The relationship among the progression of inflammation in umbilical cord, fetal inflammatory response, early-onset neonatal sepsis, and chorioamnionitis


Autoři: Jeong-Won Oh aff001;  Chan-Wook Park aff001;  Kyung Chul Moon aff002;  Joong Shin Park aff001;  Jong Kwan Jun aff001
Působiště autorů: Department of Obstetrics and Gynecology, Division of Maternal Fetal Medicine, Seoul National University College of Medicine, Seoul, Korea aff001;  Department of Pathology, Seoul National University College of Medicine, Seoul, Korea aff002
Vyšlo v časopise: PLoS ONE 14(11)
Kategorie: Research Article
doi: 10.1371/journal.pone.0225328

Souhrn

Objectives

No information exists about whether fetal inflammatory-response(FIR), early-onset neonatal sepsis(EONS) and chorioamnionitis(an advanced-stage of maternal inflammatory-response in extraplacental membranes) continuously increase according to the progression of inflammation in umbilical-cord(UC). The objective of current-study is to examine this-issue.

Methods

Study-population included 239singleton pregnant-women(gestational-age[GA] at delivery: 21.6~36weeks) who had inflammation in extraplacental membranes or chorionic plate (CP) and either preterm-labor or preterm-PROM. We examined FIR, and the frequency of fetal inflammatory-responses syndrome(FIRS), proven-EONS, suspected-EONS and chorioamnionitis according to the progression of inflammation in UC. The progression of inflammation in UC was divided with a slight-modification from previously reported-criteria as follows: stage0, inflammation-free UC; stage-1: umbilical phlebitis only; stage-2: involvement of at least one UA and either the other UA or UV without extension into WJ; stage-3: the extension of inflammation into WJ. FIR was gauged by umbilical-cord-plasma(UCP) CRP concentration(ng/ml) at birth, and FIRS was defined as an elevated UCP CRP concentration at birth(≥200ng/ml).

Results

Stage-0, stage-1, stage-2 and stage-3 of inflammation in UC were present in 48.1%, 15.5%, 6.7%, and 29.7% of cases. FIR continuously increased according to the progression of inflammation in UC(Kruskal-Wallis test,P<0.001; Spearman-rank-correlation test,P<0.000001,r = 0.546). Moreover, there was a significant and stepwise increase in the frequency of FIRS, proven-EONS, suspected-EONS and chorioamnionitis according to the progression of inflammation in UC(each for P<0.000005 in both chi-square test and linear-by-linear-association). Multiple logistic-regression analysis demonstrated that the more advanced-stage in the progression of inflammation in UC(i.e., stage-1 vs. stage-2 vs. stage-3), the better predictor of suspected-EONS (Odds-ratio[OR]3.358, 95%confidence-interval[CI]:1.020–11.057 vs. OR5.147, 95%CI:1.189–22.275 vs. OR11.040, 95%CI:4.118–29.592) and chorioamnionitis(OR6.593, 95%CI:2.717–15.999 vs. OR16.508, 95%CI:3.916–69.596 vs. OR20.167, 95%CI:8.629–47.137).

Conclusion

FIR, EONS and chorioamnionitis continuously increase according to the progression of inflammation in UC among preterm-gestations with inflammation in extraplacental membranes or CP. This finding may suggest that funisitis(inflammation in UC) is both qualitatively and quantitatively histologic-counterpart of FIRS, and a surrogate-marker for chorioamnionitis.

Klíčová slova:

Chorioamnionitis – Inflammation – Labor and delivery – Neutrophils – Preterm birth – Umbilical cord – Umbilical arteries – Umbilical veins


Zdroje

1. Goldenberg RL, Hauth JC, Andrews WW. Intrauterine infection and preterm delivery. N Engl J Med. 2000;342:1500–7. doi: 10.1056/NEJM200005183422007 10816189

2. Romero R, Mazor M. Infection and preterm labor. Clin Obstet Gynecol. 1988;31:553–84. doi: 10.1097/00003081-198809000-00006 3066544

3. Goncalves LF, Chaiworapongsa T, Romero R. Intrauterine infection and prematurity. Ment Retard Dev Disabil Res Rev. 2002;8:3–13. doi: 10.1002/mrdd.10008 11921380

4. Park CW, Kim SM, Park JS, Jun JK, Yoon BH. Fetal, amniotic and maternal inflammatory responses in early stage of ascending intrauterine infection, inflammation restricted to chorio-decidua, in preterm gestation. J Matern Fetal Neonatal Med. 2014;27:98–105. doi: 10.3109/14767058.2013.806898 23691922

5. Park CW, Moon KC, Park JS, Jun JK, Romero R, Yoon BH. The involvement of human amnion in histologic chorioamnionitis is an indicator that a fetal and an intra-amniotic inflammatory response is more likely and severe: clinical implications. Placenta. 2009;30:56–61. doi: 10.1016/j.placenta.2008.09.017 19046766

6. Yoon BH, Romero R, Park JS, Kim M, Oh SY, Kim CJ, et al. The relationship among inflammatory lesions of the umbilical cord (funisitis), umbilical cord plasma interleukin 6 concentration, amniotic fluid infection, and neonatal sepsis. Am J Obstet Gynecol. 2000;183:1124–9. doi: 10.1067/mob.2000.109035 11084553

7. Yoon BH, Romero R, Shim JY, Shim SS, Kim CJ, Jun JK. C-reactive protein in umbilical cord blood: a simple and widely available clinical method to assess the risk of amniotic fluid infection and funisitis. J Matern Fetal Neonatal Med. 2003;14:85–90. doi: 10.1080/jmf.14.2.85.90 14629087

8. Gomez R, Romero R, Ghezzi F, Yoon BH, Mazor M, Berry SM. The fetal inflammatory response syndrome. Am J Obstet Gynecol. 1998;179:194–202. doi: 10.1016/s0002-9378(98)70272-8 9704787

9. Kim CJ, Romero R, Chaemsaithong P, Chaiyasit N, Yoon BH, Kim YM. Acute chorioamnionitis and funisitis: definition, pathologic features, and clinical significance. Am J Obstet Gynecol. 2015;213:S29–52. doi: 10.1016/j.ajog.2015.08.040 26428501

10. Salafia CM, Sherer DM, Spong CY, Lencki S, Eglinton GS, Parkash V, et al. Fetal but not maternal serum cytokine levels correlate with histologic acute placental inflammation. Am J Perinatol. 1997;14:419–22. doi: 10.1055/s-2007-994172 9263563

11. Redline RW, Wilson-Costello D, Borawski E, Fanaroff AA, Hack M. The relationship between placental and other perinatal risk factors for neurologic impairment in very low birth weight children. Pediatr Res. 2000;47:721–6. doi: 10.1203/00006450-200006000-00007 10832728

12. Kim CJ, Yoon BH, Romero R, Moon JB, Kim M, Park SS, et al. Umbilical arteritis and phlebitis mark different stages of the fetal inflammatory response. Am J Obstet Gynecol. 2001;185:496–500. doi: 10.1067/mob.2001.116689 11518916

13. Rogers BB, Alexander JM, Head J, McIntire D, Leveno KJ. Umbilical vein interleukin-6 levels correlate with the severity of placental inflammation and gestational age. Hum Pathol. 2002;33:335–40. doi: 10.1053/hupa.2002.32214 11979375

14. Lee Y, Kim HJ, Choi SJ, Oh SY, Kim JS, Roh CR, et al. Is there a stepwise increase in neonatal morbidities according to histological stage (or grade) of acute chorioamnionitis and funisitis?: effect of gestational age at delivery. J Perinat Med. 2015;43:259–67. doi: 10.1515/jpm-2014-0035 25153209

15. Yoon BH, Yang SH, Jun JK, Park KH, Kim CJ, Romero R. Maternal blood C-reactive protein, white blood cell count, and temperature in preterm labor: a comparison with amniotic fluid white blood cell count. Obstet Gynecol. 1996; 87: 231–7. doi: 10.1016/0029-7844(95)00380-0 8559530

16. Yoon BH, Jun JK, Park KH, Syn HC, Gomez R, Romero R. Serum C-reactive protein, white blood cell count, and amniotic fluid white blood cell count in women with preterm premature rupture of membranes. Obstet Gynecol. 1996; 88: 1034–40. doi: 10.1016/s0029-7844(96)00339-0 8942849

17. Vintzileos A, Campbell W, Nochimson D, Connolly ME, Fuenjer MM, Hoehn GJ. The fetal biophysical profile in patients with premature rupture of membranes—an early predictor of fetal infection. Am J Obstet Gynecol 1985;152:510–6. doi: 10.1016/0002-9378(85)90617-9 4014344

18. Yoon BH, Romero R, Kim CJ, Jun JK, Gomez R, Choi JH, et al. Amniotic fluid interleukin-6: a sensitive test for antenatal diagnosis of acute inflammatory lesions of preterm placenta and prediction of perinatal morbidity. Am J Obstet Gynecol. 1995;172:960–70. doi: 10.1016/0002-9378(95)90028-4 7892891

19. Salafia CM, Weigl C, Silberman L. The prevalence and distribution of acute placental inflammation in uncomplicated term pregnancies. Obstet Gynecol. 1989;73:383–9. 2915862

20. Gibbs RS, Blanco JD, St Clair PJ, Castaneda YS. Quantitative bacteriology of amniotic fluid from patients with clinical intraamniotic infection at term. J Infect Dis 1982;145:1–8. doi: 10.1093/infdis/145.1.1 7033397

21. van Hoeven KH, Anyaegbunam A, Hochster H, Whitty JE, Distant J, Crawford C, et al. Clinical significance of increasing histologic severity of acute inflammation in the fetal membranes and umbilical cord. Pediatr Pathol Lab Med. 1996;16:731–44. 9025872

22. Redline RW, Faye-Petersen O, Heller D, Qureshi F, Savell V, Vogler C; Society for Pediatric Pathology, Perinatal Section, Amniotic Fluid Infection Nosology Committee. Amniotic infection syndrome: nosology and reproducibility of placental reaction patterns. Pediatr Dev Pathol. 2003;6:435–48. doi: 10.1007/s10024-003-7070-y 14708737

23. Blanc WA. Pathology of the placenta, membranes, and umbilical cord in bacterial, fungal, and viral infections in man. Monogr Pathol. 1981;(22):67–132. 7024790

24. Wharton KN, Pinar H, Stonestreet BS, Tucker R, McLean KR, Wallach M, et al. Severe umbilical cord inflammation-a predictor of periventricular leukomalacia in very low birth weight infants. Early Hum Dev. 2004;77:77–87. doi: 10.1016/j.earlhumdev.2004.02.001 15113634

25. Dexter SC, Pinar H, Malee MP, Hogan J, Carpenter MW, Vohr BR. Outcome of very low birth weight infants with histopathologic chorioamnionitis. Obstet Gynecol. 2000;96:172–7. doi: 10.1016/s0029-7844(00)00886-3 10908758

26. Dong Y, Hou W, Wei J, Weiner CP. Chronic hypoxemia absent bacterial infection is one cause of the fetal inflammatory response syndrome (FIRS). Reprod Sci. 2009; 16: 650–6. doi: 10.1177/1933719109333662 19351964

27. Guo R, Hou W, Dong Y, Yu Z, Stites J, Weiner CP. Brain injury caused by chronic fetal hypoxemia is mediated by inflammatory cascade activation. Reprod Sci. 2010; 17: 540–8. doi: 10.1177/1933719110364061 20360591

28. Trevisanuto D, Doglioni N, Altinier S, Zaninotto M, Plebani M, Zanardo V. High-sensitivity C-reactive protein in umbilical cord of small-for-gestational-age neonates. Neonatology. 2007; 91: 186–9. doi: 10.1159/000097451 17377404

29. Amarilyo G, Oren A, Mimouni FB, Ochshorn Y, Deutsch V, Mandel D. Increased cord serum inflammatory markers in small-for-gestational-age neonates. J Perinatol. 2011; 31: 30–2. doi: 10.1038/jp.2010.53 20410909

30. Visentin S, Lapolla A, Londero AP, Cosma C, Dalfrà M, Camerin M, et al. Adiponectin levels are reduced while markers of systemic inflammation and aortic remodelling are increased in intrauterine growth restricted mother-child couple. Biomed Res Int. 2014; 2014: 401595. doi: 10.1155/2014/401595 25045669

31. Lee J, Romero R, Lee KA, Kim EN, Korzeniewski SJ, Chaemsaithong P, et al. Meconium aspiration syndrome: a role for fetal systemic inflammation. Am J Obstet Gynecol. 2016;214:366.e1–9. doi: 10.1016/j.ajog.2015.10.009 26484777

32. Kim CJ, Yoon BH, Park SS, Kim MH, Chi JG. Acute funisitis of preterm but not term placentas is associated with severe fetal inflammatory response. Hum Pathol. 2001;32:623–9. doi: 10.1053/hupa.2001.24992 11431717.

33. Katzman PJ, Metlay LA. Fetal inflammatory response is often present at early stages of intra-amniotic infection, and its distribution along cord is variable. Pediatr Dev Pathol. 2010;13:265–72. doi: 10.2350/09-02-0604-OA.1 19642812.

34. Raio L, Ghezzi F, Di Naro E, Franchi M, Brühwiler H. Prenatal assessment of the Hyrtl anastomosis and evaluation of its function: case report. Hum Reprod. 1999;14:1890–3. doi: 10.1093/humrep/14.7.1890 10402412.

35. Gordon Z, Eytan O, Jaffa AJ, Elad D. Hemodynamic analysis of Hyrtl anastomosis in human placenta. Am J Physiol Regul Integr Comp Physiol. 2007;292:R977–82. doi: 10.1152/ajpregu.00410.2006 17038439.

36. Burton GJ, Sebire NJ, Myatt L, Tannetta D, Wang YL, Sadovsky Y, et al. Optimising sample collection for placental research. Placenta. 2014;35:9–22. doi: 10.1016/j.placenta.2013.11.005 24290528.

37. BENIRSCHKE K. A review of the pathologic anatomy of the human placenta. Am J Obstet Gynecol. 1962;84:1595–622. doi: 10.1016/0002-9378(62)90005-4 13970511.

38. Chellam VG, Rushton DI. Chorioamnionitis and funiculitis in the placentas of 200 births weighing less than 2.5 kg. Br J Obstet Gynaecol. 1985;92:808–14. doi: 10.1111/j.1471-0528.1985.tb03050.x 4027203.

39. Naccasha N, Hinson R, Montag A, Ismail M, Bentz L, Mittendorf R. Association between funisitis and elevated interleukin-6 in cord blood. Obstet Gynecol. 2001;97:220–4. doi: 10.1016/s0029-7844(00)01149-2 11165585.

40. Romero R, Chaemsaithong P, Docheva N, Korzeniewski SJ, Kusanovic JP, Yoon BH, et al. Clinical chorioamnionitis at term VI: acute chorioamnionitis and funisitis according to the presence or absence of microorganisms and inflammation in the amniotic cavity. J Perinat Med. 2016;44:33–51. doi: 10.1515/jpm-2015-0119 26352071.

41. Tsiartas P, Kacerovsky M, Musilova I, Hornychova H, Cobo T, Sävman K,et al. The association between histological chorioamnionitis, funisitis and neonatal outcome in women with preterm prelabor rupture of membranes. J Matern Fetal Neonatal Med. 2013;26:1332–6. doi: 10.3109/14767058.2013.784741 23489073.

42. Khong TY. A topographical and clinical approach to examination of the placenta. Pathology. 2001v;33:174–86. doi: 10.1080/00313020120038700 11358051.

43. Miranda RN, Omurtag K, Castellani WJ, De las Casas LE, Quintanilla NM, Kaabipour E. Myelopoiesis in the liver of stillborns with evidence of intrauterine infection. Arch Pathol Lab Med. 2006;130:1786–91. doi: 10.1043/1543-2165(2006)130[1786:MITLOS]2.0.CO;2 17149951.


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