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Proinflammatory state and metabolic dysregulation linking delayed feeding progression to extrauterine restricted head

Chih-Chia Chen1,2, Yung-Chieh Lin2, Cheng-Yang Lee3

  • 1Graduate Institute of Clinical Medicine, College of Medicine, National Cheng-Kung University, Tainan, Taiwan.

BMC Medicine
|December 30, 2025
PubMed

Insights

Delayed feeding progression in extremely preterm infants is linked to restricted head growth and impaired neurodevelopment. This is associated with inflammation and metabolic issues, suggesting an immature gut-brain axis plays a role.

Area of Science:

  • Neonatalogy
  • Neurodevelopmental Pediatrics
  • Perinatal Medicine

Background:

  • Head circumference growth is crucial for neurodevelopmental outcomes in infants.
  • Extrauterine growth restriction (EUGR) of head circumference is associated with impaired neurodevelopment.
  • The relationship between delayed feeding and EUGR in extremely preterm infants, particularly concerning inflammation and metabolic dysregulation, requires further investigation.

Purpose of the Study:

  • To investigate the association between delayed feeding progression and extrauterine head growth restriction in extremely preterm infants.
  • To determine if a proinflammatory state and metabolic dysregulation characterize this association.

Main Methods:

  • A cohort study of infants born ≤28 weeks gestation (2019-2021).
  • Feeding progression trajectories were analyzed (improvement vs. delayed improvement).
  • Plasma metabolomics, head growth, and brain MRI were assessed at specific postmenstrual ages.

Main Results:

  • Infants with delayed feeding progression showed higher rates of gastrointestinal morbidities and increased risk of head circumference EUGR (47% vs. 23%).
  • Delayed feeding was significantly associated with head circumference delta z-scores below -1.5 (aOR: 5.26).
  • Smaller brain volumes and altered plasma metabolomics (elevated inflammatory markers, reduced amino acid/carnitine metabolites) were observed in the delayed feeding group.

Conclusions:

  • Early delayed feeding progression in extremely preterm infants is linked to impaired head growth.
  • A proinflammatory and metabolically dysregulated state is associated with this impaired growth.
  • The findings highlight the potential role of the immature gut-brain axis in preterm infants' neurodevelopment.
Abstract

Keywords:
Extrauterine growth restrictionFeeding progressionHead sizeMRIMetabolomicsPreterm infantsProinflammatory

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