Editorial: Updates on the Neuropathology of Sudden Unexplained Perinatal Death and Other Neurodevelopmental Disorders

Abstract

Perinatal mortality includes both fetal demises (stillbirths) and deaths in the first week of life. Worldwide, there are over 6.3 million perinatal deaths a year, almost all of which occur in developing countries (1). Stillbirths and neonatal deaths have many common determinants, such as maternal diseases, adverse prenatal exposure, inadequate care or complications during pregnancy and delivery, and genetic mutations. The first few hours of postnatal life are also particularly sensitive, as this is a critical time for a successful transition from intrauterine to extrauterine life wherein newborns are less responsive and more vulnerable to stressors. In case of sudden perinatal death, an important first step is the post-mortem examination since it can reveal the pathology underlying the possible causes of this inauspicious event (2). However, no unique etiology can be determined in most preand post-natal deaths, even after accurate autopsy investigations. Detailed examination of the autonomic nervous system can often reveal subtle developmental alterations, potentially providing a plausible explanation for sudden death (3, 4). Other neurodevelopmental disorders characterized by profound dysautonomia caused by single gene mutations may also lead to sudden unexplained death in perinatal life and infancy. Some of these syndromes are also thought to involve a state of “immaturity” of autonomic control systems. They include Rett syndrome, Cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder, Pitt-Hopkins syndrome, Congenital central hypoventilation syndrome (CCHS), and GRIN1-Related Neurodevelopmental Disorder (5–9). The primary rationale for this Research Topic has been to advance the state of knowledge and expertise for investigating the neuropathology of unexplained perinatal deaths and, in particular: