ArticleDevelopmental neuroscience2025
Protective Effects of Early Neonatal Methylxanthine Treatment on Cognitive and Language Outcomes in Premature Infants with and without High-Risk Perinatal Factors.
Article in Developmental neuroscience, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Putative mechanisms of caffeine as a neuroprotectant in preterm infants.Pediatric research · 2026Review
- Protective versus Risk Factors for 18-month Outcomes in a multi-decade sample of preterm infants age 23-30 weeks.Medical research archives · 2025Article
- The utility of caffeine citrate as a neuroprotectant in the early life of premature newborns: a literature review of the effects on neurodevelopmental outcomes.Frontiers in pediatrics · 2025Review
- Antenatal Magnesium Sulfate Benefits Female Preterm Infants but Results in Poor Male Outcomes.Pharmaceuticals (Basel, Switzerland) · 2024Article
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3 authors.
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Abstract
introductionCaffeine and theophylline are methylxanthines and nonselective adenosine antagonists commonly used to treat apnea of prematurity. Both human and animal data suggest that xanthines also have clinically important long-term neuroprotective effects in the presence of inflammation in the perinatal period as seen following hypoxic-ischemic brain insults. Moreover, these protective effects appear to be more robust when administered shortly (<48 h) after preterm birth.
methodTo evaluate the importance of the postdelivery therapeutic window, we collected and analyzed medical data from preterm infants meeting criteria (23-30 weeks' gestational age [GA]), born at the University of Connecticut Health Center (UCHC), and cared for at the UCHC/Connecticut Children's Medical Center (CCMC) NICU from 1991 to 2017 (n = 858). Eighteen-month follow-up data included cognitive and language scores from the Neonatal Neurodevelopmental Follow-Up Clinic records, with a retention of 81% of subjects (n = 696). Differences were analyzed via multivariate ANOVA and ANCOVA.
resultsAnalyses showed that infants who received xanthine treatment within the first 48 h after preterm birth showed significantly better 18-month behavioral outcomes than those treated later than 48 h, despite a lack of a priori differences in GA, birth, or length of stay. The positive effect of early xanthine therapy was particularly robust for infants exposed prenatally to the inflammatory conditions of chorioamnionitis and/or preeclampsia.
conclusionsCurrent findings are consistent with human and animal data, showing that caffeine exerts protective effects, at least in part via attenuation of inflammation. Results add to the evidence supporting routine immediate prophylactic neuroprotective xanthine therapy (i.e., caffeine) in preterm infants. Findings also add important new evidence of the augmented value of caffeine for infants with inflammatory exposure due to mothers with preeclampsia or chorioamnionitis.
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