title: Developmental neuropathology of brainstem respiratory centers in unexplained stillbirth: What's the meaning?
abstract: Stillbirth is one of the most stressful life events affecting over 3 million pregnancies per year throughout the world. An accurate autopsy of the stillborn fetus, including the placenta and umbilical cord examination, should be performed promptly after delivery. A thorough maternal history also should be taken, including exposures to risk factors. In many cases a death cause, attributable to fetal, maternal, or placental pathology, is clearly identified. However, in 50% or more of cases the cause remains unknown. The purpose of this study is to highlight possible developmental alterations of the autonomic nervous system in unexplained stillbirths to provide an explanation of the pathogenetic mechanism of their death. We conducted a careful neuropathological study of the brainstem, where the main vital centers are located, in 85 unexplained stillbirths and 52 age-matched controls died of known cause. Information on the maternal lifestyle, including the smoking habit, was collected in all cases. Hypodevelopment of neuronal centers involved in breathing control, all connected together in a "respiratory network", precisely hypoplasia of the facial/parafacial complex, Kölliker-Fuse nucleus, pre-Bötzinger nucleus and intermediolateral nucleus, were frequently observed in unexplained deaths, significantly related to maternal cigarette smoking. We support the hypothesis of a strong action of maternal smoking during pregnancy on the development of brainstem respiratory nuclei and suggest an explanation of the high incidence of the respiratory network alterations in unexplained fetal death, when breathing not represents a vital function.
authors.affiliation: "Lino Rossi" Research Center for the Study and Prevention of Unexpected Perinatal Death and SIDS; Department of Biomedical, Surgical and Dental Sciences, University of Milan, Italy. Electronic address: anna.lavezzi@unimi.it.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Lavezzi
authors.affiliation: "Lino Rossi" Research Center for the Study and Prevention of Unexpected Perinatal Death and SIDS; Department of Biomedical, Surgical and Dental Sciences, University of Milan, Italy; Division of Pathology, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy; Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Ferrero
authors.affiliation: "Lino Rossi" Research Center for the Study and Prevention of Unexpected Perinatal Death and SIDS; Department of Biomedical, Surgical and Dental Sciences, University of Milan, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Matturri
authors.affiliation: Institute of Pathology, Hospital of Rovereto (Trento), Italy; Department of Diagnostic and Clinical Medicine and of Public Health, Section of Pathology, University of Modena and Reggio Emilia, Policlinico Hospital, Modena, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Roncati
authors.affiliation: Institute of Pathology, Hospital of Rovereto (Trento), Italy.
authors.forename: Teresa
authors.initials: T
authors.lastname: Pusiol
mesh_terms: D001342:Autonomic Nervous System Diseases / Q000209:etiology* / Q000473:pathology; D001933:Brain Stem / Q000473:pathology*; D005260:Female; D005333:Fetus / Q000473:pathology; D005865:Gestational Age; D006801:Humans; D008297:Male; D009422:Nervous System Diseases / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology*; D000069338:Neuropathology; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D011247:Pregnancy; D012125:Respiratory Center / Q000473:pathology*; D018709:Statistics, Nonparametric; D050497:Stillbirth
chemical_list: D010751:Phosphopyruvate Hydratase
keywords: Brainstem; Developmental alterations; Maternal smoking; Respiratory network; Unexplained stillbirth