Importance of Neuropathological Examination in “Unexplained Stillbirths”

I would like to point out some considerations and provide new insight that may be of interest to readers regarding fetal death, which is currently the most common adverse pregnancy outcome and the leading contributor to perinatal mortality. In developed countries, 1 in 100-200 pregnancies, particularly at or near term, ends in stillbirth. In 2015, there were 2.6 million stillbirths globally, with more than 7,178 deaths per day (1). The reasons of death generally include placental insufficiency, infections, genetic factors, fetal malformations, and maternal health problems. Autoptic investigation, including examination of the placental disk, umbilical cord, and membranes and use of appropriate and standardized diagnostic criteria, is universally considered as a fundamental step to understand the pathogenesis of stillbirths. However, it is well known that intrauterine death remains unexplained in a high percentage of cases (40%-80%) even after a careful autopsy (2). Above all, in these cases, it is very important to perform detailed examination of the autonomic nervous system (ANS) because it can highlight subtle developmental alterations, particularly in brainstem centers that can control basic vital activities, thereby providing a plausible explanation for the interruption of pregnancy.