Evidence map›Paper›PMID 41886974›Full record

ArticleEarly human development2026

Quantitative measures of autonomic cardiorespiratory maturation in preterm infants are associated with brain volumes at term age.

Julius Ngwa, Nickie N Andescavage, Sudeepta Basu, Katherine Ottolini, Kushal Kapse, Jonathan Murnick, Catherine Limperopoulos, Adre du Plessis, R B Govindan

Abstract read
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In one paragraph

Article in Early human development, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

9 authors.

Julius NgwaThe Developing Brain Institute, Children's National Hospital, Washington, DC, USA; Department of Pediatrics, The George Washington University School of Medicine, Washington, DC, USA.
Nickie N AndescavageThe Developing Brain Institute, Children's National Hospital, Washington, DC, USA; Department of Pediatrics, The George Washington University School of Medicine, Washington, DC, USA; Division of Neonatology, Children's National Hospital, Washington, DC, USA.
Sudeepta BasuThe Developing Brain Institute, Children's National Hospital, Washington, DC, USA; Department of Pediatrics, The George Washington University School of Medicine, Washington, DC, USA; Division of Neonatology, Children's National Hospital, Washington, DC, USA.
Katherine OttoliniThe Developing Brain Institute, Children's National Hospital, Washington, DC, USA; Department of Pediatrics, The George Washington University School of Medicine, Washington, DC, USA; Division of Neonatology, Children's National Hospital, Washington, DC, USA.
Kushal KapseThe Developing Brain Institute, Children's National Hospital, Washington, DC, USA.
Jonathan MurnickDivision of Diagnostic Imaging and Radiology, Children's National Hospital, Washington, DC, USA.
Catherine LimperopoulosThe Developing Brain Institute, Children's National Hospital, Washington, DC, USA; Department of Pediatrics, The George Washington University School of Medicine, Washington, DC, USA; Division of Diagnostic Imaging and Radiology, Children's National Hospital, Washington, DC, USA; Neurology School of Medicine and Health Sciences, The George Washington University, Washington, DC, USA; The Zickler Family Prenatal Pediatrics Institute, Children's National Hospital, Washington, DC, USA.
Adre du PlessisThe Developing Brain Institute, Children's National Hospital, Washington, DC, USA; Department of Pediatrics, The George Washington University School of Medicine, Washington, DC, USA; Neurology School of Medicine and Health Sciences, The George Washington University, Washington, DC, USA; The Zickler Family Prenatal Pediatrics Institute, Children's National Hospital, Washington, DC, USA.
R B GovindanThe Developing Brain Institute, Children's National Hospital, Washington, DC, USA; Department of Pediatrics, The George Washington University School of Medicine, Washington, DC, USA; The Zickler Family Prenatal Pediatrics Institute, Children's National Hospital, Washington, DC, USA. Electronic address: rgovinda@childrensnational.org.

Funding

Impaired Brain Development in a Premature Ex-utero EnvironmentR01HD099393 · NICHD · CHILDREN'S RESEARCH INSTITUTE · PI DU PLESSIS, ADRE JACQUES, LIMPEROPOULOS, CATHERINE · 2020 to 2024
$3.4M
NICHD NIH HHS R01 HD099393
6 · The paper itself

Abstract

backgroundIn preterm infants, the development of autonomic function and brain maturation has typically been studied separately. However, the relationship between the two remains poorly understood. This study investigated the association between autonomic maturation and brain volumetric growth in preterm infants. MATERIALS AND

methodsWe applied a longitudinal trajectory clustering approach to weekly averages of several daily autonomic metrics: heart rate (HR, beats per minute), standard deviation of HR, asymmetry index (ASI), percentage of HR <80 bpm, and percentage of SpO₂ <88%. Two distinct clusters were identified. Associations between cluster membership and sequential brain volumes (total, regional, and tissue-specific), measured via magnetic resonance imaging (MRI), were assessed using a linear mixed-effects model across the gestational period. At term, a multivariate linear regression model was used, adjusting for relevant clinical variables.

resultsThis prospective study enrolled 78 preterm infants (45% female), with a mean (± SD) gestational age at birth of 29.85 ± 3.52 weeks. At term, infants in the higher ASI cluster had significantly greater total and regional brain volumes (P < 0.001) compared to those in the lower ASI cluster. These associations remained significant in the longitudinal analysis.

conclusionsWe found that markers of autonomic immaturity in preterm infants were significantly associated with reduced brain volume growth. These associations emerged shortly after birth and persisted through the extrauterine third trimester. Our findings suggest that autonomic maturation metrics could help identify infants at higher risk for suboptimal brain development. STATEMENT OF SIGNIFICANCE: Preterm infants undergoing third-trimester development in an unnatural ex-utero environment are at risk for unfavorable brain development and adverse long-term neurologic outcomes due to an 'amalgam of destructive-developmental' insults. Overt destructive injury is readily detectable by routine clinical brain imaging during the neonatal intensive care unit stay. However, adverse neurologic outcomes occur even in the absence of major brain injury. In this study, we seek to evaluate the effect of common prematurity-related autonomic function events (bradycardias/desaturations) on brain growth in infants without evidence of early, overt brain injury. Using a cohort of preterm infants, we demonstrated that impairment in autonomic development through term-equivalent age is associated with brain development. Autonomic markers may serve as early prognostic factors to predict neurodevelopmental outcomes in preterm neonates.

Indexed as

Autonomic Nervous SystemBrainInfant, PrematureFemaleGestational AgeHeart RateHumansInfant, NewbornMagnetic Resonance ImagingMaleOrgan SizeAnatomical regions of the brainHeart rate metricsLinear mixed effects modelingMRIOxygen saturationPreterm infantsVolumetric brain data

Identifiers

PMID41886974
PMCPMC13077703

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.