Evidence map›Paper›PMID 40975732›Full record

ArticlePediatric research2026

Cumulative caffeine exposure predicts neurodevelopmental outcomes in premature infants.

Bridget E L Ostrem, Elizabeth Odell, Kimberly N Grelli, Katelin Kramer, Natalie Chan, Fei Jiang, Duan Xu, A James Barkovich, Matthew J Barkovich, Donna M Ferriero and 1 more

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In one paragraph

Article in Pediatric research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from 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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Developmental age and clinical illness driveFrontiers in pharmacology · 2026
    Article
  5. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Bridget E L OstremWeill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA, USA. bridget.ostrem@ucsf.edu.
Elizabeth OdellWeill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA, USA.
Kimberly N GrelliDivison of Neonatology, UCSF Benioff Children's Hospital Oakland, Oakland, CA, USA.
Katelin KramerDepartment of Pediatrics, University of California, San Francisco, San Francisco, CA, USA.
Natalie ChanDepartment of Pediatrics, University of California, San Francisco, San Francisco, CA, USA.
Fei JiangDepartment of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, USA.
Duan XuDepartment of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA, USA.
A James BarkovichDepartment of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA, USA.
Matthew J BarkovichDepartment of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA, USA.
Donna M FerrieroWeill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA, USA.
Dawn GanoWeill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA, USA. dawn.gano@ubc.ca.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundPreterm infants who receive caffeine for apnea of prematurity have improved neurodevelopmental outcomes compared to untreated infants. The optimal dosing regimen for neuroprotection is unknown. We hypothesized that higher caffeine exposure is associated with improved neurodevelopmental performance.

methodsWe quantified caffeine exposure in a previously reported cohort of 106 infants born at ≤32 gestational weeks who received brain MRIs during the neonatal hospitalization. Infants were subdivided into tertiles based on average daily caffeine exposure (ADCE). Bayley-III examinations were performed on 69 participants at 30 months corrected age. Neurodevelopmental impairment (NDI) was defined as a score of ≤85 on the Bayley-III motor, language, and/or cognitive subscales. We evaluated the relationship between caffeine exposure, neuroimaging abnormalities, and neurodevelopmental performance.

resultsHigher ADCE was associated with decreased odds of NDI (OR 0.69, 95% C.I. 0.50-0.95) but not with MRI abnormalities. High dose caffeine was associated with improved motor (mean difference 10.9, 95% C.I. 0.7-21.0), language (mean difference 15.2, 95% C.I. 3.4-27.0), and cognitive (mean difference 13.0, 95% C.I. 0.6-25.4) performance compared to low dose in multivariable analyses adjusted for gestational age and respiratory disease.

conclusionHigher sustained caffeine exposure during the neonatal hospitalization is associated with improved neurodevelopmental outcomes in preterm infants. IMPACT: Premature infants who receive caffeine for apnea of prematurity have improved neurodevelopmental outcomes compared to untreated infants. The optimal dosing strategy for neuroprotection is unknown. We found that higher average daily exposure during the neonatal hospitalization was associated with reduced neurodevelopmental impairment at 30 months corrected age. High dose caffeine was associated with improved motor, language, and cognitive performance on the Bayley-III compared to low dose caffeine in multivariable analyses adjusted for gestational age and respiratory disease. Preterm infants may benefit from higher maintenance doses and/or from continuing caffeine beyond the period of respiratory need.

Indexed as

ApneaCaffeineInfant, PrematureNeurodevelopmental DisordersBrainChild DevelopmentChild, PreschoolCognitionDose-Response Relationship, DrugFemaleGestational AgeHumansInfantInfant, NewbornMagnetic Resonance ImagingMaleCaffeine

Identifiers

PMID40975732
PMCPMC13485691

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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.