Scientists make progress towards pregnancy sickness cure

Scientists at the University of Cambridge say they have discovered a protein which causes many women to experience nausea and vomiting during pregnancy. Some women - including the Duchess of Cambridge - become so unwell when they are expecting that they need to be admitted to hospital. So, what should we know about the protein that is causing it? Chris Smith spoke to Professor Stephen O’Rahilly, director of the Medical Research Council Metabolic Diseases Unit at the University of Cambridge...

Steve - So it's called GDF15. It's a protein and a hormone, and it goes into the bloodstream of the mother and it goes up to a very special part of her brain where it goes into a docking station, which is only present in a tiny bit of the brain. That's classically the bit of the brain that makes you feel sick.

Chris - Why does the placenta make it? Does it have another role? Presumably its job is not to make mum feel sick?

Steve - The first thing I would say is, it's present in non-pregnant people. In non-pregnant people, it probably is the signal that, when you've damaged yourself by taking some toxin or maybe even had a huge amount of alcohol and you've damaged cells, a signal goes up to the brain and says, 'that's horrible. Go and lie in the corner, throw up and never do that again.' So that's the job of this hormone in the non-pregnant state. In the pregnant state - primates, only the apes and ourselves have done this - I think what's happened is, to protect the baby during the first trimester, the first three months of the pregnancy when the organs are all developing... When we were evolving, we were hunting and gathering and eating all sorts of rubbish from the forest floor. This signal came and went to the mother's brain and said, 'I feel very nauseous and not so well. I'm not going to eat anything new or anything rubbish, and I'm going to stay safely in the cave and not go out and be eaten by a sabre tooth tiger.' I think this is the signal that the placenta has sent out, in fact, the baby's bit of the placenta because it's actually the baby that's sending the signal to say, be very careful what you eat. That's the job of this hormone.

Chris - When one looks, then, at people who have very bad sickness in pregnancy, is it that the baby's making more of it or is it that the mum is more sensitive to what the baby's got and all babies make an equal amount?

Steve - That's a great question and the answer is both of what you said. When we look at women who get very sick, the baby makes more, but the other factor is how sensitive the mother is. One of our key discoveries is what determines how sensitive the mother is, is how much of this substance, how much GDF15, she's seen before she was pregnant. And that really is a key determinant of what she will feel like when the foetus comes along and makes a shed load of this stuff and she's exposed to it. Her previous exposure determines how badly she feels.

Chris - When you say previous exposure, do you mean as in, if I took a blood sample from a woman, measured the level and her baseline when she's not pregnant level that's always there, that sort of sets her sensitivity? Or is it that if she spends every day of her life throwing up because she's having too many things she shouldn't... how does it work?

Steve - It works from, we think, relatively recent blood levels. What we have done in some of our experiments is given mice small doses for about three days before we give a big dose. If we give a small dose just of saline, a mock injection, and we give them the big dose, they don't like it, they don't eat, they go into a corner and they feel unwell. If we give them very small doses for three days and then give them the big shot, they ignore it, they feel perfectly fine. Even a few days of high exposure is what is doing it and that probably explains why 80% of people feel sick in the first three months of pregnancy, but it generally fades. We think what's happening is that, as the levels are high, the women get used to it and then, for the second and third parts of the pregnancy, most women get through without many symptoms at all.

Chris - But what about women for whom that doesn't happen? Because some women do complain that it continues all the way through pregnancy and in some women it's, I mean, some of my friends have been so badly affected they've ended up in hospital.

Steve - Yes, it's a very serious condition. It's the commonest condition for women to end up in hospital in the first trimester of pregnancy, and in some women it goes on for the entire duration: they don't desensitise for some reason, and we don't quite understand why they don't. But what is true is that if you have very low levels pre-pregnancy, those women have a 10 times higher chance of that happening to them when pregnancy comes along.

Chris - Does this mean then, now you understand the mechanism of how it's working, you can engineer a way to stop it?

Steve - Yes, I think we have. Normally, I know, scientists often talk that their work will be translated into treatments. I am more confident than I've ever been that something we've done will turn into treatments. So I think two things: one is that our work has really shown how important GDF15 is, how dominant it is. I'm confident that if we gave an antibody, for example, that blocked this substance, that would immediately alleviate their symptoms. And if we engineer it so it doesn't go into the baby, we've got the safety angle covered as well. So treatment I think will happen. Then our attempts to prevent this are going to start with women who have had a previous pregnancy where they were very sick and about a third to a half of those women never ever embark on a second pregnancy because of that: they want to have another baby, but they are too terrified of having the same experience again. So what we'd like to do in those women is expose them to GDF15 gently for a few months before pregnancy to reduce their level of sensitivity to this so that when they do become pregnant, they have a reduced chance of being very unwell.