Being born slows rate of myelin growth

Preterm birth can have long-term cognitive consequences. Literature suggests that school children who were born at between 32 and 37 gestational weeks, for example, are more likely to have problems with memory and attention. Other studies have found that extreme preterm birth (before 28 weeks of gestation) is closely linked to long-term intellectual disability, problems with language and behaviour, cerebral palsy, and the development of psychiatric disorders. 

In a new paper in PNAS, a team led by Mareike Grotheer at the University of Marburg in Germany report finding what could be a key reason why preterm birth can have these impacts on the brain: myelin, the fatty sheath that insulates the axon 'bodies' of neurons, appears to grow faster in the uterus than after birth. 

Myelination is vital for healthy brain functioning, including learning. That's because myelin acts as an insulating layer around axons, protecting them and improving the speed and transmission of electrical signals along them. It also gives white matter, which connects distant brain areas, its colour. If, as this new work suggests, myelination in the cortex is impeded by preterm birth, this could explain why some of the harmful impacts on the brain occur, and even open up future avenues for mitigating these risks.

In the first step of their study, the researchers analysed 300 brain scans of newborn babies from the Developing Human Connectome Project. These babies were at various gestational ages, from 25 to 42 weeks. After using their own specially developed software to automatically identify 20 specific white matter bundles, the team adopted a modelling technique to plot myelin development in the weeks before and after birth. This technique (called the T1w/T2w technique) involved quantifying changes in a myelin-sensitive imaging contrast over time.  

The researchers also studied brain scans of another group of 34 preterm infants and a matched group of full-term infants. These scans had been conducted once shortly after birth, and again when the babies were around 37 weeks old. 

Analyses of these samples revealed that myelin grows faster along the lengths of the white matter bundles in the uterus, compared with right after birth. The team also found evidence that the delays in myelin development seen in the brains of the preterm infants could be explained by the difference in myelin growth rates in utero compared with ex utero, and the shorter time that these infants had spent in the uterus. 

The finding of faster myelination in the uterus compared to post-birth is "likely explained by the protective environment of the womb," the researchers write. Based on other work on animals and people finding a link between rates of myelination and levels of nutrition, the team suspect that the relatively high availability of nutrients in the uterus could be key to the faster rate of myelination before birth. (One recent study even found that delaying clamping the umbilical cord until about three minutes after birth, rather than after about 30 seconds, increased the supply of iron to babies' brains, and was associated with increased myelination in brain areas important for early development when those babies were four months old.) 

There are some limitations to the study. One is that the researchers couldn't quantify myelin growth directly — that would have required post-mortem samples. The T1w/T2w technique is a standard method for using MRI scans to map myelin in the cortex, but some recent studies have questioned this technique's validity. More work is needed to validate its use in newborns, the team writes. 

These new findings do fit with the results of some other studies, however. As the authors note, various papers have reported finding differences in the structure of white matter in adults who were born preterm versus full-term, and linked these differences to various developmental, neurological and cognitive disorders. This new work suggests that it's not just the infant's gestational age at birth that explains this, but a slowing in the rate of myelin growth outside the uterus — and that is something that, in theory, interventions might be able to address.   

These new findings also suggest that if a newborn preterm baby can be kept in as close to womb-like conditions as possible, it may be possible to mitigate some of these impacts. Though exactly how this may be done in practice — especially in terms of nutrient supply — is yet to be worked out. 

Read the paper in full: https://doi.org/10.1073/pnas.230349112