Interdependence in the Cardiorespiratory Network of Preterm Infants with Pulmonary Hypertension Using Mutual Information Analysis

Pravitha Ramanand1, Premananda Indic1, Samuel Gentle2, Namasivayam Ambalavanan2
1The University of Texas at Tyler, 2Department of Pediatrics, The University of Alabama


Aim: Impaired cardiorespiratory function, resulting from immature development, predisposes preterm infants to morbidities such as bronchopulmonary dysplasia (BPD) and pulmonary hypertension (PH). This study investigated interdependence in the cardiorespiratory network of preterm infants and identified differences exhibited by infants with BPD alone and those with the added complication of PH. Methods: Vital signs of heart rate (HR), respiratory rate (RR) and oxygen saturation (SpO2) from 17 infants with BPD (NoPH group) and 21 infants with BPD and PH (PH group) were analyzed using mutual information function (MI), to quantify interdependence between these signals. MI over varying time delays between pairs of signals (HR-RR, HR-SpO2, RR-SpO2) were estimated for 5 minute segments and maximum interdependence, mxMI was derived. The three mxMI measures and the delays at which they occurred for each segment were compared between groups. Results: Two way ANOVA of mxMI estimates from 204 NoPH and 252 PH segments showed that interdependencies differed based on condition (PH vs. NoPH, p <0.001) and type of coupling (p<0.001), while interaction effect was non-significant. Within both groups, MI (HR-SpO2) was the strongest (p<0.001) while the weakest coupling existed between HR and RR. HR-SpO2 coupling in the PH group was higher than in the NoPH group (p<0.001). The delay times had no subject group effect, but differed between coupling types, with the shortest mean delay occurring in the HR-RR interaction (p<0.001) compared with other two interactions. Conclusion: Cardiorespiratory interaction strengths were observed to be altered in preterm infants with BPD when they had the additional complication of PH. HR- SpO2 interaction was found to be stronger in the PH group compared with NoPH infants. Hence information transfer between cardiorespiratory network components in preterm infants may provide insights to mechanisms of disease progression and development and needs to be explored further.