The Critical Role of the Central Autonomic Nervous System in Fetal-Neonatal Transition☆
Introduction
Transition from a fetal to neonatal physiology is not only the most complex and profound event before death, it is also the first major challenge of postnatal life. The central autonomic nervous system (ANS) centers in the brain stem play a critical role in the cardiovascular and respiratory adaptations required for successful fetal-neonatal transition. At birth, the ANS centers in the brain stem, both sympathetic and parasympathetic divisions, exert coordinated control over the infant’s cardiovascular and respiratory systems. These neural systems are supported by major endocrine changes, including a powerful surge of catecholamine levels at birth which provides more sustained support to the sympathetic nervous system. Together these processes enable both brisk and sustained responses by which the cardiovascular system adapts to postnatal life.1 Prenatal maternal and fetal conditions may impair these physiological adaptive systems of the ANS in the transitioning fetus and necessitate the use of medical interventions and devices to support the neonate at transition and in the early days after birth. In addition, recent data support an important role for the mature ANS in critical higher order cortical functions involving behavior, affect or mood, and adaptive responses to stress; dysfunction in these domains may significantly affect long-term health and psychological well-being of the individual.2 Evidence is emerging that adverse early exposures, even before birth and in the neonatal period, can affect ANS maturation and function and that this can lead to infant mortality,3, 4 psychological and mood disorders,2, 5 and cardiovascular disease into adulthood.6
In spite of our growing understanding of the mature ANS, our understanding of normal ANS maturation, at both the brain stem and cerebral levels, as well as factors that disrupt normal ANS development and create additional challenge for the fetus at transition, remains limited. In this article we review the anatomy of the central ANS, review what is known about ANS maturation and development during fetal life, and how ANS function can be noninvasively measured. We then explore how the central ANS supports normal and complicated fetal-neonatal transition and discuss how ANS failure or dysfunction may lead to brain injury (or brain injury lead to ANS dysfunction). Finally, we address future areas for research and clinical advancements for the field.
Section snippets
Anatomy and Function of the Developing Central ANS
The central ANS has 2 major branches, the sympathetic nervous system, responsible for the well-known “fight-or-flight” response and the parasympathetic nervous system, responsible for relaxation and moderating control over the active sympathetic system. This is a rather simplified view of the competing roles of these systems, as in reality they are considerably complex. It is the coordinated and in some ways opposing activities of these systems that maintains the body endogenous systems in
Normal Development of the Central ANS: Current Understanding
The ANS matures during development of the central nervous system in the fetal period and continues to mature after birth.21, 22 A number of studies have demonstrated the nonsynchronous maturation of the sympathetic and parasympathetic systems. The unmyelinated and more primitive, dorsal motor nucleus of the vagus (parasympathetic) is the first to structurally appear, however is slow and not very responsive to the demands of the fetus or newborn.23 Onset of sympathetic development is next and
Current Techniques for Assessing the ANS
Fetal heart rate is the only reliable continuous physiologic signal that is readily accessible from the fetus. Within the fetal electrocardiogram (EKG) signal is embedded information regarding the ANS functional status and maturation level. Although Doppler-based measures of fetal heart rate do not have the resolution required for quantitative measures of ANS function, a number of devices have been developed capable of acquiring high-quality fetal EKG signals from the mother’s abdomen (eg,
Current Understanding of the ANS in Normal Transition
Intact ANS function, especially in the sympathetic nervous system, is critical during birth and transition. Sympathetic outflow from the brain stem and from higher brain centers, including the hypothalamus and forebrain, surges at birth,19 to support successful transition of the fetus to neonatal life.1 Cortisol and catecholamine levels in the fetus increase significantly after the 30th week of gestation, and play a critical role during transition of the fetus to the extrauterine environment by
Challenges to the Successful Role of the ANS in Transition
Success of the fetus at transition relies on ANS support of the cardiovascular, respiratory, and hypothalamic-pituitary-adrenal systems. As discussed earlier, under normal circumstances there is significant development and maturation of the ANS throughout the second half of pregnancy. However, when this development or maturation is disrupted, the fetal ANS may be significantly compromised going into labor and may not be able to support successful transition. Depending upon the severity of
How ANS Failure During Transition May Lead to Brain Injury
The fetus and transitioning newborn is at risk for brain injury. As described, the ANS is intimately involved in many aspects of successful transition of the newborn including cardiovascular, endocrine, and respiratory functions. These demands on the ANS come at a time when the ANS is still in active development, and therefore at particular risk for developmental derailment. At delivery and especially before term, the ANS itself is immature and therefore vulnerable for injury and dysmaturation.
Important Areas for Future Focus
Recent technological advancements have enhanced our ability to measure fetal physiology and ANS function using fetal EKG and advanced signal processing. Fetal brain structure can be quantified through advanced fetal magnetic resonance imaging techniques. These tools are bringing us closer to understanding the complex function of the developing ANS in supporting the fetus at transition. In addition, we are steadily improving our understanding of the multiple maternal and fetal conditions, which
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Contemporary Understanding of the Central Autonomic Nervous System in Fetal-Neonatal Transition
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2023, Seminars in Pediatric NeurologyKnowledge gaps in optimal umbilical cord management at birth
2023, Seminars in PerinatologyWhy, when and how to assess autonomic nervous system maturation in neonatal care units: A practical overview
2023, Neurophysiologie CliniqueDynamic touch induces autonomic changes in preterm infants as measured by changes in heart rate variability
2023, Brain ResearchCitation Excerpt :For this reason, these findings could reflect a more balanced and organized ANS activity in the preterm infants who received dynamic touch compared to the ones who have received static touch. Indeed, higher VLF power and SDNN are correlated with better neurodevelopment (Dimitrijević et al., 2016) and physiological or clinical outcomes, for instance, inflammation regulation and success in being extubated (Kaczmarek et al., 2013; Latremouille et al., 2018; Marsillio et al., 2019; Shaffer and Ginsberg, 2017), whereas lower LF power, due to its modulation by the baroreceptor reflex, could represent a decrease in blood pressure and, thus, a more controlled cardiac output (Mulkey and du Plessis, 2018; Shaffer and Ginsberg, 2017). Moreover, a decrease in LF power is usually seen in the postnatal period and, therefore, it is recognized as a sign of better cardiovagal modulation (Kozar et al., 2018; Mulkey and du Plessis, 2018).
Multi-level hypothalamic neuromodulation of self-regulation and cognition in preterm infants: Towards a control systems model
2022, Comprehensive PsychoneuroendocrinologyCitation Excerpt :In premature delivery, the levels of cortisol may be insufficient for optimal transition [62]. In this respect, adrenal immaturity in preterm infants is associated with lower cortisol rise at birth, further complicating transition [138] and often producing hypotension which can be treated with exogenous cortisol administration [48,98]. In addition, metabolic stress and reduced mechanisms for coping with extra-uterine environmental stress also have been related to reduced levels of thyroid hormone in preterm infants [93].
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Dr Mulkey receives support by Award numbers UL1TR001876 and KL2TR001877 from the NIH National Center for Advancing Translational Sciences. The contents are solely the responsibility of the author and do not necessarily represent the official views of the National Center for Advancing Translational Sciences or the National Institutes of Health.