Infant and perinatal pulmonary hypoplasia frequently associated with brainstem hypodevelopment

Abstract

Recent anatomo-pathological studies have revealed a frequent associated hypoplasia of both arcuate nucleus and lungs in stillbirths. The purpose of this study is to analyze the lung and brainstem development in sudden unexplained perinatal death and sudden infant death syndrome (SIDS). A total of 51 cases were investigated. A complete autopsy was performed in each case. Anatomo-pathologic examination of the central autonomic nervous system included an in-depth study on histological serial sections of the brains where the main structures participating in control of the vital functions are located. The stage of lung development was evaluated by macroscopic and microscopic criteria. In 52.9% of cases, a pulmonary hypoplasia was detected. The pulmonary hypoplasia was significantly more frequent in the SIDS group compared to the sudden perinatal unexplained death groups (p < 0.05). In 72.5% of cases, histological examination of the brainstem on serial sections showed hypodevelopment of the brainstem nuclei, particularly hypoplasia, of the arcuate nucleus (60.8%). In 47.1% of cases, pulmonary hypoplasia was associated with brainstem hypodevelopment.

Loss of ATF2 Function Leads to Cranial Motoneuron Degeneration during Embryonic Mouse Development

“…Importantly, in humans, hypoplasia of several brainstem nuclei affected in our ATF2 mutant mice, including the inferior olivary nuclei, the facial, the dorsal vagal and the hypoglossal nuclei have been reported in cases of intrauterine or neonatal sudden death as well as in sudden infant death syndrome [35]. Interestingly, cranial motoneuron nuclei hypo-development is frequently associated with pulmonary hypoplasia and aspiration pneumonia [35], [36]. It is therefore plausible that the brainstem malformation caused by ATF2 mutation leads to similar respiratory defects to those seen in some forms of human sudden death syndromes.…”

“…Cranial motoneurons innervate muscles controlling airway dimensions and exhibit an important rhythmic respiratory activity that is synchronous with the activity of respiratory neurons of the medulla during expiration and inspiration [34]. Importantly, in humans, hypoplasia of several brainstem nuclei affected in our ATF2 mutant mice, including the inferior olivary nuclei, the facial, the dorsal vagal and the hypoglossal nuclei have been reported in cases of intrauterine or neonatal sudden death as well as in sudden infant death syndrome [35]. Interestingly, cranial motoneuron nuclei hypo-development is frequently associated with pulmonary hypoplasia and aspiration pneumonia [35], [36].…”

Possible role of the α7 nicotinic receptors in mediating nicotine’s effect on developing lung – implications in unexplained human perinatal death

“…Previously, we have reported a high incidence of lung hypoplasia in subjects who died of Sudden Intrauterine Unexplained Death Syndrome (SIUDS) and Sudden Infant Death Syndrome (SIDS) [21,22]. In the present study we aimed to investigate whether the lung hypodevelopment frequently observed in these victims may be due, as shown in experimental studies, to a specific hyperactivation of the α7 nAChR subunit in cases of nicotine absorption in pregnancy.…”