68 The Journal of Maternal-Fetal and Neonatal Medicine, 2012; 25(S5): 68–71 © 2012 Informa UK, Ltd. ISSN 1476-7058 print/ISSN 1476-4954 online DOI: 10.3109/14767058.2012.714643 Multiple organ failure (MOF) syndrome, also known as multiple organ dysfunction syndrome (MODS) represents a common but complex problem in critically ill patients in neonatal intensive care unit (NICU) centers, and a major cause of morbidity and mortality in newborns. MOF is considered the result of an inap- propriate generalized inflammatory response of the newborn to a variety of acute insults. This study was aimed at analyzing, at histology, multiple organ pathological changes in two newborns admitted to the NICU center of our University Hospital, who showed a progressive clinical picture of MOF, in order to verify the pathological changes of vascular structures and of endothe- lial cells in the different organs affected by MOF. All the samples obtained at autopsy for histological examination showed specific organ pathological changes, especially related to modi- fications in vascular structures and, in particular, in endothelial cells. The most interesting findings were found in the intestinal barrier, in the lower respiratory tract and in the endothelial barrier. The loss of the gut barrier could allow the passage into the blood of microbial factors that could trigger the production of tumor necrosis factor α (TNFα) leading to endothelial damage. Our preliminary study underlines the principal role probably played by intestinal and vascular changes in the origin of MOF in newborns. Keywords: Histology, immunoistochemistry, multiple organ failure syndrome, newborn Introduction Multiple organ failure (MOF) syndrome, also known as multiple organ dysfunction syndrome (MODS) represents a common but complex problem in critically ill patients in neonatal intensive care unit (NICU) centers, and a major cause of morbidity and mortality in newborns [1,2]. he MOF syndrome has been classi- cally deined by the involvement of seven systems: the respiratory, the renal, the suprarenal, the cardiovascular, the hematologic, the hepatic, and the central nervous system [3]. Even though these seven systems should be considered as the most frequently involved in the pathogenesis of MOF, on the other hand all organ systems may be involved in MOF, including pancreas with pancreatic necrosis [4] and the gut, with necrotizing enteroco- litis followed by endotoxemia and release of proinlammatory cytokines [5]. In an experimental model of MOF, the ZIGI rat model, neonatal MOF difered signiicantly from adult MOF. In newborn rats, MOF was characterized by relative sparing of lungs from injury, and by a unique progression of organ involve- ment, liver-kidney-lung. Moreover, newborn rats sufering from MOF, diferent from adult animals, showed an early generalized capillary leak, resulting in increasing body weight [6]. In human neonates, descriptors for multiple organ dysfunction have been identiied in at least ive organ systems: cardiovascular (lactic acid), hepatic (bilirubin), respiratory (Pa O 2 /Fi O 2 ratio), hemato- logic (ibrinogen), and renal (blood urea nitrogen) [7]. In a recent study carried out on 1806 patients admitted to pediatric inten- sive care units, diferences in the outcome of MOF were shown between newborns and older children. Among neonates, the mortality rate was higher, whereas neurological, cardiovascular and hepatic dysfunctions were the only signiicant contributors to neonatal mortality [8]. MOF is considered the result of an inappropriate generalized inlammatory response of the newborn to a variety of acute insults, including respiratory distress syndrome [9] acute kidney injury (AKI) [10], perinatal asphyxia [11,12], hypoxic-ischemic encephalopathy [13], and pandemic inluenza A (H1N1) virus infection [14]. In cases in which no infectious or non infectious aetiologies are found, the deinition of systemic inlammatory response syndrome (SIRS) has been suggested [15]. he following sequence of events determining multiple organ dysfunction has been hypothesized: (i) failure of the gut barrier, endotoxemia, and release of proinlammatory cytokines, including IL1β, TNFα, IL-6, and ETX (Figure 1); (ii) upregulation of adhesion molecules in the vascular bed of multiple organs by circulating cytokines; (iii) universal TNFα-induced endothelial injury and apoptosis, causing a generalized capillary leak (Figure 2); (iv) generalized oedema and activation of intrinsic inlammatory cells in diferent organs; and (v) organ failure [2,5]. he role of circulating proinlammatory citokines on the pathogenesis of MOF has been clariied by the therapeutic role of therapeutic plasma exchange (TPE): improvement in organ function and platelet count occurred in most pediatric patients sufering from sepsis-induced MOF [16]. Moreover, recent studies have shown that hepatocyte growth factor (HGF) should be considered a new candidate for the therapy of MOF, due to its ability to inhibit the upregulation of inlammatory cytokines and target endothelial cells, protecting them from cytokine-induced apoptosis [17]. Speciic pathogenetic mechanisms may be added to this general scheme in patients Multiple organ failure syndrome in the newborn: morphological and immunohistochemical data Gavino Faa 1 , Daniela Fanni 1 , Clara Gerosa 1 , Sonia Nemolato 1 , Armando Faa 1 , Eleonora Obinu 1 , Elisabetta Puxeddu 2 , Matteo Fraschini 3 , Nicoletta Iacovidou 4 , Marco Zafanello 5 & Vassilios Fanos 2 1 Department of Pathology, University of Cagliari, Cagliari, Italy, 2 Department of Surgery, Neonatal Intensive Care Unit, Puericulture Institute and Neonatal Section, University of Cagliari, Cagliari, Italy, 3 Department of Electrical and Electronic Engineering, University of Cagliari, Cagliari, Italy, 4 Department of Obstetrics and Gynaecology, Aretaieion Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece, and 5 Department of Life and Reproduction Sciences, University of Verona, Verona, Italy Correspondence: Prof Gavino Faa, Department of Surgery, Institute of Pathology, University of Cagliari, Cagliari, Italy. 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