HISTOLOGICAL CHORIOAMNIONITIS
CHORIOAMNIONITIS HISTOLOGIQUE

Infection of chorion and amnion which is historically referred to as chorioamnionitis (CA) is a diagnostic spectrum ranging from symptomatic acute intrauterine infection to completely asymptomatic state where mother and fetus show no clinical manifestation of infection. The acute symptomatic condition which often presents with fever, uterine tenderness, genital discharge, tachycardia and evidence of fetal infection is termed clinical chorioamnionitis (CCA) while cases without the typical clinical or microbiological findings associated with acute infection are termed histological chorioamnionitis (HCA).

Ascending bacterial invasion through the uterine cervix is believed to be the most common route of infection, although bacteria are identified only in the minority of cases1. Organisms most frequently associated with chorioamnionitis are mainly of low virulence, including Ureaplasma and Mycoplasma species1,2. Both the maternal and fetal immune systems have an important role in determining the course and outcome of chorioamnionitis.

The outcomes of the symptomatic variety, CCA for mothers and babies have been well documented ³ but the implications of asymptomatic HCA are less clear. The present study from Jos, Nigeria⁴ has attempted to document maternal and fetal outcomes by 6 weeks post-partum, for diagnosed HCA compared to those without HCA. The study rigorously screened the membranes and placenta of asymptomatic mothers for histological evidence of CA which is the gold standard for diagnosis. Two pathologists had to agree after studying the slides in order to make a diagnosis of HCA. Culture for organisms was however not done. Mothers who were HIV-infected or had diabetes mellitus were excluded in order to remove immune-compromised women. Despite the rigorous exclusion criteria, the high prevalence of HCA (60.8%) and the lack of association of HCA with adverse maternal and neonatal outcomes are very interesting. Given the very low adverse outcome rate and 27.7% loss to follow-up (LTFU), the study may have lacked the power required to demonstrate subtle differences in outcome between the HCA and Non- HCA groups. Because of small sample size, determining the impact of grade or stage of HCA on outcomes was also not possible. Learning from the outcomes of this study, a bigger study that is powered to answers lingering questions is clearly warranted with better safeguards to reduce LTFU. Such a study must also seek to determine and explain the cause of such high prevalence of HCA. It has been suggested that HCA may be the result of sterile inflammation or use of insensitive microbiologic techniques. HCA in term infants is often a result of non-infectious inflammatory process5 , 6 . Indeed, HCA in asymptomatic parturients in the present study may be the result of physiological (non-infectious) inflammatory process leading to the spontaneous onset of labor and rupture of membranes. There is mounting evidence that labour is an inflammatory process7,8. Histological decidual inflammation (in the absence of infection) was shown to be uncommon before the onset of labor (6%) but increased significantly during labor before membrane rupture (29% of all cases), and was correlated with cervical dilatation8. The onset and progression of term labor results from a complex orchestration of many inflammatory and hormonal factors found in maternal, fetal, and placental tissues⁹.

Near term, it is postulated^7,9 that uterine chemokines activate peripheral immune cells and promote the expression of endothelial cell adhesion molecules. Peripheral leukocytes adhere to myometrialvascularendothelialcellsandextravasate into the uterine muscle and the maternal/fetal interface. Infiltrating leukocytes amplify the pro- inflammatory microenvironment at the myometrium and the maternal/fetal interface ultimately leading to the onset of labor. Infiltrating decidual neutrophils release several inflammatory mediators and matrix metalloproteases which degrade the extracellular matrix of the fetal membranes and contribute to physiologicalruptureofmembranesduringbothterm andpretermlabor^10-14. The activation of this pathway, eliciting a shift from an anti-inflammatory to a pro-inflammatory microenvironment in the absence of infection may account for the very high prevalence of HCA (60.8%) diagnosed in the present study. However, since the methodology of the present study did not exclude infectious causes, it would be inappropriate to presume that HCA cases in this study represent sterile inflammation.

References

• Goldenberg RL, Hauth JC, Andrews WW. Intrauterine infection and preterm delivery. N Engl J Med. 2000; 342: 1500–1507.
• Faye-Petersen OM. The placenta in preterm birth. J Clin Pathol. 2008; 61: 1261–1275.
• Gantert M, Been JV, Gavilanes AWD, Garnier Y, LJI Zimmermann LJI, Kramer BW. Chorioamnionitis: a multiorgan disease of the fetus? Journal of Perinatology. 2010; 30: S21–S30.
• Ocheke AN, Ocheke IE, Agaba PA, Imade GE, Silas OA, Ajetunmobi OI, Godwins Echejoh, Ekere C, Sendeht A, Bitrus J, Agaba EI, Sagay AS. Maternal and neonatal outcomes of histological chorioamnionitis. J West Afr Coll Surg. 2016;6(3):1-14
• Smulian JC, Shen-Schwarz S, Vintzileos AM, Lake MF, Ananth CV. Clinical choriamnionitis and histologic placental Inflammation. Obstet Gynecol. 1999; 94:1000–1005.
• Torricelli M, Voltolini C, Conti N, Vellucci FL, Orlandini C, Bocchi C, et.al. Histologic chorioamnionitis at term: implications for the progress of labor and neonatal wellbeing. J Matern Fetal Neonatal Med. 2013; 26:188–192.
• Gomez-Lopez N, St. Louis D, Lehr MA, Sanchez- Rodriguez EN, Marcia Arenas-Hernandez M. Immune cells in term and preterm labor Cellular & Molecular Immunology. 2014; 11: 571–581.
• Thomson AJ, Telfer JF, Young A, Campbell S, Stewart CJ, Cameron IT et al. Leukocytes infiltrate the myometrium during human parturition: further evidence that labour is an inflammatory process. Hum Reprod. 1999;14: 229–236.
• Oksana Shynlova, Yu-Hui Lee, Khetsopon Srikhajon and Stephen J Lye. Physiologic Uterine Inflammation and Labor Onset: Integration of Endocrine and Mechanical Signals. Reproductive Sciences. 2013; 20(2): 154-167.
• Romero R, Ceska M, Avila C, Mazor M, Behnke E, Lindley I. Neutrophil attractant/activating peptide-1/interleukin-8 in term and preterm parturition. Am J Obstet Gynecol. 1991; 165: 813–820.
• Dudley DJ, Trautman MS, Mitchell MD. Inflammatory mediators regulate interleukin-8 production by cultured gestational tissues: evidence for a cytokine network at the chorio- decidual interface. J Clin Endocrinol Metab. 1993;76:404–410.
• Vadillo OF, Gonzalez AG, Furth EE, Lei H, Muschel RJ, Stetler-Stevenson WG et al. 92-kd type IV collagenase (matrix metalloproteinase-9) activity in human amniochorion increases with labor. Am J Pathol 1995;146:148–156.
• Athayde N, Romero R, Gomez R, Maymon E, P a c o r a P, M a z o r M e t a l . M a t r i x metalloproteinases-9 in preterm and term human parturition. J Matern Fetal Med. 1999; 8: 213–219.
• Maymon E, Romero R, Pacora P, Gomez R, Athayde N, Edwin S et al. Human neutrophil collagenase (matrix metalloproteinase 8) in parturition, premature rupture of the membranes, and intrauterine infection. Am J Obstet Gynecol. 2000; 183: 94–99.

L'Infection chorion et amnion qui est historiquement appelé chorioamnionitis (CA) est un diagnostic d'evantail allant d'infection symptomatique intra- uterineaiguëcompletementàl'étatasymptomatique ou la mère et le foetus n'ont pas montré aucunes manifestationsclinicaled'infection. Laconditionaiguë symptomatique qui se presente souvent avec de fièvre, tendresse d'utérine , écoulement génital, la tachycardie et l'évidence de l'infection appelé chorioamnionitis (CCA) tandisque que les cas sans résultatscliniquesoumicrobiologiquetypiqueassocié à l'infection aiguë sont appelés chorioamniotie histologique( HCA).

Croissant invassion bactériémie à travers le col de l'autres est considéré comme la voie la plus commune d'infection. Bien que les bactériémie ne sont pas identifié que dans la minorité des cas1. Les organismes les plus fréquemment associé à chorioamnionitis sont principalement de faible virulence, y compris Ureaplasma et Mycoplasma1,2. Les deux systèmes immunitaires maternels et foetaux ont un rôle importantdansladéterminationdel'évolutionetl'issue derésultatschorioamnionitis. Lesrésultatsdelavariété symptomatique CCA, pour les mères et les bébés ont été bien documenté 3 .Mais les implications de HCA asymptomatiquesontmoinsclaires.

L'étude présente de Jos, Nigéria à essayé de documenté les résultats post-partum maternel et foetale de six semaines, pour un diagnostic HCA par rapport à ceux qui n'ont pas de HCA.

L'étude a projeté rigoureusement la membrane et le placenta des mères asymptomatique pour preuve historique de CA qui est le modèle pour le diagnostic. Deux pathologistes sont d'accord après avoir étudié les diapositives afin de faire un diagnostic de HCA. La culture pour les organismes n'a cependant pas fait.

Les mères infecté par le VIH ou atteintes de diabète sucré ont été exclus afin de retiré les femmes immunodéprimé. En dépit des critères rigoureux, la forte prévalence de HCA ( 60.8 % ) et la manque d'association de HCA, avec des résultats maternels et néonatales indésirables sont très intéressants .

Compte tenu du taux de résultat défavorable très faible et 27,7 % de perte pour le suivi (LTFU), l'étude peut manquer la puissance nécessaire pour démonter les légères différences dans les résultats de HCA et le groupe non-HCA. En raison de la taille d'echantillon,pour déterminer l'impact de la qualité de résultats ou de stade de HCA n'était pas possible. Les résultats de cette étude, une plus grande étude capable de répondre aux questions persistantes est requise avec des meilleures garanties pour réduire le LTFU. Ce genre d'étude cherche à déterminer et expliquer la haute prévalence de HCA.

Il était suggéré que le HCA peut être le résultat d'une inflammation ou l'utilisation de techniques microbiologique insensible. Le HCA chez les nourrissons à terme est souvent le résultat de 5,6 processus non-infecteux inflammatoire . En effet HCA chez les parturients asymptomatique peut être le résultat du procès inflammatoire psychologique ( non-infecteux ). Qui mène à l'apparition spontané de la membrane du labour et de la rupture.

Il existe des preuves accrues que le travail est un 7,8 procès inflammatoire . L' inflammation deciduale histologique (en absence d'infection ) a été montré d'être rare avant le debout du travail (6%) mais il a augmenté de façon significative au cours du travail avant la rupture des membranes et a été en 8 corrélation avec la dilation du col . L'apparition et la progression des resultats d'ochestration complexe, de nombreux facteurs inflammatoire et hormonaux trouvé dans la tissue maternel foetaux et placentaires ⁹.

Au terme proche , il est postulé que les chimiokines uterine activent les cellules immunitaires périphériques et il promouvoit les endothelial des molécules d'adhésion. Les leucocytes périphériques, adhére aux cellules endothéliales vascular nyometre et extravaser dans le muscle de l'utérus et de l'interface maternel foetale. Leucocytes infiltrant amplifient le microenvironnement pro-inflammatoire au myometre et l'interface maternelle/ foetale conduisant finalement au travail. Infiltration neutrophiles déciduale libèrent plusieurs médiateurs inflammatoire et metalloproteases matricielle qui degradent la matrice extracellulaire des membranes à la fois pendant le terme et le 10-14 travail .

L'activation de la voie provoquant le passage d'un anti-inflammatoire en absence d'infection peut expliquer la haute prévalence de HCA ( 60.8 % ) diagnostiqué dans cette étude. Puisque la méthodologie de cette étude n'exclus pas des causes infectieux. Il sera inapproprié de présumer que les cas de HCA dans cette étude représente une inflammation stérile.

• Goldenberg RL, Hauth JC, Andrews WW. Intrauterine infection and preterm delivery. N Engl J Med. 2000; 342: 1500–1507.
• Faye-Petersen OM. The placenta in preterm birth. J Clin Pathol. 2008; 61: 1261–1275.
• Gantert M, Been JV, Gavilanes AWD, Garnier Y, LJI Zimmermann LJI, Kramer BW. Chorioamnionitis: a multiorgan disease of the fetus? Journal of Perinatology. 2010; 30: S21–S30.
• Ocheke AN, Ocheke IE, Agaba PA, Imade GE, Silas OA, Ajetunmobi OI, Godwins Echejoh, Ekere C, Sendeht A, Bitrus J, Agaba EI, Sagay AS. Maternal and neonatal outcomes of histological chorioamnionitis. J West Afr Coll Surg. 2016;6(3):1-14
• Smulian JC, Shen-Schwarz S, Vintzileos AM, Lake MF, Ananth CV. Clinical choriamnionitis and histologic placental Inflammation. Obstet Gynecol. 1999; 94:1000–1005.
• Torricelli M, Voltolini C, Conti N, Vellucci FL, Orlandini C, Bocchi C, et.al. Histologic chorioamnionitis at term: implications for the progress of labor and neonatal wellbeing. J Matern Fetal Neonatal Med. 2013; 26:188–192.
• Gomez-Lopez N, St. Louis D, Lehr MA, Sanchez- Rodriguez EN, Marcia Arenas-Hernandez M. Immune cells in term and preterm labor Cellular & Molecular Immunology. 2014; 11: 571–581.
• Thomson AJ, Telfer JF, Young A, Campbell S, Stewart CJ, Cameron IT et al. Leukocytes infiltrate the myometrium during human parturition: further evidence that labour is an inflammatory process. Hum Reprod. 1999;14: 229–236.
• Oksana Shynlova, Yu-Hui Lee, Khetsopon Srikhajon and Stephen J Lye. Physiologic Uterine Inflammation and Labor Onset: Integration of Endocrine and Mechanical Signals. Reproductive Sciences. 2013; 20(2): 154-167.
• Romero R, Ceska M, Avila C, Mazor M, Behnke E, Lindley I. Neutrophil attractant/activating peptide-1/interleukin-8 in term and preterm parturition. Am J Obstet Gynecol. 1991; 165: 813–820.
• Dudley DJ, Trautman MS, Mitchell MD. Inflammatory mediators regulate interleukin-8 production by cultured gestational tissues: evidence for a cytokine network at the chorio- decidual interface. J Clin Endocrinol Metab. 1993;76:404–410.
• Vadillo OF, Gonzalez AG, Furth EE, Lei H, Muschel RJ, Stetler-Stevenson WG et al. 92-kd type IV collagenase (matrix metalloproteinase-9) activity in human amniochorion increases with labor. Am J Pathol 1995;146:148–156.
• Athayde N, Romero R, Gomez R, Maymon E, P a c o r a P, M a z o r M e t a l . M a t r i x metalloproteinases-9 in preterm and term human parturition. J Matern Fetal Med. 1999; 8: 213–219.
• Maymon E, Romero R, Pacora P, Gomez R, Athayde N, Edwin S et al. Human neutrophil collagenase (matrix metalloproteinase 8) in parturition, premature rupture of the membranes, and intrauterine infection. Am J Obstet Gynecol. 2000; 183: 94–99.