{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T22:59:27Z","timestamp":1773701967159,"version":"3.50.1"},"reference-count":44,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2024,1,2]],"date-time":"2024-01-02T00:00:00Z","timestamp":1704153600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Deputyship for Research and Innovation, \u201cMinistry of Education\u201d in Saudi Arabia","award":["IFKSUOR3-110-3"],"award-info":[{"award-number":["IFKSUOR3-110-3"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Long-term health consequences are influenced by circumstances that occur during pregnancy. The convergence of the maternal and fetal circulations occurs in the placenta, which is the first organ to develop. Placental pathology provides an accurate diagnosis of amniotic sac inflammation, and pathological alterations in preterm placentas provide evidence for the causes of numerous perinatal pathologies, including spontaneous preterm births. This retrospective study aimed to re-examine placentas regarded as normal by the Obstetrics and Gynecology Department at our institution. Thirty-seven male and forty-seven female placentas were collected following full-term delivery, and the grading and staging of any evident inflammatory responses were evaluated and correlated with the babies\u2019 sex. Full-thickness placental samples that were considered normal and not sent to the histopathology department were obtained from the central and marginal regions of placental discs. Morphological examination of the fresh placenta was conducted, and fetal and maternal inflammatory response syndromes were assessed. In addition, placental villitis of unknown etiology (VUE) and chronic deciduitis were evaluated. Immunohistochemistry was performed to evaluate the patterns of inflammation in the placenta using anti-CD8 and anti-CD68 antibodies. The correlation between silent pathologies and clinical complications or the development of fetal inflammatory response syndrome was measured. In this study, 17 (20%) maternal and 10 (12%) fetal samples showed inflammatory responses. The frequencies of chronic deciduitis and VUE were higher among pregnant Saudi women than previously reported, probably because fetal inflammatory response syndrome goes unnoticed in Saudi Arabia. In addition, the prevalence of fetal and maternal inflammatory responses was higher in the placentas of the mothers of males than in those of females, suggesting that differences occur in the inflammatory response in the placenta depending on the sex of the newborn. Grading placental inflammation (in cases of VUE) typically predicts the degree of maternal anti-fetal cellular rejection; therefore, increasing the number of placental samples sent for microscopic inspection may be preferable because of their significance in identifying the causes of chronic disorders.<\/jats:p>","DOI":"10.3390\/life14010079","type":"journal-article","created":{"date-parts":[[2024,1,2]],"date-time":"2024-01-02T10:36:59Z","timestamp":1704191819000},"page":"79","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Prevalence of Fetal Inflammatory Response Syndrome and Villitis of Unknown Etiology in the Placenta of Saudi Women and Their Association with Baby Sex"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8423-3586","authenticated-orcid":false,"given":"Waleed","family":"Aldahmash","sequence":"first","affiliation":[{"name":"Zoology Department, College of Science, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Khaldoon","family":"Aljerian","sequence":"additional","affiliation":[{"name":"Pathology Department, College of Medicine, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saleh","family":"Alwasel","sequence":"additional","affiliation":[{"name":"Zoology Department, College of Science, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"531543","DOI":"10.3389\/fimmu.2020.531543","article-title":"Maternal-Fetal Inflammation in the Placenta and the Developmental Origins of Health and Disease","volume":"11","author":"Goldstein","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1055\/s-0029-1237424","article-title":"Developmental Origins of Health and Disease: Brief History of the Approach and Current Focus on Epigenetic Mechanisms","volume":"27","author":"Wadhwa","year":"2009","journal-title":"Semin. Reprod. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1334985","DOI":"10.1080\/16549716.2017.1334985","article-title":"Understanding and acting on the developmental origins of health and disease in Africa would improve health across generations","volume":"10","author":"Norris","year":"2017","journal-title":"Glob. Heal. Action"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1017\/S2040174417000010","article-title":"DOHaD at the intersection of maternal immune activation and maternal metabolic stress: A scoping review","volume":"8","author":"Goldstein","year":"2017","journal-title":"J. Dev. Orig. Heal. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1097\/01.AOG.0000255663.47512.23","article-title":"Value of Placental Microbial Evaluation in Diagnosing Intra-amniotic Infection","volume":"109","author":"Pettker","year":"2007","journal-title":"Obstet. Gynecol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1136\/jcp.2008.055244","article-title":"The placenta in preterm birth","volume":"61","year":"2008","journal-title":"J. Clin. Pathol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1016\/j.siny.2006.02.011","article-title":"Inflammatory responses in the placenta and umbilical cord","volume":"11","author":"Redline","year":"2006","journal-title":"Semin. Fetal Neonatal Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1515\/jpm-2014-0249","article-title":"Clinical chorioamnionitis at term I: Microbiology of the amniotic cavity using cultivation and molecular techniques","volume":"43","author":"Romero","year":"2015","journal-title":"J. Perinat. Med."},{"key":"ref_9","unstructured":"Redline, R.W. (2004). Seminars in Neonatology, Elsevier."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.siny.2011.08.003","article-title":"Inflammatory response in acute chorioamnionitis","volume":"17","author":"Redline","year":"2012","journal-title":"Semin. Fetal Neonatal Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"412831","DOI":"10.1155\/2013\/412831","article-title":"The Consequences of Chorioamnionitis: Preterm Birth and Effects on Development","volume":"2013","author":"Galinsky","year":"2013","journal-title":"J. Pregnancy"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"693.e1","DOI":"10.1016\/j.ajog.2017.09.013","article-title":"Are amniotic fluid neutrophils in women with intraamniotic infection and\/or inflammation of fetal or maternal origin?","volume":"217","author":"Romero","year":"2017","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"S29","DOI":"10.1016\/j.ajog.2015.08.040","article-title":"Acute chorioamnionitis and funisitis: Definition, pathologic features, and clinical significance","volume":"213","author":"Kim","year":"2015","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1016\/j.ajog.2004.07.030","article-title":"Severe fetal placental vascular lesions in term infants with neurologic impairment","volume":"192","author":"Redline","year":"2005","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1457","DOI":"10.1016\/S0046-8177(98)90016-8","article-title":"Chronic chorioamnionitis: A clinicopathologic and immunohistochemical study","volume":"29","author":"Jacques","year":"1998","journal-title":"Hum. Pathol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1038\/modpathol.2010.73","article-title":"The frequency, clinical significance, and pathological features of chronic chorioamnionitis: A lesion associated with spontaneous preterm birth","volume":"23","author":"Kim","year":"2010","journal-title":"Mod. Pathol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"S53","DOI":"10.1016\/j.ajog.2015.08.041","article-title":"Chronic inflammation of the placenta: Definition, classification, pathogenesis, and clinical significance","volume":"213","author":"Kim","year":"2015","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"7244","DOI":"10.4049\/jimmunol.0803517","article-title":"Soluble TLR2 Is Present in Human Amniotic Fluid and Modulates the Intraamniotic Inflammatory Response to Infection","volume":"182","author":"Dulay","year":"2009","journal-title":"J. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1093\/aje\/kwm168","article-title":"Histologic Chorioamnionitis and Preterm Delivery","volume":"166","author":"Holzman","year":"2007","journal-title":"Am. J. Epidemiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1515\/jpme.1998.26.1.17","article-title":"TNF, IL-1, IL-6, IL-8 and soluble TNF receptors in relation to chorioamnionitis and premature labor","volume":"26","author":"Arntzen","year":"1998","journal-title":"JPME"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1016\/j.clp.2012.06.010","article-title":"Effects of Chorioamnionitis on the Fetal Lung","volume":"39","author":"Jobe","year":"2012","journal-title":"Clin. Perinatol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"698","DOI":"10.5858\/arpa.2015-0225-CC","article-title":"Sampling and Definitions of Placental Lesions: Amsterdam Placental Workshop Group Consensus Statement","volume":"140","author":"Khong","year":"2016","journal-title":"Arch. Pathol. Lab. Med."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Khong, T.Y., Mooney, E.E., Gordijn, S.J., Morgan, T.K., and Nikkels, P.G. (2019). Introduction: An Approach to Placental Pathology. Pathology of the Placenta: A Practical Guide, Springer.","DOI":"10.1007\/978-3-319-97214-5"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1677\/JOE-10-0174","article-title":"Maternal growth factor regulation of human placental development and fetal growth","volume":"207","author":"Forbes","year":"2010","journal-title":"J. Endocrinol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1509","DOI":"10.1152\/physrev.00029.2015","article-title":"Placental Origins of Chronic Disease","volume":"6","author":"Burton","year":"2016","journal-title":"Physiol. Rev."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"S14","DOI":"10.1016\/j.ajog.2015.08.030","article-title":"The placenta is the center of the chronic disease universe","volume":"213","author":"Thornburg","year":"2015","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Roberts, D.J., Celi, A.C., Riley, L.E., Onderdonk, A.B., Boyd, T.K., Johnson, L.C., and Lieberman, E. (2012). Acute Histologic Chorioamnionitis at Term: Nearly Always Noninfectious. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0031819"},{"key":"ref_28","first-page":"802","article-title":"Placental microbiology and histology and the pathogenesis of chorioamnionitis","volume":"64","author":"Pankuch","year":"1984","journal-title":"Obstet. Gynecol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1382","DOI":"10.1016\/0002-9378(92)91609-E","article-title":"The relationship between acute inflammatory lesions of the preterm placenta and amniotic fluid microbiology","volume":"166","author":"Romero","year":"1992","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.placenta.2021.02.020","article-title":"Chronic villitis of unknown etiology: Investigations into viral pathogenesis","volume":"107","author":"Ernst","year":"2021","journal-title":"Placenta"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1439","DOI":"10.1016\/j.humpath.2007.05.025","article-title":"Villitis of unknown etiology: Noninfectious chronic villitis in the placenta","volume":"38","author":"Redline","year":"2007","journal-title":"Hum. Pathol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1590","DOI":"10.1172\/JCI22906","article-title":"Role of C5 in the development of airway inflammation, airway hyperresponsiveness, and ongoing airway response","volume":"115","author":"Peng","year":"2005","journal-title":"J. Clin. Investig."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"585134","DOI":"10.3389\/fimmu.2020.585134","article-title":"Interleukin (IL)-12 and IL-18 Synergize to Promote MAIT Cell IL-17A and IL-17F Production Independently of IL-23 Signaling","volume":"11","author":"Cole","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1093\/molehr\/7.12.1133","article-title":"Perforin-independent expression of granzyme B and proteinase inhibitor 9 in human testis and placenta suggests a role for granzyme B-mediated proteolysis in reproduction","volume":"7","author":"Hirst","year":"2001","journal-title":"Mol. Hum. Reprod."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1016\/j.placenta.2015.02.004","article-title":"Increased expression of perforin, granzyme B, and C5b-9 in villitis of unknown etiology","volume":"36","author":"Ito","year":"2015","journal-title":"Placenta"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1111\/j.1600-0897.2011.01066.x","article-title":"Maternal HLA Panel-Reactive Antibodies in Early Gestation Positively Correlate with Chronic Chorioamnionitis: Evidence in Support of the Chronic Nature of Maternal Anti-fetal Rejection","volume":"66","author":"Lee","year":"2011","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1097\/00005373-200005000-00006","article-title":"Sex Differences in Posttraumatic Cytokine Release of Endotoxin-Stimulated Whole Blood: Relationship to the Development of Severe Sepsis","volume":"48","author":"Majetschak","year":"2000","journal-title":"J. Trauma Inj. Infect. Crit. Care"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2470","DOI":"10.3109\/14767058.2012.684165","article-title":"Male gender promotes an increased inflammatory response to lipopolysaccharide in umbilical vein blood","volume":"25","author":"Regnault","year":"2012","journal-title":"J. Matern. Neonatal Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1053\/plac.2001.0782","article-title":"Mitchell Cytokines of the Placenta and Extra-placental Membranes: Roles and Regulation During Human Pregnancy and Parturition","volume":"23","author":"Bowen","year":"2002","journal-title":"Placenta"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"349","DOI":"10.3109\/14767058.2015.1006620","article-title":"A rapid interleukin-6 bedside test for the identification of intra-amniotic inflammation in preterm labor with intact membranes","volume":"29","author":"Chaemsaithong","year":"2016","journal-title":"J. Matern. Neonatal Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1046\/j.1471-0528.2003.00022.x","article-title":"Gender aspects of preterm birth","volume":"110","author":"Ingemarsson","year":"2003","journal-title":"BJOG"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/0029-7844(96)00106-8","article-title":"Excess males in preterm birth: Interactions with gestational age, race, and multiple birth","volume":"88","author":"Cooperstock","year":"1996","journal-title":"Obstet. Gynecol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1111\/j.1469-1809.1983.tb00968.x","article-title":"Sex ratio in spontaneous abortions","volume":"47","author":"Hassold","year":"1983","journal-title":"Ann. Hum. Genet."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3110","DOI":"10.3109\/14767058.2015.1114090","article-title":"Villitis of unknown etiology \u2013 prevalence and clinical associations","volume":"29","author":"Kovo","year":"2016","journal-title":"J. Matern. Neonatal Med."}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/14\/1\/79\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T13:38:34Z","timestamp":1760103514000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/14\/1\/79"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,2]]},"references-count":44,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,1]]}},"alternative-id":["life14010079"],"URL":"https:\/\/doi.org\/10.3390\/life14010079","relation":{},"ISSN":["2075-1729"],"issn-type":[{"value":"2075-1729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,2]]}}}