Supplementary Material for: Effects of Moderate Hyperbilirubinemia on Nutritive Swallowing and Swallowing-Breathing Coordination in Preterm Lambs

Background: Hyperbilirubinemia (HB) occurs in 90% of preterm newborns. HB induces acute neurological disorders (somnolence, abnormal tone, feeding difficulties, auditory dysfunction) and alterations in respiratory control. These findings suggest brainstem neurotoxicity that could also affect swallowing centers. Objective: To test the hypothesis that HB impairs nutritive swallowing (NS) and swallowing-breathing coordination. Methods: Two groups of preterm lambs (born 14 days prior to term), namely control (n = 6) and HB (n = 5), were studied. On day 5 of life (D0), moderate HB (150-250 µmol/l) was induced during 17 h in the HB group. Swallowing was assessed via recording of pharyngeal pressure and respiration by respiratory inductance plethysmography and pulse oximetry. The effect of HB on NS was assessed during standardized bottle-feeding. A second recording was performed 48 h after recovery from HB (D3). Results: Swallows were less frequent (p = 0.003) and of smaller volume (p = 0.01) in HB lambs while swallowing frequency was decreased (p = 0.004). These differences disappeared after HB normalization. Swallowing-breathing coordination was impaired in HB lambs, with a decrease in percent time with NS burst-related apneas/hypopneas at D0 and D3. Simultaneously, HB lambs tended to experience more severe desaturations (Conclusions: Swallowing and swallowing-breathing coordination are altered by acute moderate HB in preterm lambs. Decreased efficiency at bottle-feeding is accompanied by continuation of breathing during swallow bursts, which may promote lung aspiration.背景：高胆红素血症（Hyperbilirubinemia, HB）在90%的早产新生儿中发生。HB可引发急性神经系统疾病（嗜睡、肌张力异常、喂养困难、听觉功能障碍）以及呼吸调控异常。上述表现提示存在脑干神经毒性，该毒性亦可累及吞咽中枢。 研究目的：验证HB可损害营养性吞咽（Nutritive Swallowing, NS）以及吞咽-呼吸协调功能这一假说。 研究方法：本研究纳入两组早产羔羊（分娩时间较足月提前14天），即对照组（n=6）与HB组（n=5）。在出生后第5天（记为D0），HB组羔羊接受时长17小时的中度HB造模，血清胆红素水平维持于150~250 µmol/l。通过咽部压力记录、呼吸感应体积描记法与脉搏血氧饱和度测定法评估吞咽功能，并在标准化奶瓶喂养过程中评估HB对营养性吞咽的影响。在高胆红素血症缓解48小时后（记为D3），完成第二次数据记录。 研究结果：HB组羔羊的吞咽频次更低（p=0.003）、吞咽体积更小（p=0.01），且吞咽频率下降（p=0.004）。上述差异在HB指标恢复正常后消失。HB组羔羊的吞咽-呼吸协调功能受损，在D0与D3时间点，与营养性吞咽爆发相关的呼吸暂停/低通气时长占比均降低。同时，HB组羔羊更易出现严重的血氧饱和度降低事件。 研究结论：急性中度HB可改变早产羔羊的吞咽功能与吞咽-呼吸协调能力。奶瓶喂养效率下降的同时，吞咽爆发过程中呼吸持续存在，这一现象可能增加肺误吸风险。