Influence of Moderate Hyperbilirubinemia on Cardiorespiratory Control in Preterm Lambs

Hyperbilirubinemia (HB) is responsible for neonatal jaundice in 60% of term newborns and 90% of preterm infants. Neonatal HB can induce neurological damage (acute HB encephalopathy) and has been associated with persistent apneas. The objective of the present study was to investigate the immediate and delayed effects of moderate, clinically-relevant HB on cardiorespiratory control in preterm lambs. Two groups of five preterm lambs, namely control and HB, were studied. At day five of life, moderate HB (150-250 μmol/L) was induced and maintained during 17h in the HB group while control lambs received a placebo solution. Six hours after HB onset, seven-hour polysomnographic recordings with electrocardiogram (ECG) and respiratory (RESP) signals were performed to assess the immediate effects of HB on heart rate variability (HRV), respiratory rate variability (RRV) and cardiorespiratory interrelations. Identical recordings were repeated 72h after HB induction to examine the delayed effects of HB on HRV, RRV and cardiorespiratory interrelations. Our results demonstrate a higher HRV and vagal activity immediately after induction of moderate HB. Meanwhile, a decrease in respiratory rate with an increase in both long- and short-term RRV was also noted, as well as a higher amplitude of the respiratory sinus arrhythmia and cardiorespiratory coupling. Seventy-two hours later, the alterations in HRV, RRV and cardiorespiratory interrelations were attenuated, although a number of them were still present, suggesting a lasting influence of HB on the basal control of the cardiorespiratory system. Our results pave the way for studies in human preterms to assess the relevance of monitoring HRV, RRV and cardiorespiratory interrelations to detect the acute neurological effects of HB and consequently adapt the treatment of neonatal jaundice.