescribe recurrent courses of metoclopramide.

Professor Cathy Nelson-Piercy: 46:59

So I'm not GP bashing here, I'm simply saying that we have to. This is a policy implementation issue. Yes, and most women will approach their general practitioners before they go to an emergency gynae unit, their general practitioners before they go to an emergency gynae unit. So we need to imagine all the gynae time that would be freed up if this condition was properly treated in primary care it's. You know we plan to do cost-effective analyses to demonstrate that it's really worthwhile prescribing antiemetics according to the guideline to prevent visits to early gynae unit, prevent admissions, prevent lost time of work, as kath was saying earlier. Yes, sorry, I forgot what the question was.

Florence Wilcock: 47:40

Now, that's fine, melanie I?

Dr Melanie Nana: 47:44

um, I was just going to say I mean, gps have have such wide knowledge, don't they?

Dr Melanie Nana: 47:49

And I think the thing that came out of that study that we did on in the gps in wales was that they they wanted access to evidence-based guidance, they wanted to be signposted to the right thing so that that they could do the right thing.

Dr Melanie Nana: 48:01

Um, and just to kind of reiterate Cathy's point about people go to primary care first. We did a service evaluation of the patients that came to St Thomas's and in our obstetric unit the most severe hyperemesis patients come to us. So we looked at the 30 patients that had been referred most recently and between 30 patients they bounced between 206 appointments, whether that be in primary or secondary care between them, and for the majority it was only once they were prescribed an antiemetic that they stopped moving between the different services. So we watched, we kind of plotted every single place that they went and over half of those 206 appointments was in primary care and most patients for the first three, four, five visits didn't actually receive an antiemetic. So I think that by implementing the guidelines as we're discussing will reduce not only the patient burden but the burden on the wider NHS.

Florence Wilcock: 49:01

That sounds such a valuable piece of work. I mean, I know women are bouncing around, but that's that's really quite disproportionate amount. That's that's really useful.

Dr Melanie Nana: 49:13

And these are patients that are largely bed-bound.

Professor Cathy Nelson-Piercy: 49:16

It's because they're desperate and they don't get what they want.

Florence Wilcock: 49:19

Yes, I can see that.

Professor Cath Williamson: 49:22

Another outcome that I'm just so delighted Melanie has achieved is to obtain some funding so we can do a health economic evaluation of models of care for HG and, if nothing else, will change practice. Hopefully, if we do show objectively with proper health economists, that managing women well will save money as well as improving outcomes, we hope that will make a difference.

Florence Wilcock: 49:47

Yeah, I can see that that, plus what Cathy was saying earlier about making it easy for the GPs, so they've got this clear summary of this is the go-to making it easy, implementation and saving money. You're you're definitely kind of on the right tracks there. I wanted to talk a little bit about the future, because there's been such an incredible recent development or certainly for me, recent the advent of, or discovery of, the impact of, gdf 15, the hope that that might bring to women in terms of a people appreciating this is a physiological, physical issue again, like we've been talking about with um, a hormonal basis, so that we can actually understand what it is and why it's happening, but also hope in terms of, therefore, potential future ideas for treatment. I didn't know if you wanted to talk about that a bit.

Professor Cath Williamson: 50:51

I could tell you a little bit about this beautiful piece of work that has recently been highlighted. The person who really brought our GDF-15 to our attention in the context of HG was Marlena Fascio, who works in the States. She's a scientist who had HG in her own pregnancy and subsequently did some really lovely work, including genetic studies. Where she did. She looked at all the potential markers across all the genome and found a couple of main hits. One of them was GDF-15. And she did this with a really smart idea. She worked with 23andMe. They had a question about vomiting in pregnancy and then looked at all the data that had been collected. So it was a very smart way to try to understand whether there's anything genetic underlying HG, and she found this. In a sense, one of the top people in the world working on GDF-15 is Steve O'Reilly from the UK, who's based in Cambridge. So his team and they got together and their collaborators looked at this in a number of ways and they showed a variety of things, but essentially what they showed was that GDF-15 concentrations in the blood are a bit higher in people who have HG compared to those that don't. And then Marlena did another study of almost 1,000 women where she confirmed the association with GDF-15. And she found 10 people with a genetic change that was almost certainly disease-causing in GDF15. So there are certainly a subgroup of people where there could be mutations in the gene and where the concentrations are different. But the strange thing which they demonstrated very elegantly, the genetic change that they identified in those 10 cases actually causes less to be in the blood. But Steve's work in collaboration with the team in Cambridge had shown higher concentrations in the blood, so they went on to show that it comes from the baby and the placenta. So what they're proposing is that women who have genetic changes in GDF-15 may have lower levels when they're not pregnant, so then they're more sensitive to the higher levels when they are. And the other interesting thing about GDF-15, it binds one receptor in the brain that mediates aversion responses and also nausea and vomiting from chemotherapy agents. So it almost certainly is a trigger zone for clinical features of HG and this raises the possibility of designing new treatments.

Professor Cath Williamson: 53:23

But of course there's a lot of work to do because GDF-15 is up in all pregnancies, so it needs to be established how necessary it is, whether it would matter blocking it. But we've got the right people working on it. They've done beautiful work to delineate this so far, so I think it's very positive, as you say, firstly, women with HG know that there's a biological explanation for why this can happen and there's the potential for new medicines. One or two other things people might be interested in the work that they've done has primarily used samples from women of European background. So we do have to do more work looking at other ethnicities and other possible causes because, as with all conditions in pregnancy that I'm sure you talk about a lot, there isn't just one cause and it's very likely that there will be other causes genetically found, and we all know there are other clinical conditions associated with hg as well. But if we individualize what we understand about causes, we can individualize treatments and that can only make the treatment better yeah, thank you.

Florence Wilcock: 54:27

It did seem to me like a massive stride forward very much so yeah, so and there to be applauded for that.

Florence Wilcock: 54:35

Yeah yeah, really incredible. And I listened to him uh, talk on it on another podcast um, the midwife's cauldron, which is fantastic, and he talked about that fact that it's the same receptor for vomiting after chemotherapy, and that was like a light bulb for me. You know, we're telling women on the one hand, oh, man up, it's just a bit of sickness, and then we're telling people on the other hand, oh, you're having chemotherapy, you need lots and lots of drugs, and that massive disparity that actually they're identical. It's just it really kind of brought it home to me. It's just it really kind of brought it home to me. So I'm conscious we're coming up to an hour and whether we should think about what's our take home message. So I normally end the podcast with a kind of zesty bit a bit. If you remember this one thing what do you want people to remember from our conversation?

Professor Cathy Nelson-Piercy: 55:38

Any thoughts? Listen to the women. Listen to the women and take them seriously. And I guess what I?

Professor Cath Williamson: 55:50

want to say is follow the guideline. You took the words out of my mouth, Cathy. Those were the two comments I was going to make. Listen to the women and follow the guideline.

Florence Wilcock: 56:04

It has been written by Cathy and Melanie, amongst others, and is fantastic. Yeah, I think that's very simple and very straightforward Listen to and believe the women and follow the guideline. I don't think you could say anything better than that, really, so, yeah, thank you very, very much. It's been absolutely brilliant to have the three of you share your wisdom on this topic and I really hope that by doing this today, hopefully we can get the word out to a few more people and a few more women who can advocate for the right treatment as well as hopefully steering some can advocate for the right treatment as well as hopefully steering some health professionals in the right way. So, thank you, so so much. Thank you. Thanks, florence. Thank you.

Florence Wilcock: 56:45

Florence, I very much hope you found this episode of the OBSPod interesting. If you have, it'd be fantastic if you could subscribe, rate and review, on whatever platform you find your podcasts, as well as recommending the OBS pod to anyone you think might find it interesting. There's also tons of episodes to explore in my back catalogue, from clinical topics, my career and journey as an obstetrician and life in the NHS more generally. I'd like to assure women I care for that I take confidentiality very seriously and take great care not to use any patient identifiable information unless I have expressly asked the permission of the person involved on that rare occasion when it's been absolutely necessary.

Florence Wilcock: 57:45

If you found this episode interesting and want to explore the subject a little more deeply, don't forget to take a look at the programme notes, where I've attached some links. If you want to get in touch to suggest topics for future episodes, you can find me at theobspod, on Twitter and Instagram, and you can email me theobspod at gmailcom. Finally, it's very important to me to keep the Obst Pod free and accessible to as many people as possible, but it does cost me a very small amount to keep it going and keep it live on the internet. So if you've enjoyed my episodes and, by chance, you do have a tiny bit to spare. You can now contribute to keep the podcast going and keep it free via my link to buy me a coffee. Don't feel under any obligation, but if you'd like to contribute, you now can. Thank you for listening.