Neonatal pulmonary hypoplasia frequently associated with brainstem hypodevelopment

Our recent studies in stillbirths have reported the frequent detection of hypoplasia of both the arcuate nucleus and the lungs. The objective of this study was to correlate neonatal lung and brainstem development. A total of 58 sudden perinatal unexplained deaths were investigated. A complete autopsy was performed, including an in-depth examination of the brainstem as well as of the cardiac conduction system on serial sections, according to our guidelines. The stage of lung development was evaluated by a macroscopic criterion, i.e. the correlation between lung weight and body weight (LW/BW), and by a microscopic criterion, namely the radial alveolar count (RAC). In 65% of cases pulmonary hypoplasia was diagnosed, on both the gross and microscopic criteria. In over 50% of cases histological examination of the brainstem showed concomitant hypodevelopment of the brainstem, particularly bilateral hypoplasia, monolateral hypoplasia, partial hypoplasia, delayed neuronal maturation, as well as decreased neuronal density of the arcuate nucleus, an important chemoreceptor center that controls the breathing activity. Hypodevelopment of the pre-Bötzinger and parabrachial Kölliker-Fuse complex cardiorespiratory nuclei was also detected. The possibility of analyzing the development of fetal specific structures in utero by magnetic resonance techniques and so making a prenatal diagnosis of lung hypoplasia associated with arcuate nucleus hypoplasia could have clinical applications in prenatal counseling, allowing early therapeutic planning.