Prophylactic Caffeine Reduced BPD or Death Composite in Very Preterm Infants

Prophylactic caffeine started within 24 hours after birth reduced the composite outcome of bronchopulmonary dysplasia (BPD) or death compared with caffeine initiated for diagnosed apnea in very preterm infants, according to a randomized trial reported in BMC Pediatrics.

The single-center trial enrolled 372 infants born before 32 weeks’ gestation at Shanghai First Maternity and Infant Hospital in China, with 186 assigned to each group. Prophylaxis used caffeine citrate at an intravenous loading dose of 20mg/kg, followed by 10mg/kg daily intravenously or enterally. The comparison group received the same caffeine regimen after apnea was diagnosed. Median caffeine initiation was 1 hour versus 72 hours after birth.

The primary outcome combined BPD at 36 weeks’ postmenstrual age with death before discharge. It occurred in 69 of 186 infants (37.1%) receiving prophylaxis and 88 of 186 (47.3%) receiving therapeutic caffeine (reported risk ratio, 0.77; P=.013). The primary analysis accounted for clustering among twins.

Death before discharge occurred in 15 of 185 infants (8.1%) versus 12 of 185 (6.5%), respectively, without a statistically significant difference (risk ratio, 1.26; P=.54). Adverse events, such as increased urine output and poor weight gain, gastroesophageal reflux, and tachycardia,were reported in three infants during treatment receiving caffeine prophylaxis and none in the comparison group. Symptoms resolved after caffeine was stopped; the investigators reported no severe caffeine-associated adverse events.

Blinding ended after the first 24 hours. The authors identified potential bias from subsequent unblinding, limited generalizability from the single-center population, and possible selection bias from missed enrollment windows. Long-term outcomes were not assessed.

Source: Tao F, Zhou M, Fu Y, et al. Prophylactic administration of caffeine reduces bronchopulmonary dysplasia in very preterm infants: a single center, randomized controlled trial. BMC Pediatr. 2026. Article in press. doi:10.1186/s12887-026-07625-5