Preterm Babies: Predicting the Consequences

To the Editor:

More than 1 in 10 babies worldwide are born prematurely every year. Although the survival rates have improved over the past two decades, especially for babies born extremely prematurely, over three-quarters of extremely preterm infants have at least one chronic health condition as adolescents or adults.[1] Examples include various neurodevelopment disorders that can make school/work performance more challenging. We need to determine how premature birth leads to these disabilities later in life and ultimately help preterm babies face these complications when they occur.

Very preterm birth could be associated with long-standing brain metabolite alterations, which appear responsible for the deficits reported in executive functions at school age. For instance, very preterm children aged 8 to 13 years exhibit higher choline-to-creatine ratio and myoinositol-to-creatine ratio and lower glutamate plus glutamine-to-creatine ratio in frontal white matter, as compared with term-born peers.[2] Lower executive function abilities (including inhibition and interference, working memory, cognitive flexibility, fluency, and planning) were associated with lower frontal glutamate plus glutamine-to-creatine ratios in both groups and higher myoinositol-to-creatine ratio only in children born very preterm.[2] Assessing brain metabolism in preterm babies may thus allow for the early identification of children at risk of developing deficits and even provide a vehicle for innovative metabolic interventions. This approach should blend state-of-the-art neuroimaging techniques (such as magnetic resonance spectroscopy [MRS]) to study brain metabolism with the expertise of longitudinal neurodevelopmental evaluation. An assessment of crucial brain metabolites (such as creatine, choline, and N-acetyl aspartate) could perhaps become an adjunct component of routine screening in preterm children following clinical findings, biochemical profiling, and other imaging studies. This would lead to developing a diagnostic (and prognostic) testing algorithm in a child born very preterm suspected of having indicative neurodevelopmental findings and impaired brain metabolism.

Building an international database that collects metabolic signatures of preterm babies from birth to adulthood, complemented by developmental screening upshots, would enable better prediction of long-term outcomes after premature birth. In addition, data should be made available to navigate future therapeutic regimens and perhaps tackle possible disabilities of very preterm children in later life. In a perfect world, all preterm children should receive MRS and be enrolled into this database. This initiative should follow the steps of neonatal neuroimaging for hypoxic-ischemic injury (and therapeutic hypothermia) in which magnetic resonance imaging with MRS shifted from experimental diagnostics into a critical component of standard practice for this subpopulation and has already been integrated into routine protocol, at least in the United States. This might be of exceptional public health relevance having in mind a relatively high prevalence of disability from premature deliveries and the high economic burden of health consequences in preterm children. The fragile population of very preterm children requires advanced medical care not only by improving clinical practices but also by paving the way of meeting these challenges for the future of society as a whole.

Publication History

Received: 22 November 2022

Accepted: 05 January 2023

Article published online:
06 February 2023

• References

• 1 Dance A. Survival of the littlest: the long-term impacts of being born extremely early. Nature 2020; 582 (7810): 20-23
• 2 Schnider B, Tuura R, Disselhoff V, Latal B, Wehrle FM, Hagmann CF. EpoKids Research Group. Altered brain metabolism contributes to executive function deficits in school-aged children born very preterm. Pediatr Res 2020; 88 (05) 739-748