Kadar heat shock protein 70 cairan amnion yang tinggi sebagai faktor risiko terjadinya ketuban pecah dini pada kehamilan aterm

Ines Kurniaty Hartono; Ketut Suwiyoga; I Ketut Surya Negara; I Gede Mega Putra; Made Bagus Dwi Aryana; I Gde Sastra Winata; I Wayan Megadhana

doi:10.15562/ism.v13i1.1220

Kadar heat shock protein 70 cairan amnion yang tinggi sebagai faktor risiko terjadinya ketuban pecah dini pada kehamilan aterm

Ines Kurniaty Hartono ,

Ketut Suwiyoga ,

I Ketut Surya Negara ,

I Gede Mega Putra ,

Made Bagus Dwi Aryana ,

I Gde Sastra Winata ,

I Wayan Megadhana ,

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DOI: https://doi.org/10.15562/ism.v13i1.1220 |
Published: 2022-03-25

Abstract

Background: Premature rupture of membranes (PROM) is a condition that complicates labor with an unclear pathogenesis. HSP70 is thought to be involved in this pathogenesis process and the presence of HSP in the extracellular compartment reflects tissue damage and induces an immunologic response. Therefore, this study aimed to study the relationship between HSP70 levels in amniotic fluid and the incidence of PROM.

Methods: This study used a case-control design in the ER delivery room and the laboratory of Sanglah Hospital, Denpasar. Samples were taken from mothers who gave full term delivery in the emergency room at Sanglah Hospital Denpasar with mothers who gave birth at term with KPD as cases and mothers who gave full term delivery without KPD as controls. Data was taken from medical records and measured levels of HSP70 at the Sanglah Hospital Denpasar Laboratory. Data analysis was performed using the Mann-Whitney test and ROC test.

Results: A total of 28 cases and 28 controls were recruited. There were no significant differences in baseline characteristics between cases and controls. The MannWhitney test found significant differences in the mean levels of HSP70, 11.58 (±8.16) ng/mL in controls and 17.15 (±6.51) ng/mL in cases, respectively. ROC analysis found an AUC of 0.737 with an optimal cutoff value of 12.5 ng/mL. An amniotic fluid HSP70 level of more than 12.5 ng/mL was associated with PROM with an OR of 17.33 (95% CI 3.43 - 87.70).

Conclusion: High amniotic fluid HSP 70 level is a risk factor for PROM in term pregnancy.

Latar belakang: Ketuban pecah dini (KPD) merupakan suatu kondisi yang mempersulit persalinan dengan patogenesis yang belum jelas. HSP70 dianggap terlibat dalam proses patogenesis ini dan keberadaan HSP di kompartemen ekstraseluler mencerminkan kerusakan jaringan dan menginduksi respon imunologi. Oleh karena itu, penelitian ini bertujuan untuk mempelajari hubungan kadar HSP70 dalam cairan ketuban dengan kejadian KPD.

Metode: Penelitian ini menggunakan desain kasus kontrol di ruang bersalin IGD dan Laboratorium RSUP Sanglah Denpasar. Sampel diambil dari ibu yang bersalin cukup bulan di ruang bersalin IGD RSUP Sanglah Denpasar dengan ibu yang melahirkan cukup bulan dengan KPD sebagai kasus dan ibu yang bersalin cukup bulan tanpa KPD sebagai kontrol. Data diambil dari rekam medis dan dilakukan pengukuran kadar HSP70 di Laboratorium RSUP Sanglah Denpasar. Analisis data dilakukan dengan menggunakan uji Mann-Whitney dan uji ROC.

Hasil: Sebanyak 28 kasus dan 28 kontrol direkrut. Tidak ada perbedaan yang signifikan dalam karakteristik dasar antara kasus dan kontrol. Uji MannWhitney menemukan perbedaan yang signifikan dalam tingkat rata-rata HSP70, masing-masing 11,58 (± 8,16) ng/mL pada kontrol dan 17,15 (± 6,51) ng/mL dalam kasus. Analisis ROC menemukan AUC 0,737 dengan nilai cutoff optimal 12,5 ng/mL. Tingkat HSP70 cairan ketuban lebih dari 12,5 ng/mL dikaitkan dengan PROM dengan OR 17,33 (95% CI 3,43 - 87,70).

Simpulan: kadar HSP 70 cairan amnion yang tinggi merupakan faktor risiko terjadinya KPD pada kehamilan aterm.

References

Parry S, Strauss JF. Premature Rupture of the Fetal Membranes. N Engl J Med. 1998;338(10):663–70. Available from: http://dx.doi.org/10.1056/nejm199803053381006
Bryant-Greenwood GD, Yamamoto SY, Lowndes KM, Webster LE, Parg SS, Amano A, et al. Human Decidual Relaxin and Preterm Birth. Ann N Y Acad Sci. 2005;1041(1):338–44. Available from: http://dx.doi.org/10.1196/annals.1282.054
Di Sarno R, Raffone A, Saccone G. Effects of progestogens in women with preterm premature rupture of membranes. Minerva Ginecol. 2019;71(2). Available from: http://dx.doi.org/10.23736/s0026-4784.18.04335-6
Lawn JE, Gravett MG, Nunes TM, Rubens CE, Stanton C, Group GR. Global report on preterm birth and stillbirth (1 of 7): definitions, description of the burden and opportunities to improve data. BMC Pregnancy Childbirth. 2010;10 Suppl 1(Suppl 1):S1–S1. Available from: https://pubmed.ncbi.nlm.nih.gov/20233382
Romero R, Yoon BH, Mazor M, Gomez R, Diamond MP, Kenney JS, et al. The diagnostic and prognostic value of amniotic fluid white blood cell count, glucose, interleukin-6, and Gram stain in patients with preterm labor and intact membranes. Am J Obstet Gynecol. 1993;169(4):805–16. Available from: http://dx.doi.org/10.1016/0002-9378(93)90009-8
Fortunato SJ, Menon R, Lombardi SJ. Role of tumor necrosis factor-? in the premature rupture of membranes and preterm labor pathways. Am J Obstet Gynecol. 2002;187(5):1159–62. Available from: http://dx.doi.org/10.1067/mob.2002.127457
Kalish RB, Vardhana S, Gupta M, Perni SC, Chasen ST, Witkin SS. Polymorphisms in the tumor necrosis factor-? gene at position ?308 and the inducible 70 kd heat shock protein gene at position +1267 in multifetal pregnancies and preterm premature rupture of fetal membranes. Am J Obstet Gynecol. 2004;191(4):1368–74. Available from: http://dx.doi.org/10.1016/j.ajog.2004.07.007
Menon R, Fortunato SJ. Infection and the role of inflammation in preterm premature rupture of the membranes. Best Pract Res Clin Obstet Gynaecol. 2007;21(3):467–78. Available from: http://dx.doi.org/10.1016/j.bpobgyn.2007.01.008
Chang A, Zhang Z, Jia L, Zhang L, Gao Y, Zhang L. Alteration of heat shock protein 70 expression levels in term and preterm delivery. J Matern Neonatal Med. 2013;26(16):1581–5. Available from: http://dx.doi.org/10.3109/14767058.2013.795535
Chaiworapongsa T, Erez O, Kusanovic JP, Vaisbuch E, Mazaki-Tovi S, Gotsch F, et al. Amniotic fluid heat shock protein 70 concentration in histologic chorioamnionitis, term and preterm parturition. J Matern Fetal Neonatal Med. 2008;21(7):449–61. Available from: https://pubmed.ncbi.nlm.nih.gov/18570125
Kanninen TT, Sisti G, Witkin SS. Induction of the 70 kDa heat shock protein stress response inhibits autophagy: possible consequences for pregnancy outcome. J Matern Neonatal Med. 2014;29(1):159–62. Available from: http://dx.doi.org/10.3109/14767058.2014.991916
Redzovic A, Gulic T, Laskarin G, Eminovic S, Haller H, Rukavina D. Heat-Shock Proteins 70 Induce Pro-Inflammatory Maturation Program in Decidual CD1a+Dendritic Cells. Am J Reprod Immunol. 2015;74(1):38–53. Available from: http://dx.doi.org/10.1111/aji.12374
Saglam A, Ozgur C, Derwig I, Unlu BS, Gode F, Mungan T. The role of apoptosis in preterm premature rupture of the human fetal membranes. Arch Gynecol Obstet. 2013;288(3):501–5. Available from: http://dx.doi.org/10.1007/s00404-013-2774-3
Noguchi T, Sado T, Naruse K, Shigetomi H, Onogi A, Haruta S, et al. Evidence for activation of Toll-like receptor and receptor for advanced glycation end products in preterm birth. Mediators Inflamm. 2010/11/28. 2010;2010:490406. Available from: https://pubmed.ncbi.nlm.nih.gov/21127710
Shaheen SO, Macdonald-Wallis C, Lawlor DA, Henderson AJ. Hypertensive disorders of pregnancy, respiratory outcomes and atopy in childhood. Eur Respir J. 2015/11/05. 2016;47(1):156–65. Available from: https://pubmed.ncbi.nlm.nih.gov/26541530

[1] Parry S, Strauss JF. Premature Rupture of the Fetal Membranes. N Engl J Med. 1998;338(10):663–70. Available from: http://dx.doi.org/10.1056/nejm199803053381006

[2] Bryant-Greenwood GD, Yamamoto SY, Lowndes KM, Webster LE, Parg SS, Amano A, et al. Human Decidual Relaxin and Preterm Birth. Ann N Y Acad Sci. 2005;1041(1):338–44. Available from: http://dx.doi.org/10.1196/annals.1282.054

[3] Di Sarno R, Raffone A, Saccone G. Effects of progestogens in women with preterm premature rupture of membranes. Minerva Ginecol. 2019;71(2). Available from: http://dx.doi.org/10.23736/s0026-4784.18.04335-6

[4] Lawn JE, Gravett MG, Nunes TM, Rubens CE, Stanton C, Group GR. Global report on preterm birth and stillbirth (1 of 7): definitions, description of the burden and opportunities to improve data. BMC Pregnancy Childbirth. 2010;10 Suppl 1(Suppl 1):S1–S1. Available from: https://pubmed.ncbi.nlm.nih.gov/20233382

[5] Romero R, Yoon BH, Mazor M, Gomez R, Diamond MP, Kenney JS, et al. The diagnostic and prognostic value of amniotic fluid white blood cell count, glucose, interleukin-6, and Gram stain in patients with preterm labor and intact membranes. Am J Obstet Gynecol. 1993;169(4):805–16. Available from: http://dx.doi.org/10.1016/0002-9378(93)90009-8

[6] Fortunato SJ, Menon R, Lombardi SJ. Role of tumor necrosis factor-? in the premature rupture of membranes and preterm labor pathways. Am J Obstet Gynecol. 2002;187(5):1159–62. Available from: http://dx.doi.org/10.1067/mob.2002.127457

[7] Kalish RB, Vardhana S, Gupta M, Perni SC, Chasen ST, Witkin SS. Polymorphisms in the tumor necrosis factor-? gene at position ?308 and the inducible 70 kd heat shock protein gene at position +1267 in multifetal pregnancies and preterm premature rupture of fetal membranes. Am J Obstet Gynecol. 2004;191(4):1368–74. Available from: http://dx.doi.org/10.1016/j.ajog.2004.07.007

[8] Menon R, Fortunato SJ. Infection and the role of inflammation in preterm premature rupture of the membranes. Best Pract Res Clin Obstet Gynaecol. 2007;21(3):467–78. Available from: http://dx.doi.org/10.1016/j.bpobgyn.2007.01.008

[9] Chang A, Zhang Z, Jia L, Zhang L, Gao Y, Zhang L. Alteration of heat shock protein 70 expression levels in term and preterm delivery. J Matern Neonatal Med. 2013;26(16):1581–5. Available from: http://dx.doi.org/10.3109/14767058.2013.795535

[10] Chaiworapongsa T, Erez O, Kusanovic JP, Vaisbuch E, Mazaki-Tovi S, Gotsch F, et al. Amniotic fluid heat shock protein 70 concentration in histologic chorioamnionitis, term and preterm parturition. J Matern Fetal Neonatal Med. 2008;21(7):449–61. Available from: https://pubmed.ncbi.nlm.nih.gov/18570125

[11] Kanninen TT, Sisti G, Witkin SS. Induction of the 70 kDa heat shock protein stress response inhibits autophagy: possible consequences for pregnancy outcome. J Matern Neonatal Med. 2014;29(1):159–62. Available from: http://dx.doi.org/10.3109/14767058.2014.991916

[12] Redzovic A, Gulic T, Laskarin G, Eminovic S, Haller H, Rukavina D. Heat-Shock Proteins 70 Induce Pro-Inflammatory Maturation Program in Decidual CD1a+Dendritic Cells. Am J Reprod Immunol. 2015;74(1):38–53. Available from: http://dx.doi.org/10.1111/aji.12374

[13] Saglam A, Ozgur C, Derwig I, Unlu BS, Gode F, Mungan T. The role of apoptosis in preterm premature rupture of the human fetal membranes. Arch Gynecol Obstet. 2013;288(3):501–5. Available from: http://dx.doi.org/10.1007/s00404-013-2774-3

[14] Noguchi T, Sado T, Naruse K, Shigetomi H, Onogi A, Haruta S, et al. Evidence for activation of Toll-like receptor and receptor for advanced glycation end products in preterm birth. Mediators Inflamm. 2010/11/28. 2010;2010:490406. Available from: https://pubmed.ncbi.nlm.nih.gov/21127710

[15] Shaheen SO, Macdonald-Wallis C, Lawlor DA, Henderson AJ. Hypertensive disorders of pregnancy, respiratory outcomes and atopy in childhood. Eur Respir J. 2015/11/05. 2016;47(1):156–65. Available from: https://pubmed.ncbi.nlm.nih.gov/26541530

Kadar heat shock protein 70 cairan amnion yang tinggi sebagai faktor risiko terjadinya ketuban pecah dini pada kehamilan aterm

Abstract

References

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