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DOI: 10.1055/a-1926-0335
Autonomic Nervous System in Preterm Very Low Birth Weight Neonates with Intraventricular Hemorrhage
Funding This study was supported by Grants-in-Aid for Scientific Research (MEXT KAKENHI no.: 21243039) from the Ministry of Education, Culture, Sports, Science and Technology, Japan.

Abstract
Objective Heart rate variability (HRV) indicates cardiac autonomic nerve activity and is influenced by brain damage during the neonatal period. We aimed to determine whether a correlation exists between the HRV of extremely preterm neonates and neurodevelopmental test scores.
Study Design Electrocardiogram data of neonates were assessed and HRV patterns in extremely preterm neonates with severe intraventricular hemorrhage (IVH; n = 6) and those with no/mild IVH (n = 28) were compared. We analyzed the relationship between HRV and neurodevelopmental outcomes at 18 months (n = 21) and 3 years (n = 23) in extremely preterm neonates.
Results HRV was significantly associated with IVH severity in extremely preterm neonates (p < 0.05). Neonates with severe IVH exhibited increased HR and decreased mean R-to-R interval (NN) compared with neonates with no/mild IVH. HRV parameters significantly decreased in the severe IVH group, but not in the no/mild IVH group, suggesting that both sympathetic and parasympathetic activities decreased in neonates with severe IVH. Additionally, decreased HR and increased NN were significantly related to impaired neurodevelopmental outcomes in the no/mild IVH group at corrected ages of 18 months and 3 years, respectively (all p < 0.05).
Conclusion HRV was significantly associated with IVH severity and neurodevelopmental outcome in extremely preterm neonates. HRV can distinguish extremely preterm neonates who subsequently had severe IVH from those who had no/low-grade IVH. HRV may identify extremely preterm neonates needing adjuvant neuroprotective interventions. These findings warrant further investigation in a larger population of extremely preterm neonates.
Key Points
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HRV was associated with IVH severity.
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HRV can predict subsequent severe IVH in extremely preterm neonates.
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HRV are predictive of neurodevelopmental outcomes in extremely premature neonates with low-grade IVH.
Keywords
extremely preterm neonates - heart rate variability - intraventricular hemorrhage - neurodevelopmental impairmentEthics Approval
This was a prospective monocentric observational study performed in the NICU of the National Hospital Organization Mie-Chuo Medical Center, Mie, Japan, between January 2014 and April 2016. This study was approved by the local ethics committee (identifier: 2020–07). Written informed consent was obtained from the parents at the time of admission of the neonates. The study was performed in accordance with the Declaration of Helsinki.
Authors' Contributions
A.S. conceptualized and designed the study, participated in data acquisition, and analyzed and interpreted the data. M.B. conceptualized the study, supervised data collection, and reviewed the manuscript. H.T. conceptualized the study, analyzed and interpreted the data, and wrote the manuscript. M.O. participated in acquisition of data and revised the article critically for content. S.T. and M.H. conceptualized the study, supervised data collection, and reviewed the manuscript. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.
Consent for Publication
Written informed consent was obtained from the parents of the neonates.
Availability of Data and Materials
Correspondence and requests for materials should be addressed to Hidemi Toyoda.
Publication History
Received: 07 February 2022
Accepted: 02 August 2022
Accepted Manuscript online:
17 August 2022
Article published online:
23 September 2022
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