Association of Early Postnatal Transfer and Birth Outside a Tertiary Hospital With Mortality and Severe Brain Injury in Extremely Preterm Infants: Observational Cohort Study With Propensity Score Matching

Approximately 1 in 20 preterminfants in high-income countries are born at less than 28 weeks' gestation with increased risk of death and morbidity. Previous studies have shown improved outcomes when care is provided in tertiary hospitals as compared with nontertiary hospitals; this study aims to examine the rate of adverse outcomes for those preterm infants who underwent postnatal transfer to a tertiary facility in England. The hypothesis was that rates of mortality and severe brain injury in transferred infants would exceed those of nontransferred infants born in tertiary hospitals. The study performed was a retrospective cohort study of all infants born before 28weeks' gestation and admitted to neonatal units in England from 2008 to 2015, using data extracted from the UK National Neonatal Research Database (NNRD). Case record forms from a multicentered, randomized controlled trial allowed a formal comparison with NNRD data. It showed high data agreement and a high coverage of infants included in the NNRD compared with national statistics. The NNRD covers approximately 70% and 90% of infants born at 23 and 24 gestational weeks, respectively, as well as close to 100% of national live births. In English hospitals, neonatal units are classified as special care baby units, local neonatal units, and neonatal intensive care units (NICUs). In this study, NICUs are referred to as tertiary neonatal units. The intent of the framework is to encourage delivery of extremely preterm infants at hospitals with tertiary neonatal units, but since the introduction of a networked model of neonatal care, postnatal transfers in England have become more frequent. The study defined 4 groups of neonatal infants: upward transfer group (the upward comprised infants born in a hospital with a local neonatal unit and transferred to a tertiary hospital within 48 hours), the nontertiary care group (comprised of infants born in a hospital with a local neonatal unit and not transferred within 48 hours), the horizontal transfer group (comprised infants born in a tertiary hospital and transferred within 48 hours to a different tertiary hospital for nonclinical reasons such as insufficient capacity), and the control group (comprised infants born in a tertiary hospital and not transferred within 48 hours). For the primary analysis, matched groups of infants were identified from nontertiary care, upward transfer, and control. In a secondary analysis, matched groups of infants in horizontal transfer and control groups were identified to evaluate the association between early postnatal transfer and initial stabilization in a tertiary hospital. Strengths of the study included prespecified protocols and analysis plan, which allowed focus to be maintained on the objective and clinically important outcomes (death and severe brain injury). Individual data from a population-level data set of more than 17,000 extremely preterm infants allowed this to be one of the largest studies ever conducted. Formed groups were well balanced for distributions of covariates, and findings were confirmed via independently matched pairwise sensitivity analyses. The main weakness of the study was propensity score matching, which does not account for unmeasured confounders. However, the application of careful matching limited the potential for measured confounders to influence the result. The total retained population of the study was 17,577 infants. Within that population, 10,866 (61.8%) were in the control group, 2158 (12.3%) in the upward transfer group, 2668 (15.2%) in the nontertiary care group, and 306 (1.7%) in the horizontal transfer group. As the fourth group was significantly smaller than the other 3, it was not included in the 3-way matching. Compared with controls, the following results were ascertained: the upward transfer group had no significant difference in the odds of death before discharge (1.22; 95% confidence interval, 0.92-1.61) but significantly higher odds of severe brain injury (2.32, 1.78-3.06) and significantly lower odds of survival without severe brain injury (0.60, 0.47-0.76). Infants in the nontertiary care group had significantly higher odds of death before discharge (1.34, 1.02-1.77) but no significant difference in the odds of severe brain injury (0.95, 0.70-1.30) or survival without severe brain injury (0.82, 0.64-1.05). The multiple analyses demonstrated that extremely preterm infants born in a site without tertiary neonatal care had a higher risk of adverse outcomes, both for infants who underwent early postnatal transfer and infants who remained in a nontertiary neonatal hospital. This finding indicates a need to focus on development of care pathways that ensure extremely preterm infants are born in a setting with tertiary neonatal care whenever possible.