Gebeliğin İntrahepatik Kolestazı ve Gebelik Sonuçlarının Değerlendirilmesi

Abstract

Amaç: Gebeliğin intrahepatik kolestazı(GİK) spontan preterm doğum, fetal distress, mekonyum boyalı amnion sıvısı ve ölü doğum gibi obstetrik komplikasyonlara yol açabilen, gebeliğe spefisik en sık görülen hepatik hastalıktır. Bu çalışmada GİK tanısı konulan hastaların gebelik ve fetal sonuçlarının retrospektif olarak değerlendirilmesi amaçlandı.

Materyal Metot: Retrospektif olgu çalışmasında Kasım 2017-Eylül 2019 tarihleri arasında kaşıntı şikayeti ile başvuran, herhangi bir karaciğer ve cilt patolojisi yokken devamlı kaşıntı ve maternal kanda artmış safra asitleri (≥10 μmol/L) bulunan gebeler GİK olarak kabul edildi. Çalışmaya dahil edilen 44 olgunun demografik özellikleri, karaciğer enzimleri, tanı aldığı gebelik haftası, hastalığa maruz kalınan süre, doğum şekli, doğum zamanı, doğumda APGAR skoru ve yenidoğanın kilosu bilgileri hastane kayıtlarından alındı.

Bulgular: Olguların yaş ortalaması 26,77 ± 6,23, %61,4’ ü nullipar gebe idi. Ortalama tanı alma zamanı 35,52±1,72 hafta, doğum haftası 36,64± 1,78 hafta bulundu. Hastalığa maruz kalınan süre 7,54 ± 8,14 gün olarak hesaplandı. Gebelerin 17’ si (% 38,6) normal vajinal yolla, 27’ si (%61,4) sezaryen ile doğurdu. Gebelik komplikasyonları, preterm doğum (n=1), gestasyonel diyabet (n=1) ve preeklampsi (n=1)  olarak bulundu. İnutero fetal ölüm gerçekleşmedi.

Sonuç: Gebeliğin intrahepatik kolestazı önemli maternal ve fetal komplikasyonlara neden olur. Bu komplikasyonların önlenmesinde yakın takip ve aktif yönetim gereklidir. 

Keywords

• Gebelik,intrahepatik kolestaz,komplikasyon,neonatal sonuç

Intrahepatic Cholestasis of Pregnancy and Evaluation of Obstetric Outcomes

Abstract

Aim: Intrahepatic cholestasis of pregnancy(ICP) is the most frequently encountered pregnancy-specific hepatic disease that may cause obstetric complications such as spontaneous preterm birth, fetal distress, meconium-stained amnion fluid and stillbirth. This study aimed to retrospectively analyze the pregnancy and fetal outcomes of patients who were diagnosed with ICP.

Material and Method: In the retrospective case study, pregnant women who visited with the complaint of itching between November 2017 and September 2019 and had constant itching and increased bile acids in the maternal blood (≥10 μmol/L) without any liver or skin pathology were accepted as ICP. For the 44 cases that were included in the study, demographic characteristics, liver enzymes, week of pregnancy at diagnosis, duration of exposure to the disease, type of delivery, time of delivery, APGAR scores and the weight of the newborn were collected from the hospital records.

Results: The mean age of the participants was 26,77±6,23, while 61,4% were nulliparous. The mean time of diagnosis was 35,52±1,72 weeks, while the mean week of pregnancy was 36,64±1,78. The mean duration of exposure to the disease was calculated as 7,54±8,14 days. 17 of the pregnant women (38,6%) gave birth via normal vaginal delivery, while 27 (61,4%) gave birth by Cesarean section delivery. Pregnancy complications were found as preterm birth (n=1), gestational diabetes (n=1) and preeclampsia (n=1). There was no in utero fetal death.

Conclusion: Intrahepatic cholestasis of pregnancy causes significant maternal and fetal complications. Close monitoring and active management are required in prevention of these complications. 

Keywords

• Pregnancy,Intrahepatic Cholestasis,Complication,Neonatal Outcomes

References

1. 1. Frise CJ, Williamson C. Gastrointestinal and liver disease in pregnancy. Clin Med 2013;13(3):269–74.
2. 2. Kondrackiene J, Kupcinskas L. Intrahepatic cholestasis of pregnancy-current achievements and unsolved problems. World J Gastroenterol 2008;14(38):5781–8.
3. 3. Joshi D, James A, Quaglia A, Westbrook RH, Heneghan MA. Liver disease in pregnancy. Lancet 2010;375(9714):594–605.
4. 4. Geenes V, Williamson C. Intrahepatic cholestasis of pregnancy. World J Gastroenterol 2009;15(17):2049–66.
5. 5. Chappell LC, Gurung V, Seed PT, Chambers J, Williamson C, Thornton JG; PITCH Study Consortium. Ursodeoxycholic acid versus placebo, and early term delivery versus expectant management, in women with intrahepatic cholestasis of pregnancy: semifactorial randomised clinical trial. BMJ. 2012;344:e3799. doi:10.1136/bmj.e3799.
6. 6. Rook M, Vargas J, Caughey A, Bacchetti P, Rosenthal P, Bull L. Fetal outcomes in pregnancies complicated by intrahepatic cholestasis of pregnancy in a northern California cohort. PLOS ONE . 2012; 7:e28343.
7. 7. Azzaroli F, Turco L, Lisotti A, Calvanese C, Mazzella G. The pharmacological management of intrahepatic cholestasis of pregnancy. Curr Clin Pharmacol 2011;6(1): 12–7.
8. 8. Wikstrom Shemer E, Marschall HU, Ludvigsson JF, Stephansson O. Intrahepatic cholestasis of pregnancy and associated adverse pregnancy and fetal outcomes: A 12-year population-based cohort study. British Journal of Obstetrics and Gynaecology 2013;120:717–723.

9. 9. Martineau M, Raker C, Powrie R, Williamson C. Intrahepatic cholestasis of pregnancy is associated with an increased risk of gestational diabetes. Eur J Obstet Gynecol Reprod Biol. 2014;176:80-5.
10. 10. Germain AM, Kato S, Carvajal JA, Valenzuela GJ, Valdes GL, Glasinovic JC. Bile acids increase response and expression of human myometrial oxytocin receptor. Am J Obstet Gynecol. 2003;189(2):577-82.
11. 11. Sepulveda WH, Gonzalez C, Cruz MA, Rudolph MI. Vasoconstrictive effect of bile acids on isolated human placental chorionic veins. Eur J Obstet Gynecol Reprod Biol 1991;42(3):211-15
12. 12. Perez MJ, Macias RI, Duran C, Monte MJ, Gonzalez-Buitrago JM, Marin JJ. Oxidative stress and apoptosis in fetal rat liver induced by maternal cholestasis. Protective effect of ursodeoxycholic acid. J Hepatol. 2005;43(2):324-32.
13. 13. Williamson C, Gorelik J, Eaton BM, Lab M, de Swiet M, Korchev Y. The bile acid taurocholate impairs rat cardiomyocyte function: a proposed mechanism for intra-uterine fetal death in obstetric cholestasis. Clin Sci (Lond). 2001;100(4):363-9.
14. 14. Sheikh Abdul Kadir SH, Miragoli M, Abu-Hayyeh S, Moshkov AV, Xie Q, Keitel V,et al. Bile acid-induced arrhythmia is mediated by muscarinic M2 receptors in neonatal rat cardiomyocytes. PLoS One. 2010;5(3):e9689. doi: 10.1371/journal.pone.0009689.
15. 15. Glantz A, Marschall HU, Mattsson LA. Intrahepatic cholestasis of pregnancy: Relationships between bile acid levels and fetal complication rates. Hepatology 2004; 40(2):467-74
16. 16. Gurung V, Williamson C, Chappell L, Chambers J, Briley A, Broughton Pipkin F, et al. Pilot study for a trial of ursodeoxycholic acid and/or early delivery for obstetric cholestasis. BMC Pregnancy Childbirth. 2009;9:19. doi:10.1186/1471-2393-9-19.
17. 17. Kondrackiene J, Kupcinskas L. Intrahepatic cholestasis of pregnancy-current achievements and unsolved problems. World J Gastroenterol 2008;14(38):5781-8.
18. 18. Oztekin D, Aydal I, Oztekin O, Okcu S, Borekci R, Tinar S. Predicting fetal asphyxia in intrahepatic cholestasis of pregnancy. Arch Gynecol Obstet 2009;280:975-9.
19. 19. Puljic A, Kim E, Page J, Esakoff T, Shaffer B, LaCoursiere DY, et al. The risk of infant and fetal death by each additional week of expectant management in intrahepatic cholestasis of pregnancy by gestational age. Am J Obstet Gynecol. 2015;212(5):667.e1-5. doi: 10.1016/j.ajog.2015.02.012.
20. 20. Alsulyman OM, Ouzounian JG, Ames-Castro M, Goodwin TM. Intrahepatic cholestasis of pregnancy: perinatal outcome associated with expectant manegement. Am J Obstet Gynecol 1996;175:957–960.
21. 21. Herrera CA, Manuck TA, Stoddard G, Varner M, Esplin S, Clark EAS, et al. Perinatal outcomes associated with intrahepatic cholestasis of pregnancy. J Matern Fetal Neonatal Med. 2018;31(14):1913-1920.
22. 22. Marathe JA, Lim WH, Metz MP, Scheil W, Dekker GA, Hague WM. A retrospective cohort review of intrahepatic cholestasis of pregnancy in a South Australian population. Eur J Obstet Gynecol Reprod Biol. 2017;218:33-38.
23. 23. Madazli R, Yuksel MA, Oncul M, Tuten A, Guralp O, Aydin B. Pregnancy outcomes and prognostic factors in patients with intrahepatic cholestasis of pregnancy. J Obstet Gynaecol. 2015;35(4):358-61.
24. 24. Geenes V, Lövgren-Sandblom A, Benthin L, Lawrance D, Chambers J, Gurung V,et al. The reversed feto-maternal bile acid gradient in intrahepatic cholestasis of pregnancy is corrected by ursodeoxycholic acid. PLoS One. 2014;9(1):e83828. doi:10.1371/journal.pone.0083828.
25. 25. Henderson CE, Shah RR, Gottimukkala S, Ferreira KK, Hamaoui A, Mercado R. Primum non nocere: how active management became modus operandi for intrahepatic cholestasis of pregnancy. Am J Obstet Gynecol. 2014;211(3):189-96. doi:10.1016/j.ajog.2014.03.058.