Objective To evaluate incidence of minimally invasive surfactant therapy (MIST) failure, identify risk factors and assess the impact of MIST failure on neonatal outcome.

Design Retrospective cohort study. MIST failure was defined as need for early mechanical ventilation (<72 hours of life). Multivariate logistic regression analysis was performed to identify risk factors for MIST failure and compare outcomes between groups.

Setting Two tertiary neonatal intensive care centres in the Netherlands.

Patients Infants born between 24 weeks’ and 31 weeks’ gestational age (GA) (n=185) with MIST for respiratory distress syndrome.

Interventions MIST procedure with poractant alfa (100–200 mg/kg).

Main outcome measures Continuous positive airway pressure (CPAP) failure after MIST in the first 72 hours of life.

Results 30% of the infants failed CPAP after MIST. In a multivariate logistic regression analysis, four risk factors were independently associated with failure: GA <28 weeks, C reactive protein ≥10 mg/L, absence of antenatal corticosteroids and lower surfactant dose. Infants receiving 200 mg/kg surfactant had a failure rate of 14% versus 35% with surfactant dose <200 mg/kg. Mean body temperature was 0.4°C lower at neonatal intensive care unit admission and before the procedure in infants with MIST failure.

Furthermore, MIST failure was independently associated with an increased risk of severe intraventricular haemorrhage.

Conclusion We observed moderate MIST failure rates in concordance with the results of earlier studies. Absence of corticosteroids and lower surfactant dose are risk factors for MIST failure that may be modifiable in order to improve MIST success and patient outcome.