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Updated: Nov 15, 2025

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Association Between Preterm-Birth Phenotypes and Differential Morbidity, Growth, and Neurodevelopment at Age 2 Years:

Jose Villar1,2, María C Restrepo-Méndez1,2, Rose McGready3,4

  • 1Nuffield Department of Women's & Reproductive Health, University of Oxford, Oxford, United Kingdom.

JAMA Pediatrics
|March 1, 2021
PubMed

Insights

Classifying preterm birth by phenotype, not just timing, improves understanding of causes and outcomes. This approach reveals distinct clinical, growth, and neurodevelopmental differences in newborns up to age 2 years.

Area of Science:

  • Neonatal research
  • Developmental pediatrics
  • Obstetrics

Background:

  • Preterm birth etiology is complex and poorly understood, hindering effective prevention and treatment strategies.
  • Current understanding often treats preterm birth as a singular event, overlooking diverse underlying causes and clinical trajectories.

Purpose of the Study:

  • To investigate the association between specific preterm birth phenotypes and clinical, growth, and neurodevelopmental outcomes in infants up to two years of age.
  • To compare these outcomes between preterm and term newborns.

Main Methods:

  • The INTERBIO-21st study enrolled preterm and term singletons globally, with ultrasonography dating pregnancies.
  • Infants were followed from birth to age two, with assessments including size, health, nutrition, motor development, and neurodevelopment using the INTERGROWTH-21st Neurodevelopment Assessment (INTER-NDA) tool.
  • Data from 6529 infants (1381 preterm) were analyzed between November 2019 and October 2020.

Main Results:

  • Eight preterm birth phenotypes were identified, with infections and preeclampsia being common. Previous preterm birth was a risk factor for recurrence.
  • Each phenotype showed distinct neonatal morbidity and infant outcomes; for example, 'no main condition' phenotypes had low initial morbidity but increased later hospitalization.
  • Newborns with the fetal distress phenotype exhibited the highest risk of impaired fine motor development compared to term infants.

Conclusions:

  • Phenotypic classification of preterm birth offers a more nuanced understanding of its etiologic factors and mechanisms than a time-based definition alone.
  • This approach can inform targeted interventions and improve developmental outcomes for diverse preterm infant populations.
Abstract

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