Cerebral Oxygenation and Autoregulation in Very Preterm Infants Developing IVH During the Transitional Period: A Pilot Study

Abstract

Background: The transitional period, defined as the first 72 h after preterm birth, is often characterized by a significant hemodynamic instability, which represents an important risk factor for such neurological complications of prematurity as intraventricular hemorrhage (IVH). The impairment of cerebral autoregulation plays a key role in the pathogenesis of IVH, whose incidence is highest during the transitional period. This pilot study aimed to evaluate whether patterns of cerebral autoregulation and oxygenation differ in relation to IVH development in very preterm infants during the transitional period. Methods: Infants <32 weeks' gestation were enrolled within 12 h from birth. A simultaneous monitoring of cerebral oxygenation (CrSO₂) by near-infrared spectroscopy and of heart rate and peripheral oxygen saturation by pulse oximetry was performed over the first 72 h. Cerebral fractional oxygen extraction (cFTOE) and tissue oxygenation-heart rate reactivity index (TOHRx), which represents a marker of cerebrovascular reactivity, were calculated. Daily cranial and cardiac ultrasound scans were performed, in order to assess the hemodynamic status and to detect a possible IVH onset. CrSO₂ and cFTOE, clustered on 6-hour epochs, were compared between infants who developed IVH during the study period and those who did not. A between-group comparison of TOHRx before and after IVH detection was also performed. Results: Twenty preterm infants with a median gestational age of 27 weeks (interquartile range, IQR: 25-30 weeks) and median birth weight of 895 g (IQR: 822-1208 g) were enrolled. Of these, 8 developed IVH. The median age at IVH detection was 40 h (IQR: 30-48 h). Pre-IVH TOHRx was significantly higher compared to matched control periods (p <0.001). CrSO₂ was significantly lower from 12 to 30 h and from 42 h onwards in cases compared to controls; however, a temporary CrSO₂ rise preceded IVH detection. Similarly, cFTOE was significantly higher in IVH infants from 12 to 30 h and from 48 to 72 h, with a transient decrease between the two periods. Conclusions: In preterm infants during the transitional period, the development of IVH is preceded by transient changes in cerebral oxygenation and oxygen extraction which, in turn, may underlie an early impairment of cerebral autoregulation. Larger studies are needed to confirm these preliminary findings.

Keywords: IVH; NIRS; cerebral autoregulation; cerebral oxygenation; echocardiography; preterm infants; transitional period.

Figure 1

Example of the calculation of the moving correlation coefficient between heart rate (HR) and cerebral oxygenation (CrSO₂), defined as TOHRx, over a 6-h period using the ICM+ software.

Figure 2

Flow-chart of the study phases. GA, gestational age; BW, birth weight; NIRS, near-infrared spectroscopy; IVH, intraventricular hemorrhage.

Figure 3

Patterns of cerebral oxygenation (CrSO₂,) (A) and of cerebral fractional oxygen extraction (cFTOE) (B), evaluated at 6-hour intervals over the first 72 h of life in infants who developed GMH-IVH (in gray) and those who did not (in white). The arrow indicates the median age at GMH-IVH detection, whereas the gray shadow represents the related interquartile time range. Linear mixed-model regression significances for time*IVH interaction are provided (^◦p < 0.01; ^§p < 0.05).

Figure 4

Tissue oxygenation-heart rate reactivity index (TOHRx) before and after GMH-IVH detection in infants who developed GMH-IVH and during matched time periods in the control group. *p < 0.001.