Original Article Histo-topographic distribution of acute inflammation of the human umbilical cord Chong Jai Kim, 1,3 Bo Hyun Yoon, 2,3 Miha Kim, 2,3 Jung Ok Park, 1,3 So Young Cho 1,3 and Je G. Chi 1,3 Departments of 1 Pathology and 2 Obstetrics and Gynecology, Seoul National University College of Medicine and 3 Laboratory of Fetal Medicine Research, Clinical Research Institute, Seoul National University Hospital, Seoul, Korea identification of fetal infection indicators is important because of the association with increased short- and long-term mor- bidity. Several clinicopathological parameters including signs of clinical chorioamnionitis, amniotic fluid microbiology, and histological chorioamnionitis have been traditionally used as surrogate markers of intrauterine infection. 4,5 In a broad sense, the definition of acute chorioamnionitis encompasses acute inflammation of the fetal membrane, placenta (chorionic plate) and the umbilical cord. In terms of leukocytic response, however, inflammation of the fetal mem- brane and the chorionic plate are largely a result of the migra- tion of maternal leukocytes, while umbilical cord inflammation (funisitis) is a purely fetal type of acute vasculitis involving either the umbilical vein or artery. 6 In this respect, it seems reasonable to speculate that funisitis can potentially precipi- tate more ominous sequences in the fetus, and in this context we have recently shown that the presence of funisitis is asso- ciated with higher fetal plasma interleukin (IL)-6, and higher incidence of amniotic fluid infection and congenital sepsis. 7 Improved understanding of these issues raises the need for a more detailed histopathological examination of acute funisitis; moreover, the evolutionary changes of funisitis are not fully appreciated. In the present study, we investigated the topographic distribution of funisitis by histopathologically examining umbilical cords with inflammation along their entire lengths by serial sectioning, to assess the propagation pattern and the significance of acute funisitis. MATERIALS AND METHODS Study design and histo-topographic analysis of funisitis Of 125 consecutive deliveries at the Department of Obstetrics and Gynecology, Seoul National University Hospital, a total of five umbilical cords with acute funisitis were selected by frozen section of both ends during the period 1–14 December 1998. For further clarification of the funisitis pattern, five umbilical Pathology International 2001; 51: 861–865 Acute inflammation of the umbilical cord, acute funisitis, is a sign of fetal inflammatory response, and the clinicopatho- logical need for its identification is increasing. This study was conducted in order to describe the topographic dis- tribution of acute funisitis, and thereby to provide more information on the intrinsic nature of acute funisitis and find a better way of pathologically examining the umbilical cord. A total of 10 umbilical cords affected by acute funisitis were histopathologically examined throughout their entire lengths at 1 mm intervals. Pathological examination was done to characterize the extent of the funisitis, the involve- ment of the vein (phlebitis) or of one or both arteries (arteri- tis), and the presence of inflammation in Wharton’s jelly. Umbilical cord plasma interleukin (IL)-6 was measured by specific immunoassay to assess whether or not the severity of acute funisitis correlates with fetal cytokine response. It would appear that the inflammatory reaction begins as a discrete, multifocal process which eventually becomes con- tiguous as the inflammatory reaction proceeds. Umbilical cord plasma IL-6 concentrations tended to correlate with the extent of umbilical cord inflammation. The initial phase of acute funisitis involves discrete and multiple foci along the length of the umbilical cord. Moreover, the extent of acute funisitis reflects the severity of systemic fetal cytokine response. Therefore, adequate sampling using multiple sec- tions would facilitate the identification of acute funisitis. We propose a standard sampling procedure taking one section from each third of the umbilical cord. Key words: inflammation, interleukin-6, topography, umbilical cord Intrauterine infection resulting from microbial invasion of the amniotic cavity seriously affects the well-being of a fetus, and is associated with a significantly higher incidence of prema- ture rupture of the membrane and preterm delivery. 1–3 The Correspondence: Chong Jai Kim, MD, Department of Pathology, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, Seoul 110-799, Korea. Email: cjkim@plaza.snu.ac.kr Received 23 February 2001. Accepted for publication 3 August 2001.