Genetic insights into pregnancy problem

Scientists have discovered why some pregnant mothers develop the potentially life-threatening condition preeclampsia. Obstetrician and researcher Catherine Aiken from the University of Cambridge spoke to Chris Smith about the findings...

Catherine - Preeclampsia - it’s one of the great obstetric conundrums. It kills over 75,000 women worldwide each year, and yet really, we struggle to have any handle on what it is, how to tackle it, and truly what’s the root of causing this.

What we have here is a new study that brings a different angle to tackling preeclampsia. Lots and lots of people have looked at mum’s genetics in trying to find susceptibility here. This paper has a clever twist in that they’ve actually looked at the genetics of the baby to try to find out how they might be driving disease in the mum.

Chris - When a person has preeclampsia, how would you recognise and how would a person know they’d got it?

Catherine - About 1 in 20 women develop preeclampsia during pregnancy so it’s actually a really common condition. As doctors we struggle though because people present in lots and lots of different ways. People come with a headache, people come with a small baby, people come with very high blood pressure, and that enormous range of symptoms and signs, trying to disentangle exactly what is preeclampsia becomes really tricky.

Chris - So you don’t know you’re at risk of it, you don’t know it’s going to be a problem until you get pregnant, and then it’s not until you’re quite far through the pregnancy when you get problems and then it might even be a bit late?

Catherine - That’s exactly it. And that’s why this kind of study is really important because what we need, what we really urgently need are ways of telling who’s at risk.

Chris - What have this group done?

Catherine - What this group have done is take an enormous number of baby’s genomes. So they’ve got the genetics of almost 5,000 babies whose mums have had preeclampsia during the pregnancy from both Iceland and the UK. They’ve also got 300,000 babies whose mums didn’t have preeclampsia during the pregnancy that they can compare the DNA. Remarkably, from that enormous amount of information they’ve managed to pinpoint a single variant in the babies whose mums did have preeclampsia that’s more common than in the ones whose mums didn’t.

Chris - What area of the DNA is involved, or what change do they think is in these infants that means they’re at increased risk of their mum having preeclampsia?

Catherine - The little piece that they’ve found that’s different in these babies is right beside a gene that’s involved in forming the placenta. Now the placenta is the interface
between mum and baby; if the placenta doesn’t form properly then that can be the driver for preeclampsia. It’s very possible that what they’ve found is a developmental problem with the placenta. So it’s a really attractive theory that the baby has this genetic variance that that then means that the placenta doesn’t develop properly, and then that drives changes in the mum that we see as this high blood pressure, protein in the urine and, ultimately, risky preeclampsia pregnancy.

Chris - What proportion, roughly, of babies in which preeclampsia happens would this account for?

Catherine - The actual increased risk is about a 20% increase in the risk of preeclampsia, so it’s certainly not the answer to finding all of preeclampsia cases but this is the kind of insight that we need. The really interesting thing is that having found this little piece of DNA has then given them a rationale to go to look at other bits around the same region of the gene. They’ve also found a new novel variant based on this knowledge and that's the kind of snowballing effect that this study gives us to be able to bring in other insights that all piece together to form a big picture of how we can tackle preeclampsia.

Chris - Ultimately, does this give us the ‘holy grail’, to use a horrible cliche, which is a test of who might be at risk, so when you’re booking in with your GP and having your antenatal screen this could be included, or something like this in the long term in order to look at who might be at risk and worth keeping an eye on?

Catherine - That would be fantastic. That’s the ultimate goal with this kind of research. We’re quite far off that at the minute - I don’t think they’ve found the single basis of a test that would work that way. But, ultimately, when we’re reading these studies, we allow ourselves to get a little bit excited at the thought that one day this might be contributing to that kind of test.