Search

Background: Previous 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., Methods: We 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., Results: The 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., Conclusions: Prematurity-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., (© 2021. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Background: In premature infants, we investigated whether the duration of extrauterine development influenced autonomic nervous system (ANS) maturation., Methods: We 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) (≥37 weeks)., Results: One hundred 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., Conclusion: Premature 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., Impact: Heart rate variability can evaluate the maturation of the autonomic nervous system. Metrics of both the sympathetic and parasympathetic nervous system show maturation in the premature extrauterine milieu. The autonomic nervous system in preterm infants shows comparable maturation across a wide range of birth gestational ages. Preterm newborns with low medical morbidity have maturation of their autonomic nervous system while in the NICU. Modern NICU advances appear to support autonomic development in the preterm infant.

Investigations of the cellular and molecular mechanisms that mediate the development of the autonomic nervous system have identified critical genes and signaling pathways that, when disrupted, cause disorders of the autonomic nervous system. This review summarizes our current understanding of how the autonomic nervous system emerges from the organized spatial and temporal patterning of precursor cell migration, proliferation, communication, and differentiation, and discusses potential clinical implications for developmental disorders of the autonomic nervous system, including familial dysautonomia, Hirschsprung disease, Rett syndrome, and congenital central hypoventilation syndrome., Competing Interests: None., (Thieme. All rights reserved.)

The Neurovisceral Integration Model (NIM) is one of the most influential psychophysiological models addressing the interplay between the autonomic (ANS) and central nervous system (CNS). In their groundbreaking conceptual work, integrating autonomic, attentional, and affective systems into a functional and structural network, Thayer & Lane laid the foundation for empirical research in the past two decades. The present paper provides a principal outline aiming to reflect and further elaborate on the model from a dynamic developmental perspective. The central question at hand is, how does neurovisceral integration develop (early in life)? By reviewing the existing evidence, it is illustrated that key components of the model, both, on a physiological and psychological level, undergo extensive change early in the course of life. This sensitive period of human development seems key for our understanding of the integrated action of the ANS and CNS in emotion across the lifespan. Early life events may interfere with the fine-tuned interplay of this shared neural circuitry resulting in long-term dysfunction and psychiatric illness. In the absence of longitudinal data covering the entire co-development of the ANS and CNS from early childhood to adolescence into early adulthood, it is suggested, that vagal activity and its normative increase in adolescence is a key premise for normative brain development on a structural and functional level, subsequent psychological functioning and adaptive regulation. Implications from this dynamic perspective and suggestions for future research in the field of developmental psychophysiology are discussed., (© 2020 The Authors. Psychophysiology published by Wiley Periodicals, Inc. on behalf of Society for Psychophysiological Research.)

Deficits in social engagement emerge in autism during the infant and toddler period and may be related to emotion regulation and stress response systems. This study examined patterns of growth in autonomic functioning related to autism diagnosis and addresses the hypothesis that there are differences in autonomic functioning related to autism in infancy. Heart rate (HR) and respiratory sinus arrhythmia (RSA) were measured at 8 time points from 1 to 72 months of age in infants later diagnosed with autism (n = 12) and a non-autistic comparison group (n = 106). Multilevel models were used to describe the developmental course of HR and RSA and to test the effect of autism diagnosis on growth trajectories. Both groups showed an expected age-related decrease in HR and increase in RSA. Groups did not differ in the rate of decrease of HR over time. However, infants with autism demonstrated a smaller linear increase in RSA, indicating slower growth in RSA over time in comparison to controls. These results suggest that differences in physiological regulation may develop with age in autism. The slowed RSA growth in autism was most evident after 18 months of age, at a time when behavioral symptoms become prominent. This is consistent with the view that RSA is a marker of functional status in autism rather than a cause of social deficits in autism., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The central autonomic nervous system (ANS) is essential for maintaining cardiovascular and respiratory homeostasis in the newborn and has a critical role in supporting higher cortical functions. At birth, the central ANS is maturing and is vulnerable to adverse environmental and physiologic influences. Critical connections are formed early in development between the ANS and limbic system to integrate psychological and body responses. The Polyvagal Theory, developed by Stephen Porges, describes how modulation of the autonomic vagal impulse controls social responses and that a broad range of neuropsychiatric disorders may be due to impaired vagal balance, with either deficient vagal tone or excessive vagal reactivity. Under additional circumstances of prematurity, growth restriction, and environmental stress in the fetus and newborn, the immature ANS may undergo "dysmaturation". Maternal stress and health as well as the intrauterine environment are also quite important and have been implicated in causing ANS changes in the infant and neuropsychiatric diseases in children. This review will cover the aspects of ANS development and maturation that have been associated with neuropsychiatric disorders in children.

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., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Fetal heart rate variability (fHRV) of normal-to-normal (NN) beat intervals provides high-temporal resolution access to assess the functioning of the autonomic nervous system (ANS)., Aim: To determine critical periods of fetal autonomic maturation. The developmental pace is hypothesized to change with gestational age (GA)., Study Design: Prospective longitudinal observational study., Subjects: 60 healthy singleton fetuses were followed up by fetal magnetocardiographic heart rate monitoring 4-11 times (median 6) during the second half of gestation., Outcome Measure: FHRV parameters, accounting for differential aspects of the ANS, were studied applying linear mixed models over four predefined pregnancy segments of interest (SoI: <27; 27+0-31+0; 31+1-35+0; >35+1 weeks GA). Periods of fetal active sleep and quiescence were accounted for separately., Results: Skewness of the NN interval distribution VLF/LF band power ratio and complexity describe a saturation function throughout the period of interest. A decreasing LF/HF ratio and an increase in pNN5 indicate a concurrent shift in sympathovagal balance. Fluctuation amplitude and parameters of short-term variability (RMSSD, HF band) mark a second acceleration towards term. In contrast, fetal quiescence is characterized by sequential, but low-margin transformations; ascending overall variability followed by an increase of complexity and superseded by fluctuation amplitude., Conclusions: An increase in sympathetic activation, connected with by a higher ability of parasympathetic modulation and baseline stabilization, is reached during the transition from the late 2nd into the early 3rd trimester. Pattern characteristics indicating fetal well-being saturate at 35 weeks GA. Pronounced fetal breathing efforts near-term mirror in fHRV as respiratory sinus arrhythmia., Competing Interests: The authors state that there are no conflicts of interest in submitting this manuscript of original research.

Adverse prenatal environmental influences to the developing fetus are associated with mental and cardiovascular disease in later life. Universal developmental characteristics such as self-organization, pattern formation, and adaptation in the growing information processing system have not yet been sufficiently analyzed with respect to description of normal fetal development and identification of developmental disturbances. Fetal heart rate patterns are the only non-invasive order parameter of the developing autonomic brain available with respect to the developing complex organ system. The objective of the present study was to investigate whether universal indices, known from evolution and phylogeny, describe the ontogenetic fetal development from 20 weeks of gestation onwards. By means of a 10-fold cross-validated data-driven multivariate regression modeling procedure, relevant indices of heart rate variability (HRV) were explored using 552 fetal heart rate recordings, each lasting over 30 min. We found that models which included HRV indices of increasing fluctuation amplitude, complexity and fractal long-range dependencies largely estimated the maturation age (coefficients of determination 0.61-0.66). Consideration of these characteristics in prenatal care may not only have implications for early identification of developmental disturbances, but also for the development of system-theory-based therapeutic strategies., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Heart rate variability (HRV) has emerged as a predictor of later cardiac risk. This study tested whether pregnancy complications that may have long-term offspring cardiac sequelae are associated with differences in HRV at birth, and whether these HRV differences identify abnormal cardiovascular development in the postnatal period., Methods: Ninety-eight sleeping neonates had 5-min electrocardiogram recordings at birth. Standard time and frequency domain parameters were calculated and related to cardiovascular measures at birth and 3 months of age., Results: Increasing prematurity, but not maternal hypertension or growth restriction, was associated with decreased HRV at birth, as demonstrated by a lower root mean square of the difference between adjacent NN intervals (rMSSD) and low (LF) and high-frequency power (HF), with decreasing gestational age (p < 0.001, p = 0.009 and p = 0.007, respectively). We also demonstrated a relative imbalance between sympathetic and parasympathetic tone, compared to the term infants. However, differences in autonomic function did not predict cardiovascular measures at either time point., Conclusions: Altered cardiac autonomic function at birth relates to prematurity rather than other pregnancy complications and does not predict cardiovascular developmental patterns during the first 3 months post birth. Long-term studies will be needed to understand the relevance to cardiovascular risk.

Objective: Early life stress has been shown to influence the developing autonomic nervous system. Stressors in infancy may program the autonomic nervous system resting state set point, affecting cardiovascular function in later life. Excessive crying may be an indicator of increased stress arousal in infancy. We hypothesized that excessive infant crying is related to altered cardiac autonomic nervous system activity and increased blood pressure at age 5-6 years., Methods: In the Amsterdam Born Children and their Development study, excessive crying, maternal burden of infant care and maternal aggressive behavior in the 13th week after birth (range 11-16 weeks) were reported using questionnaires. Blood pressure, heart rate, heart rate variability and indicators of cardiac autonomic nervous system activity (sympathetic drive by pre-ejection period, parasympathetic drive by respiratory sinus arrhythmia) were measured at age 5-6 years during rest. Inclusion criteria were singleton birth, term-born, and no reported congenital or cardiovascular problems (N = 2153 included)., Results: Excessive crying (2.8%) was not associated with resting heart rate, heart rate variability, pre-ejection period, respiratory sinus arrhythmia nor with blood pressure at age 5-6 years., Conclusions: Excessive infant crying as an indicator of increased stress arousal does not seem to be related to resting activity of the autonomic nervous system or blood pressure at age 5-6. Potential associations may become visible under stressed conditions., Competing Interests: The authors have declared that no competing interests exist.

Heart rate (HR) and heart rate variability (HRV) are valuable markers of health. Although the underlying mechanism(s) are controversial, it is well documented that n-3 long chain polyunsaturated fatty acid (LCPUFA) intake improves HR and HRV in various populations. Autonomic modulation and/or alterations in cardiac electrophysiology are commonly cited as potential mechanisms responsible for these effects. This article reviews existing evidence for each and explores a separate mechanism which has not received much attention but has scientific merit. Based on presented evidence, it is proposed that n-3 LCPUFAs affect HR and HRV directly by autonomic modulation and indirectly by altering circulating factors, both dependently and independently of the autonomic nervous system. The evidence for changes in cardiac electrophysiology as the mechanism by which n-3 LCPUFAs affect HR and HRV needs strengthening., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objective: Autonomic nervous system activity is recognized as a major component of emotional responses. Future reward/punishment expectations depend upon the process of decision making in the frontal lobe, which is considered to play an important role in executive function. The aim of this study was to investigate the relationship between autonomic responses and decision making during reinforcement tasks using sympathetic skin responses (SSR)., Methods: Nine adult and 9 juvenile (mean age, 10.2years) volunteers were enrolled in this study. SSRs were measured during the Markov decision task (MDT), which is a reinforcement task. In this task, subjects must endure a small immediate loss to ultimately get a large reward. The subjects had to undergo three sets of tests and their scores in these tests were assessed and evaluated., Results: All adults showed gradually increasing scores for the MDT from the first to third set. As the trial progressed from the first to second set in adults, SSR appearance ratios remarkably increased for both punishment and reward expectations. In comparison with adults, children showed decreasing scores from the first to second set. There were no significant inter-target differences in the SSR appearance ratio in the first and second set in children. In the third set, the SSR appearance ratio for reward expectations was higher than that in the neutral condition., Conclusions: In reinforcement tasks, such as MDT, autonomic responses play an important role in decision making. We assume that SSRs are elicited during efficient decision making tasks associated with future reward/punishment expectations, which demonstrates the importance of autonomic function. In contrast, in children around the age of 10years, the autonomic system does not react as an organized response specific to reward/punishment expectations. This suggests the immaturity of the future reward/punishment expectations process in children., (Copyright © 2017 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Clarias gariepinus is a facultative air-breathing catfish that exhibits changes in heart rate (ƒ H ) associated with air-breaths (AB). A transient bradycardia prior to the AB is followed by sustained tachycardia during breath-hold. This study evaluated air-breathing and cardiac responses to sustained aerobic exercise in juveniles (total length~20cm), and how exercise influenced variations in f H associated with AB. In particular, it investigated the role of adrenergic and cholinergic control in cardiac responses, and effects of pharmacological abolition of this control on air-breathing responses. Sustained exercise at 15, 30 and 45cms -1 in a swim tunnel caused significant increases in f AB and f H , from approximately 5breathsh -1 and 60heartbeatsmin -1 at the lowest speed, to over 60breathsh -1 and 100beatsmin -1 at the highest, respectively. There was a progressive decline in the degree of variation in f H , around each AB, as f AB increased with exercise intensity. Total autonomic blockade abolished all variation in f H during exercise, and around each AB, but f AB responses were the same as in untreated animals. Cardiac responses were exclusively due to modulation of inhibitory cholinergic tone, which varied from >100% at the lowest speed to <10% at the highest. Cholinergic blockade had no effect on f AB compared to untreated fish. Excitatory β-adrenergic tone was approximately 20% and did not vary with swimming speed, but its blockade increased f AB at all speeds, compared to untreated animals. This reveals complex effects of autonomic control on air-breathing during exercise in C. gariepinus, which deserve further investigation., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Familial dysautonomia (FD) is a debilitating disorder that affects derivatives of the neural crest (NC). For unknown reasons, people with FD show marked differences in disease severity despite carrying an identical, homozygous point mutation in IKBKAP, encoding IκB kinase complex-associated protein. Here we present disease-related phenotypes in human pluripotent stem cells (PSCs) that capture FD severity. Cells from individuals with severe but not mild disease show impaired specification of NC derivatives, including autonomic and sensory neurons. In contrast, cells from individuals with severe and mild FD show defects in peripheral neuron survival, indicating that neurodegeneration is the main culprit for cases of mild FD. Although genetic repair of the FD-associated mutation reversed early developmental NC defects, sensory neuron specification was not restored, indicating that other factors may contribute to disease severity. Whole-exome sequencing identified candidate modifier genes for individuals with severe FD. Our study demonstrates that PSC-based modeling is sensitive in recapitulating disease severity, which presents an important step toward personalized medicine.

The bHLH transcription factor Hand2 is essential for the acquisition and maintenance of noradrenergic properties of embryonic sympathetic neurons and controls neuroblast proliferation. Hand2 is also expressed in embryonic and postnatal parasympathetic ganglia and remains expressed in sympathetic neurons up to the adult stage. Here, we address its function in developing parasympathetic and adult sympathetic neurons. We conditionally deleted Hand2 in the parasympathetic sphenopalatine ganglion by crossing a line of floxed Hand2 mice with DbhiCre transgenic mice, taking advantage of the transient Dbh expression in parasympathetic ganglia. Hand2 elimination does not affect Dbh expression and sphenopalatine ganglion size at E12.5 and E16.5, in contrast to sympathetic ganglia. These findings demonstrate different functions for Hand2 in the parasympathetic and sympathetic lineage. Our previous Hand2 knockdown in postmitotic, differentiated chick sympathetic neurons resulted in decreased expression of noradrenergic marker genes but it was unclear whether Hand2 is required for maintaining noradrenergic neuron identity in adult animals. We now show that Hand2 elimination in adult Dbh-expressing sympathetic neurons does not decrease the expression of Th and Dbh, in contrast to the situation during development. However, gene expression profiling of adult sympathetic neurons identified 75 Hand2-dependent target genes. Interestingly, a notable proportion of down-regulated genes (15%) encode for proteins with synaptic and neurotransmission functions. These results demonstrate a change in Hand2 target genes during maturation of sympathetic neurons. Whereas Hand2 controls genes regulating noradrenergic differentiation during development, Hand2 seems to be involved in the regulation of genes controlling neurotransmission in adult sympathetic neurons. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 76: 1111-1124, 2016., (© 2016 Wiley Periodicals, Inc.)

The autonomic nervous system (ANS) consists of two branches, the parasympathetic and sympathetic nervous systems, and controls the function of internal organs (e.g., heart rate, respiration, digestion) and responds to everyday and adverse experiences (1). ANS measures in children have been found to be related to behavior problems, emotion regulation, and health (2-7). Therefore, understanding the factors that affect ANS development during early childhood is important. Both branches of the ANS affect young children's cardiovascular responses to stimuli and have been measured noninvasively, via external monitoring equipment, using valid and reliable measures of physiological change (8-11). However, there are few studies of very young children with simultaneous measures of the parasympathetic and sympathetic nervous systems, which limits understanding of the integrated functioning of the two systems. In addition, the majority of existing studies of young children report on infants' resting ANS measures or their reactivity to commonly used mother-child interaction paradigms, and less is known about ANS reactivity to other challenging conditions. We present a study design and standardized protocol for a non-invasive and rapid assessment of cardiac autonomic control in 18 month old children. We describe methods for continuous monitoring of the parasympathetic and sympathetic branches of the ANS under resting and challenge conditions during a home or laboratory visit and provide descriptive findings from our sample of 140 ethnically diverse toddlers using validated equipment and scoring software. Results revealed that this protocol can produce a range of physiological responses to both resting and developmentally challenging conditions, as indicated by changes in heart rate and indices of parasympathetic and sympathetic activity. Individuals demonstrated variability in resting levels, responses to challenges, and challenge reactivity, which provides additional evidence that this protocol is useful for the examination of ANS individual differences for toddlers.

Most early studies of the role of nucleotides in development have evidenced their crucial importance as carriers of energy in all organisms. However, an increasing number of studies are now available to suggest that purines and pyrimidines, acting as extracellular ligands specifically on receptors of the plasma membrane, may play a pivotal role throughout pre- and postnatal development in a wide variety of organisms including amphibians, birds, and mammals. Purinergic receptor expression and functions have been studied in the development of many organs, including the autonomic nervous system (ANS). Nucleotide receptors can induce a multiplicity of cellular signalling pathways via crosstalk with bioactive molecules acting on growth factors and neurotransmitter receptors which are fundamental for the development of a mature and functional ANS. Purines and pyrimidines may influence all the stages of neuronal development, including neural cell proliferation, migration, differentiation and phenotype determination of differentiated cells. Indeed, the normal development of the ANS is disturbed by dysfunction of purinergic signalling in animal models. To establish the primitive and fundamental nature of purinergic neurotransmission in the ontogeny of the ANS, in this review the roles of purines and pyrimidines as signalling molecules during embryological and postnatal development are considered., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Heart rate variability (HRV) analyses can provide a non-invasive evaluation of cardiac autonomic activity. How autonomic control normally develops in childhood and how this is affected by obesity remain incompletely understood. In this review we examine the evidence that childhood age and weight status influence autonomic control of the heart as assessed using HRV. Electronic databases (Pubmed, EMBASE and Cochrane Library) were searched for studies examining HRV in healthy children from birth to 18 years who adhered to the Task Force (1996) guidelines. Twenty-four studies met our inclusion criteria. Seven examined childhood age and HRV. A reduction in 24-hour LF:HF was reported from birth to infancy (1 year), while overall HRV (SDNN) showed a marked and progressive increase. From infancy to early-to-late childhood (from 12 months to 15 years) LF:HF ratio was reported to decline further albeit at a slower rate, while RMSSD and SDNN increased. Twenty studies examined the effects of weight status and body composition on HRV. In a majority of studies, obese children exhibited reductions in RMSSD (n = 8/13), pNN50% (n = 7/9) and HF power (n = 14/18), no difference was reported for LF (n = 10/18), while LF:HF ratio was elevated (n = 10/15). HRV changes during childhood are consistent with a marked and progressive increase in cardiac parasympathetic activity relative to sympathetic activity. Obesity disrupts the normal maturation of cardiac autonomic control., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: Early environmental exposures may help shape the development of the autonomic nervous system (ANS) and hypothalamic-pituitary-adrenal (HPA) axis, influencing vulnerability for health problems across the lifespan. Little is known about the role of maternal sensitivity in influencing the development of the ANS in early life., Aims: To examine associations among maternal sensitivity and infant behavioral distress and ANS and HPA axis reactivity to the Repeated Still-Face Paradigm (SFP-R), a dyadic stress task., Study Design: Observational repeated measures study., Subjects: Thirty-five urban, sociodemographically diverse mothers and their 6-month-old infants., Outcome Measures: Changes in infant affective distress, heart rate, respiratory sinus arrhythmia (RSA), and T-wave amplitude (TWA) across episodes of the SFP-R were assessed. A measure of cortisol output (area under the curve) in the hour following cessation of the SFP-R was also obtained., Results: Greater maternal insensitivity was associated with greater infant sympathetic activation (TWA) during periods of stress and tended to be associated with greater cortisol output following the SFP-R. There was also evidence for greater affective distress and less parasympathetic activation (RSA) during the SFP-R among infants of predominantly insensitive mothers., Conclusions: Caregiving quality in early life may influence the responsiveness of the sympathetic and parasympathetic branches of the ANS as well as the HPA axis. Consideration of the ANS and HPA axis systems together provides a fuller representation of adaptive versus maladaptive stress responses. The findings highlight the importance of supporting high quality caregiving in the early years of life, which is likely to promote later health., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

In a study recently published in Science, Magnon et al. show that both the sympathetic and parasympathetic components of the autonomic nervous system play an integral part in the development and dissemination of prostate cancer (PCa). Inhibition of the sympathetic nervous system (SNS) and disruption of the adrenergic receptors, specifically Ardβ 2, resulted in the prevention of primary PCa tumor development in mice. The authors found that inhibition of the SNS is only successful in preventing murine tumor development if completed early enough, and the parasympathetic nervous system (PNS) predominates in later stages of PCa. Inhibition of the PNS by way of the cholinergic receptor, muscarinic 1 (Chrm1), caused mice to develop less metastases to the pelvic lymph nodes, intestines, and bones. A PCa progression scheme has been outlined where initial tumor engraftment is controlled by the SNS but then becomes less prominent than the PNS, which promotes metastasis. The investigators showed the dependence of the autonomic nervous system on development of PCa and present opportunities for prevention; further studies are needed to confirm these results in humans.

In a significant translational study, Magnon et al. investigated the role that the autonomic nervous system plays in the development and spread of prostate cancer in both mice and human models. The study shows different roles for both branches of the autonomic nervous system, with the sympathetic system promoting early stages of tumorigenesis, and the parasympathetic system promoting cancer dissemination. This information could lead to important new foundations for treatment, therapies and management of prostate cancer.

In the July 12 issue of Science magazine, researchers from the Albert Einstein College of Medicine, the Mount Sinai School of Medicine, the Durham VA Medical Centre and Duke University published an elegant study demonstrating that the sympathetic nervous system, acting through β2 and β3-adrenoceptors in the prostate, plays an important role in the initiation of prostate cancer, while the parasympathetic nervous system plays a role in the dissemination of tumour metastases via M1 muscarinic receptors. These findings are significant because they indicate that receptors associated with the autonomic nervous system may be viable targets for prostate cancer therapy.

Nerves are a common feature of the microenvironment, but their role in tumor growth and progression remains unclear. We found that the formation of autonomic nerve fibers in the prostate gland regulates prostate cancer development and dissemination in mouse models. The early phases of tumor development were prevented by chemical or surgical sympathectomy and by genetic deletion of stromal β2- and β3-adrenergic receptors. Tumors were also infiltrated by parasympathetic cholinergic fibers that promoted cancer dissemination. Cholinergic-induced tumor invasion and metastasis were inhibited by pharmacological blockade or genetic disruption of the stromal type 1 muscarinic receptor, leading to improved survival of the mice. A retrospective blinded analysis of prostate adenocarcinoma specimens from 43 patients revealed that the densities of sympathetic and parasympathetic nerve fibers in tumor and surrounding normal tissue, respectively, were associated with poor clinical outcomes. These findings may lead to novel therapeutic approaches for prostate cancer.

The aim of this study was to evaluate and compare the effects of early and physiological menopause on cardiac autonomic parameters in aged female rats. To this end, female Wistar rats (22 and 82 weeks old, N=96) were divided into 4 groups: Young Sham-operated Rats, Aged Sham-operated Rats, Young Ovariectomised (OVX) Rats, and Aged OVX Rats. Young Sham-operated and OVX rats were used as controls. The cardiac autonomic parameters were investigated using different approaches: 1) pharmacological evaluation of the autonomic tonus with methylatropine and propranolol; 2) isolated cardiac contractility with β-adrenergic agonists; and 3) quantification of the mRNA and protein level expression of cardiac β-adrenergic receptors. Among the groups of aged female rats, both the Sham-operated and OVX rats showed higher basal mean arterial pressure and heart rate (HR) values compared to their respective young counterparts. The aged groups also showed a predominance of the sympathetic autonomic component in the determination of HR, whereas the young rats showed a vagal predominance. An assessment of cardiac contractility showed that aged Sham-operated and OVX rats had lower contractile responses following the administration of dobutamine compared to their respective young counterparts. In addition, the aged groups showed higher mRNA and protein expression levels of the β1-adrenergic receptors. In conclusion, our results show that haemodynamic alterations and impairment of the autonomic parameters were similar between the groups of rats subjected to early and physiological menopause. Moreover, these results seem to be due to the ageing process and not ovarian hormone deprivation., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Age has been identified as an independent risk factor for cardiovascular diseases. A shift of the cardiac autonomic nervous system towards an increase in sympathetic tone has been reported in the elderly. Nerve growth factor (NGF) is the main neurotrophic factor that increases the sympathetic activity of the heart. If there is a shift of NGF expression in old compared to young cardiomyocytes and whether there are regional differences in the heart still remain unclear. Therefore, we chose a rat model of different-aged rats (3-4 days = neonatal, 6-8 weeks = young, 20-24 months = old), and isolated cardiomyocytes from the left and the right atrium (LA, RA), as well as from the left and the right ventricle (LV, RV), were used to determine NGF expression on mRNA and protein levels. In neonatal, young, and old rats, NGF amount in LA and RA was significantly lower as compared to LV and RV. In young and old rats, we found significant higher NGF protein levels in LA compared to RA. In addition, both atria showed an increase in NGF expression between age groups neonatal, young, and old. In both ventricles, we observed a significant decrease in NGF expression from neonatal to young rats and a significant increase from young to old rats. The highest NGF amount in LV and RV was observed in neonatal rats. Regarding tyrosine kinase A receptor (TrkA) expression, the main receptor for NGF signaling, both atria showed the largest expression in old rats; while in LV and RV, TrkA was expressed mainly in young rats. These results point to a contribution of nerve growth factors to the change of autonomic tone observed in elderly patients.

Aims: This paper will review literature that examines the psychological and neuropsychological correlates of orthostatic blood pressure regulation., Results: The pattern of change in systolic blood pressure in response to the shift from supine to upright posture reflects the adequacy of orthostatic regulation. Orthostatic integrity involves the skeletal muscle pump, neurovascular compensation, neurohumoral effects and cerebral flow regulation. Various physiological states and disease conditions may disrupt these mechanisms. Clinical and subclinical orthostatic hypotension has been associated with impaired cognitive function, decreased effort, reduced motivation and increased hopelessness as well as dementia, diabetes mellitus, and Parkinson's disease. Furthermore, inadequate blood pressure regulation in response to orthostasis has been linked to increased depression and anxiety as well as to intergenerational behavioral sequalae., Conclusions: Identifying possible causes and consequences of subclinical and clinical OH are critical in improving quality of life for both children and older adults.

Emerging evidence reveals that the incidence of allergic disorders commencing during childhood is influenced by pre-, peri- and early postnatal environmental challenges. We here highlight biomarkers involved in the purported interaction of a challenged intrauterine environment during pregnancy and the risk for allergies in the children later in life. We propose that the identification of biomarkers during pregnancy may allow early detection of children prone to develop allergies and possibly other chronic immune diseases. Subsequently, therapeutic interventions designed to prevent negative consequences of prenatal environmental challenges on children's immune system would be within reach., (Copyright © 2012 S. Karger AG, Basel.)

Adaptive capacities were studied in 6-7-year-ol apparently healthy children in relation to the number of congenital morphogenetic variants (CMVs). The most markedly reduced adaptive capacities were revealed in children with 5 CMVs or more.

Background: Nerve growth factor (NGF) up-regulation during inflammation has been demonstrated to occur in several different tissues. Herein, the expression of aortic nerve growth factor and its association with nerve sprouting in a rodent model of self-limited peritonitis were investigated., Materials and Methods: Male Wistar rats were randomized into one of three groups: gastric perforation (GP), sham group, and GP group treated with methylprednisolone (GP-M). Aortic expression of NGF and growth associated protein 43 (GAP43) were evaluated at several different time points (range, 6 h to 2 wk) after GP or sham., Results: Compared with the sham group, expression of NGF was significantly elevated during the inflammatory period (the first week post-GP) in GP rats. The GP group also had enhanced nerve sprouting, which persisted after the peritonitis recovered. Methylprednisolone abrogated NGF up-regulation and nerve sprouting induced by GP., Conclusions: GP resulted in up-regulation of aortic NGF that coincided with aortic nerve sprouting. Methylprednisolone effectively blocked GP-induced NGF up-regulation. Further studies are necessary to decipher the causality of these observed changes., (Copyright © 2011 Elsevier Inc. All rights reserved.)

The present study examined the role of cardiovascular regulation in predicting pediatric obesity. Participants for this study included 268 children (141 girls) obtained from a larger ongoing longitudinal study. To assess cardiac vagal regulation, resting measures of respiratory sinus arrhythmia (RSA) and RSA change (vagal withdrawal) to three cognitively challenging tasks were derived when children were 5.5 years of age. Heart period (HP) and HP change (heart rate (HR) acceleration) were also examined. Height and weight measures were collected when children were 5.5, 7.5, and 10.5 years of age. Results indicated that physiological regulation at age 5.5 was predictive of both normal variations in BMI development and pediatric obesity at age 10.5. Specifically, children with a cardiovascular regulation profile characterized by lower levels of RSA suppression and HP change experienced significantly greater levels of BMI growth and were more likely to be classified as overweight/at-risk for overweight at age 10.5 compared to children with a cardiovascular regulation profile characterized by high levels of RSA suppression and HP change. However, a significant interaction with racial status was found suggesting that the association between cardiovascular regulation profile and BMI growth and pediatric obesity was only significant for African-American children. An autonomic cardiovascular regulation profile consisting of low parasympathetic activity represents a significant individual risk factor for the development of pediatric obesity, but only for African-American children. Mechanisms by which early physiological regulation difficulties may contribute to the development of pediatric obesity are discussed.

Background: Electrocardiography remains the best diagnostic tool and therapeutic biomarker for a spectrum of pediatric diseases involving cardiac or autonomic nervous system defects. As genetic links to these disorders are established and transgenic mouse models produced in efforts to understand and treat them, there is a surprising lack of information on electrocardiograms (ECGs) and ECG abnormalities in neonate mice. This is likely due to the trauma and anaesthesia required of many legacy approaches to ECG recording in mice, exacerbated by the fragility of many mutant neonates. Here, we use a non-invasive system to characterize development of the heart rate and electrocardiogram throughout the growth of conscious neonate FVB/N mice., Results: We examine ECG waveforms as early as two days after birth. At this point males and females demonstrate comparable heart rates that are 50% lower than adult mice. Neonatal mice exhibit very low heart rate variability. Within 12 days of birth PR, QRS and QTc interval durations are near adult values while heart rate continues to increase until weaning. Upon weaning FVB/N females quickly develop slower heart rates than males, though PR intervals are comparable between sexes until a later age. This suggests separate developmental events may contribute to these gender differences in electrocardiography., Conclusions: We provide insight with a new level of detail to the natural course of heart rate establishment in neonate mice. ECG can now be conveniently and repeatedly used in neonatal mice. This should serve to be of broad utility, facilitating further investigations into development of a diverse group of diseases and therapeutics in preclinical mouse studies.

The von Economo neurons (VENs) are large bipolar neurons located in frontoinsular (FI) and anterior cingulate cortex in great apes and humans, but not other primates. We performed stereological counts of the VENs in FI and LA (limbic anterior, a component of anterior cingulate cortex) in great apes and in humans. The VENs are more numerous in humans than in apes, although one gorilla approached the lower end of the human range. We also examined the ontological development of the VENs in FI and LA in humans. The VENs first appear in small numbers in the 36th week post-conception, are rare at birth, and increase in number during the first 8 months after birth. There are significantly more VENs in the right hemisphere than in the left in FI and LA in postnatal brains of apes and humans. This asymmetry in VEN numbers may be related to asymmetries in the autonomic nervous system. The activity of the inferior anterior insula, which contains FI, is related to physiological changes in the body, decision-making, error recognition, and awareness. The VENs appear to be projection neurons, although their targets are unknown. We made a preliminary study of the connections of FI cortex based on diffusion tensor imaging in the brain of a gorilla. The VEN-containing regions connect to the frontal pole as well as to other parts of frontal and insular cortex, the septum, and the amygdala. It is likely that the VENs in FI are projecting to some or all of these structures and relaying information related to autonomic control, decision-making, or awareness. The VENs selectively express the bombesin peptides neuromedin B (NMB) and gastrin releasing peptide (GRP) which are also expressed in another population of closely related neurons, the fork cells. NMB and GRP signal satiety. The genes for NMB and GRP are expressed selectively in small populations of neurons in the insular cortex in mice. These populations may be related to the VEN and fork cells and may be involved in the regulation of appetite. The loss of these cells may be related to the loss of satiety signaling in patients with frontotemporal dementia who have damage to FI. The VENs and fork cells may be morphological specializations of an ancient population of neurons involved in the control of appetite present in the insular cortex in all mammals. We found that the protein encoded by the gene DISC1 (disrupted in schizophrenia) is preferentially expressed by the VENs. DISC1 has undergone rapid evolutionary change in the line leading to humans, and since it suppresses dendritic branching it may be involved in the distinctive VEN morphology.

Maternal separation of rat pups for 15 min each day over the first one to two postnatal weeks (MS15) has been shown to increase the active maternal care received by pups and to decrease their later neuroendocrine and behavioral stress reactivity compared to non-separated (NS) controls. Stress responses prominently feature altered gastric secretion and motility, and we previously reported that the developmental assembly of forebrain circuits underlying gastric autonomic control, including gastric responses to stress, is delayed by MS15 in neonatal rats [Card JP, Levitt P, Gluhovsky M, Rinaman L (2005) J Neurosci 25(40):9102-9111]. To determine how this early delay affects the later organization of central gastric autonomic circuits, the present study examined the effects of neonatal MS15 on central pre-gastric circuits assessed in post-weaning, juvenile rats. For this purpose, the retrograde transynaptic viral tracer, pseudorabies virus (PRV), was microinjected into the stomach wall of 28-30 day old male rats with an earlier developmental history of either MS15 or NS. Rats were perfused 72 h later and tissue was processed to reveal PRV-positive cells. Transynaptic PRV immunolabeling was quantified in selected preautonomic brainstem and forebrain regions, including the area postrema, bed nucleus of the stria terminalis, central nucleus of the amygdala, paraventricular nucleus of the hypothalamus (PVN), and visceral cortices. Compared to NS controls, MS15 rats displayed a significantly greater amount of PRV labeling within the PVN, including both the dorsal cap and ventral subnuclei. There were no postnatal group differences in the amount of PRV labeling within any other brain region examined in this study. This effect of MS15 to enhance hypothalamic preautonomic circuit structure indicates a strengthening of this pathway and may provide insight into how early life experience produces differential effects on later stress reactivity, including gastric secretory and motor responses to stress.

The basic helix-loop-helix transcription factor Hand2 is induced by bone morphogenetic proteins (BMPs) in neural crest-derived precursor cells during the early stage of development of the autonomic nervous system (ANS). Previous studies showed that Hand2 was essential for the ANS differentiation. However, regulatory mechanism of pluripotent genes has not been elucidated in ANS differentiation. Here, we show that Hand2 regulated nanog expression in ANS differentiation. Our studies demonstrated that the forced expression of Hand2 promoted the ANS differentiation program in P19 embryonal carcinoma (EC) cells without aggregation. Furthermore, our results suggested that Hand2 bound to the promoter of nanog, a gene required for embryonic stem cells self-renewal, and suppressed nanog expression after Hand2 induction. The rapid downregulation of nanog mRNA during ANS differentiation correlated with the Hand2 transcriptional activity and nanog promoter methylation. These findings are evidence for a presence of the novel regulatory mechanism of nanog in ANS differentiation.

In developed countries, sudden infant death syndrome (SIDS) is the most common cause of death for infants between 1 month and 1 year of age. The etiology of SIDS is likely to be multifactorial, and current paradigms often describe three overlapping elements of risk. Those elements are a critical developmental period, a vulnerable infant, and one or more exogenous stressors. In the triple-risk model, SIDS infants are described as having an underlying vulnerability in cardiorespiratory control in the central nervous system during a critical period when autonomic control is developing. This vulnerability might affect the response to exogenous stressors, including prone sleeping position, hypoxia, and increased carbon dioxide. In the common bacterial hypothesis and fatal triangle, the focus is on the stressors. In the first, a combination of common respiratory infections can cause SIDS in an infant during a developmentally vulnerable period. This theory also includes 3 factors of vulnerability: a genetic predisposition, a vulnerable developmental age, and infectious stressors. In the fatal triangle theory, infection, inflammation, and genetics each play a role in triggering a SIDS fatality. From our work in an animal model, we have found that rat pups die from a combination of infectious insults during a critical time of development. This is exacerbated by perinatal nicotine exposure, a condition shown to alter the autonomic response in exposed offspring. We are proposing that shock and cardiovascular collapse is a key element that links these theories.

Background: Being born preterm, small, and to a mother who smokes are common perinatal complications with major public health implications. Evidence suggests that each affects the body's structure and function in ways that could increase susceptibility to cardiovascular dysfunction later in life. Here, we used 2 routine stress reactivity tests to identify incipient "silent" programming of cardiovascular dysfunction associated with adverse perinatal events., Methods and Results: We studied 29 control babies born at term to nonsmokers, 18 term-born babies of mothers who smoked throughout pregnancy (mean, 15 cigarettes a day), and 31 babies born preterm to nonsmokers. All infants were compared at the same age after conception (ie, at 40 to 42 weeks), during sleep. We analyzed blood pressure (BP) and heart rate responses to breathing 4% CO(2) for 4 minutes or to passive head-up tilt to 60 degrees . BP was measured continuously from a wrist cuff. CO(2) exposure raised heart rate and BP in controls by 10%, and tilt increased their BP by 5%. CO(2) elicited the expected BP but no heart rate response from preterm infants but a much-greater-than-expected BP and heart rate response from babies of smokers. Tilt elicited a 3- to 4-fold greater rise in BP from preterm and tobacco-exposed babies., Conclusions: Vascular, cardiac, and blood pressure reactivity is heightened in babies born preterm or to smokers. The findings are consistent with in utero and early postnatal "programming" of human cardiovascular dysfunction by adverse circumstances. This incipient dysfunction may be an early manifestation of processes that lead to other problems or complications later on (eg, higher BP or sudden infant death syndrome).

A decrease in maximal exercise heart rate (HR(max)) is a key contributor to reductions in aerobic exercise capacity with aging. However, the mechanisms involved are incompletely understood. We sought to gain insight into the respective roles of intrinsic heart rate (HR(int)) and chronotropic beta-adrenergic responsiveness in the reductions in HR(max) with aging in healthy adults. HR(max) (Balke treadmill protocol to exhaustion), HR(int) (HR during acute ganglionic blockade with intravenous trimethaphan), and chronotropic beta-adrenergic responsiveness (increase in HR with incremental intravenous infusion of isoproterenol during ganglionic blockade) were determined in 15 older (65 +/- 5 yr) and 15 young (25 +/- 4 yr) healthy men. In the older men, HR(max) was lower (162 +/- 9 vs. 191 +/- 11 beats/min, P < 0.0001) and was associated with a lower HR(int) (58 +/- 7 vs. 83 +/- 9 beats/min, P < 0.0001) and chronotropic beta-adrenergic responsiveness (0.094 +/- 0.036 vs. 0.154 +/- 0.045 DeltaHR/[isoproterenol]: P < 0.0001). Both HR(int) (r = 0.87, P < 0.0001) and chronotropic beta-adrenergic responsiveness (r = 0.61, P < 0.0001) were positively related to HR(max). Accounting for the effects of HR(int) and chronotropic beta-adrenergic responsiveness reduced the age-related difference in HR(max) by 83%, rendering it statistically nonsignificant (P = 0.2). Maximal oxygen consumption was lower in the older men (34.9 +/- 8.1 vs. 48.6 +/- 6.7 ml x kg(-1) x min(-1), P < 0.0001) and was positively related to HR(max) (r = 0.62, P < 0.0001), HR(int) (r = 0.51, P = 0.002), and chronotropic beta-adrenergic responsiveness (r = 0.47, P = 0.005). Our findings indicate that, together, reductions in HR(int) and chronotropic responsiveness to beta-adrenergic stimulation largely explain decreases in HR(max) with aging, with the reduction in HR(int) playing by far the greatest role.

One objective of this paper is to confirm the coupling between heart rate (HR) changes and electroencephalographic (EEG) bursts (as reported for the first time in Pfurtscheller et al. [K. Pfurtscheller, G.R. Müller-Putz, B. Urlesberger, W. Müller, G. Pfurtscheller, Relationship between slow-wave EEG bursts and heart rate changes in preterm infants, Neurosci. Lett. 385 (2) (2005) 126-130]) in a larger group of preterm infants. Other objectives are to report on semi-automatic detection of burst-to-burst intervals (BBI, time period between the onsets of 2 consecutive EEG bursts) and on correlations between BBI and HR changes. A group of 34 preterm infants with a conceptional age (CA) of 35.9+/-0.6 weeks (mean+/-S.D.) was studied. Periods with a length of about 10 min with low HR variability and discontinuous EEG were selected from long-term EEG and ECG registrations and analyzed. From the automated detection of EEG bursts, an estimate for the mean burst-to-burst interval was obtained. EEG trials with a duration of 16s and a single EEG burst in the middle, were selected and averaged together with the corresponding instantaneous HR trials. It was found that preterm infants without evidence of neurological deficit and with normal development revealed a mean BBI of 13.4+/-2.6s (mean+/-S.D.) and a HR increase of 1.7+/-0.9 bpm (mean+/-S.D.) during the occurrence of EEG bursts. This HR increase is comparable with the earlier reported increase of 1.9+/-0.8 bpm. A significant negative correlation of r=0.453 (p<0.01) was found between BBI and HR increase and a positive correlation between CA and HRV (r=0.438, p<0.01) and between CA and HRI (r=0.452, p<0.01).

A reliable basal heart rate (HR) measurement in freely moving newborn mice was accomplished for the first time by using a novel noninvasive piezoelectric transducer (PZT) sensor. The basal HR was approximately 320 beats/min at postnatal day (P)0 and increased with age to approximately 690 beats/min at P14. Contribution of autonomic control to HR was then assessed. Sympathetic blockade with metoprolol significantly reduced basal HR at both P6 (-236 +/- 23 beats/min; mean +/- SE) and P12 (-105 +/- 8 beats/min), but atropine was without effect, indicating the predominant tonic adrenergic stimulation and absence of vagal control for basal HR in newborn mice. In contrast to stable basal HR during 5-min recording, HR measured by ECG (ECG-HR) was markedly decreased because of the restraint stress of attaching ECG electrodes, with accompanying freezing behavior. ECG-HR lowered and further decreased gradually during 5 min (slow cardiodeceleration) at P0-P3 and rapidly decreased and gradually recovered within 5 min (transient bradycardia) at P9-P14. The response was not uniform in P4-P8 mice: they showed either of these two patterns or sustained bradycardia (9-29%), and the number of mice that showed transient bradycardia increased with age (30-100%) during the period. Studies with autonomic blockade suggest that the slow cardiodeceleration and transient bradycardia are mediated mainly by withdrawal of adrenergic stimulation and phasic vagal activation, respectively, and the autonomic control of HR response to restraint stress is likely to change from the withdrawal of adrenergic stimulation to the phasic vagal activation at different stages during P4-P8 in individual mice. The PZT sensor may offer excellent opportunities to monitor basal HR of small animals noninvasively.

Results obtained from complex medical-physiological investigations performed during 10 scientific expeditions in the Arkhangel'sk Region in 2003-2005 are presented. The effects of climatological-geographic, biogeochemical, and social conditions of the conditions obtaining in the Far North region of Russia on sexual maturation, formation of the structural-functional organization of the brain, autonomic functions, and immunological and biochemical status of schoolchildren were studied using state-of-the-art neurophysiological methods (computerized electroencephalography, computerized rheoencephalography, computerized electric dipole origin tomography, etc.), psychophysiological and psychometric methods (assessment of the state of cognitive and memory functions, Wechsler intellectual scale), along with biochemical assay of monoamine oxidase (MAO, the key enzyme in adrenergic neurotransmitter metabolism) and the liver enzyme butyrylcholinesterase (BuChE) and physicochemical analysis of the levels of macroelements and trace elements in the body.

The premature population reaching theoretical term suffers from a major deficit in autonomic nervous system (ANS) activity, as can be seen from heart rate variability indices. Whether this autonomic function recovers in the long term is not yet established. Thus, we analyzed and compared ANS activity indices, at birth or at the time of the theoretical term, and at ages 2-3 and 6-7 years, in two populations: a group of 30 premature children and a reference group of 14 full-term age-matched newborns. Using Fourier Transform analysis, we studied 24-h ECG Holter recordings to establish heart rate variability indices: Ptot, VLF, LF, HF, ratio LF/HF, LFnu, HFnu. In the neonatal period, sympathetic and even more markedly, parasympathetic activities were very low in prematures compared to the reference full-term group. At ages 2-3 and 6-7 years, prematures had recovered and had similar ANS activity as the full-term group. These data suggest a fast ANS maturation in prematures during the two first years of life, with a higher speed of recovery for the parasympathetic arm. Furthermore, compared evolution shows a faster ANS maturation in premature. Potential mechanisms are discussed.