近日，美国阿拉巴马大学伯明翰分校Waldemar A. Carlo团队研究了延长咖啡因摄入治疗中度早产儿呼吸暂停的疗效。2025年4月28日，《美国医学会杂志》发表了这一成果。

中度早产儿的住院时间可能会延长，同时等待停止摄入咖啡因后早产儿呼吸暂停问题得到解决。

为了探讨延长咖啡因治疗是否能缩短住院时间，从2019年2月到2022年12月，研究组在29家美国医院进行了一项随机临床试验，招募妊娠29至33周出生的婴儿，这些婴儿在校正胎龄33至35周接受咖啡因治疗，并计划停止咖啡因治疗，同时接受全量喂养（≥120 mL/kg/d）。随访于2023年3月20日完成。

婴儿被随机分配到口服柠檬酸咖啡因（10mg/kg/d）或安慰剂组，直到出院后28天。主要结局是随机分组后出院天数。次要结局包括生理成熟的天数（连续5天无呼吸暂停，接受全口喂养，并在保温箱外至少48小时）、出院时的月经后年龄、全因再入院、全因生病和急诊就诊、安全结局和死亡。

在达到预设的徒劳阈值之前，共有827名婴儿（中位胎龄，31周；414名女性[51%]）随机分配（416名咖啡因；411名安慰剂）。随机分组后的住院天数在两组之间没有差异（咖啡因组为18.0天[IQR，10至30天]，安慰剂组为16.5天[IQR，10至27天]；调整后的中位数差异为0天[95%CI，-1.7至1.7天]），生理成熟的天数也没有差异（14.0天vs 15.0天，调整后的中值差异为-1天[95%置信区间，-2.4至0.4天]）。 

接受咖啡因治疗的婴儿更快地无呼吸暂停（6.0比10.0天；调整后的中位数差异为-2.7天[95%CI，-3.4至-2.0天]），但与完全口服喂养的天数相似（7.5比6.0天，调整后的中值差异为0天[95%CI,-0.1至0.1]）。两组之间的再入院率和病假率没有差异。两组之间的不良事件没有统计学上的显著差异。

研究结果表明，在中度早产儿中，与安慰剂相比，继续咖啡因治疗并没有缩短住院时间。

附：英文原文

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

Author: Waldemar A. Carlo, Eric C. Eichenwald, Benjamin A. Carper, Edward F. Bell, Martin Keszler, Ravi M. Patel, Pablo J. Sánchez, Ronald N. Goldberg, Carl T. D’Angio, Krisa P. Van Meurs, Anna Maria Hibbs, Namasivayam Ambalavanan, Shirley S. Cosby, Nancy S. Newman, Betty R. Vohr, Michele C. Walsh, Abhik Das, Robin K. Ohls, Janell Fuller, Matthew A. Rysavy, Sarvin Ghavam, Luc P. Brion, Karen M. Puopolo, Ryan Moore, Michelle L. Baack, Tarah T. Colaizy, Mariana Baserga, Ahmed F. Osman, Stephanie L. Merhar, Brenda B. Poindexter, Sara B. DeMauro, Vasanth Kumar, C. Michael Cotten, Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network, Rachel L. Benz, Cindie L. Buie, Katie M. Foshee, Samuel J. Gentle, Tara E. McNair, Lee A. Merin, Sharon E. Owen, Ariel A. Salas, Vivek S. Shukla, Colm P. Travers, Sandra M. Turner, Pren Fort, Angelita M. Hensman, Abbot R. Laptook, Kim Porras, Lucille St. Pierre, Elisa Vieira, Satyan Lakshminrusimha, Emily Li, Anne Marie Reynolds, Kelsey Voelker, Deanne E. Wilson-Costello, Arlene Zadell, Juanita Dudley, Amy Graber-Pels, Cathy Grisby, Jae Kim, Kristin Kirker, Greg Muthig, Lisa Radcliff, Cynthia Reid, David Russell, Kurt Schibler, Julia Thompson, Sandra Wuertz, Richard A. Polin, Natalie Dellavalle, Joanne Duran, Frances Eubanks, Sonia Gonzales, Michelle Harrod

Issue&Volume: 2025-04-28

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.

DOI: 10.1001/jama.2025.5791

Source: https://jamanetwork.com/journals/jama/fullarticle/2833418