An overview of developmental dysregulation of autonomic control in infants

Abstract

In this short review, we provide an overview of developmental disorders causing autonomic nervous system dysregulation. We briefly discuss perinatal conditions that adversely impact developmental outcomes including apnea of prematurity, sudden infant death syndrome, and Rett syndrome. We provide a brief clinical description, an overview of known or hypothesized mechanisms for the disorder, and current standard of practice for treatment of each condition. Additionally, we consider preventative measures and complications of these disorders to provide further insight into the pathogenesis of specific autonomic dysregulation in neonates. The goal of this short review is to provide an updated understanding of the impact of autonomic dysregulation on development of brainstem circuits and to briefly highlight promising future treatment options and controversies.

SubSol-HIe is an AMPK-dependent hypoxia-responsive subnucleus of the nucleus tractus solitarius that coordinates the hypoxic ventilatory response and protects against apnoea in mice

“…When considered alongside the emergence of apnoea during severe poikilocapnic hypoxia [ 59 ], this provides further support for the view that AMPK gain of function may represent a major maturational element underlying the central nervous system component of the shift from neonatal HVR to adult HVR patterning [ 32 ]. Conversely, AMPK deficiency might precipitate apnoea of prematurity, which contributes to cardiopulmonary arrest and respiratory failure in neonates [ 4 , 64 ] (requiring longer-term intensive care) and SIDS [ 12 ], when apnoea of prematurity occurs in concert with cyclical tachypnoea and brief apnoea [ 12 , 64 ]. In accordance with this and the site of SubSol-HIe within the NTS, it has been highlighted that with respect to SIDS, there is a critical gap in our knowledge regarding the integration and regulation of peripheral afferents and descending autonomic ventilatory control mechanisms at the NTS [ 4 ], where reduced chemoreceptor sensitivity and reduced CNS oxygenation [ 72 ] may contribute to dysregulation of respiratory rhythm and autoresuscitation failure [ 4 , 17 , 64 ].…”

“…Conversely, AMPK deficiency might precipitate apnoea of prematurity, which contributes to cardiopulmonary arrest and respiratory failure in neonates [ 4 , 64 ] (requiring longer-term intensive care) and SIDS [ 12 ], when apnoea of prematurity occurs in concert with cyclical tachypnoea and brief apnoea [ 12 , 64 ]. In accordance with this and the site of SubSol-HIe within the NTS, it has been highlighted that with respect to SIDS, there is a critical gap in our knowledge regarding the integration and regulation of peripheral afferents and descending autonomic ventilatory control mechanisms at the NTS [ 4 ], where reduced chemoreceptor sensitivity and reduced CNS oxygenation [ 72 ] may contribute to dysregulation of respiratory rhythm and autoresuscitation failure [ 4 , 17 , 64 ]. This is all the more intriguing, because cell-specific AMPK deficiency accompanies obesity and type 2 diabetes [ 30 , 76 , 91 ], which represent maternal stressors strongly associated with SIDS [ 43 , 84 ], and these stressors are also strongly associated with central sleep apnoea in adults [ 26 , 62 , 74 , 79 , 89 ].…”