Preterm birth associated with long-term cognitive issues in children | Image Credit: © Rattanachat - © Rattanachat - stock.adobe.com.

In a cross-sectional study, published on April 14, 2025 in JAMA Network Open, among children aged 9 to 10 years, long-term cognitive problems were associated with moderately preterm birth, independent of socioeconomic status (SES), genetics and other risk factors.¹

Importance of gestational age and cognitive development

According to the study authors, Samson Nivins, PhD, Nelly Padilla, PhD, Hedvig Kvanta, PhD, and Ulrika Ådén, PhD, preterm birth (<37 weeks' gestational age) is a leading cause of child morbidity and mortality, globally affecting 13 million births every year.^2,3 Infants born prematurely face higher risk for neurodevelopmental problems, with an emphasis on cognitive deficits.¹

"Between 24 and 40 weeks of gestation, multiple critical brain developmental processes take place," stated Nivins and authors. "Premature birth disrupts these processes, leading to dysmaturational events in gray and white matter structures, which have been strongly associated with cognitive deficits. Previous studies have found impaired cognitive functions in preterm children, but most studies have focused on extremely preterm (<28 weeks’ gestational age) or very preterm (<32 weeks’ gestational age) births, overlooking moderate to late-preterm (32-36 weeks’ gestational age) births, which make up a substantial portion of preterm births," added the authors.¹

With this group in mind, the investigative team sought to investigate long-term cognitive outcomes for those born at various gestational ages, including very preterm (28-31 weeks), moderately preterm (32-33 weeks), late preterm (34-36 weeks), and early term (37-38 weeks). Outcomes among these populations were compared to full-term (39 weeks), accounting for genetics and other risk factors.

Methods to determine cognitive performance

In a prospective, multicenter, longitudinal, and cross-section design, the investigators studied children aged 9 to 10 years, recruited from the Adolescent Brain and Cognitive Development Study between January 1, 2016, and December 31, 2018. Cognitive assessments used were the National Institutes of Health Toolbox, Little Man Task, and Rey Auditory Verbal Learning Test. Using the results of a genome-wide association study, polygenic scores for cognitive performance (cogPGS) were generated from the genetic variants related to cognitive performance, educational attainment, and mathematical ability.

Results: Gestational age and cognitive development

In all, there were 5946 children in the study with a mean age of 9.9 years, of which 51.8% were male. Fifty-five were born very preterm, 110 moderately preterm, 454 late preterm, 261 early term, and 5066 were born full term. CogPGS was positively associated with the composite cognitive score in the overall cohort (β = 0.14; 95% CI, 0.12-0.17; P < .001).

Composite cognitive score was the primary outcome of the study, with secondary outcomes of individual cognitive domain scores. Associations between gestational age and cognitive outcomes were determined by hierarchial regression models that adjusted for SES, cogPGS, prenatal risks, and child-specific factors.

Compared to full-term children, those born moderately preterm had lower:

• Composite cognitive scores (β = −0.39; 95% CI, −0.55 to −0.22; P < .001)
• Scores in vocabulary (β = −0.36; 95% CI, −0.53 to −0.19; P < .001)
• Working memory (β = −0.27; 95% CI, −0.45 to −0.09; P = .003)
• Episodic memory (β = −0.32; 95% CI, −0.50 to −0.14; P < .001)
• Both both short-delay recall (β = −0.36; 95% CI, −0.54 to −0.18; P < .001) and long-delay recall (β = −0.29; 95% CI, −0.48 to −0.11; P = .002)

According to the study, each association was independent of SES, cogPGS, and other risk factors. Of note, the lowest cognitive scores appeared in children born at 32 weeks or less, while late-preterm and early-term children performed similarly to full-term infants.

Conclusion

"These findings underscore the need for continued follow-up of all preterm children, with particular focus on those born before 34 weeks’ gestational age, because they may face greater developmental challenges over time," concluded the study investigators.

References:

1. Nivins S, Padilla N, Kvanta H, Ådén U. Gestational Age and Cognitive Development in Childhood. JAMA Netw Open. 2025;8(4):e254580. doi:10.1001/jamanetworkopen.2025.4580

2. World Health Organization. Preterm birth. May 10, 2023. Accessed June 16, 2024. https://www.who.int/news-room/fact-sheets/detail/preterm-birth

3. Ohuma EO, Moller AB, Bradley E, et al. National, regional, and global estimates of preterm birth in 2020, with trends from 2010: a systematic analysis. Lancet. 2023;402(10409):1261-1271. doi:10.1016/S0140-6736(23)00878-4