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Clinical Trial
. 2025 Jun 24;333(24):2154-2163.
doi: 10.1001/jama.2025.5791.

Extended Caffeine for Apnea in Moderately Preterm Infants: The MoCHA Randomized Clinical Trial

Waldemar A Carlo  1 , Eric C Eichenwald  2 , Benjamin A Carper  3 , Edward F Bell  4 , Martin Keszler  5 , Ravi M Patel  6 , Pablo J Sánchez  7 , Ronald N Goldberg  8 , Carl T D'Angio  9 , Krisa P Van Meurs  10 , Anna Maria Hibbs  11 , Namasivayam Ambalavanan  1 , Shirley S Cosby  1 , Nancy S Newman  11 , Betty R Vohr  5 , Michele C Walsh  12 , Abhik Das  13 , Robin K Ohls  14 , Janell Fuller  15 , Matthew A Rysavy  16 , Sarvin Ghavam  17 , Luc P Brion  18 , Karen M Puopolo  19 , Ryan Moore  20 , Michelle L Baack  21 , Tarah T Colaizy  4 , Mariana Baserga  22 , Ahmed F Osman  7 , Stephanie L Merhar  22   23 , Brenda B Poindexter  24 , Sara B DeMauro  2 , Vasanth Kumar  25 , C Michael Cotten  8 ; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network
Collaborators, Affiliations
Clinical Trial

Extended Caffeine for Apnea in Moderately Preterm Infants: The MoCHA Randomized Clinical Trial

Waldemar A Carlo et al. JAMA. .

Abstract

Importance: Hospitalization of moderately preterm infants may be prolonged while waiting for apnea of prematurity to resolve after discontinuing caffeine.

Objective: To evaluate whether extending caffeine treatment reduces the duration of hospitalization.

Design, setting, and participants: From February 2019 to December 2022, this randomized clinical trial in 29 US hospitals enrolled infants born at 29 to 33 weeks' gestation who at 33 to 35 weeks' postmenstrual age were receiving caffeine treatment with plans to discontinue it plus receiving full feeds (≥120 mL/kg/d). Follow-up was completed on March 20, 2023.

Interventions: Infants were randomized to oral caffeine citrate (10 mg/kg/d) or placebo until 28 days after discharge.

Main outcomes and measures: The primary outcome was days to discharge after randomization. Secondary outcomes included days to physiological maturity (apnea free for 5 consecutive days, receiving full oral feeds, and out of the incubator for at least 48 hours), postmenstrual age at discharge, all-cause hospital readmissions, all-cause sick and emergency department visits, safety outcomes, and death.

Results: A total of 827 infants (median gestational age, 31 weeks; 414 female [51%]) were randomized (416, caffeine; 411, placebo) out of the 878 planned before reaching the prespecified futility threshold. Days of hospitalization after randomization did not differ between groups (18.0 days [IQR, 10 to 30 days] for caffeine vs 16.5 [IQR, 10 to 27 days] for placebo; adjusted median difference, 0 days [95% CI, -1.7 to 1.7 days]), nor did days to physiological maturity differ (14.0 vs 15.0 days, adjusted median difference, -1 day [95% CI, -2.4 to 0.4 days]). Infants receiving caffeine were apnea free sooner (6.0 vs 10.0 days; adjusted median difference, -2.7 days [95% CI, -3.4 to -2.0 days ]) but had similar days to full oral feeding (7.5 vs 6.0 days, adjusted median difference, 0 days [95% CI, -0.1 to 0.1]). Rates of readmissions and sick visits did not differ between groups. There was no statistically significant difference in adverse events between the 2 groups.

Conclusions and relevance: In moderately preterm infants, continuation of caffeine treatment compared with placebo did not shorten hospitalization.

Trial registration: ClinicalTrials.gov Identifier: NCT03340727.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Das reported receiving grants from NICHD and National Institutes of Health (NIH) during the conduct of the study. Dr Ohls reported receiving grants from NIH during the conduct of the study. Dr DeMauro reported receiving grants from NIH during the conduct of the study. Dr Hibbs reported receiving grants from NIH during the conduct of the study. No other conflicts were disclosed.

References

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    1. Eichenwald EC, Blackwell M, Lloyd JS, Tran T, Wilker RE, Richardson DK. Inter-neonatal intensive care unit variation in discharge timing: influence of apnea and feeding management. Pediatrics. 2001;108(4):928-933. doi: 10.1542/peds.108.4.928 - DOI - PubMed
    1. Walsh MC, Bell EF, Kandefer S, et al. Neonatal outcomes of moderately preterm infants compared to extremely preterm infants. Pediatr Res. 2017;82(2):297-304. doi: 10.1038/pr.2017.46 - DOI - PMC - PubMed
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    1. Davis PG. When to start and stop caffeine and why respiratory status matters. Semin Fetal Neonatal Med. 2020;25(6):101175. doi: 10.1016/j.siny.2020.101175 - DOI - PubMed

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