Little numbers and tiny lives
Pregnancy and childbirth are entirely normal and natural processes, but they are not without risk. Very occasionally, things can go wrong that put the life of the mother and child in grave danger. And in even rarer cases lives are lost. For more than 40 years the National Perinatal Epidemiology Unit (NPEU) at the NDPH has been carrying out research into pregnancy and early childhood, making a lifesaving difference to vulnerable babies and their mothers by gathering data, running clinical trials and informing medical practice and policy.
Here in the UK, around 9 mothers die for every 100,000 that give birth. Childbirth is even more risky for babies, with an average of 4.5 per 1,000 dying within the first month of life. We still have one of the lowest maternal and childbirth death rates in the world, but there is always room for improvement.
“It’s a tiny number but it still works out at around three mothers lost every week and 14 babies per day, and every single one of those is tragic,” explains Marian Knight, Professor of Maternal and Child Population Health at the NPEU. “Our perinatal death rates are still unacceptably high compared with similar countries in western Europe – and, of course, rates are much higher in other parts of the world – so there’s still an awful lot more to be done.”
Small numbers, big questions
Fortunately for families but unfortunately for researchers, the fact that death in childbirth is mercifully rare in the UK makes it difficult to gather meaningful data on outcomes, and even harder to run statistically robust clinical trials. In search of answers, the UK was the first country in the world to start investigating every single maternal death back in 1952. This task now carried out by Knight and her team through the national Confidential Enquiries into Maternal Deaths, is widely regarded as a global gold standard for monitoring deaths in childbirth and early life.
“We focus on very rare complications of pregnancy where you can’t easily do randomised controlled trials,” explains Knight. “If there are only 200 babies born every year with a particular condition, how do you know what’s the best treatment? If you just look at one hospital, it could take ten years to get enough data to tell you something useful – and the longer it takes to gather that data, the more babies and mothers are dying.”
Today the NPEU also gathers figures from all maternity units in the UK on mothers and babies with specific complications, such as uterine rupture (where the womb tears during labour), which is hard to get from routinely-gathered hospital data. Initially set up by Knight, the system has now been adopted by many countries around the world, creating an international information network.
“It’s a very simple system but it’s very powerful,” she says. “We may have small numbers compared with some of the much larger studies being run by other groups here at the NDPH, but if it’s the right number then there are still some important questions you can answer.”
Another approach for getting the numbers up is to gather together data from many studies and crunch it together. Back in the 1980s, founding director Professor Sir Ian Chalmers and his colleagues at the NPEU pulled together all the studies that had been done around the world looking at risks and interventions in childbirth, reviewing the evidence and combining data in order to draw meaningful conclusions about the best thing to do. This approach eventually grew into the Cochrane Collaboration – a global network of experts that sifts through evidence on health topics ranging from nutritional labelling on menus to lung disease and cancer.
Despite the small numbers and even smaller patients, researchers at the NPEU still try to run clinical trials wherever possible, with several notable successes. For example, they were the first team in the UK to carry out a trial of a treatment called ECMO (extracorporeal membrane oxygenation), which is a type of temporary heart and lung bypass for newborns with severe cardiac or respiratory failure. Today they collaborate with researchers running trials all over the world, including low-resource countries such as India and Sudan, in search of life-saving evidence
More recently, the team ran a study called TOBY, a randomised controlled trial involving more than 300 babies, investigating whether whole body cooling could reduce brain damage in newborns who suffer low oxygen levels (asphyxia) around the time of birth. Babies given the treatment had their temperature dropped to around 33-34 degrees Celsius for three days and were then gradually warmed back up again. The results, published in the New England Journal of Medicine in 2009, were impressive: far fewer of the cooled babies had severe disabilities or cerebral palsy 18-21 months on, although it didn’t change the chances of dying.
“It’s counterintuitive because you think you’d want to keep such a fragile baby nice and warm,” Knight says, “but the trial showed that this cooling treatment really could reduce disability. We’ve already seen a complete change in practice, and we’re now following these children as they grow up. Neonatal care has changed out of all recognition in past 20-30 years in terms of the babies that survive, which has made a huge difference, but this isn’t just whether you die or survive: it’s about whether you have a disability and what kind of level that is – will you be in a normal school or not, for example?”
NPEU researchers also ran the first trial of magnesium sulphate to prevent epileptic fits after birth – a condition known as eclampsia – which results from high blood pressure and circulatory problems due to problems with the placenta. Full eclampsia is rare in the UK, as the early signs are usually picked up during prenatal blood pressure checks. Working together with hospitals in Africa, where prenatal care is less widely available, the team found that magnesium sulphate could stop fits in women with eclampsia and prevent fits from starting in those with high blood pressure at the highest risk. As a result, magnesium sulphate is now on the World Health Organisation’s list of essential medicines, which are considered to be the highest priority treatments for every healthcare system.
As well as gathering national data and running trials, Knight and her colleagues use this information to answer important questions about health policy. In turn, this builds evidence that the Department of Health can use to develop guidelines to ensure women and their babies are getting the best care – for example, how to decide whether it’s safer for a particular woman to give birth in a hospital, midwifery unit, or at home.
“Our maternal population is getting more complicated,” Knight says. “We’ve done really well at reducing deaths from bleeding and high blood pressure, but mothers now tend to be older, and more of them are overweight or obese. They are also more likely to have other complications, such as heart conditions or mental health problems that get worse during pregnancy. This is the group we really need to improve care for.”
As an example, Knight points to current guidelines recommending that obese women should not give birth in midwife-led units due to their increased risk of complications, but there is no hard data to support this policy. She and her team are now gathering information about obese women who have given birth in these units, to find out whether their outcomes are any different from those who go to hospital.
“Guidelines should be based on evidence. Women aren’t usually offered that choice, but we don’t know whether it’s safer or not. By simply collecting that information it might then open it up as a choice for more women,” she says.
One life-saving policy intervention came as a result of the H1N1 ‘Swine flu’ epidemic in 2009 and 2010. At the time, most people with the flu could get antiviral drugs from a local pharmacy simply by phoning a helpline, but pregnant women could only be prescribed the treatment with a doctor’s visit. This acted as a barrier, slowing down their access to the drugs and making it more likely that the infection would become more serious.
Knight and her team used the NPEU’s data collection system to gather information on a monthly basis about the pregnant women who had been admitted to hospital with flu and fed the data back to the Department of Health. The figures revealed that women who got antiviral drugs within 2 days of onset of symptoms were 90 per cent less likely to need to go into intensive care. As a result, the policy was changed almost immediately, scrapping the need for a doctor’s appointment and enabling pregnant women to access antivirals as quickly as anyone else. The same system has recently been used to collect information on women who have been exposed to Zika virus, gathering data to inform public health policy in the future.
“Not only did our data change the policy ‘on the hoof’ during the epidemic, it’s now routine for pregnant women to get a flu jab,” says Knight. “Up to 40 pregnant women died from flu in that pandemic year, and since then there’s only been one death in total. By being able to respond quickly, we can save lives.”
From finding out the best feeding patterns for premature infants to monitoring post-partum depression and post-traumatic stress disorder resulting from a difficult birth, the NPEU’s work touches on almost every aspect of maternal and newborn health. They’re also following up on the long-term impacts of complications in childbirth, and investigating how best to manage babies with developmental disorders and genetic abnormalities. It all adds up to a job that Knight finds incredibly rewarding.
“I initially trained in obstetrics but knew that by doing research I could make more of difference to many women and their babies, rather than just one at a time,” she says. “Fortunately, most births here in the UK proceed without any serious complications. We’re working at the extreme end and it can be really hard, but in my job you have to see the longer view – this is the stuff that’s making a difference.”