Abstract:

Objective: To compare the clinical efficacy and short-term safety of short- and long-course caffeine citrate therapy for apnea of prematurity. Methods: This single-center retrospective cohort included 90 preterm infants with apnea of prematurity born at 28⁺⁰ to 31⁺⁶ weeks of gestation and admitted to Sanming Second Hospital between January 2022 and December 2025. According to the caffeine discontinuation strategy documented in the medical records, 44 infants were assigned to the short-course group and 46 to the long-course group. Both groups received routine supportive care and caffeine citrate. In the short-course group, caffeine was discontinued after withdrawal of positive-pressure respiratory support and 5 consecutive days without clinically significant apnea; in the long-course group, maintenance treatment was continued until 34 weeks of postmenstrual age. Apnea episodes after treatment, recurrence within 7 days after discontinuation, duration of respiratory support and oxygen therapy, time to full enteral feeding, length of hospital stay, adverse reactions, and major in-hospital morbidities were compared. Results: The numbers of apnea episodes within 24 h, 24-72 h, and after 72 h following medication were (2.48±0.86) episodes/24 h vs. (2.41±0.82) episodes/24 h, (1.11±0.52) episodes/24 h vs. (1.05±0.49) episodes/24 h, and (0.30±0.16) episodes/24 h vs. (0.28±0.15) episodes/24 h in the short-course group and long-course group, respectively, with no statistically significant inter-group differences (t=0.395, P=0.694; t=0.563, P=0.575; t=0.611, P=0.543). The 7-day post-discontinuation recurrence rate was lower in the long-course group than in the short-course group (6.52% (3/46) vs. 22.73% (10/44), χ²=4.779, P=0.029). There were no statistically significant differences between the short-course group and long-course group regarding non-invasive respiratory support duration ((5.92±1.84) days vs. (5.47±1.76) days), oxygen therapy duration ((7.86±2.15) days vs. (7.31±2.04) days), time to achieve full enteral feeding ((15.64±2.37) days vs. (15.18±2.26) days), and length of hospital stay ((24.75±4.83) days vs. (24.09±4.57) days)(t=1.185, P=0.239; t=1.244, P=0.217; t=0.942, P=0.349; t=0.665, P=0.508). The overall incidence of adverse reactions was 15.91% (7/44) in the short-course group and 17.39% (8/46) in the long-course group, without a statistically significant difference (Fisher’s exact test, P=1.000). Conclusion: Long-course caffeine citrate reduced apnea recurrence within 7 days after discontinuation but did not improve respiratory-support, feeding, or hospitalization outcomes.

Key words: Caffeine citrate, Infant, premature, Apnea, Treatment outcome, Comparative study