Intermittent hypoxia and caffeine in infants born preterm: the ICAF Randomized Clinical Trial

Authors

Eric Eichenwald, Pediatrics/Neonatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA eichenwald@email.chop.edu.
Michael Corwin, Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts, USA.
Betty McEntire, American SIDS Institute, Naples, Florida, USA.
Susan Knoblach, Department of Genetic Medicine, Research Institute of Children's National Hospital, Washington, District of Columbia, USA.
Catherine Limperopoulos, Fetal and Transitional Medicine, Children's National Medical Center, George Washington University School of Medicine and Health Sciences, Washington, District of Columbia, USA.
Kushal Kapse, Fetal and Transitional Medicine, Children's National Medical Center, George Washington University School of Medicine and Health Sciences, Washington, District of Columbia, USA.
Stephen Kerr, Boston University, Boston, Massachusetts, USA.
Timothy C. Heeren, Boston University, Boston, Massachusetts, USA.
Christine Ikponmwonba, American SIDS Institute, Naples, Florida, USA.
Carl E. Hunt, Pediatrics, Uniformed Services University, Bethesda, Maryland, USA.

Document Type

Journal Article

Publication Date

11-24-2025

Journal

Archives of disease in childhood. Fetal and neonatal edition

DOI

10.1136/archdischild-2025-329230

Keywords

Intensive Care Units, Neonatal; Neonatology; Respiratory Medicine

Abstract

OBJECTIVE: To determine whether extending caffeine therapy through 43 weeks' postmenstrual age (PMA) decreases intermittent hypoxia (IH) in convalescing preterm infants. Secondary objectives were to assess caffeine effects on changes in inflammation-related plasma biomarkers and brain MRI. DESIGN: Multicentre masked randomised trial. SETTING: 16 US hospitals. PATIENTS: Infants at <30 weeks + 6 days gestational age on caffeine between 32 weeks and 36+5 days PMA in room air with routine caffeine discontinuation prior to 36 weeks +6 days. INTERVENTION: Randomisation to caffeine or placebo and treated through 42 completed weeks. Pulse oximetry was recorded from enrolment through 1 week after stopping study drug. Blood for 12 inflammation-related biomarkers obtained at enrolment and 38 weeks' PMA and brain imaging after enrolment or <3 days of randomisation, and study end. MAIN OUTCOME MEASURE: Seconds/hour of oxygen saturation <90% from randomisation to study end. RESULTS: Randomised 160 subjects, 78 placebo, 82 caffeine. IH was less at every PMA with caffeine treatment from 34 (172.7 (123.4, 241.7); 84.7 (64.4, 111.4, p<0.01) through 41 weeks (73.0 (51.3, 103.7); 26.6 (18.5, 38.2, p<0.001). Adjusted TNF-α levels were 23% lower at follow-up in the caffeine group compared with placebo (p<0.02), without other biomarker differences. Paired brain imaging found no significant differences. CONCLUSIONS: Extended caffeine reduced the burden of IH in very preterm infants and may reduce inflammation. Further study is needed to determine if this effect of caffeine is associated with reduced risk of adverse outcomes. TRIAL REGISTRATION NUMBER: NCT03321734.

APA Citation

Eichenwald, Eric; Corwin, Michael; McEntire, Betty; Knoblach, Susan; Limperopoulos, Catherine; Kapse, Kushal; Kerr, Stephen; Heeren, Timothy C.; Ikponmwonba, Christine; and Hunt, Carl E., "Intermittent hypoxia and caffeine in infants born preterm: the ICAF Randomized Clinical Trial" (2025). GW Authored Works. Paper 8063.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/8063

Department

Pediatrics