Neurodevelopmental outcomes of preterm infants after randomisation to initial resuscitation with lower (FiO 0.3) or higher (FiO 0.6) initial oxygen levels. An individual patient meta-analysis.

Objective: To determine the effects of lower (≤0.3) versus higher (≥0.6) initial fractional inspired oxygen (FiO) for resuscitation on death and/or neurodevelopmental impairment (NDI) in infants <32 weeks' gestation.

Design: Meta-analysis of individual patient data from three randomised controlled trials.

Setting: Neonatal intensive care units.

Patients: 543 children <32 weeks' gestation.

Intervention: Randomisation at birth to resuscitation with lower (≤0.3) or higher (≥0.6) initial FiO.

Outcome Measures: Primary: death and/or NDI at 2 years of age.Secondary: post-hoc non-randomised observational analysis of death/NDI according to 5-minute oxygen saturation (SpO) below or at/above 80%.

Results: By 2 years of age, 46 of 543 (10%) children had died. Of the 497 survivors, 84 (17%) were lost to follow-up. Bayley Scale of Infant Development (third edition) assessments were conducted on 377 children. Initial FiO was not associated with difference in death and/or disability (difference (95% CI) -0.2%, -7% to 7%, p=0.96) or with cognitive scores <85 (2%, -5% to 9%, p=0.5). Five-minute SpO >80% was associated with decreased disability/death (14%, 7% to 21%) and cognitive scores >85 (10%, 3% to 18%, p=0.01). Multinomial regression analysis noted decreased death with 5-minute SpO ≥80% (odds (95% CI) 09.62, 0.98 to 0.96) and gestation (0.52, 0.41 to 0.65), relative to children without death or NDI.

Conclusion: Initial FiO was not associated with difference in risk of disability/death at 2 years in infants <32 weeks' gestation but CIs were wide. Substantial benefit or harm cannot be excluded. Larger randomised studies accounting for patient differences, for example, gestation and gender are urgently needed.