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Abstract

High risk pregnancy defines pregnancies that affects mother or fetus, and experience one or more health problems. Pre-eclampsia, intrauterine growth retardation, preterm labor, preterm premature rupture of membranes is the leading cause of fetal morbidity and mortality. Preeclampsia is still continuing actuality as the most common risk increasing factor on maternal and fetal morbidity and mortality in highrisk pregnancies. Especially, in recent years, steps have been taken to identify high-risk pregnancies during the first trimester. Among the molecules studied in soluble HLA-G associated with defect in placental trophoblast invasion, pregnancy-associated plasma protein A, free beta human chorionic gonadotrophin, alpha feto-protein, inhibin, estriol are included. In the case of detection of high risk pregnancies in the first trimester, closer monitoring will be provided and strategies for preventing pregnancy complications will be improved

Keywords

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Yüksek Riskli Gebelikleri Belirlemede Down Sendromu Tarama Belirteçleri ve HLA-G

Abstract

Yüksek riskli gebelik, anneyi ya da fetüsü etkileyen bir ya da daha fazla sağlık problemi olan gebelikleri tanımlar. Preeklampsi, intrauterin gelişme geriliği, preterm doğum, preterm erken membran rüptürü fetal morbidite ve mortalitenin önde gelen nedenlerindendir. Preeklampsi; yüksek riskli gebelikler içerisinde maternal, fetal morbidite ve mortaliteyi en sık artıran risk olarak hala güncelliğini devam ettirmektedir. Özellikle son yıllarda yüksek riskli gebelikleri ilk trimesterde belirlemeye yönelik adımlar atılmıştır. Çalışılan moleküller arasında plasental trofoblastik invazyon defekti ile ilişkili çözünebilir HLA-G, gebelikle ilişkili plazma proteini A, serbest beta insan koryonik gonadotropini, alfa feto-protein, inhibin, östriol yer almaktadır. Yüksek riskli gebelerin ilk trimesterde saptanması durumunda daha yakın takibi sağlanacak, gebelik komplikasyonlarını önlemeye yönelik stratejiler geliştirilecektir

Keywords

• Yüksek Riskli Gebelik, Down Sendromu Tarama Belirteçleri, HLA-G

References

1. Akman AC. Gebelikte hipertansif bozukluklar. Williams Doğum Bilgisi. 21. baskı. İstanbul: Nobel Tıp Kitapevi, 2005;567-618.
2. Report of the National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy. Am J Obstet Gynecol 2000;183(1):1-22.
3. Meler E, Figueras F, Mula R, et al. Prognostic role of uterine artery doppler in patients with preeclampsia. Fetal Diagn Ther 2010;27(1):8-13.
4. Güler SA. İntrauterin Büyüme Kısıtlılığı. In Gabbe SG, ed. Obstetri normal ve sorunlu gebelikler. 1. baskı. İstanbul: Nobel &Güneş Tıp Kitabevi, 2009;771-814.
5. Maulik D. Fetal growth compromise: definitions, standards, and classification. Clin Obstet Gynecol 2006;49(2):214-8.
6. Maulik D, Frances Evans J, Ragolia L. Fetal growth restriction: pathogenic mechanisms. Clin Obstet Gynecol 2006;49(2):219-27.
7. Bozdağ G, Çelik NY. Oligohidramnios. In Williams Obstetrik El Kitabı. Gebelik Komplikasyonları. Ankara: Güneş Tıp Kitabevleri, 2010;65-7.
8. Hill LM. Oligohydramnios: sonographic diagnosis and clinical implications. Clin Obstet Gynecol 1997;40(2):314-27.

9. Kim YM, Chaiworapongsa T, Gomez R, et al. Failure of physiologic transformation of the spiral arteries in the placental bed in preterm premature rupture of membranes. Am J Obstet Gynecol 2002;187(5):1137-42.
10. Kim YM, Bujold E, Chaiworapongsa T, et al. Failure of physiologic transformation of the spiral arteries in patients with preterm labor and intact membranes. Am J Obstet Gynecol 2003;189(4):1063-9.
11. ACOG Practice Bulletin No. 80: premature rupture of membranes. Clinical management guidelines for obstetrician-gynecologists. Obstet Gynecol 2007;109(4):1007-19.
12. Tanır HM, Turp AB. Erken membran rüptürü. In Gabbe SG ed. Obstetri normal ve sorunlu gebelikler. 1. baskı. İstanbul: Nobel & Güneş Tıp Kitabevi, 2009;713-32.
13. Jauniaux E, Burton GJ. Pathophysiology of histological changes in early pregnancy loss. Placenta 2005;26(2-3):114-23.
14. Ober C. HLA and pregnancy: the paradox of the fetal allograft. Am J Hum Genet 1998;62(1):1-5.
15. Geraghty DE, Koller BH, Orr HT. A human major histocompatibility complex class I gene that encodes a protein with a shortened cytoplasmic segment. Proc Natl Acad Sci USA 1987;84(24):9145-9.
16. Puppo F, Costa M, Contini P, et al. Determination of soluble HLA-G and HLA-A, -B, and –C molecules in pregnancy. Transplant Proc 1999;31(4):1841-3.
17. Roussev RG, Coulam CB. HLA-G and its role in implantation (review). J Assist Reprod Genet 2007;24(7):288-95.
18. Cecati M, Giannubilo SR, Emanuelli M, et al. HLA-G and pregnancy adverse outcomes. Med Hypotheses 2011;76(6):782-4.
19. Ishitani A, Geraghty DE. Alternative splicing of HLA-G transcripts yields proteins with primary structures resembling both class I and class II antigens. Proc Natl Acad Sci USA 1992;89(9):3947-51.
20. Carosella ED, Paul P, Moreau P, et al. HLA-G and HLA-E: fundamental and pathophysiological aspects. Immunol Today 2000;21(11):532-4.
21. Le Bouteiller P, Blaschitz A. The functionality of HLA-G is emerging. Immunol Rev 1999;167:233-44.
22. Hunt JS, Petroff MG, McIntire RH, et al. HLA-G and immune tolerance in pregnancy. FASEB J 2005;19(7):681-93.
23. Roussev RG, Ng SC, Coulam CB. Natural killer cell functional activity suppression by intravenous immunoglobulin, intralipid and soluble human leukocyte antigen-G. Am J Reprod Immunol 2007;57(4):262-9.
24. Le Bouteiller P. HLA-G in the human thymus: a subpopulation of medullary epithelial but not CD83(+) dendritic cells expresses HLA-G as a membrane-bound and soluble protein. Int Immunol 1999;11(6):889- 98.
25. Le Bouteiller P, Solier C, Pröll J, et al. Placental HLA-G protein expression in vivo: where and what for? Hum Reprod Update 1999;5(3):223-33.
26. Steinborn A, Varkonyi T, Scharf A, et al. Early detection of decreased soluble HLA-G levels in the maternal circulation predicts the occurrence of preeclampsia and intrauterine growth retardation during further course of pregnancy. Am J Reprod Immunol 2007;57(4):277-86.
27. Hunt JS, Langat DK, McIntire RH, et al. The role of HLA-G in human pregnancy. Reprod Biol Endocrinol 2006;4(Suppl 1):S10.
28. Rizzo R, Andersen AS, Lassen MR, et al. Soluble human leukocyte antigen-G isoforms in maternal plasma in early and late pregnancy. Am J Reprod Immunol 2009;62(5):320-38.
29. O'Brien M, Dausset J, Carosella ED, et al. Analysis of the role of HLA-G in preeclampsia. Hum Immunol 2000;61(11):1126-31.
30. Goldman-Wohl DS, Ariel I, Greenfield C, et al. Lack of human leukocyte antigen-G expression in extravillous trophoblasts is associated with pre-eclampsia. Mol Hum Reprod 2000;6(1):88-95.
31. Somigliana E, Viganò P, Vignali M. Endometriosis and unexplained recurrent spontaneous abortion: pathological states resulting from aberrant modulation of natural killer cell function? Hum Reprod Update 1999;5(1):40-51.
32. Van der Ven K, Pfeiffer K, Skrablin S. HLA-G polymorphisms and molecule function-questions and more questions-a review. Placenta 2000;21(Suppl A):S86-92.
33. Athanassakis I, Paflis M, Ranella A, et al. Detection of soluble HLA-G levels in maternal serum can be predictive for a successful pregnancy. Transplant Proc 1999;31(4):1834-7.
34. Goldman-Wohl DS, Ariel I, Greenfield C, et al. HLA-G expression in extravillous trophoblasts is an intrinsic property of cell differentiation: a lesson learned from ectopic pregnancies. Mol Hum Reprod 2000;6(6):535-40.
35. Steinborn A, Rebmann V, Scharf A, et al. Placental abruption is associated with decreased maternal plasma levels of soluble HLA-G. J Clin Immunol 2003;23(4):307-14.
36. Gall SA, Halbert SP. Antigenic constituents in pregnancy plasma which are undetectable in normal non- pregnant female or male plasma. Int Arch Allergy Appl Immunol 1972;42(4):503-15.
37. McIntyre JA, Hsi B, Faulk WP, et al. Immunological studies of the human placenta: functional and morphological analysis of pregnancy-associated plasma protein A (PAPP-A). Immunology 1981;44(3):577- 83.
38. Smith GC, Stenhouse EJ, Crossley JA, et al. Early pregnancy levels of pregnancy-associated plasma protein a and the risk of intrauterine growth restriction, premature birth, preeclampsia, and stillbirth. J Clin Endocrinol Metab 2002;87(4):1762-7.
39. Cole LA. Biological functions of hCG and hCG-related molecules. Reprod Biol Endocrinol 2010;24;8:102.
40. Chandra S, Scott H, Dodds L, et al. Unexplained elevated maternal serum alpha-fetoprotein and/or human chorionic gonadotropin and the risk of adverse outcomes. Am J Obstet Gynecol 2003;189(3):775-81.
41. Davidson EJ, Riley SC, Roberts SA, et al. Maternal serum activin, inhibin, human chorionic gonadotrophin and alpha-fetoprotein as second trimester predictors of pre-eclampsia. BJOG 2003;110(1):46-52.
42. Çalışkan E. Gebelik endokrinolojisi. In: Speroff L (ed). Klinik jinekolojik endokrinoloji ve infertilite. Ankara: Güneş Tıp Kitabevleri, 2007;259-315.
43. Williams MA, Hickok DE, Zingheim RW, et al. Elevated maternal serum alpha-fetoprotein levels and midtrimester placental abnormalities in relation to subsequent adverse pregnancy outcomes. Am J Obstet Gynecol 1992;167(4Pt1):1032-7.
44. Waller DK, Lustig LS, Cunningham GC, et al. The association between maternal serum alpha-fetoprotein and preterm birth, small for gestational age infants, preeclampsia, and placental complications. Obstet Gynecol 1996;88(5):816-22.
45. Baschat AA, Harman CR, Farid G, et al. Very low second-trimester maternal serum alpha-fetoprotein: Association with high birth weight. Obstet Gynecol 2002;99(4):531-6.
46. Shenhav S, Gemer O, Sassoon E, et al. Mid-trimester triple test levels in early and late onset severe pre- eclampsia. Prenat Diagn 2002;22(7):579-82.
47. Lindheimer MD, Roberts JM, Gary F. Hypertensive disorders in pregnancy. In Chesley’s ed. 3rd ed. San Diego: Elseiver, 2009.
48. Wallace EM, Crossley JA, Groome NP, et al. Amniotic fluid inhibin-A in chromossomally normal and Down's syndrome pregnancies. J Endocrinol 1997;152(1):109-12.
49. Petraglia F. Inhibin, activin and follistatin in the human placenta-a new family of regulatory proteins. Placenta 1997;18(1):3-8.
50. Muttukrishna S, Child TJ, Groome NP. Source of circulating levels of inhibin A, pro alpha C-containing inhibins and activin A in early pregnancy. Hum Reprod 1997;12(5):1089-93.
51. Spencer K, Yu CK, Savvidou M, et al. Prediction of preeclampsia by uterine artery Doppler ultrasonography and maternal serum pregnancy associated plasma protein-A, free beta-human chorionic gonadotropin, activin A and inhibin A at 22 + 0 to 24 + 6 weeks' gestation. Ultrasound Obstet Gynecol 2006;27(6):658-63.
52. Spencer K, Cowans NJ, Chefetz I, et al. First-trimester maternal serum PP-13, PAPP-A and second- trimester uterine artery doppler pulsatility index as markers of preeclampsia. Ultrasound Obstet Gynecol 2007;29(2):128-34.
53. Smith GC, Shah I, White IR, et al. Maternal and biochemical predictors of antepartum stillbirth among nulliparous women in relation to gestational age of fetal death. BJOG 2007;114(6):705-14.
54. Huang T, Hoffman B, Meschino W, et al. Prediction of adverse pregnancy outcomes by combinations of first and second trimester biochemistry markers used in the routine prenatal screening of Down syndrome. Prenat Diagn 2010;30(5):471-7.
55. Goetzinger KR, Singla A, Gerkowicz S, et al. Predicting the risk of pre-eclampsia between 11 and 13 weeks' gestation by combining maternal characteristics and serum analytes, PAPP-A and free β-hCG. Prenat Diagn 2010;30(12-13):1138-42.
56. Ranta JK, Raatikainen K, Romppanen J, et al. Decreased PAPP-A is associated with preeclampsia, premature delivery and small for gestational age infants but not with placental abruption. Eur J Obstet Gynecol Reprod Biol 2011;157(1):48-52.
57. Carbone IF, Cruz JJ, Sarquis R, et al. Assisted conception and placental perfusion assessed by uterine artery Doppler at 11-13 weeks' gestation. Hum Reprod 2011;26(7):1659-64.
58. Poon LC, Stratieva V, Piras S, et al. Hypertensive disorders in pregnancy: combined screening by uterine artery Doppler, blood pressure and serum PAPP-A at 11-13 weeks. Prenat Diagn 2010;30(3):216-23.
59. Mikat B, Zeller A, Scherag A, et al. βhCG and PAPP-A in first trimester: Predictive factors for preeclampsia? Hypertens Pregnancy 2011;9 (Epub ahead of print).
60. Vandenberghe G, Mensink I, Twisk JW, et al. First trimester screening for intra-uterine growth restriction and early-onset pre-eclampsia. Prenat Diagn 2011;31(10):955-61.
61. Cuckle H, Sehmi I, Jones R. Maternal serum inhibin A can predict pre-eclampsia. Br J Obstet Gynaecol 1998;105(10):1101-3.
62. Aquilina J, Barnett A, Thompson O, et al. Second-trimester maternal serum inhibin A concentration as an early marker for preeclampsia. Am J Obstet Gynecol 1999;181(1):131-6.
63. D'Anna R, Baviera G, Corrado F, et al. Is mid-trimester maternal serum inhibin-A a marker of preeclampsia or intrauterine growth restriction? Acta Obstet Gynecol Scand 2002;81(6):540-3.
64. Kang JH, Farina A, Park JH, et al. Down syndrome biochemical markers and screening for preeclampsia at first and second trimester: correlation with the week of onset and the severity. Prenat Diagn 2008;28(8):704- 9.
65. Ree PH, Hahn WB, Chang SW, et al. Early detection of preeclampsia using inhibin-A and other second- trimester serum markers. Fetal Diagn Ther 2011;29(4):280-6.
66. Gagnon A, Wilson RD, Audibert F, et al. Obstetrical complications associated with abnormal maternal serum markers analytes. J Obstet Gynaecol Can 2008;30(10):918-49.
67. Dugoff L, Hobbins JC, Malone FD, et al. Quad screen as a predictor of adverse pregnancy outcome. Obstet Gynecol 2005;106(2):260-7.
68. Wald NJ, Morris JK. Multiple marker second trimester serum screening for pre-eclampsia. J Med Screen 2001;8(2):65-8.
69. Lambert-Messerlian GM, Silver HM, Petraglia F, et al. Second-trimester levels of maternal serum human chorionic gonadotropin and inhibin a as predictors of preeclampsia in the third trimester of pregnancy. J Soc Gynecol Investig 2000;7(3):170-4.
70. Stamilio DM, Sehdev HM, Morgan MA, et al. Can antenatal clinical and biochemical markers predict the development of severe preeclampsia? Am J Obstet Gynecol 2000;182(3):589-94.
71. Benn PA, Horne D, Briganti S, et al. Elevated second-trimester maternal serum hCG alone or in combination with elevated alpha-fetoprotein. Obstet Gynecol 1996;87(2):217-22.