Supplementary Material for: Association of heart rate variability with postnatal maturation in preterm infants

Introduction
We assessed whether longitudinal measurements of sample entropy (SampEn) of heart rate time series reflect postnatal maturation in preterm infants and evaluated its predictive value at 32 weeks postmenstrual age (PMA) for estimating discharge home. We further compared SampEn of preterm infants at discharge with that of term infants.
Methods
We conducted a prospective study at the University Children's Hospital Basel, Switzerland from 2018 to 2022. We included preterm infants born before 32 weeks of gestation and a control group of term infants. Heart rate was recorded using the clinical monitoring system. We assessed preterm infants at 32 and 36 weeks PMA, and at discharge; term infants were evaluated between 3 to 28 days of life. SampEn was calculated from 90-min recordings using custom analytical software.
Results
We obtained valid data from 183/183 preterm infants (mean (range) 28.4 (23.3-31.7) weeks gestation) and from 80/104 (76%) term infants. In preterm infants, SampEn increased from 32 to 36 weeks PMA (0.35 vs. 0.40; p<0.01) without further increase to discharge. SampEn was positively associated with maturation and growth, and negatively with complications of prematurity, particularly with bronchopulmonary dysplasia. SampEn at 32 weeks PMA did not improve clinical predictions of PMA at discharge. At discharge, SampEn did not differ significantly between preterm and term infants.
Conclusion
SampEn of heart rate time series increased with postnatal maturation in preterm infants, reaching values of term infants at discharge. It was negatively associated with complications of prematurity but its prognostic value for discharge timing is limited.

引言
本研究旨在评估心率时间序列的样本熵（sample entropy, SampEn）的纵向测量值是否可反映早产儿的出生后成熟进程，并评估其在校正胎龄（postmenstrual age, PMA）32周时对出院回家的预测价值。我们还对比了早产儿出院时与足月儿的样本熵值。

方法
本研究于2018至2022年在瑞士巴塞尔大学儿童医院开展前瞻性研究，纳入妊娠32周前出生的早产儿，并设置足月儿对照组。通过临床监护系统记录心率数据。我们分别在校正胎龄32周、36周以及出院时对早产儿进行评估；足月儿则于出生后3至28天内接受评估。采用定制分析软件对90分钟的记录数据计算样本熵。

结果
本研究从183名早产儿（妊娠均值[范围]：28.4[23.3~31.7]周）中获得全部有效数据，从104名足月儿中的80名（占比76%）获得有效数据。在早产儿中，样本熵值从校正胎龄32周至36周显著升高（0.35 vs. 0.40；p<0.01），至出院时未进一步升高。样本熵值与成熟度及生长情况呈正相关，与早产儿并发症（尤其是支气管肺发育不良（bronchopulmonary dysplasia））呈负相关。校正胎龄32周时的样本熵值并未提升出院时校正胎龄的临床预测效能。出院时，早产儿与足月儿的样本熵值无显著差异。

结论
心率时间序列的样本熵值随早产儿的出生后成熟进程升高，至出院时已达到足月儿的样本熵水平。该指标与早产儿并发症呈负相关，但其对出院时机的预后价值有限。