Transitional Cerebrovascular Reactivity in Very Preterm Infants

Cerebral Autoregulation, Premature Infant Disease, Preterm Birth

cerebral autoregulation, cerebrovascular reactivity, preterm infants, transitional period

The transitional period, defined as the first 72 hours after preterm birth, is often characterized by a significant hemodynamic instability and may also be associated with an impairment of cerebral autoregulation, with relevant clinical implications. The moving correlation coefficient between cerebral oxygenation and heart rate, also defined as TOHRx, has been previously proposed as a marker of cerebrovascular reactivity and provides an indirect estimation of cerebral autoregulation in preterm infants. This study aims to evaluate whether different antenatal, perinatal and postnatal factors may influence cerebrovascular reactivity in very preterm infants during the transitional period.

The transitional period, defined as the first 72 hours after preterm birth, is often characterized by a significant hemodynamic instability and may also be associated with an impairment of cerebral autoregulation, with relevant clinical implications. The moving correlation coefficient between cerebral oxygenation and heart rate, also defined as TOHRx, has been previously proposed as a marker of cerebrovascular reactivity and provides an indirect estimation of cerebral autoregulation in preterm infants. This prospective observational study aims to evaluate whether different antenatal, perinatal, and postnatal factors may influence cerebrovascular reactivity in very preterm infants during the transitional period. Infants \<32 weeks' gestation are enrolled within 12h from birth. A simultaneous monitoring of cerebral oxygenation (CrSO2) by near-infrared spectroscopy and of heart rate (HR) by pulse oximetry and electrical velocimetry is performed continuously over the first 72h. The moving correlation coefficient between CrSO2 and HR is calculated using the ICM+ software (Cambridge Enterprise Ltd) using 5-min, 30-point epochs. Time periods with evidence of major artefacts, or with a missing data proportion \>50% are excluded from this calculation. Positive TOHRx values will be interpreted as markers of impaired autoregulation. A screening echocardiogram is routinely performed at the time of enrollment and repeated 6-12 hourly in the presence of a patent ductus arteriosus (PDA) or 12-24 hourly if there is no evidence of PDA. Based on echocardiographic features, the ductal status is classified as follows: no evidence of PDA, restrictive PDA (restrictive shunt pattern and left atrium to aortic root ratio \[LA:Ao\] ratio \<1.5), hemodynamically significant PDA (pulsatile shunt pattern, LA:Ao ratio ≥1.5 or presence of reversed end-diastolic flow either in the descending aorta or in the anterior cerebral artery). A concomitant cerebral ultrasound scan, aimed at evaluating brain parenchyma and the occurrence of prematurity-related complications, such as intraventricular hemorrhage, is also performed. During the study period, the following antenatal and neonatal data are tracked down on a specific case report form: gestational age (GA); birth weight (BW); non-invasive blood pressure; antenatal steroids (complete course vs. incomplete course or not given); evidence of reversed end-diastolic flow at antenatal umbilical Doppler (uREDF) (present vs. absent); ventilatory status over the first 72 hours of life (mechanical ventilation, continuous positive airway pressure \[CPAP\], nasal cannulas or self-ventilating in air \[SVIA\]); surfactant administration; development of IVH over the first 72 hours of life; ongoing inotropes (dopamine, dobutamine or both). The correlation between antenatal, perinatal, and postnatal clinical variables and TOHRx is going to be evaluated using generalized linear mixed models or generalized estimating equations.

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