You have full access to this article via your institution. Download PDF Preterm birth and associated complications are a leading cause of death for children under 5.1 For Late Preterm

Infants (LPI), defined as 34.0 to 36.6 weeks completed gestational age, mortality is thankfully much, much lower thanks to advancements in therapy over the last several decades. LPI,

however, still face significant challenges compared to term infants, including both short-term morbidities such as jaundice and hypoglycemia as well as long term neurologic, psychiatric, and

developmental disorders. Though often mistakenly overlooked because of their size similarity to term infants, this population, comprising nearly 75% of all preterm births, is vulnerable to

after a 2005 National Institute of Health sponsored workshop, “Optimizing Care and Outcome of the Near-Term Pregnancy and the Near-Term Newborn Infant”.2 Two years later, a Clinical Report

from the American Academy of Pediatrics Committee on Fetus and Newborn, “Late-Preterm Infants: A Population at Risk”, highlighted the need for more knowledge and research on the “long-term

medical, neurologic, and developmental outcomes for late-preterm infants”.3 There are a number of challenges to this directive, including funding as well as the fact that most high-risk

neonatal follow up clinics (“preemie clinics”) are focused on extremely premature infants and do not routinely follow LPI. In the current issue of _Pediatric Research_, Shah et al.4 examine

the developmental trajectories of LPI and predictors of academic performance. The goal was to identify risk factors to help those LPI who are most at developmental risk and could

subsequently benefit the most from more rigorous monitoring and early intervention before kindergarten. Importantly, the authors also looked not only at academic risk but also academic

resilience, factors associated with optimal trajectories that could lead to positive outcomes. To do this, a nationally representative, population-based United States sample, the “Early

Childhood Longitudinal Study, Birth Cohort (ECLS-B)” was compared to a full-term group. Maternal and psychosocial characteristics, parent-child interactions, child characteristics and

neonatal health risks were used to create developmental trajectories. The study found, surprisingly, that most LPI (70%) had early reading skills that were at or above the full-term

population mean. The opposite held true with math skills, in which most (79%) LPI had lower mean math scores. It is unclear why this would be the case, although the authors speculate that

the “unique” characteristics of late preterm brain development including “structural changes in the neural pathways related to visuo-constructive skills or neurodevelopmental immaturity in

neurocognitive domains associated with math processing” may play a role. This is yet another area in which additional research will help to further this important area of neurodevelopment.

The brain experiences rapid growth in the last trimester of pregnancy, due to neuronal proliferation and synaptogenesis, increasing its sensitivity to hypoxia and poor nutrition. Widespread

brain white matter microstructural changes have been discovered among LPIs relative to term controls, offering some explanation for specific developmental delays.5 Despite reportedly

advanced reading skills, LPIs often experience speech and language delays with poor school performance and increased need for special educational support. Furthermore, neurobehavioral

problems, such as attention deficit hyperactivity disorder (ADHD), internalizing problems and autism are more prevalent among LPI. Recent school age outcomes studies have reported that late

preterm infants are twice as likely as term controls to have IQ scores less than 85, independent of socioeconomic factors and maternal IQ.6 The current study identified factors in several

domains associated with academic risk. Looking at psychosocial risk, less than high school maternal education was associated with at risk trajectories in reading, math, and combined groups.

Similar findings, although with some notable differences in the specific trajectories at risk, were seen in the biological factors of twin or multiple gestation, history of prenatal tobacco

exposure, and male sex. The observation of increased academic risk among male LPIs correlates with prior reports of lower IQ for late preterm male adolescents. Yet, _why_ male sex is

associated with increased academic risk is unclear and a subject for further research. Significantly, the study also found important predictors of academic resilience. These included

experiencing early sensitive caregiving as well as preschool attendance. There are already effective techniques available to support sensitive caregiving, such as the “Video-feedback

Intervention to promote Positive Parenting and Sensitive Discipline (VIPP-SD)”.7 Additionally, there is substantial room for improvement in preschool attendance, as less than half of the

study population were enrolled. Though the majority of LPIs thrive in the long term, their increasing birth rate coupled with their substantial health care and educational needs leads to

significant economic and resource utilization burdens for the future. Their physiologic immaturity, which is hidden by their larger size makes them a perfect target for emergency room visits

and hospital readmission. Yet, despite these known risks, little progress has been made in the prevention of preterm birth. Furthermore, the lack of financial resources to provide adequate

long-term follow-up data on this forgotten cohort continues to limit progress in improving their outcomes. Studies such as this one are essential to enhance our knowledge about this growing

high-risk population. More work is also needed to evaluate the outcomes of LPIs needing intensive care compared to those LPIs born healthy. Perhaps parental questionnaires and virtual

neurodevelopmental assessment tools, such as the National Institute of Health (NIH) Toolbox, could provide inexpensive methods to improve follow-up. Pediatrics can no longer afford to

restrict neonatal outcomes research to the smallest NICU infants, leaving the vast majority of preterm births unstudied. Improved understanding of the medical and educational needs of this

high-risk LPI population will enhance the targeting of services to improve long term outcomes. The timing of this study is excellent given the recent publication of the American Academy of

Pediatrics Clinical Report “Primary Care Framework to Monitor Preterm Infants for Neurodevelopmental Outcomes in Early Childhood”.8 REFERENCES * Perin, J. et al. Global, regional, and

national causes of under-5 mortality in 2000–19: an updated systematic analysis with implications for the Sustainable Development Goals. _Lancet Child Adolesc. Health_ 6, 106–115 (2022).

Article  PubMed  PubMed Central  Google Scholar  * Raju, T. N., Higgins, R. D., Stark, A. R. & Leveno, K. J. Optimizing care and outcome for late-preterm (near-term) gestations and for

late-preterm infants: a summary of the workshop sponsored by the National Institutes of Health and Human Development. _Pediatrics_ 118, 1207–1214 (2006). Article  PubMed  Google Scholar  *

Clinical Report: Late preterm infants: a population at risk. _Pediatrics_ 120, 1390–1401 (2007). * Shah, P. E. et al. Developmental trajectories of late preterm infants and predictors of

academic performance. _Pediatr Res._ https://doi.org/10.1038/s41390-023-02756-2 (2023). * Kelly, C. et al. Moderate and late preterm infants exhibit widespread brain white matter

microstructure alterations at term-equivalent relative to term-born controls. _Brain Imaging Behav._ 10, 41–49 (2016). Article  PubMed  Google Scholar  * Talge, N. et al. Late-preterm birth

and its association with cognitive and socioemotional outcomes at 6 years of age. _Pediatrics_ 126, 1124–1131 (2010). Article  PubMed  Google Scholar  * Juffer, F., Struis, E., Werner, C.

& Bakermans-Kranenburg, M. J. Effective preventive interventions to support parents of young children: illustrations from the Video-feedback Intervention to promote Positive Parenting

and Sensitive Discipline (VIPP-SD). _J. Prev. Inter. Community_ 45, 202–214 (2017). Article  Google Scholar  * Davis, B. E. et al. Primary care framework to monitor preterm infants for

neurodevelopmental outcomes in early childhood. _Pediatrics_ 152, e2023062511 (2023). Article  PubMed  Google Scholar  Download references AUTHOR INFORMATION AUTHORS AND AFFILIATIONS *

Division of Neonatology, University Hospitals Rainbow Babies & Children’s Hospital, 11100 Euclid Avenue, Cleveland, OH, 44106-1716, USA Jonathan M. Fanaroff & Deanne E.

Wilson-Costello Authors * Jonathan M. Fanaroff View author publications You can also search for this author inPubMed Google Scholar * Deanne E. Wilson-Costello View author publications You

can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to Jonathan M. Fanaroff. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no competing

interests. ADDITIONAL INFORMATION PUBLISHER’S NOTE Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. RIGHTS AND

PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Fanaroff, J.M., Wilson-Costello, D.E. Late preterm infants: undercooked and overlooked. _Pediatr Res_ 95, 605–606

(2024). https://doi.org/10.1038/s41390-023-02832-7 Download citation * Received: 23 August 2023 * Accepted: 02 September 2023 * Published: 27 September 2023 * Issue Date: February 2024 *

DOI: https://doi.org/10.1038/s41390-023-02832-7 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get shareable link Sorry, a shareable link is

not currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative