What pre-eclampsia means for the baby's brain

Maria is 35 years old and nearly eight months pregnant. She’s been feeling very unwell the last couple weeks and she’s worried something could be wrong. She has pounding headaches and blurred vision and her hands and feet are abnormally swollen. There's also sharp, unusual stomach pains that she puts down to indigestion but knows that’s probably not it. She’s concerned, more about her baby’s health than her own, and goes to see her GP. Although she’s always been in good health before, when the doctor checks her blood pressure, it’s sky-high. Maria is admitted to hospital where she is soon diagnosed with pre-eclampsia (PE).

“I’ve never heard of pre-eclampsia before – is it common?”

Actually, it is – more than 10 million women like Maria are diagnosed with it every year. It’s surprising how many people have never heard of the condition, considering just how common it is – it affects about 5% of pregnancies and causes 76,000 maternal deaths every year (that’s about as many human deaths caused by snakes every year). PE is a “hypertensive disorder of pregnancy”, which means it involves chronically high blood pressure related to a woman’s pregnancy. While we don’t know exactly what causes PE, it’s thought to involve the placenta not growing quite the way it should, early on and long before any symptoms show up. The only cure is delivery of the baby and placenta and if left untreated, the mother can develop serious complications such as eclampsia, which is essentially PE with seizures, and often leads to death. Even when the mother recovers, her long-term risk has gone up for type 2 diabetes, kidney disease and cardiovascular disease.

And yet the baby can be affected by PE almost as much as the mother. The construction of a complex human from a tiny ball of cells is a delicate process, and it’s very sensitive to things like toxins, drugs, stress or infection. Unsurprisingly, a pre-eclamptic womb is no friendly place to grow up for these first 9 months of life (or less, if the baby is delivered pre-term, as is often the case in PE). In fact, PE is responsible for half a million new-born deaths every year, and even if the baby survives, just like the mother, they are more likely to have high blood pressure, high BMI, and cardiovascular disease.

What’s interesting is that PE can specifically affect the developing brain. Neurodevelopmental disorders are conditions where the brain fails to develop properly, and these include autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD). It’s wonderful that so many people today with ASD and ADHD are healthy, active members of society, and that the world is slowly beginning to accept and celebrate their neurodiversity. Yet tragically, this is often not the case – perhaps every second person with autism will never speak, and a large amount of these people have limited opportunities in life with no prospect of independent living, and this can have a profound emotional impact on them and their families. When we look at the population over time, we see that the children of mothers with PE have a 30-35% higher chance of receiving a diagnosis of ASD or ADHD than their peers, and it’s even been linked to other brain conditions like schizophrenia, epilepsy and cerebral palsy.

This means that if a child’s likelihood of developing autism is, say, 2%, the same figure for a child born to a pre-eclamptic mother goes up by a third, to about 2.67%. This is actually quite a lot when we consider there’s 140 million babies born every year and 5% of these pregnancies are affected by PE, and it may account for thousands of additional cases of ASD and ADHD each year. This makes PE an “environmental risk factor” – something that, without affecting a person’s genes, increases their risk of a certain condition. Along with genetic and other environmental risk factors (such as parental age, low birthweight, certain environmental toxins; and no, not vaccines!), PE places stress on the foetal brain, tipping the scales towards ASD or ADHD.

“But how does PE affect the baby’s brain?”

Well, the short answer is we just don’t know. We can, however, make some good guesses based on the research that’s out there and then we can do our own experiments too. When you break it down, there’s really two different questions here: firstly, what’s happening inside the foetal brain in PE; and secondly, what is it about PE that’s causing these brain changes? Each of these questions contains a thousand more, but let’s not get too into that; instead, let’s discuss what we’re doing in the lab to try and answer these two (thousand) questions.

It’s hard to see what’s going on in the foetal brain – you can’t exactly peer inside someone’s head and watch the brain develop. But you can grow neurons in a plate and peer pretty easily into that, so this is what we do – we grow neurons and watch them as they enlarge, stretch, move around, breathe, and connect; essentially, we let them do what they do inside a developing brain. As they do this, half the cells are given something to mimic PE (certain proteins, for example, or blood from women with PE), while the other half gets the equivalent from a healthy pregnancy, and we look to see if there’s any differences. Although neurons aren’t exactly brains, they’re the protagonists of the brain, and these experiments are giving us some really interesting insights into what PE does to neuronal development.

And what about that second question – how does PE cause neurons to grow differently? This one’s a bit more complicated, because there’s so much more going on in PE than just high blood pressure, including a lot that we don’t fully understand yet. To try work this out, we are looking at that enigmatic organ that some people like to eat – the placenta. Scientists love the placenta, not because it’s so delicious, but because it’s a window into what went on during a woman’s pregnancy and how it may have affected the baby. Your placenta (if you have one) is a truly amazing organ – it’s not just a barrier between the mother and baby, and certainly not just superfluous afterbirth. It controls everything that reaches the foetus, and it sends out all sorts of chemical messages that play a pivotal role in guiding pregnancy and foetal development. This, of course, includes neurodevelopment. So, what we’re doing is taking tiny samples from the placenta of women – some healthy and others with PE – and then looking at whether there’s something going on in the placenta in PE that might cause it to send different messages to the foetal brain.

“Yes, but why should I care about any of this – how is it meaningful?”

That’s always the big question in science, and fairly so. Put simply, we know that PE affects brain development, and if we can find out exactly how, then maybe we could prevent this. Women at high risk of developing PE, or who, like Maria, have recently been diagnosed with the condition, could be started on lifestyle or pharmacological interventions that would protect her baby’s brain – much the same way that women are advised to supplement with folic acid to protect her baby from neural tube defects like spina bifida. It might also tell us something about PE or neurodevelopmental disorders more generally, and eventually lead to improvements in the health and wellbeing of the mother and child. So, watch this space!