Department of Neural and Behavioral Sciences (Drs Meister, Browning, Travagli, and Doheny), and Division of Neonatal-Perinatal Medicine, Department of Pediatrics (Drs Gardner, Palmer and Doheny), College of Medicine, The Pennsylvania State University, Hershey.
Adv Neonatal Care. 2021 Dec 1;21(6):452-461. doi: 10.1097/ANC.0000000000000959.
Necrotizing enterocolitis (NEC) is the leading cause of death due to gastrointestinal disease in preterm neonates; yet, clinicians lack reliable and noninvasive predictive tools.
We aimed to test that diminished high-frequency heart rate variability (HF-HRV) and elevated levels of proinflammatory cytokines would have utility in NEC prediction.
In this multisite prospective study, we enrolled 250 preterm (26-34 weeks' postmenstrual age [PMA]) neonates with physiological stability at 72 hours of life. HRV was measured noninvasively using electrocardiograhic data from standardized cardiorespiratory monitors at postnatal week 1 of life and weekly thereafter until 35 weeks' PMA or discharge; blood was collected for cytokines at postnatal weeks 1 and 3. NEC was diagnosed via Modified Bell's Staging Criteria.
HF-HRV was decreased at weeks 1 and 2 in neonates (47% females) who developed feeding intolerance or stage 2+ NEC. In addition, these neonates displayed elevated levels of IL-8 at week 1 and increased levels of IL-1β, IL-6, TNF-α, and IL-8 at week 3 of life. Low HF-HRV was associated with elevated IL-6 or IL-8 levels at weeks 1 and 3 of life. Logistic regression indicated that only HF-HRV was a significant predictor of feeding intolerance or NEC development.
HRV is a promising noninvasive modality for NEC risk detection. The association of low HF-HRV with elevated proinflammatory cytokines provides evidence for a putative role of the vagal cholinergic pathway in NEC pathogenesis. Future studies should focus on application of these techniques to test clinical therapeutics.Video Abstract available at https://journals.lww.com/advancesinneonatalcare/Pages/videogallery.aspx?autoPlay=false&videoId=54.
坏死性小肠结肠炎（NEC）是导致早产儿胃肠道疾病死亡的主要原因；然而，临床医生缺乏可靠和非侵入性的预测工具。
我们旨在测试低频心率变异性（HF-HRV）降低和促炎细胞因子水平升高是否对 NEC 预测具有作用。
在这项多中心前瞻性研究中，我们纳入了 250 名胎龄为 26-34 周（校正后胎龄[PMA]）、生后 72 小时生命体征稳定的早产儿。使用标准心肺监测仪的心电数据在生后第 1 周和此后每周进行非侵入性 HRV 测量，直至校正后胎龄 35 周或出院；在生后第 1 周和第 3 周采集血液以检测细胞因子。通过改良的 Bell 分期标准诊断 NEC。
在出现喂养不耐受或 2 期及以上 NEC 的新生儿（47%为女性）中，HF-HRV 在第 1 周和第 2 周降低。此外，这些新生儿在第 1 周时白细胞介素 8（IL-8）水平升高，在第 3 周时白细胞介素 1β（IL-1β）、白细胞介素 6（IL-6）、肿瘤坏死因子-α（TNF-α）和 IL-8 水平升高。第 1 周和第 3 周时，HF-HRV 降低与 IL-6 或 IL-8 水平升高相关。Logistic 回归表明，只有 HF-HRV 是喂养不耐受或 NEC 发生的显著预测因子。
HRV 是一种很有前途的非侵入性 NEC 风险检测方法。HF-HRV 降低与促炎细胞因子升高相关，为迷走神经胆碱能通路在 NEC 发病机制中的作用提供了证据。未来的研究应集中于应用这些技术来检验临床治疗方法。
