Development Of Autonomic Nervous System Research Articles

Impact of a music intervention on heart rate variability in very preterm infants.

Infants born very preterm spend their early postnatal life in a neonatal intensive care unit, where irregular and unpredictable sounds replace the structured and familiar intrauterine auditory environment. Music interventions may contribute to alleviate these deleterious effects by reducing stress and providing a form of environmental enrichment. This was an ancillary study as part of a blinded randomised controlled clinical trial entitled the effect of music on preterm infant's brain development. It measured the impact of music listening on the autonomic nervous system (ANS), we assessed heart rate variability (HRV) through high-resolution recordings of heart rate monitoring, at three specific postmenstrual ages in premature infants. From 29 included subjects, 18 were assessed for complete HRV dataset, including nine assigned to the music intervention and nine to the control group. Postmenstrual age appeared to be the main factor influencing HRV from 33 weeks to term equivalent age. Further analyses did not reveal any detectable effect of music intervention on ANS response. This study found that ANS responses were not modified by recorded music intervention in very preterm infants during wakefulness or sleep onset. Further research is warranted to explore other factors influencing ANS development in this population.

Heart Rate Variability and Cerebral Autoregulation in Patients with Traumatic Brain Injury with Paroxysmal Sympathetic Hyperactivity Syndrome.

Severe traumatic brain injury (TBI) can lead to transient changes in autonomic nervous system (ANS) functioning and development of paroxysmal sympathetic hyperactivity (PSH) syndrome. Clinical manifestation of ANS disorders may be obscured by therapeutic interventions in TBI. This study aims to analyze ANS metrics and cerebral autoregulation in patients with PSH syndrome to determine their significance in early prognostication. This single-center retrospective study investigated the relationship between changes in ANS metrics, cerebral autoregulation, and PSH syndrome. Arterial blood pressure and intracranial pressure signals were monitored for 5 days post TBI. ANS metrics included time and frequency domain heart rate variability (HRV) metrics. Cerebral autoregulation was assessed using the pressure reactivity index. Sixty-six patients with severe TBI (median age 33 [interquartile range 26-50] years) were analyzed, and PSH was confirmed in nine cases. Impairment of cerebral autoregulation was observed in 67% of patients with PSH and 72% without the syndrome. Patients with PSH had higher HRV in the low-frequency range (LF; 253 ± 178 vs. 176 ± 227 ms2; p = 0.035) and lower heart rates (HRs; 70 ± 7 vs. 78 ± 19 bpm; p = 0.027) compared to those without PSH. A receiver operating characteristic curve analysis indicated that HR (area under the curve(AUC) = 0.73, p = 0.006) and HRV in the LF (AUC = 0.70, p = 0.009) are moderate predictors of PSH. In the multiple logistic regression model for PSH, diffuse axonal trauma (odds ratio(OR) = 10.82, 95% confidence interval(CI) = 1.70-68.98, p = 0.012) and HR (OR =0.91, 95% CI 0.84-0.98, p = 0.021) were significant factors. Elevated HRV in the LF and decreased HR may serve as early predictors of PSH syndrome development, particularly in patients with diffuse axonal trauma. Further research is needed to investigate the utility of the cerebral autoregulation-ANS relationship in PSH prognostication.

Reliability of an "At-Home" Method for Monitoring Resting and Reactive Autonomic Nervous System Activity in Children: A Pilot Study.

Heart rate variability (HRV), an index of the functional status of the autonomic nervous system (ANS), provides an opportunity for early detection of ANS dysfunction. Lower resting, vagally related HRV parameters are associated with increased risk of physical and mental illness. External factors influencing the ANS, such as the testing environment, may impact the interpretation of HRV. This study's main aim was to determine the reliability of HRV resting and reactivity tests performed at home with children aged 4-9 years. Fourteen healthy children (female n = 8) aged 6.8 ± 1.5 years participated. Two HRV tests were performed at home via online supervision 7 days apart using a Polar H10 heart rate monitor. The absolute and relative reliability of the pre-exercise resting (5 min) and sub-maximal exercise step test recovery (4 × 30 s segments) HRV time and frequency domains were calculated. The Pearson correlation coefficients for day 1 versus day 7 for the vagal activity HRV domains (RMSSD log) at rest and in the first 30 s and 30-60 s of recovery indicated good-to-excellent relative reliability (r > 0.8, p < 0.01). Absolute reliability was moderate for the resting RMSSD log, with a coefficient of variation (CV) of 5.2% (90% CI: 3.9, 7.8%), high for the first 30 s of standing recovery, with a CV of 10.7% (90% CI: 8.2, 15.7%), and moderate for 30-60 s of recovery, with a CV of 8.7% (90% CI: 6.6, 12.9%). The findings of this pilot study indicate that the resting and exercise recovery HRV measures of vagal activity can be measured reliably at home in children. This represents a novel "at-home" protocol for monitoring ANS health and development in children.

Molecular Characterization of Nodose Ganglia Development Reveals a Novel Population of Phox2b+ Glial Progenitors in Mice.

The vagal ganglia, comprised of the superior (jugular) and inferior (nodose) ganglia of the vagus nerve, receive somatosensory information from the head and neck or viscerosensory information from the inner organs, respectively. Developmentally, the cranial neural crest gives rise to all vagal glial cells and to neurons of the jugular ganglia, while the epibranchial placode gives rise to neurons of the nodose ganglia. Crest-derived nodose glial progenitors can additionally generate autonomic neurons in the peripheral nervous system, but how these progenitors generate neurons is unknown. Here, we found that some Sox10+ neural crest-derived cells in, and surrounding, the nodose ganglion transiently expressed Phox2b, a master regulator of autonomic nervous system development, during early embryonic life. Our genetic lineage-tracing analysis in mice of either sex revealed that despite their common developmental origin and extreme spatial proximity, a substantial proportion of glial cells in the nodose, but not in the neighboring jugular ganglia, have a history of Phox2b expression. We used single-cell RNA-sequencing to demonstrate that these progenitors give rise to all major glial subtypes in the nodose ganglia, including Schwann cells, satellite glia, and glial precursors, and mapped their spatial distribution by in situ hybridization. Lastly, integration analysis revealed transcriptomic similarities between nodose and dorsal root ganglia glial subtypes and revealed immature nodose glial subtypes. Our work demonstrates that these crest-derived nodose glial progenitors transiently express Phox2b, give rise to the entire complement of nodose glial cells, and display a transcriptional program that may underlie their bipotent nature.

Mapping Early Brain-Body Interactions: Associations of Fetal Heart Rate Variation with Newborn Brainstem, Hypothalamic, and Dorsal Anterior Cingulate Cortex Functional Connectivity.

The autonomic nervous system (ANS) regulates the body's physiology, including cardiovascular function. As the ANS develops during the second to third trimester, fetal heart rate variability (HRV) increases while fetal heart rate (HR) decreases. In this way, fetal HR and HRV provide an index of fetal ANS development and future neurobehavioral regulation. Fetal HR and HRV have been associated with child language ability and psychomotor development behavior in toddlerhood. However, their associations with postbirth autonomic brain systems, such as the brainstem, hypothalamus, and dorsal anterior cingulate cortex (dACC), have yet to be investigated even though brain pathways involved in autonomic regulation are well established in older individuals. We assessed whether fetal HR and HRV were associated with the brainstem, hypothalamic, and dACC functional connectivity in newborns. Data were obtained from 60 pregnant individuals (ages 14-42) at 24-27 and 34-37 weeks of gestation using a fetal actocardiograph to generate fetal HR and HRV. During natural sleep, their infants (38 males and 22 females) underwent a fMRI scan between 40 and 46 weeks of postmenstrual age. Our findings relate fetal heart indices to brainstem, hypothalamic, and dACC connectivity and reveal connections with widespread brain regions that may support behavioral and emotional regulation. We demonstrated the basic physiologic association between fetal HR indices and lower- and higher-order brain regions involved in regulatory processes. This work provides the foundation for future behavioral or physiological regulation research in fetuses and infants.

Exploring the Influence of Fetal Sex on Heart Rate Dynamics Using Fetal Magnetocardiographic Recordings.

Fetal sex has been associated with different development trajectories that cause structural and functional differences between the sexes throughout gestation. Fetal magnetocardiography (fMCG) recordings from 123 participants (64 females and 59 males; one recording/participant) from a database consisting of low-risk pregnant women were analyzed to explore and compare fetal development trajectories of both sexes. The gestational age of the recordings ranged from 28 to 38 weeks. Linear metrics in both the time and frequency domains were applied to study fetal heart rate variability (fHRV) measures that reveal the dynamics of short- and long-term variability. Rates of linear change with GA in these metrics were analyzed using general linear model regressions with assessments for significantly different variances and GA regression slopes between the sexes. The fetal sexes were well balanced for GA and sleep state. None of the fHRV measures analyzed exhibited significant variance heterogeneity between the sexes, and none of them exhibited a significant sex-by-GA interaction. The absence of a statistically significant sex-by-GA interaction on all parameters resulted in none of the regression slope estimates being significantly different between the sexes. With high-precision fMCG recordings, we were able to explore the variation in fHRV parameters as it relates to fetal sex. The fMCG-based fHRV parameters did not show any significant difference in rates of change with gestational age between sexes. This study provides a framework for understanding normal development of the fetal autonomic nervous system, especially in the context of fetal sex.

Contemporary Understanding of the Central Autonomic Nervous System in Fetal-Neonatal Transition

THE CRITICAL ROLE OF THE CENTRAL AUTONOMIC NERVOUS SYSTEM IN FETAL-NEONATAL TRANSITION: Sarah B. Mulkey, Adre dú Plessis Seminars in Pediatric Neurology Volume 28, December 2018, Pages 29-37 The objective of this article is to understand the complex role of the central autonomic nervous system in normal and complicated fetal-neonatal transition and how autonomic nervous system dysfunction can lead to brain injury. The central autonomic nervous system supports coordinated fetal transitional cardiovascular, respiratory, and endocrine responses to provide safe transition of the fetus at delivery. Fetal and maternal medical and environmental exposures can disrupt normal maturation of the autonomic nervous system in utero, cause dysfunction, and complicate fetal-neonatal transition. Brain injury may both be caused by autonomic nervous system failure and contribute directly to autonomic nervous system dysfunction in the fetus and newborn. The central autonomic nervous system has multiple roles in supporting transition of the fetus. Future studies should aim to improve real-time monitoring of fetal autonomic nervous system function and in supporting typical autonomic nervous system development even under complicated conditions.

Investigating the development of the autonomic nervous system in infancy through pupillometry.

We aim to investigate early developmental trajectories of the autonomic nervous system (ANS) as indexed by the pupillary light reflex (PLR) in infants with (i.e. preterm birth, feeding difficulties, or siblings of children with autism spectrum disorder) and without (controls) increased likelihood for atypical ANS development. We used eye-tracking to capture the PLR in 216 infants in a longitudinal follow-up study spanning 5 to 24months of age, and linear mixed models to investigate effects of age and group on three PLR parameters: baseline pupil diameter, latency to constriction and relative constriction amplitude. An increase with age was found in baseline pupil diameter (F(3,273.21) = 13.15, p < 0.001, [Formula: see text] = 0.13), latency to constriction (F(3,326.41) = 3.84, p = 0.010, [Formula: see text] = 0.03) and relative constriction amplitude(F(3,282.53) = 3.70, p = 0.012, [Formula: see text] = 0.04). Group differences were found for baseline pupil diameter (F(3,235.91) = 9.40, p < 0.001, [Formula: see text] = 0.11), with larger diameter in preterms and siblings than in controls, and for latency to constriction (F(3,237.10) = 3.48, p = 0.017, [Formula: see text] = 0.04), with preterms having a longer latency than controls. The results align with previous evidence, with development over time that could be explained by ANS maturation. To better understand the cause of the group differences, further research in a larger sample is necessary, combining pupillometry with other measures to further validate its value.

Developing and Evaluating a Virtual Reality Videogame Using Biofeedback for Stress Management in Sports

AbstractStress is a reaction of the body to external challenges, whether physical or psychological. In sports, there are stress factors that affect the athlete's performance, especially in team sports that involve short, high-intensity exercise cycles followed by short recovery periods, such as American football. The lack of stress regulation mechanisms can be detrimental to the individual and collective performance of athletes. Biofeedback systems have shown promising clinical results in regulating stress for sports competitions. However, there is a lack of scientific evidence to support their efficacy, and technologies, such as virtual reality videogames, have not been extensively explored. In this article, we present the development and pilot testing of Virtual Autonomic Nervous System (VANS), a virtual reality videogame using biofeedback that supports stress management training in athletes. VANS uses an optical heart rate sensor and aims at keeping the heart rate below a given threshold to control features within the game. We evaluated the usability and user experience of VANS through a 1-week deployment study with 10 American footballers. Our results show that VANS outperformed a commercial videogame used for biofeedback training and considerably reduced stress in our participants. Therefore, VANS could provide stress management training for future matches and competitions. Finally, we reflect on aspects of our design and discuss future directions of our work.

Music Modulates Autonomic Nervous System Activity in Human Fetuses.

ContextFetal Autonomic Nervous sysTem Evaluation (FANTE) is a non-invasive tool that evaluates the autonomic nervous system activity in a fetus. Autonomic nervous system maturation and development during prenatal life are pivotal for the survival and neuropsychiatric development of the baby.ObjectiveAim of the study is to evaluate the effect of music stimulation on fetal heart rate and specific parameters linked to ANS activity, in particular fetal heart rate variability.MethodsThirty-two women between the 32nd and 38th week with a singleton uncomplicated pregnancy were recruited. All FANTE data collections were acquired using a 10-derivation electrocardiograph placed on the maternal abdomen. In each session (5 min basal, 10 min with music stimulus, and 5 min post-stimulus), FANTE was registered. The music stimulus was “Clair de lune” Debussy, played through headphones on the mother’s abdomen (CTR: 31927).ResultsMusic does not change the mean value of fetal heart rate. However, indices of total fetal heart rate variability statistically increase (RRsd p = 0.037, ANNsd p = 0.039, SD2 p = 0.019) during music stimulation in comparison to the basal phase. Heart rate variability increase depends mainly on the activation of parasympathetic branches (CVI p = 0.013), meanwhile, no significant changes from basal to stimulation phase were observed for indices of sympathetic activity. All the parameters of heart rate variability and parasympathetic activity remained activated in the post-stimulus phase compared to the stimulus phase. In the post-stimulus phase, sympathetic activity resulted in a significant reduction (LFn p = 0.037).ConclusionMusic can influence the basal activity of the fetal autonomic nervous system, enhancing heart rate variability, without changing fetal heart rate mean value. Music is enabled to induce a relaxation state in a near-to-term fetus, mediated by parasympathetic activation and by a parallel sympathetic inhibition.

W34. BIAS IN THE USE OF POLYGENIC SCORES TO EXPLORE GENETIC NURTURING EFFECTS IN BIOLOGICAL PARENT-OFFSPRING TRIOS

This study examined the development of baseline autonomic nervous system (ANS) and hypothalamic–pituitary–adrenal (HPA) physiological activity from 12 to 36 months as well as antecedents (poverty) and consequents (behavior problems) of individual differences in physiological development. Children (N = 179; 50% poor; 56% African American; 52% male) provided saliva samples at 12, 18, 24, 30, and 36 months of age. Latent growth curve models indicated that nonlinear change was evident for both sAA and cortisol, with sAA increasing and cortisol decreasing with age. Children residing in poor households exhibited lower initial levels of sAA, but not cortisol. African-American children showed slightly smaller decreases in cortisol over time. Initial levels of sAA predicted higher levels of internalizing behaviors at 36 months and both initial levels of and total change in sAA predicted higher levels of externalizing behaviors at 36 months. There was no evidence that sAA or cortisol mediated the relationship between poverty and later behavior problems.

Effects of Prenatal Exposure to Alcohol and Smoking on Fetal Heart Rate and Movement Regulation.

Negative associations of prenatal tobacco and alcohol exposure (PTE and PAE) on birth outcomes and childhood development have been well documented, but less is known about underlying mechanisms. A possible pathway for the adverse fetal outcomes associated with PTE and PAE is the alteration of fetal autonomic nervous system development. This study assessed PTE and PAE effects on measures of fetal autonomic regulation, as quantified by heart rate (HR), heart rate variability (SD-HR), movement, and HR-movement coupling in a population of fetuses at ≥ 34 weeks gestational age. Participants are a subset of the Safe Passage Study, a prospective cohort study that enrolled pregnant women from clinical sites in Cape Town, South Africa, and the Northern Plains region, United States. PAE was defined by six levels: no alcohol, low quit early, high quit early, low continuous, moderate continuous, and high continuous; while PTE by 4 levels: no smoking, quit early, low continuous, and moderate/high continuous. Linear regression analyses of autonomic measures were employed controlling for fetal sex, gestational age at assessment, site, maternal education, household crowding, and depression. Analyses were also stratified by sleep state (1F and 2F) and site (South Africa, N = 4025, Northern Plains, N = 2466). The final sample included 6491 maternal-fetal-dyad assessed in the third trimester [35.21 ± 1.26 (mean ± SD) weeks gestation]. PTE was associated with a decrease in mean HR in state 2F, in a dose dependent fashion, only for fetuses of mothers who continued smoking after the first trimester. In state 1F, there was a significant increase in mean HR in fetuses whose mother quit during the first trimester. This effect was driven by the Norther Plains cohort. PTE was also associated with a significant reduction in fetal movement in the most highly exposed group. In South Africa a significant increase in mean HR both for the high quit early and the high continuous group was observed. In conclusion, this investigation addresses a critical knowledge gap regarding the relationship between PTE and PAE and fetal autonomic regulation. We believe these results can contribute to elucidating mechanisms underlying risk for adverse outcomes.

Assessment of human fetal cardiac autonomic nervous system development using color tissue Doppler imaging.

ObjectivesFunctional development of the fetal cardiac autonomic nervous system (cANS) plays a key role in fetal maturation and can be assessed through fetal heart rate variability (fHRV)‐analysis, with each HRV parameter representing different aspects of cANS activity. Current available techniques, however, are unable to assess the fHRV parameters accurately throughout the whole pregnancy. This study aims to test the feasibility of color tissue Doppler imaging (cTDI) as a new ultrasound technique for HRV analysis. Secondly, we explored time trends of fHRV parameters using this technique.Methods18 healthy singleton fetuses were examined sequentially every 8 weeks from 10 weeks GA onwards. From each examination, 3 cTDI recordings of the four‐chamber view of 10 seconds were retrieved to determine accurate beat‐to‐beat intervals. The fHRV parameters SDNN, RMSSD, SDNN/RMSSD, and pNN10, each representing different functional aspects of the cANS, were measured, and time trends during pregnancy were explored using spline functions within a linear mixed‐effects model.ResultsIn total, 77% (95% Cl 66–87%) of examinations were feasible for fHRV analysis from the first trimester onwards, which is a great improvement compared to other techniques. The technique is able to determine different maturation rates of the fHRV parameters, showing that cANS function, presumably parasympathetic activity, establishes around 20 weeks GA and matures rapidly until 30 weeks GA.ConclusionsThis is the first study able to assess cANS function through fHRV analysis from the first trimester onwards. The use of cTDI to determine beat‐to‐beat intervals seems feasible in just 3 clips of 10 seconds, which holds promise for future clinical use in assessing fetal well‐being.

Establishment of an Individualized Chronotherapy, Autonomic Nervous System, and Variability-Based Dynamic Platform for Overcoming the Loss of Response to Analgesics

Control of chronic pain and mainly the partial or complete loss of response to analgesics is a major unmet need. Multiple mechanisms underline the development of tolerance to analgesics in general and specifically to opioids. The autonomic nervous system (ANS) plays a role in the development of analgesic tolerance and chronobiology. To review the mechanisms associated with the development of nonresponsiveness to analgesics. Literature review. The review is followed by a description of a new method for overcoming resistance and improving the response to analgesics. Conducted a detailed review of the relevant studies describing the mechanisms that underlie tolerance to pain medications, and the potential roles of the ANS and chronobiology in the development of drug resistance. The autonomic balance is reflected by heart rate variability, an example of a fundamental variability that characterizes biological systems. Chronotherapy, which is based on the circadian rhythm, can improve the efficacy and reduce the toxicity of chronic medications. In this article, we present the establishment of an individualized variability- and chronobiology-based therapy for overcoming the compensatory mechanisms associated with a loss of response to analgesics. We describe the premise of implementing personalized signatures associated with the ANS, and chronobiology, as well as with the pathophysiology of pain for establishing an adaptive model that could improve the efficacy of opioids, in a highly dynamic system. The studies presented were selected based on their relevance to the subject. The described variability-based system may ensure prolonged effects of analgesics while reducing the toxicity associated with increasing dosages.

Autonomic development in preterm infants is associated with morbidity of prematurity.

BackgroundPrevious studies have described an association between preterm birth and maturation of the autonomic nervous system (ANS); however, this may be impacted by multiple factors, including prematurity-related complications. Our aim was to evaluate for the effect of prematurity-related morbidity on ANS development in preterm infants in the NICU.MethodsWe compared time and frequency domains of heart rate variability (HRV) as a measure of ANS tone in 56 preterm infants from 2 NICUs (28 from each). One cohort was from a high-morbidity regional referral NICU, the other from a community-based inborn NICU with low prematurity-related morbidity. Propensity score matching was used to balance the groups by a 1:1 nearest neighbor design. ANS tone was analyzed.ResultsThe two cohorts showed parallel maturational trajectory of the alpha 1 time-domain metric, with the cohort from the high-morbidity NICU having lower autonomic tone. The maturational trajectories between the two cohorts differed in all other time-domain metrics (alpha 2, RMS1, RMS2). There was no difference between groups by frequency-domain metrics.ConclusionsPrematurity-associated morbidities correlate with autonomic development in premature infants and may have a greater impact on the extrauterine maturation of this system than birth gestational age.Impact Autonomic nervous system development measured by time-domain metrics of heart rate variability correlate with morbidities associated with premature birth.This study builds upon our previously published work that showed that development of autonomic tone was not impacted by gestational age at birth.This study adds to our understanding of autonomic nervous system development in a preterm extrauterine environment.Our study suggests that gestational age at birth may have less impact on autonomic nervous system development than previously thought.

Maturation of the Autonomic Nervous System in Premature Infants: Estimating Development Based on Heart-Rate Variability Analysis.

This study aims at investigating the development of premature infants' autonomic nervous system (ANS) based on a quantitative analysis of the heart-rate variability (HRV) with a variety of novel features. Additionally, the role of heart-rate drops, known as bradycardias, has been studied in relation to both clinical and novel sympathovagal indices. ECG data were measured for at least 3 h in 25 preterm infants (gestational age ≤32 weeks) for a total number of 74 recordings. The post-menstrual age (PMA) of each patient was estimated from the RR interval time-series by means of multivariate linear-mixed effects regression. The tachograms were segmented based on bradycardias in periods after, between and during bradycardias. For each of those epochs, a set of temporal, spectral and fractal indices were included in the regression model. The best performing model has R2 = 0.75 and mean absolute error MAE = 1.56 weeks. Three main novelties can be reported. First, the obtained maturation models based on HRV have comparable performance to other development models. Second, the selected features for age estimation show a predominance of power and fractal features in the very-low- and low-frequency bands in explaining the infants' sympathovagal development from 27 PMA weeks until 40 PMA weeks. Third, bradycardias might disrupt the relationship between common temporal indices of the tachogram and the age of the infant and the interpretation of sympathovagal indices. This approach might provide a novel overview of post-natal autonomic maturation and an alternative development index to other electrophysiological data analysis.

Higher maternal weight is related to poorer fetal autonomic function.

Maternal obesity is an established risk factor for poor infant neurodevelopmental outcomes; however, the link between maternal weight and fetal development in utero is unknown. We investigated whether maternal obesity negatively influences fetal autonomic nervous system (ANS) development. Fetal heart rate variability (HRV) is an index of the ANS that is associated with neurodevelopmental outcomes in the infant. Maternal-fetal magnetocardiograms were recorded using a fetal biomagnetometer at 36 weeks (n = 46). Fetal HRV was represented by the standard deviation of sinus beat-to-beat intervals (SDNN). Maternal weight was measured at enrollment (12-20 weeks) and 36 weeks. The relationships between fetal HRV and maternal weight at both time points were modeled using adjusted ordinary least squares regression models. Higher maternal weight at enrollment and 36 weeks were associated with lower fetal HRV, an indicator of poorer ANS development. Further study is needed to better understand how maternal obesity influences fetal autonomic development and long-term neurodevelopmental outcomes.

Autonomic nervous system maturation in the premature extrauterine milieu.

BackgroundIn premature infants, we investigated whether the duration of extra-uterine development influenced autonomic nervous system (ANS) maturation.MethodsWe performed a longitudinal cohort study of ANS maturation in preterm infants. Eligibility included birth gestational age (GA) <37 weeks, NICU admission, and expected survival. The cohort was divided into three birth GA groups: Group 1 (≤29 weeks), Group 2 (30–33 weeks), and Group 3 (≥34 weeks). ECG data were recorded weekly and analyzed for sympathetic and parasympathetic tone using heart rate variability (HRV). Quantile regression modeled the slope of ANS maturation among the groups by postnatal age to term equivalent age (TEA) (≥37weeks).Results100 infants, median (Q1-Q3) birth GA of 31.9 (28.7–33.9) weeks, were enrolled: Group 1 (n=35); Group 2 (n=40); and Group 3 (n=25). Earlier birth GA was associated with lower sympathetic and parasympathetic tone. However, the rate of autonomic maturation was similar, and at TEA there was no difference in HRV metrics across the three groups. The majority of infants (91%) did not experience significant neonatal morbidities.ConclusionPremature infants with low prematurity-related systemic morbidity have maturational trajectories of ANS development that are comparable across a wide range of ex-utero durations regardless of birth GA.

EP10.07: The development of the fetal cardiac autonomic nervous system using colour tissue Doppler imaging

EP10.07: The development of the fetal cardiac autonomic nervous system using colour tissue Doppler imaging

Causative and common PHOX2B variants define a broad phenotypic spectrum.

Paired Like homeobox 2B (PHOX2B) is a gene crucial for the differentiation of the neural lineages of the autonomic nervous system (ANS), whose coding mutations cause congenital central hypoventilation syndrome (CCHS). The vast majority of PHOX2B mutations in CCHS is represented by expansions of a polyalanine region in exon 3, collectively defined PARMs (PolyAlanine Repeat Mutations), the minority being frameshift, missense and nonsense mutations, defined as NPARMs (Non-PARMs). While PARMs are nearly exclusively associated with isolated CCHS, most of NPARMs is detected in syndromic CCHS, presenting with neuroblastoma and/or Hirschsprung disease. More recently, evidence of a complex role of PHOX2B in the pathogenesis of a wider spectrum of ANS disorders has emerged. Indeed, common and hypomorphic PHOX2B variants, including synonymous, polyalanine-contractions, gene deletions may influence the occurrence of either apparent life-threatening event (ALTE), Sudden Infant Death Syndrome (SIDS), neuroblastoma, or isolated HSCR, likely through small effects on PHOX2B expression levels. After an introduction to the role of PHOX2B in the ANS development, causative mutations, common variants, and gene expression deregulation of the PHOX2B gene are discussed, though the involvement of synonymous variants and contractions requires further confirmations with respect to ANS disorders and molecular mechanisms underlying the PHOX2B phenotypic heterogeneity.