Hyperbilirubinemia Influences Sleep-Wake Cycles of Term Newborns in a Non-Linear Manner

<div><p>Hyperbilirubinemia is a common cause for irreversible neuronal influence in the brain of term newborns, while the feature of neurological symptoms associated with hyperbilirubinemia has not been well characterized yet. In the present study, we examined a total of 203 neonates suffering from hyperbilirubinemia with a bedside amplitude-integrated Electroencephalography (aEEG) device, in order to determine whether there is any special change in sleep-wake cycles (SWCs). Among these patients, 14 cases showed no recognizable SWCs with the total serum bilirubin (TSB) level at 483.9–996.2 μmol/L; 75 cases exhibited reduced SWCs with the TSB level at 311.2–688.5 μmol/L; and the rest cases had the normal SWCs. The number of the normal SWCs occurrence had a significant negative correlation with the increased TSB level in a non-linear manner (<i>r = -0</i>.<i>689</i>, <i>p <0</i>.<i>001</i>). In addition, the increased TSB reshaped the structure of SWC by narrowing down the broadband and broadening the narrowband. Spearman’s correlation analysis indicated a significant negative correlation between the TSB level and the ratio of broadband (<i>r = -0</i>.<i>618</i>, <i>p < 0</i>.<i>001</i>), a significant positive correlation between the TSB level and the narrowband ratio (<i>r = 0</i>.<i>618</i>, <i>p < 0</i>.<i>001</i>), respectively. Furthermore, the change of SWC seemed like a continuous phenomenon, and the hyperbilirubinemia caused SWC changes was fit into a loess model in this paper. In summary, the hyperbilirubinemia influenced SWC of term newborns significantly at a non-linear manner, and these results revealed the feature of the neurological sequela that is associated with TSB.</p></div

Negative correlation between TSB level and SWC occurrence numbers within 12 hours.

<p>The color shade of the scatterplot represented different levels of EEG abnormality grades from normal, mild abnormal, moderate abnormal to severe respectively.</p

Basic clinical characteristics.

<p>Basic clinical characteristics.</p

Loess model indicates the impact of TSB on SWC occurrence and Broadband ratio.

<p>The relationship of TSB with SWC occurrence and Broadband ratio were summarized in one picture. The two nonparametric regression curves with confidence belt indicated the predicted value of SWC occurrence and Broadband ratio respectively.</p

Clinical Profiles of 14 Patients without SWC.

<p>Clinical Profiles of 14 Patients without SWC.</p

SWC on aEEG was recognized as periodic changes in bandwidth of the aEEG tracing.

<p>A: Normal SWC, more than ten consecutive changes in bandwidth are presented during a 12-hour aEEG tracing. B: Reduced SWC, four consecutive cycles. C: No SWC, no sinusoidal variations on aEEG background.</p

Scatterplot of increased TSB level with increased Narrowband ratio (A) and decreased Broadband ratio (B).

<p>Fitted and smoothed by LOWESS, span = 0.5, the different diameter of the scatterplots represented the grades of EEG abnormality.</p