ReviewPaediatric drugs2014
Use of methylxanthine therapies for the treatment and prevention of apnea of prematurity.
Review in Paediatric drugs, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 2 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
23 citing papers in PubMed, 2 syntheses or guidelines pooled it, 63 citations in OpenAlex.
- Methylxanthine for the prevention and treatment of apnea in preterm infants.The Cochrane database of systematic reviews · 2023Pooled it
- Pooled it
- [Clinical effect and safety of different maintenance doses of caffeine citrate in treatment of apnea in very low birth weight preterm infants: a prospective randomized controlled trial].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2019Trial
- Caffeine for the Treatment of Apnea in Bronchiolitis: A Randomized Trial.The Journal of pediatrics · 2016Trial
- Putative mechanisms of caffeine as a neuroprotectant in preterm infants.Pediatric research · 2026Review
- Methylxanthines: The Major Impact of Caffeine in Clinical Practice in Patients Diagnosed with Apnea of Prematurity.Journal of clinical medicine · 2025Review
- Early aminophylline is a potential therapy for preventing bronchopulmonary dysplasia in premature infants: a retrospective study.BMC pediatrics · 2025Article
- The Use of Caffeine Citrate in the Management of Neonatal Apnea in Low- and Middle-Income Countries: A Rapid Systematic Review.Health science reports · 2025Review
- Caffeine: how early is too early?Pediatric research · 2024Article
- Predictors for poor daily weight gain in preterm neonates exposed to different dose regimens of caffeine in ICU- a retrospective cohort study.BMC pediatrics · 2024Article
- Caffeine versus other methylxanthines for the prevention and treatment of apnea in preterm infants.The Cochrane database of systematic reviews · 2023Review
- Specific Premature Groups Have Better Benefits When Treating Apnea With Caffeine Than Aminophylline/Theophylline.Frontiers in pediatrics · 2022Article
- Caffeine versus aminophylline in combination with oxygen therapy for apnea of prematurity: A retrospective cohort study.Experimental and therapeutic medicine · 2020Article
- Diprophylline inhibits non-small cell lung cancer A549 cell proliferation and migration, and promotes apoptosis, by downregulating PI3K signaling pathway.Oncology letters · 2019Article
- Adenosine AMolecular medicine (Cambridge, Mass.) · 2018Article
- [Application of real world study in neonatal medicine].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2018Article
- Caffeine preferentially protects against oxygen-induced retinopathy.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2017Article
- [Current research status of drug therapy for apnea of prematurity].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2016Article
- Structure-Bioactivity Relationships of Methylxanthines: Trying to Make Sense of All the Promises and the Drawbacks.Molecules (Basel, Switzerland) · 2016Review
- Incorporating pharmacodynamic considerations into caffeine therapeutic drug monitoring in preterm neonates.BMC pharmacology & toxicology · 2016Observational
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 1 institution in 1 country.
Funding
Abstract
Apnea of prematurity (AOP) is a common complication of preterm birth, which affects more than 80 % of neonates with a birth weight less than 1,000 g. Methylxanthine therapies, including caffeine and theophylline, are a mainstay in the treatment and prevention of AOP. Despite their frequent use, little is known about the long-term safety and efficacy of these medications. In this review, we systematically evaluated the literature on neonatal methylxanthine therapies and found that caffeine is associated with fewer adverse effects and a wider therapeutic window when compared with theophylline. When used as a therapeutic agent, larger doses of caffeine citrate have been shown to improve acute neonatal outcomes when administered promptly, although further studies are needed to assess the long-term neurological consequences associated with the use of large loading doses. In a secondary analysis of data obtained from a randomized controlled trial, the prophylactic use of caffeine was associated with substantial cost savings and improved clinical outcomes. However, there remains a paucity of well-controlled, randomized clinical trials that have examined the use of caffeine as a prophylactic agent, and further prospective trials are needed to determine if caffeine is a safe and effective prophylactic agent. Additionally, measuring plasma concentrations longitudinally as a marker of therapeutic efficacy and/or toxicity has not been shown to be clinically useful in neonates who are responsive to treatment and exhibit no signs or symptoms of toxicity. However, in cases where toxicity is of concern or for neonates with congenital or pathophysiologic process that may alter the pharmacokinetics of these drugs, therapeutic drug monitoring may be warranted to monitor for methylxanthine toxicity.
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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.