Optimising neonatal services for very preterm births between 27+0 and 31+6 weeks gestation in England: the OPTI-PREM mixed-methods study.

AIM: To investigate, for preterm babies born between 27+0 and 31+6 weeks gestation in England, optimal place of birth and early care. DESIGN: Mixed methods. SETTING: National Health Service neonatal care, England. METHODS: To investigate whether birth and early care in neonatal intensive care units (tertiary units) compared to local neonatal units (non-tertiary units) influenced gestation-specific survival and other major outcomes, we analysed data from the National Neonatal Research Database, for 29,842 babies born between 27+0 and 31+6 weeks gestation and discharged from neonatal care between 1 January 2014 and 31 December 2018. We utilised an instrumental variable (maternal excess travel time between local neonatal units and neonatal intensive care units) to control for unmeasured differences. Sensitivity analyses excluded postnatal transfers within 72 hours of birth and multiple births. Outcome measures were death in neonatal care, infant mortality, necrotising enterocolitis, retinopathy of prematurity, severe brain injury, bronchopulmonary dysplasia, and receipt of breast milk at discharge. We also analysed outcomes by volume of neonatal intensive care activity. We undertook a health economic analysis using a cost-effectiveness evaluation from a National Health Service perspective and using additional lives saved as a measure of benefit, explored differences in quality of care in high compared with low-performing units and performed ethnographic qualitative research. RESULTS: The safe gestational age cut-off for babies to be born between 27+0 and 31+6 weeks and early care at either location was 28 weeks. We found no effect on mortality in neonatal care (mean difference -0.001; 99% confidence interval -0.011 to 0.010; p = 0.842) or in infancy (mean difference -0.002; 99% confidence interval -0.014 to 0.009; p = 0.579) (n = 18,847), including after sensitivity analyses. A significantly greater proportion of babies in local neonatal units had severe brain injury (mean difference -0.011; 99% confidence interval -0.022 to -0.001; p = 0.007) with the highest mean difference in babies born at 27 weeks (-0.040). Those transferred in the first 72 hours were more likely to have severe brain injury. For 27 weeks gestation, birth in centres with neonatal intensive care units reduced the risk of severe brain injury by 4.2% from 11.9% to 7.7%. The number needed to treat was 25 (99% confidence interval 10 to 59) indicating that 25 babies at 27 weeks would have to be delivered in a neonatal intensive care unit to prevent one severe brain injury. For babies born at 27 weeks gestation, birth in a high-volume unit (> 1600 intensive care days/year) reduced the risk of severe brain injury from 0.242 to 0.028 [99% confidence interval 0.035 to 0.542; p = 0.003; number needed to treat = 4 (99% confidence interval 2 to 29)]. Estimated annual total costs of neonatal care were £262 million. The mean (standard deviation) cost per baby varied from £75,594 (£34,874) at 27 weeks to £27,401 (£14,947) at 31 weeks. Costs were similar between neonatal intensive care units and local neonatal units for births at 27+0 to 29+6 weeks gestation, but higher for local neonatal units for those born at 30+0 to 31+6 weeks. No difference in additional lives saved were observed between the settings. These results suggested that neonatal intensive care units are likely to represent value for money for the National Health Service. However, careful interpretation of this results should be exercised due to the ethical and practical concerns around the reorganisation of neonatal care for very preterm babies from local neonatal units to neonatal intensive care units purely on the grounds of cost savings. We identified a mean reduction in length of stay (1 day; 95% confidence interval 1.029 to 1.081; p