JESS and Kate Murphy* are two months younger than their birth certificates suggest. Although they should have been born in May 1985, their stint in the womb was cut short by pre-eclampsia, a serious condition that saw their mother’s blood pressure go through the roof. Fearing for the lives of the mother and her twins, doctors performed a caesarean section at 32 weeks, eight weeks short of a full-term pregnancy.
Both girls were in intensive care for months. Jess was the larger and healthier twin, although at 1.75 kilograms she was still only half the weight of the average baby born at full term. Kate weighed just 1.3 kg and was sicklier. These disparities continued as the non-identical twins grew into young adulthood. Jess thrived at school and was active and sociable; Kate lagged behind academically, was quieter and more reserved, and got bullied.
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Eventually Kate was diagnosed with a rare genetic condition called Rubinstein-Taybi syndrome, characterised by learning difficulties. However, her genes may provide only a partial explanation of her troubles.
There is mounting evidence that people who were born prematurely are often subtly different to those who were carried to term. Physical health problems aside, they are also more prone to introversion and neuroticism, and more likely to struggle with certain cognitive skills. Children born too early are often more sensitive to the effects of poor parenting and neglect, which itself can increase the risk of interpersonal difficulties, while in adult life they tend to earn less and find it harder to form romantic relationships.
Even success stories like Jess – a film producer with a first-class degree – have subtle differences in the wiring of their brains. As the rate of preterm birth, and the number who survive it, increases, researchers are racing to understand why the Jesses of this world thrive, while the Kates fall behind, and to identify ways of protecting and nurturing brain development to ensure that all premature babies grow up to realise their full potential.
“Preterm children tend to be more withdrawn and less likely to take risks“
The average length of human pregnancy is 40 weeks, but there are many reasons why women sometimes deliver earlier. One is an internal infection, which can cause the cervix to relax, triggering labour. On other occasions, doctors may deliberately deliver babies early because either the baby or the mother becomes seriously ill.
The World Health Organization estimates that some 15 million babies each year are born early – that’s one in every 10 births. Many of the countries with the highest rates are in sub-Saharan Africa. But even in the US, 12 per cent of births are premature. And the number is increasing, in part because women are having babies later in life, and IVF is resulting in more twins – both factors that increase the likelihood. Another influence is that doctors are more likely to deliver babies early as neonatal care steadily improves. “The steady reduction in birth age is really all down to the fact that we’ve got pretty good at looking after premature babies,” says Neil Marlow, a neonatologist at University College London.
Prior to the 1980s, babies born before 30 weeks rarely survived, and those that did were at high risk of neurological conditions like cerebral palsy. Today, however, nearly 80 per cent of babies born at 26 weeks survive, 85 per cent of them without serious health consequences. Even babies born at 22 weeks have a shot at survival.
Even so, premature birth is still a major risk for health complications. And now that large numbers of premature babies have survived long enough to reach adulthood, some subtler and longer-term consequences are also becoming apparent.
In the past two years, a flurry of studies has discovered previously unknown effects on cognition, personality and relationships. “For those who do develop problems, there is a particular phenotype,” says Dieter Wolke, a psychologist at the University of Warwick, UK. Besides scoring an average 5 or 10 points lower on IQ, children who were born early often struggle with mathematics, reading, planning and problem-solving. They are more likely to experience attention problems and anxiety, tend to be more withdrawn and introverted, and are less likely to take risks.
Unsurprisingly, these deficits conspire to reduce success and happiness in life. “Taking all of these things together, they tend to have fewer employment opportunities and lower wealth,” says Wolke. For instance, one of his studies revealed that at the age of 42, those born prematurely are, on average, – largely the result of poor educational qualifications.
They’re also more likely to get picked on at school and find it harder to develop romantic and sexual relationships. In a study of 26-year-olds, Wolke found that among those born earlier than 32 weeks, about a third had never had a sexual relationship, compared with 0.8 per cent of full-term controls.
There are some upsides: premature babies who reach adulthood are less likely to drink, smoke or take drugs, and often have closer-than-usual relationships with their parents. But on balance, prematurity is not an asset.
“The doctors said we might struggle with life skills; I didn’t but my sister did“
These are, of course, generalisations. Somewhere between a quarter and a third of children born before 32 weeks experience significant long-term problems, says Wolke, and the earlier they were born the greater the risk appears to be. However, he says, “about a third are indistinguishable from term children”.
Some preterm children are extremely successful. Isaac Newton was premature, as were Albert Einstein and John Keats. Despite being born eight weeks early, Jess says she’s never felt at a disadvantage. “The doctors said that both of us may struggle with life skills and development, but I never did; my sister on the other hand, really did,” she says.
So what causes these deficits in the first place? Cynthia Rogers at Washington University School of Medicine in St Louis and her colleagues recently used brain imaging to compare the brains of full-term newborns with those of babies who were born at least 10 weeks early, once they had reached their due date. This revealed – which transmits signals from one part of the brain to another – in brain areas involved in attention, communication and emotion.
Similar differences in white matter have also been identified in the brains of adults who were born prematurely. For instance, Chiara Nosarti of King’s College London and her colleagues have been studying the brain structure of adults who were born prematurely, including Jess and Kate. “Different parts of the brain are not efficiently communicating with one another, or they are communicating in a different way from a typically developing brain,” says Nosarti.
One study showed that young adults who had been born prematurely had smaller volumes of white matter in the main routes connecting parts of the brain, including the corpus callosum – a large structure that links the left and right hemispheres. These differences were associated with poorer performance on .
Other studies are also hinting why some, like Jess, are largely unaffected. Essentially, their brains have found a workaround. Nosarti recently ran an experiment asking adult pretermers to perform working memory tests inside a brain scanner: compared with controls, they showed less activation in areas usually associated with working memory, but more activation in an area involved in language processing. Those with the best working memory performance showed the greatest activation in this area. “They seem to be recruiting another brain area, which is not normally used in working memory, to compensate,” Nosarti says.
It is possible that some of the traits are down to nurture rather than nature – being mollycoddled by parents or bullied by peers, for example. A study by Wolke found no significant difference in parenting style between parents of premature and full-term children, but he agrees that bullying probably makes emotional problems worse.
As more and more preterm babies survive, the need to identify the root causes of such troubles becomes increasingly pressing. Between 1995 and 2006, the percentage of babies born between 22 and 25 weeks who survived rose from 40 per cent to 53 per cent.
Among them is Reece Gautam, now 8, who was born at 23 weeks and one day (every day counts when you’re born that early). His parents were warned that his chances of survival were 1 in 10; if he did survive, there was a 50:50 chance he’d be severely disabled.
At 22 or 23 weeks of gestation, a fetus is roughly 30 centimetres long. Its lungs are rudimentary, lacking the delicate latticework that enables unsupported breathing, and its skin is so thin that fluid leaks out, taking heat with it. The brain, too, is a work in progress. In particular, the cortex – that wrinkled, outermost layer of the brain where higher functions such as reasoning occur – is still smooth and in the process of organising itself.
Fighting for life
Keeping a preterm baby alive isn’t easy. They need food and oxygen at a time when their lungs and stomach aren’t necessarily ready to receive them, they’re exposed to light and sounds they wouldn’t usually experience and they’re no longer protected by their mother’s immune system. They’re also missing a placenta, which produces hormones and growth factors in its own right. “By being born early and having your placenta cut off, you lose what biology has provided for you in quite a profound way,” says David Edwards, a neonatologist at King’s College London.
Reece was born weighing 595 grams. He spent 80 days on a ventilator and required bowel surgery. He also needed laser surgery on his eyes, and contracted MRSA. “He gave everything a whirl,” says his mother Claire.
Yet even some of the things that doctors do to ensure the survival of babies like Reece could potentially have negative side effects. “If you ventilate the lungs, even if you’re quite careful, you tend to set up an inflammatory state, which is probably bad for the baby and bad for the brain,” says Edwards. But because neonatal intensive care units predominantly focus on immediate survival needs, they haven’t necessarily considered the long-term effects of the type of care they provide.
That’s starting to change but there’s still a lot more that could be done, says Annemarie Stroustrup, a neonatologist at Mount Sinai Hospital in New York. “Preterm babies are essentially third-trimester fetuses,” she says. “This is an important time for neurodevelopment.”
One worry is exposure to artificial chemicals. For instance, plastic softeners called phthalates are common constituents of medical materials used in the baby unit. Several studies have suggested that babies undergoing high-intensity treatments have of phthalates in their urine. “We know that they’re not good for term babies, so there’s no reason to think that they would be good for preterm babies,” Stroustrup says.
Realising the unique vulnerabilities of the preterm brain, efforts are under way to find ways of protecting it. One idea is to replace some of the substances that the placenta would usually provide, such as the hormones melatonin and erythropoietin, both of which seem to protect cells against injury. “The placenta is a very active part of the baby,” says Edwards. “Trying to replace it seems a reasonable way of moving forward.”
There’s also the possibility of intervening during childhood. At present, preterm babies receive intensive care in the hospital and lots of follow-up as infants. But once the children reach school age, unless they have obvious health problems, they are considered to be just another kid. Often they aren’t.
Given how much is invested in treating premature infants, that seems like an oversight. Although people who are born prematurely make up just 7 per cent of the UK population, they absorb 35 per cent of the paediatric budget. Just getting a very preterm infant through their stint in intensive care can cost more than £250,000, says Wolke: “If the decision is made to invest so much money in early care, I think there’s a moral obligation to continue to invest to ensure they have a good life, an education, and that they’re supported.”
Things are changing. One approach being piloted is the use of computer-based tasks to strengthen working memory in 8-year-olds who were born prematurely. “There is some indication that if you try and reinforce specific structures while the brain is still developing, you might be able to obtain long-term benefits,” says Nosarti, who is involved in the research. “We hope this will have wider implications for academic achievement.”
Preliminary results look promising, she says, although nothing has yet been published. Training does seem to alter the connectivity of the brain, and these subtle changes seem to be associated with better performance, although it is too soon to say if this will result in long-term gains.
“These are often the forgotten children; they get lost in the crowd“
Refining such training methods will obviously take time, but there are already things that teachers and parents could do to support preterm children as they get older. Most of all, says Wolke, there’s a need for greater awareness about some of the difficulties they may encounter. “These are often the forgotten children,” he says. “They are not usually particularly risk-taking or naughty kids, so they don’t necessarily attract much attention.”
Reece, for example, has a limited vocabulary for his age and has severe attention problems. Yet his mother had to push hard to get his difficulties taken seriously by his primary school. Last year he moved to a new school where he now receives some one-on-one tutoring. “If he’s sat in a classroom it’s very difficult for him to concentrate; he just gets lost in the crowd,” says Claire. “His working memory is very poor and he can’t deal with a lot of instructions all at once.”
Wolke has drawn up recommendations for teachers on how to help children such as Reece. These include breaking learning down into smaller chunks to overcome attention difficulties and encouraging group work and mentoring by peers to increase social interactions.
Claire now volunteers on a unit supporting parents who are going through the same emotional roller coaster she went through. “I always say to them: don’t think too far ahead because it will drive you crazy, but I find myself doing it sometimes.” She worries what the future will hold for her son. Society has made a decision that children like Reece deserve to survive. Isn’t it time that we helped them with living as well?
*Not their real names
This article appeared in print under the headline “Forever premature”
