Association of early probiotic exposure with age at NEC onset in preterm Infants: A retrospective multicenter study

The use of probiotics for preventing necrotizing enterocolitis (NEC) in preterm infants remains controversial. Specifically, whether the outcomes of infants with NEC are associated with prior probiotic administration remains unknown. This study aimed to examine the association between early supplementation with mixed-species probiotics and the timing of NEC onset as well as clinical outcomes in preterm infants who subsequently developed NEC. This retrospective study enrolled 216 preterm infants (gestational age < 35 weeks) diagnosed with stage II/III NEC from two hospitals in China. The patients were divided into a probiotics group and a nonprobiotics group. The timing of NEC onset, disease characteristics (intestinal perforation, surgery, mortality), and the occurrence of other preterm comorbidities were compared between the two groups. Among the infants who developed NEC, the median age at onset was observed to be later in the probiotic-exposed group compared with the unexposed group (22.5 days vs. 12 days). The probiotics group had a shorter duration of fasting after NEC onset (p < 0.05). However, no statistically significant differences were observed between the groups in terms of rates of surgery, intestinal perforation, mortality, shock, bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), or extrauterine growth restriction (EUGR). Among infants who developed NEC, early mixed-species probiotic exposure was associated with later NEC onset. This association should be interpreted cautiously because probiotic exposure was non-protocolized and time-dependent. No clear evidence was observed for an association with reduced disease severity or lower rates of major complications, including surgery, bowel perforation, or mortality. These associational findings are exploratory and require further investigation.