Effect of the timing of caffeine citrate discontinuation on the recurrence of apnea in very low birth weight infants

Background Apnea and intermittent hypoxemia (IH) are common developmental morbidities in infants born before 37 weeks of gestation. Caffeine citrate (CC) effectively reduces their incidence in preterm infants, but no unified consensus exists on the optimal discontinuation timing. This study aimed to provide clinical evidence by comparing the incidence of recurrent apnea of prematurity (RAP) and IH after CC discontinuation between very low birth weight infants (VLBWIs) with postmenstrual ages (PAMs) < 34 weeks and ≥ 34 weeks. Methods This retrospective study included 175 VLBWIs who received caffeine citrate treatment in the Neonatology Department of Women's Hospital, Zhejiang University School of Medicine, from November 2020 to October 2021. According to the PMA at the time caffeine was discontinued, the infants were divided into the early discontinuation group (CC was discontinued when apnea-free for 5–7 consecutive days and the PMA was < 34 weeks) and the late discontinuation group (CC was discontinued when apnea was not present for 5‒7 consecutive days and the PMA was ≥ 34 weeks). Baseline characteristics, the number of RAP and IH episodes at 1 week (0–7 days) and at 1–2 weeks (8–14 days) after CC discontinuation, the use of caffeine, bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP) requiring laser, and adverse reactions of CC were compared between the two groups. Results The early and late groups included 109 and 66 infants, respectively. No significant differences were found in RAP (29.4% vs 36.4%, p  > 0.05) or IH (41.3% vs 45.5%, p  > 0.05) within 1 week after CC was discontinued. Two weeks after discontinuation of CC, 103 and 62 neonates in the early and late discontinuation groups, respectively, remained in the hospital, and there were also no statistically significant differences in RAP (29.1% vs 33.9%, p  > 0.05) and IH (38.8% vs 43.5%, p  > 0.05) during 1–2 weeks after discontinuation of CC. Conclusion For VLBWIs, discontinuing CC treatment when there is apnea-free for 5–7 consecutive days is a feasible approach, and extending the treatment course to PMA beyond 34 weeks may be unnecessary.