Giulia Spoto
Antonio Gennaro Nicotera
Ambra Butera
Gabriella Di Rosa- 1Unit of Child Neurology and Psychiatry, Department of Biomedical Sciences, Dental Sciences, and Morphofunctional Imaging, University of Messina, Messina, Italy
- 2Unit of Child Neurology and Psychiatry, Department of Maternal-Infantile, University of Messina, Messina, Italy
- 3Unit of Child Neurology and Psychiatry, Department of Chemical, Biological, Pharmaceutical, and Environmental Science, University of Messina, Messina, Italy
Editorial on the Research Topic
Neurodevelopment and preterm birth
According to the World Health Organization, in 2020, the global rate of preterm birth ranged from 4% to 16%, and its complications represented the leading cause of death among children under 5 years of age (1). Despite the advances in neonatal care, children born preterm show a considerably higher risk of adverse outcomes compared to term-born babies. Notably, the risk of mortality and morbidity increased according to the degree of prematurity (2).
Premature birth can result in short- and long-term consequences, including poor health and growth, respiratory and gastrointestinal complications, and neurodevelopmental impairments that persist into adulthood. Particularly, motor, cognitive, communicative, and emotional/behavioral skills can be compromised, causing a significant burden on these children, their caregivers, and the healthcare systems (3).
Even though robust research has been conducted to address the underlying causes of prematurity, little change has been observed in the global preterm birth rate during the last decade (2). Numerous clinical and environmental factors have been considered as etiological aspects of prematurity (4). Perinatal factors such as brain injury, lower birth weight, late-onset sepsis, necrotizing enterocolitis, patent ductus arteriosus, and bronchopulmonary dysplasia have all been associated with adverse neurodevelopmental outcomes. In addition, exposure to the neonatal intensive care unit (NICU) environment can impact the neurodevelopmental outcome since children are exposed to reduced positive sensory stimuli (i.e., nurturing contact with the parents), and increased negative sensory exposures (bright and noisy environment, painful procedures). In very preterm babies, longer hospitalization in the NICU has been linked with worse cognitive, language, and motor outcomes at 1–2 years of corrected age (5).
In the last few decades, a growing body of research has focused on early detection tools to achieve prompt and accurate diagnosis and provide a timely intervention, optimizing neuroplasticity and function. These include neuroimaging, Prechtls' General Movements Assessment (GMA), and Hammersmith Infant Neurological Examination (HINE), which are currently considered the most validated assessments to diagnose cerebral palsy, the most severe motor outcome of prematurity (6).
Magnetic resonance imaging (MRI) is particularly effective in detecting nervous system lesions. Commonly, hypoxic-ischemic lesions occurring in preterm infants result in brain injuries involving both white and gray matter (7). Cystic periventricular leukomalacia and intraventricular hemorrhage (IVH) have been historically described as the most frequent preterm white matter injury, especially in children born very preterm or very low birth-weighted (8). Nowadays, more subtle lesions have been reported, such as diffuse microscopic punctate lesions, decreased white matter volume, and thinning of the white matter tracts (9). The pathological mechanism underlying the white matter damage of prematurity is the disturbed maturation of oligodendrocytes, especially of the oligodendrocytes progenitor cells (OPCs) (10). This connectivity damage can also alter the gray matter structures, including the cerebral and cerebellar cortex, thalamus, hippocampus, and basal ganglia (9, 11). Advanced techniques, such as functional MRI and diffusion-weighted imaging (DWI), have been recently used to understand the neurodevelopmental alterations underlying the long-term sequelae of prematurity (12). In this Research Topic, Zhao et al. used the diffusion tensor imaging (DTI), DWI, and diffusion kurtosis imaging (DKI) to assess the white matter development in 26 preterm infants and 26 full-term infants. Interestingly, they found that DKI is more useful in diagnosing delayed white matter development in premature infants than traditional techniques. Parameters such as the mean kurtosis (MK) and radial kurtosis (RK) allowed a more comprehensive characterization of the microstructural changes, especially in the posterior limbs of the internal capsule (PLIC) and anterior limbs of the internal capsule, proving to be superior to fractional anisotropy in diagnosing premature infants with delayed brain development. MK and RK were also more sensitive in analyzing the gray matter, playing an important role in detecting subtle structural changes of thalamic neurons in premature infants. Alternatively, Zhang et al., in their study on 15 preterm infants with low-grade IVH vs. 35 premature infants without intracranial hemorrhages, found that the synthetic MRI is also very sensitive in detecting microstructural modifications in the white matter of premature children with IVH. In their study, the analysis of T1 and T2 relaxation times and proton density values have been found excellent in detecting alterations in the PLIC, central white matter, and cerebellum. These findings support the notion that synthetic MRI might provide early prognostic biomarkers for neurodevelopmental disorders in preterm children.
In parallel to neuroimaging, clinical assessments and blood biomarkers have been studied in premature infants in order to early detect neurodevelopmental trajectories. GMA and HINE are emerging as efficacious detection tools in populations of preterm babies with low-risk of cerebral palsy, yet at risk of different neurodevelopmental disorders (13, 14). In the paper of Dicanio et al., significant correlations were found between the GMA at 3-months corrected age and the quality of movements, posture, and tone assessed with the HINE at 3-, 6-, and 9-months corrected age evaluations. Furthermore, the HINE showed that precocious visual and auditory abilities assessed with the Cranial Nerves subsection predicted communicative skills and auditory function, influencing the early language development in 1 year old preterm babies.
Regarding the blood biomarkers, Dong et al. focused their attention on serum peptide expression in the neonatal umbilical cord of children with hypoxic-ischemic encephalopathy (HIE). Their study identified potential endogenous functional peptides that may be involved in the progression of HIE and could be used as potential biomarkers. Among them, 21 peptides belong to the fibrinogen family, which is known to inhibit the differentiation of OPCs and, thus, myelination.
In the matter of myelination, Wang et al. conducted a remarkable study proving that transplanted human OPCs restored the myelin of injured white matter and led to neurobehavioral improvements in a mouse model of premature white matter injury. These results provide a new and promising perspective for the treatment of premature children.
Prematurity is a critical issue, given its long-term sequelae that profoundly impact patients' lives, families, and healthcare systems. This highlights the constant necessity for innovative interventions to enhance premature children's quality of life.
Author contributions
GS: Data curation, Writing – original draft, Writing – review & editing. AN: Supervision, Writing – review & editing. AB: Data curation, Writing – review & editing. GD: Conceptualization, Supervision, Writing – review & editing.
Funding
The author(s) declare that no financial support was received for the research, authorship, and/or publication of this article.
Conflict of interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.
References
1. World Health Organization. Preterm Birth. (2024) Available online at: https://www.who.int/news-room/fact-sheets/detail/preterm-birth (accessed March 31, 2024).
2. Ohuma EO, Moller AB, Bradley E, Chakwera S, Hussain-Alkhateeb L, Lewin A, et al. National, regional, and global estimates of preterm birth in 2020, with trends from 2010: a systematic analysis. Lancet. (2023) 402:1261–71. doi: 10.1016/S0140-6736(23)00878-4
3. Sarda SP, Sarri G, Siffel C. Global prevalence of long-term neurodevelopmental impairment following extremely preterm birth: a systematic literature review. J Int Med Res. (2021) 49:3000605211028026. doi: 10.1177/03000605211028026
4. Mitrogiannis I, Evangelou E, Efthymiou A, Kanavos T, Birbas E, Makrydimas G, et al. Risk factors for preterm birth: an umbrella review of meta-analyses of observational studies. BMC Med. (2023) 21:494. doi: 10.1186/s12916-023-03171-4
5. Kellner P, Kwon J, Smith J, Pineda R. Neurodevelopmental outcomes following preterm birth and the association with postmenstrual age at discharge. Am J Perinatol. (2024) 41:561–8. doi: 10.1055/a-1733-2690
6. Novak I, Morgan C, Adde L, Blackman J, Boyd RN, Brunstrom-Hernandez J, et al. Early, accurate diagnosis and early intervention in cerebral palsy: advances in diagnosis and treatment. JAMA Pediatr. (2017) 171:897–907. doi: 10.1001/jamapediatrics.2017.1689
7. Laptook AR. Birth asphyxia and hypoxic-ischemic brain injury in the preterm infant. Clin Perinatol. (2016) 43:529–45. doi: 10.1016/j.clp.2016.04.010
8. Novak CM, Ozen M, Burd I. Perinatal brain injury: mechanisms, prevention, and outcomes. Clin Perinatol. (2018) 45:357–75. doi: 10.1016/j.clp.2018.01.015
9. Ophelders DRMG, Gussenhoven R, Klein L, Jellema RK, Westerlaken RJJ, Hütten MC, et al. Preterm brain injury, antenatal triggers, and therapeutics: timing is key. Cells. (2020) 9:1871. doi: 10.3390/cells9081871
10. van Tilborg E, Heijnen CJ, Benders MJ, van Bel F, Fleiss B, Gressens P, et al. Impaired oligodendrocyte maturation in preterm infants: potential therapeutic targets. Prog Neurobiol. (2016) 136:28–49. doi: 10.1016/j.pneurobio.2015.11.002
11. Spoto G, Amore G, Vetri L, Quatrosi G, Cafeo A, Gitto E, et al. Cerebellum and prematurity: a complex interplay between disruptive and dysmaturational events. Front Syst Neurosci. (2021) 15:655164. doi: 10.3389/fnsys.2021.655164
12. Kanel D, Counsell SJ, Nosarti C. Advances in functional and diffusion neuroimaging research into the long-term consequences of very preterm birth. J Perinatol Off J California Per Assoc. (2021) 41:689–706. doi: 10.1038/s41372-020-00865-y
13. Brogna C, Romeo DM, Cervesi C, Scrofani L, Romeo MG, Mercuri E, et al. Prognostic value of the qualitative assessments of general movements in late-preterm infants. Early Hum Dev. (2013) 89:1063–6. doi: 10.1016/j.earlhumdev.2013.08.008
Keywords: prematurity, neurodevelopment, white matter injury, gray matter, preterm
Citation: Spoto G, Nicotera AG, Butera A and Di Rosa G (2024) Editorial: Neurodevelopment and preterm birth. Front. Neurol. 15:1412711. doi: 10.3389/fneur.2024.1412711
Received: 05 April 2024; Accepted: 15 April 2024;
Published: 24 April 2024.
Edited and reviewed by: Jo Madeleine Wilmshurst, University of Cape Town, South Africa
Copyright © 2024 Spoto, Nicotera, Butera and Di Rosa. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Gabriella Di Rosa, gdirosa@unime.it