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Cumulative caffeine exposure predicts neurodevelopmental outcomes in premature infants

Bridget E L Ostrem1, Elizabeth Odell2, Kimberly N Grelli3

  • 1Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA, USA. bridget.ostrem@ucsf.edu.

Pediatric Research
|September 20, 2025
PubMed

Insights

Higher caffeine exposure in preterm infants is linked to better neurodevelopmental outcomes. This suggests optimal dosing strategies may improve long-term cognitive, motor, and language development in premature infants.

Area of Science:

  • Neonatal Medicine
  • Developmental Pediatrics
  • Pharmacology

Background:

  • Caffeine administration in preterm infants with apnea of prematurity is associated with improved neurodevelopmental outcomes.
  • The optimal caffeine dosage for neuroprotection remains undetermined.
  • Higher caffeine exposure is hypothesized to correlate with enhanced neurodevelopmental performance.

Purpose of the Study:

  • To investigate the association between caffeine exposure levels and neurodevelopmental outcomes in preterm infants.
  • To determine if higher caffeine exposure correlates with reduced neurodevelopmental impairment (NDI).

Main Methods:

  • A cohort of 106 preterm infants (≤32 weeks gestational age) with neonatal brain MRIs was analyzed.
  • Infants were categorized into tertiles based on average daily caffeine exposure (ADCE).
  • Neurodevelopmental assessments (Bayley-III) were conducted at 30 months corrected age on 69 participants.

Main Results:

  • Higher ADCE was associated with decreased odds of NDI (OR 0.69).
  • No significant association was found between caffeine exposure and MRI abnormalities.
  • High-dose caffeine correlated with improved motor, language, and cognitive scores compared to low-dose caffeine.

Conclusions:

  • Sustained higher caffeine exposure during neonatal hospitalization is linked to improved neurodevelopmental outcomes in preterm infants.
  • Higher maintenance doses of caffeine may benefit preterm infants' long-term development.
  • Caffeine therapy may be beneficial beyond the period of respiratory support.
Abstract

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