Neonatal autonomic regulation as a predictor of autism symptoms in very preterm infants.
Neonatal autonomic regulation as a predictor of autism symptoms in very preterm infants.
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新生儿自主调节作为极早产儿自闭症症状的预测因子。
DOI：
10.1038/s41372-024-01942-2
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发表时间：
2024
期刊：
影响因子：
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通讯作者：
Dail,RobinB
中科院分区：
文献类型：
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作者：
Bradshaw,Jessica;O'Reilly,Christian;Everhart,KaylaC;Dixon,Elizabeth;Vinyard,Amy;Tavakoli,Abbas;Dail,RobinB
方法从一项大型、多地点临床试验[3]中选取一组出生时就被纳入研究的VPT婴儿（N= 20）。鉴于先前的研究将ASD与异常HRCs联系起来，并提供ANS功能障碍的多模态测量，从出生到28天（>,40,000个样本/婴儿）收集每分钟的TGs（由中央和外周温度差异[3]定义）和每小时异常心率特征（HRCs）（使用HeRO评分[4]测量）的连续测量。HeRO评分由HeRO监测器（医疗预测科学公司）生成，根据专有算法计算，该算法考虑了三种hrc的异常：心跳间隔的标准偏差、心率偏度或不对称以及熵（见补充信息）。ANS功能障碍表现为HRCs异常（HeRO评分> 1）或TGs阴性升高（外周>中心体温[5]）。在新生儿重症监护室出院后，在6、9和12个月的矫正年龄收集认知、语言和运动技能的标准化测量（见补充信息）。在12个月时，进行社会沟通评估和直接观察早期ASD症状（系统性观察危险信号；SORF）[6,7,8]（见补充信息）。SORF已用于具有复杂发育和ASD特征的婴儿（9-24个月）。在任何研究程序之前，经医院和大学机构审查委员会批准，与母亲完成知情同意。采用单因素、多因素和稳健回归模型评估新生儿ASD预后的预测因素。所有测量的描述性统计数据见表1和补充图s1。收集了N= 20名出生时登记的婴儿的ANS功能的连续测量数据。在新生儿重症监护室出院后，n= 12例完成了1年的发育随访（10例男性），其中n= 1例因严重的医学发病率而无法进行有效的ASD评估而被排除在分析之外（见补充图s1）。在所有出生后28天的婴儿中，平均HeRO得分略高于1，婴儿在大约20%的时间（28天中的6天）出现异常阴性TGs。在发育轨迹方面，直到12个月后才出现明显的延迟，超过50%的样本表现出社交沟通延迟，超过了ASD风险的临床临界值（见补充表s1和补充图s2）。新生儿hrc异常与12个月时的ASD症状密切相关（r= 0.81, p< 0.01；图1），出生胎龄（GA）、出生体重（BW）和异常阴性tg也是如此。包括GA、BW和异常HRCs在内的回归模型显示异常HRCs对ASD结局的预测作用显著且独特（模型r= 0.86, p= 0.017; HRC r= 0.72, p= 0.029）。
MethodsA subset of VPT infants from a large, multisite clinical trial [3] were enrolled in this study at birth (N= 20). Given previous studies linking ASD to abnormal HRCs and to provide a multimodal measurement of ANS dysfunction, continuous measures of minute-by-minute TGs, defined by the difference between central and peripheral temperatures [3], and hour-by-hour abnormal heart rate characteristics (HRCs), measured using HeRO scores [4], were collected from birth-28 days (> 40,000 samples/infant). HeRO scores are generated by a HeRO monitor (Medical Predictive Science Corp), calculated from a proprietary algorithm that considers abnormality of three HRCs: standard deviation of inter-beat intervals, heart rate skewness or asymmetry, and entropy (see Supplementary Information). ANS dysfunction is indicated by abnormal HRCs (HeRO scores> 1) or elevated negative TGs (peripheral> central body temperature)[5]. Following NICU discharge, standardized measures of cognition, language, and motor skills were collected at corrected ages 6, 9, and 12 months (see Supplementary Information). At 12 months, assessments of social communication and direct observation of early ASD symptoms (Systematic Observation of Red Flags; SORF) were administered [6, 7, 8](see Supplementary Information). The SORF has been used with infants (9–24 months) with complex developmental and ASD profiles. Informed consent was completed with the mother prior to any study procedures, which were approved by hospital and university institutional review boards. Univariate, multivariate, and robust regression models were used to evaluate neonatal predictors of ASD outcomes.ResultsDescriptive statistics for all measures are presented in Table 1 and Supplementary Fig. S 1. Continuous measures of ANS function were collected for N= 20 infants enrolled at birth. Following NICU discharge, n= 12 completed 1-year developmental follow-up (10 males) and n= 1 was excluded from analyses due to significant medical morbidities that precluded a valid ASD assessment (see Supplementary Fig. S 1). Across all infants in the first 28 days of life, the average HeRO score was just above 1 and infants experienced abnormal negative TGs for about 20% of the time (6 of 28 days). In terms of developmental trajectories, significant delays did not emerge until 12 months when over 50% of the sample exhibited social-communication delays and exceeded the clinical cutoff for ASD risk (see Supplementary Table S 1 and Supplementary Fig S 2). Neonatal abnormal HRCs were strongly associated with ASD symptoms at 12 months (r= 0.81, p< 0.01; Fig. 1), as was birth gestational age (GA), birth weight (BW), and abnormal negative TGs. A regression model including GA, BW, and abnormal HRCs revealed a significant, unique predictive effect of abnormal HRCs on ASD outcomes (model r= 0.86, p= 0.017; HRC r= 0.72, p= 0.029).