Respiratory stabilization before umbilical cord clamping in preterm neonates: a systematic review and network meta-analysis

Aim: To evaluate the comparative effectiveness of deferred cord clamping (DCC), umbilical cord milking (UCM); time-based cord clamping with respiratory support prior to umbilical cord clamping (TBCC) and physiological-based cord clamping (PBCC) in preterm neonates. Methods: Medline, Embase and CENTRAL were searched until April 2025. Bayesian random effects network meta-analysis (NMA) was utilized. DCC for 30–60 s (DCC_60), TBCC with respiratory support for at least 60 s (DCC_ICR_60) or more (DCC_ICR_more_60), PBCC, UCM and immediate cord clamping (ICC) were evaluated. Results: 11 RCTs and 8 non-RCTs were included. Clinical benefit or harm could not be ruled out for mortality, severe IVH and MBI. DCC_60 possibly decreased the risk of periventricular leukomalacia (PVL) and necrotising enterocolitis (NEC) ≥ stage 2 compared to DCC_ICR_60 (very low-certainty). PBCC possibly decreased the risk of delivery room adrenaline compared to DCC_ICR_60 and DCC_60 (very low-certainty). DCC_ICR_more_60 and UCM were probably similar in efficacy with respect to mean admission temperature (moderate-certainty). DCC_60, most TBCC interventions and PBCC probably had similar effect on patent ductus arteriosus requiring intervention, blood transfusion requirement and bronchopulmonary dysplasia (moderate-certainty). DCC_ICR_more_60 compared to ICC possibly decreased the risk of mortality or neurodevelopmental impairment at 2 years’ corrected age (low-certainty). Conclusions: This NMA indicates that DCC, TBCC and PBCC probably have comparable effects on the important clinical outcomes in preterm neonates. Since the evidence certainty was very low for the critical outcomes, adequately powered multi-centric RCTs are warranted.