Caffeine Does Not Reduce Hospital Stay for Preterm Infants

Source: Carlo WA, Eichenwald EC, Carper BA, et al. Extended caffeine for apnea in moderately preterm infants: the MoCHA randomized clinical trial. JAMA. 2025;333(24):2154-2163; doi: 10.1001/jama.2025.5791.Investigators from multiple institutions conducted a randomized controlled trial to assess the effectiveness of prolonged caffeine administration in reducing the duration of remaining hospitalization in moderately preterm infants. Study participants were infants born at 29 to <34 weeks’ gestation who were 33 to <36 weeks postmenstrual age (PMA) at the time of enrollment and being treated at 1 of 29 NICUs in the US. Eligibility criteria included receiving caffeine with plans to discontinue treatment as part of routine clinical care and receiving no respiratory support. Study infants were randomized 1:1 to the prolonged caffeine treatment or placebo group. Those randomized to the caffeine group received caffeine citrate (10/mg/kg/dose) throughout the remainder of their hospitalization and for 28 days after discharge. The primary study outcome was time from randomization until hospital discharge. Secondary outcomes included time until 'physiological maturity'—defined as being out of the incubator for >48 hours, receiving ≥140 mL/kg/day of feeds or gaining weight, and being apnea-free for 5 days—and rates of readmission and 'sick' outpatient visits in the 8 weeks after discharge. Regression analysis was used to compare outcomes among infants in the caffeine and placebo groups.There were 827 infants enrolled in the study, 416 randomized to caffeine and 411 to the placebo group. Median PMA among infants in the 2 treatment groups at randomization were 34.5 and 34.4 weeks, respectively. The median number of days from randomization to hospital discharge was 18.0 days for those in the caffeine group and 16.5 days for infants randomized to placebo (P >0.99). There also was no significant difference between groups in time to physiologic maturity (median, 14.0 days for caffeine group, 15.0 days for placebo group; adjusted difference, -1 day; 95% confidence interval [CI], -2.4, 0.4). The time to apnea or bradycardia free for 5 days was significantly shorter in those receiving caffeine than in those randomized to placebo (median, 6.0 and 10 days, respectively; adjusted difference, -2.7; 95% CI, -3.4, -2.0), but there were no differences between groups in time to exit from the incubator or time to full feeds (≥140 mL/kg/day) or gaining weight. Following hospitalization, there were no significant differences between groups in rates of readmission or 'sick' outpatient visits.The authors conclude that prolonged use of caffeine in moderately preterm infants was not effective in shortening hospitalization.Dr King has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.The care of preterm infants in the NICU is costly, primarily driven by length of stay (LOS), and moderately preterm infants account for close to 50% of the total hospitalization costs.1 Recent quality improvement efforts have focused on using NICU care wisely, including opportunities to optimize care for the 'low-acuity' infant.2 In a survey of providers, close to 50% felt LOS was 'too long.'2 The latter portion of the hospital stay for a preterm infant involves low-acuity care that focuses on developing key signs of physiological maturity required for discharge.3Continuing caffeine through discharge has been suggested as one tool to reduce LOS, and the current trial was designed to test this hypothesis.4 While patients that were continued on caffeine indeed had a shorter time to resolution of apnea/bradycardia, there were no significant differences in either LOS or reaching physiological maturity. The results highlight the multifactorial nature of discharge readiness and the lack of a 'one size fits all' tool to reduce LOS. Other opportunities to reduce LOS in this population may include nasogastric home feeding programs, home oxygen programs, and improvements to infant follow-up and family readiness for discharge. Regardless of what intervention is studied, optimizing discharge planning likely will require customizing the approach to each patient’s individual needs.While caffeine is primarily used for its efficacy at treating apnea of prematurity, it also has long term benefits related to reductions in chronic lung disease, and improvement in neurodevelopmental outcomes.5,6 While the current researchers did not report any differences in readmissions after discharge, they did not measure the burden of intermittent hypoxia with home oximetry; the trial was not designed to assess neurodevelopmental outcomes. Long-term follow-up will be helpful, though the moderately preterm population may not be those infants who stand to benefit most from prolonged caffeine therapy.7Extended caffeine treatment may effectively address persistent apnea of prematurity as a discharge barrier, but it does not shorten overall LOS due to the multifactorial nature of discharge readiness.While we support efforts to decrease preterm infant NICU LOS (eg, decreased opportunity for nosocomial infection as discussed on the next page of this issue8), we also underscore the importance of outpatient/community support (eg, respiratory, nutritional) for families with these infants.