Trial reportPediatric research2015
A pilot randomized trial of high-dose caffeine therapy in preterm infants.
Trial report in Pediatric research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 56 papers, 6 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Pharmacokinetics (PK) and Safety of Caffeine in Neonates With Hypoxic Ischemic Encephalopathy Receiving Therapeutic Hypothermia
The Effect of an Additional Pre-extubational Loading Dose of Caffeine-citrate
Who cites it
56 citing papers in PubMed, 6 syntheses or guidelines pooled it, 124 citations in OpenAlex.
- Methylxanthine for the prevention and treatment of apnea in preterm infants.The Cochrane database of systematic reviews · 2023Pooled it
- Interventions to Reduce Severe Brain Injury Risk in Preterm Neonates: A Systematic Review and Meta-analysis.JAMA network open · 2023Pooled it
- Eligibility Criteria and Representativeness of Randomized Clinical Trials That Include Infants Born Extremely Premature: A Systematic Review.The Journal of pediatrics · 2021Pooled it
- Confounding biases in studies on early- versus late-caffeine in preterm infants: a systematic review.Pediatric research · 2020Pooled it
- Cerebellar Hemorrhage in Preterm Infants: A Meta-Analysis on Risk Factors and Neurodevelopmental Outcome.Frontiers in physiology · 2019Pooled it
- Systematic review and meta-analysis of clinical outcomes of early caffeine therapy in preterm neonates.British journal of clinical pharmacology · 2017Pooled it
- High versus standard dose caffeine in prevention of apnea of prematurity: an assessor-blinded randomized controlled trial (HI-CAF trial).European journal of pediatrics · 2026Trial
- Predictors of Failure of Conventional Dose Caffeine Therapy in Neonates Below 32 Weeks' Gestation: An Ambispective Cohort Study.Indian journal of pediatrics · 2026Article
- Discharging Preterm Infants on Caffeine-Practise Variation Across Europe: Results of a Cross-Sectional Survey.Acta paediatrica (Oslo, Norway : 1992) · 2026Article
- Putative mechanisms of caffeine as a neuroprotectant in preterm infants.Pediatric research · 2026Review
- Caffeine citrate increases ciliary beat frequency in human respiratory epithelial cells.Molecular and cellular pediatrics · 2026Article
- Caffeine and preterm infants: multiorgan effects and therapeutic creep: scope to optimise dose and timing.Pediatric research · 2026Review
- Association Between Serum Caffeine Concentrations, Intermittent Hypoxia and Apnea in Preterm Infants: A Prospective Observational Study.Children (Basel, Switzerland) · 2026Article
- Caffeine as a Treatment for Perinatal Hypoxic-Ischemic Brain Injury: The Potential Risks and Benefits.Developmental neuroscience · 2026Review
- Clinical and biological impact of caffeine therapy in premature infants with apnea of prematurity: a prospective observational study.Frontiers in medicine · 2026Article
- Article
- The Neuroprotective Effects of Caffeine in a Neonatal Hypoxia-Ischemia Model are Regulated through the AMPK/mTOR Pathway.International journal of biological sciences · 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
- What is the Role of Caffeine in the Management of Preterm Infants?Current treatment options in pediatrics · 2025Review
- Caffeine use in preterm neonates: national insights into Turkish NICU practices.Frontiers in pediatrics · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundStandard-dose caffeine improves white matter microstructural development assessed by diffusion magnetic resonance imaging (MRI). We hypothesized that early high-dose caffeine would result in further improvement in white matter microstructural development.
methodsSeventy-four preterm infants (≤30 wk gestational age) were randomly assigned to either a high (80 mg/kg i.v.) or standard (20 mg/kg i.v.) loading dose of caffeine citrate in the first 24 h of life. MRI and neurobehavioral testing were undertaken at term equivalent age. Infants returned at 2 y of age for developmental testing.
resultsClinical characteristics were similar between groups, with the exception of higher maternal age in the high-dose caffeine group. There was an increased incidence of cerebellar hemorrhage in infants randomized to high-dose caffeine (36 vs. 10%, P = 0.03). Infants in the high-dose caffeine group also demonstrated more hypertonicity (P = 0.02) and more deviant neurologic signs (P = 0.04) at term equivalent age. Diffusion measures at term equivalent age and developmental outcomes at 2 y of age did not differ between groups.
conclusionPreterm infants randomized to early high-dose caffeine had a higher incidence of cerebellar injury with subsequent alterations in early motor performance. The results of this pilot trial discourage a larger randomized controlled trial.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.