Factors Associated with Severe Neurological Injury in Extremely Preterm Outborn Neonates

Introduction: Severe neurological injury (SNI), defined as neuroimaging-detected haemorrhage, ischemia, infarction, or cerebral ventricular enlargement, is common in extremely low gestational age neonates (ELGANs), and greatly increases the risk of adverse long-term neurodevelopmental outcomes. Being born outside a level III perinatal centre and then transferred to one (i.e., being “outborn”) is associated with increased likelihood of SNI. We aim to describe the incidence and types of SNIs in outborn ELGANs. Methods: We conducted a retrospective cohort study of 168 ELGANs born at <29 weeks GA, admitted to the Royal Alexandra Hospital Neonatal Intensive Care Unit (NICU) between 2010 and 2020, excluding neonates with congenital anomalies or unavailable neuroimaging. Patients were divided into 2 groups, with or without SNI. We collected infant demographics, ante-, intra-, and post-partum infant factors, and geographical measures. SNI included ventriculomegaly in the 1st week after birth with or without post-hemorrhagic hydrocephalus (PHHC), periventricular hemorrhagic ischemia or infarction (PVHI), cerebellar haemorrhage, or periventricular leukomalacia (PVL). Results: Of 168 ELGANs, 38 (23%) had SNI: 23 out of 38 (61%) were <26w GA vs 15 out of 38 (39%) were 26-28w GA (p= 0.0023). The mean distance travelled during transport to level 3 NICU was not significantly associated with SNI. Male ELGANs had significantly higher rates of both PHHC and PVHI (p<0.05). ELGANs with SNI had significantly lower BW and Apgar scores, and were significantly more likely to have early cord clamping, >2 intubation attempts prior to level 3 admission, fluid boluses, and inotropic support in the first 72 hours. There was no significant difference in antenatal steroid use. We observed the following incidences of SNI: 50% (19/38) PVHI and PHHC together; 32% (12/38) PVHI alone; 13% PHHC alone (5/38); 5.3% (2/38) with PVL; and 5.3% (2/38) cerebellar haemorrhages. Delayed cord clamping for at least one minute was associated with lower rates of PHHC (OR= 2.25) but it was not associated with decrease in PVHI (OR= 0.32). Administration of fluid bolus and inotropes within the first 72 hours were associated with PHHC and PVHI, respectively (OR= 4.17 and 10.9). pCO2 levels outside 35-65 mmHg range in the 1st 72 hours after birth was significantly associated with SNI (p=0.0023). pCO2 levels outside the range of 35-65 mmHg in the 1st 72 hours of life was significantly associated with SNI (p=0.0023). Use of a Mean airway pressure (MAP) above 18mmHg was noticed more frequently among neonates with SNI but it was not statistically significant (p=0.08). Conclusions: SNI, most commonly PVHI, is more frequent in more preterm and male outborn ELGANs and is unrelated to the distance transported or antenatal steroid use. SNI is associated with early cord clamping, multiple intubation attempts, fluid boluses, and inotrope use. Increasing early maternal transfers and implementation of a pre-transport bundle addressing peripartum interventions would be important quality improvement goals.