Dom 08 Feb 2015


Neuroscience: The brain, interrupted
Premature birth lasting consequences

Babies are increasingly surviving premature birth — but researchers are only beginning to understand the lasting consequences for their mental development

Early birthday

Prematurity — also called pre-term birth — is extremely common. According to World Health Organization statistics from 2012, more than one in 10 babies — around 15 million in total — are born prematurely each year. The great majority are born between 32 and 37 weeks of gestation, but 1.6 million are born between 28 and 32 weeks and 780,000 are born 'extremely pre-term', before 28 weeks (see 'Born too soon').

Just a few studies have so far followed up the long-term fate of premature babies, because it is time-consuming and expensive to track them with sophisticated cognitive and behavioural tests over many years.

One of the first studies to show the extent of developmental problems was EPIPAGE, which looked at a cohort of all live births between 22 and 32 weeks of gestation from 9 regions of France in 1997, and a reference group of 664 full-term babies

Larroque, B. et al. Neurodevelopmental disabilities and special care of 5-year-old children born before 33 weeks of gestation (the EPIPAGE study): a longitudinal cohort study Lancet 371, 813–820 (2008)

 Up to half of the premature babies who survived to five years of age had some sort of neurodevelopmental problem by then, and the impairments in cognitive development grew more pronounced for each extra week of prematurity. On a score of cognitive ability, the team observed impairment in 44% of those born between 24 and 25 weeks of gestation and 26% of those born at 32 weeks, compared with 12% of full-term controls.

The effects seem to continue into adulthood. Developmental psychologist Dieter Wolke led an unusual study of hundreds of children born between 26 and 31 weeks of gestation in Bavaria in the mid-1980s. He assessed them at six years old, and again at 26 years.

Wolke, D. & Meyer, R. Cognitive status, language attainment, and prereading skills of 6-year-old very preterm children and their peers: the Bavarian Longitudinal Study Dev. Med. Child Neurol. 41, 94–109 (1999)
Eryigit Madzwamuse, S., Baumann, N., Jaekel, J., Bartmann, P. & Wolke, D. J. Child Neuro-cognitive performance of very preterm or very low birth weight adults at 26 years Psychol. Psychiatry (2014) 2014 Nov 8. doi: 10.1111/jcpp.12358

Last year, he reported that most of those who had cognitive problems as children still had them as adults: one-quarter of them had moderate to severe cognitive deficits, and half had mild cognitive deficits. Most of those who experienced problems had short attention spans, and as a group they tended to underachieve academically and career-wise.

Too much too soon

Scientists suspect that when the brain is forced to carry out a crucial part of its development while the child is in the outside world instead of a warm, watery womb, it receives inappropriate signals from the environment that affect how its neurons are linked into networks.

Pioneering brain-scanning studies support the idea that altered networks play a part in cognitive problems. Hüppi's Swiss collaboration looked at 52 six-year-olds who had been born prematurely, using MRI scans optimized to reveal tracts of neurons connecting brain regions. Compared with children born at term, the premature children's neuronal tracts were organized less efficiently, often taking a more meandering path.
These changes in organization were correlated with reduced social and cognitive skills
Fischi-Gómez, E. et al. Structural Brain Connectivity in School-Age Preterm Infants Provides Evidence for Impaired Networks Relevant for Higher Order Cognitive Skills and Social Cognition. Cereb. Cortex (2014)

In another study, neonatologist Jeffrey Neil, then at St. Louis Children's Hospital in Missouri, and his team used functional MRI to study the premature brain at rest.
The low-level, idling activity of a resting brain gives a read-out of its working connections, whose general topology is laid out before birth
Smith K. Neuroscience: Idle minds Nature. 2012 Sep 20;489(7416):356-8. doi: 10.1038/489356a

The team showed that in babies born between 23 and 29 weeks of gestation, this 'resting-state connectivity' tends on average to be less complex and active at term-equivalent age than it is in full-term babies at birth. Another study — on the 26-year-old Bavarians — showed that this reduced complexity of resting-state connectivity stretches into adulthood

Smyser, C. D. et al. Resting-State Network Complexity and Magnitude Are Reduced in Prematurely Born Infants Cereb. Cortex  (2014).
Bäuml, J. G. et al. Correspondence Between Aberrant Intrinsic Network Connectivity and Gray-Matter Volume in the Ventral Brain of Preterm Born Adults Cereb. Cortex  (2014)]

In France, EPIPAGE 2 is now running, and has recruited more than 4,200 premature babies from all over the country..  In the United Kingdom, a team led by neonatologist David Edwards of King's College London has launched a study that will track children from their time in utero until they are two years old, collecting brain scans and blood samples along the way. Some of these children will inevitably be born prematurely, and the plan is to identify molecular signatures that might predict which of those infants are particularly vulnerable, or resistant, to altered neurodevelopment.

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