How Early Is Too Early?

Source: Rossetti L, Pascoe L, Mainzer RM, et al. Executive function outcomes at school age in children born moderate-to-late preterm. J Pediatr. 2025:284:114634; doi: 10.1016/j.jpeds.2025.114634.Investigators from Murdoch Children’s Research Institute and the University of Melbourne, both in Melbourne, Australia, conducted a study to assess the impact of moderate-to-late preterm (MLP) birth on executive function (EF) at school age. Study participants included a cohort of children with MLP birth, defined as birth at 32–36 weeks’ gestation, and a cohort with uncomplicated term births (≥37 weeks’ gestation). Demographic and clinical information were collected on these children. EF was assessed when study participants were approximately 9 years old using a variety of neurodevelopmental tests across 3 subdomains, including attentional control, cognitive flexibility, and goal setting. EF behaviors were evaluated using the Behavior Rating Inventory of Executive Function, Second Edition (BRIEF2) global executive composite (GEC) score. Differences in EF function and behavior scores were compared between the MLP and term cohorts using regression analyses after adjusting for confounding. In addition, using threshold values to define impairment, the relative risk (RR) of impairment in EF function and behavior among children in the MLP cohort also was evaluated.The original cohort included 201 MLP children and 201 in the term cohort; 159 (79%) of those in the MLP group and 134 (67%) born at term were assessed at 9 years of age. Among these participants, those in the MLP cohort were more likely to have repeated a school year than those born at term (3.2% vs 0%) and have a diagnosis of attention-deficit hyperactivity disorder (11.1% vs 5.5%). When EF was assessed, there were no significant differences in scores between children in the 2 cohorts in the attentional control subdomain. However, for the cognitive flexibility subdomain, scores on the working memory task (digit span backwards test) were significantly worse among those in the MLP group than the term cohort (P = 0.02). The composite score for goal setting was also significantly lower in the MLP cohort than in children born at term (P = 0.03). Based on the composite score for the 3 subdomains, there was no significant difference between groups for risk of impairment. There was a significantly increased risk for impairment in working memory for those in the MLP group (RR, 1.80; 95% confidence interval [CI], 1.05, 3.09), and, in the goal setting subdomain, for visual-spatial reasoning and planning tasks (block design test; RR, 1.69; 95% CI, 1.08, 2.65). There also was an increased risk in MLP children for impairment in EF behaviors as assessed with the GEC (RR, 1.86; 95% CI, 1.05, 3.27).The authors conclude that children with MLP birth had a pattern of EF difficulties when assessed at school.Dr Badawi has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.Previous researchers have indicated that MLP infants are at risk for delays as toddlers.1,2 Although significant cognitive differences are not seen at school age in this population, the results of the current study are a necessary next step in breaking down the more subtle neurodevelopmental differences noted in children born MLP.EF plays a role in multiple aspects of life, and certainly in academic and occupational success.3 As the current authors describe, EF is a complex composite of skills ranging from the ability to shift and maintain focus to identifying and carrying out the steps of a task, to problem solving when challenges arise. Twice as many MLP infants in this cohort had a diagnosis of ADHD, and 1.5 times as many had a diagnosis of autism. Both diagnoses are associated with EF deficits.Prior researchers have examined measures of EF at school age in this population and found that overall, the MLP population demonstrates lower performance.4,5 One common theme is the very large variation in individual performance. Microstructural white matter differences in MLP infants compared to babies at term age have been identified,6 which may be responsible for some of these more subtle cognitive challenges.Schools typically do not provide services for such subtle EF differences, but as pediatric providers this information allows us to counsel parents and have a low threshold for referring for neuropsychological testing. From a public health standpoint, this information is critical in making obstetric decisions about the risks and benefits of MLP delivery. Given the higher prevalence of ADHD and autism in this cohort, and the consistently wide variation in EF function, future researchers ought to separate out children with neurodevelopmental diagnoses and divide the MLP cohort by weeks of gestation to detect critical differences in outcome.MLP infants are at higher risk for EF deficits at school age, which can have a significant impact on long-term outcomes. (See related article on Page 29 of this issue.)The authors of this study chose not to adjust for multiple comparisons. If they had, it is likely that many of the identified differences would not have been statistically significant.