Brief Report: Can a Composite Heart Rate Variability Biomarker Shed New Insights About Autism Spectrum Disorder in School-Aged Children?

Digital medicine is an interdisciplinary field, drawing together stakeholders with expertize in engineering, manufacturing, clinical science, data science, biostatistics, regulatory science, ethics, patient advocacy, and healthcare policy, to name a few. Although this diversity is undoubtedly valuable, it can lead to confusion regarding terminology and best practices. There are many instances, as we detail in this paper, where a single term is used by different groups to mean different things, as well as cases where multiple terms are used to describe essentially the same concept. Our intent is to clarify core terminology and best practices for the evaluation of Biometric Monitoring Technologies (BioMeTs), without unnecessarily introducing new terms. We focus on the evaluation of BioMeTs as fit-for-purpose for use in clinical trials. However, our intent is for this framework to be instructional to all users of digital measurement tools, regardless of setting or intended use. We propose and describe a three-component framework intended to provide a foundational evaluation framework for BioMeTs. This framework includes (1) verification, (2) analytical validation, and (3) clinical validation. We aim for this common vocabulary to enable more effective communication and collaboration, generate a common and meaningful evidence base for BioMeTs, and improve the accessibility of the digital medicine field.

show abstract

“…Can heart rate variability identify the presence of autism spectrum disorder in 8-year-old children 48 ?…”

Section: Example Use Casesmentioning

confidence: 99%

Verification, analytical validation, and clinical validation (V3): the foundation of determining fit-for-purpose for Biometric Monitoring Technologies (BioMeTs)

Goldsack¹,

et al. 2020

View full text Add to dashboard Cite

show abstract

“…To test the clinical utility and relative contribution of the measured parameters we classified the participants as SG or CG using ML approaches on the collected demographic, clinical, biophysical (i.e., FSI) and biochemical features (scikit-learn on Dataiku DSS 8.0.2) 54 . Binary features were expressed as categorical variables and dummy-encoded.…”

Section: Methodsmentioning

confidence: 99%

Prenatal stress perturbs fetal iron homeostasis in a sex specific manner

Zimmermann

Antonelli

Sharma

et al. 2022

Sci Rep

Self Cite

View full text Add to dashboard Cite

The adverse effects of maternal prenatal stress (PS) on child’s neurodevelopment warrant the establishment of biomarkers that enable early interventional therapeutic strategies. We performed a prospective matched double cohort study screening 2000 pregnant women in third trimester with Cohen Perceived Stress Scale-10 (PSS-10) questionnaire; 164 participants were recruited and classified as stressed and control group (SG, CG). Fetal cord blood iron parameters of 107 patients were measured at birth. Transabdominal electrocardiograms-based Fetal Stress Index (FSI) was derived. We investigated sex contribution to group differences and conducted causal inference analyses to assess the total effect of PS exposure on iron homeostasis using a directed acyclic graph (DAG) approach. Differences are reported for p < 0.05 unless noted otherwise. Transferrin saturation was lower in male stressed neonates. The minimum adjustment set of the DAG to estimate the total effect of PS exposure on fetal ferritin iron biomarkers consisted of maternal age and socioeconomic status: SG revealed a 15% decrease in fetal ferritin compared with CG. Mean FSI was higher among SG than among CG. FSI-based timely detection of fetuses affected by PS can support early individualized iron supplementation and neurodevelopmental follow-up to prevent long-term sequelae due to PS-exacerbated impairment of the iron homeostasis.

show abstract

“…Maternal stress during pregnancy alters fetal ANS by entraining fetal heart rate (fHR) with maternal HR decelerations during respiratory effort (Lobmaier et al, 2020). Eight-years old children with autism spectrum disorders (ASD), depression or conduct disorder showed, respectively, distinct signatures of HRV compared to controls and it has been proposed that, at least for ASD etiology, such abnormalities in HRV may be detected as early as in utero where they may be induced by asymptomatic inflammatory events altering ANS, among other systems (Frasch et al, 2019(Frasch et al, , 2021.…”

Section: Long-term Consequencesmentioning

confidence: 99%

A Review on the Vagus Nerve and Autonomic Nervous System During Fetal Development: Searching for Critical Windows

Cerritelli¹,

Frasch²,

Antonelli³

et al. 2021

Front. Neurosci.

Self Cite

View full text Add to dashboard Cite

The autonomic nervous system (ANS) is one of the main biological systems that regulates the body's physiology. Autonomic nervous system regulatory capacity begins before birth as the sympathetic and parasympathetic activity contributes significantly to the fetus' development. In particular, several studies have shown how vagus nerve is involved in many vital processes during fetal, perinatal, and postnatal life: from the regulation of inflammation through the anti-inflammatory cholinergic pathway, which may affect the functioning of each organ, to the production of hormones involved in bioenergetic metabolism. In addition, the vagus nerve has been recognized as the primary afferent pathway capable of transmitting information to the brain from every organ of the body. Therefore, this hypothesis paper aims to review the development of ANS during fetal and perinatal life, focusing particularly on the vagus nerve, to identify possible “critical windows” that could impact its maturation. These “critical windows” could help clinicians know when to monitor fetuses to effectively assess the developmental status of both ANS and specifically the vagus nerve. In addition, this paper will focus on which factors—i.e., fetal characteristics and behaviors, maternal lifestyle and pathologies, placental health and dysfunction, labor, incubator conditions, and drug exposure—may have an impact on the development of the vagus during the above-mentioned “critical window” and how. This analysis could help clinicians and stakeholders define precise guidelines for improving the management of fetuses and newborns, particularly to reduce the potential adverse environmental impacts on ANS development that may lead to persistent long-term consequences. Since the development of ANS and the vagus influence have been shown to be reflected in cardiac variability, this paper will rely in particular on studies using fetal heart rate variability (fHRV) to monitor the continued growth and health of both animal and human fetuses. In fact, fHRV is a non-invasive marker whose changes have been associated with ANS development, vagal modulation, systemic and neurological inflammatory reactions, and even fetal distress during labor.

show abstract

Brief Report: Can a Composite Heart Rate Variability Biomarker Shed New Insights About Autism Spectrum Disorder in School-Aged Children?

Cited by 12 publications

References 56 publications

Verification, analytical validation, and clinical validation (V3): the foundation of determining fit-for-purpose for Biometric Monitoring Technologies (BioMeTs)

Verification, analytical validation, and clinical validation (V3): the foundation of determining fit-for-purpose for Biometric Monitoring Technologies (BioMeTs)

Prenatal stress perturbs fetal iron homeostasis in a sex specific manner

A Review on the Vagus Nerve and Autonomic Nervous System During Fetal Development: Searching for Critical Windows

Contact Info

Product

Resources

About