The relationship between bile acid levels and adverse pregnancy outcomes in patients with intrahepatic pregnancy cholestasis: a retrospective analysis of 120 cases

Abstract

Aim: It has been shown that fasting serum bile acid (SBA) levels above 40 µmol/L are better in predicting adverse perinatal outcomes in women with a diagnosis of intrahepatic cholestasis of pregnancy (ICP) in many studies in the literature. We aimed to measure the relationship between disease severity and adverse perinatal outcomes between groups according to serum SBA levels (10-40 and >40 mmol/L) in patients diagnosed with ICP in our study. Materials and Method: 120 patients diagnosed with ICP were included in this retrospective study conducted in our hospital between September 1, 2019 and December 31, 2020. Obstetric outcomes, maternal and fetal complications were analyzed. Results: 88 cases with fasting SBA levels in the range of 10-40 umol/L and 32 cases with fasting SBA levels above 40 umol/L were compared. Maternal and fetal complication rates were significantly increased in the group with fasting bile acid level >40 umol/L (p<0.01). In the group with serum ASA >40 umol/L, 1st minute and 5th minute Apgar scores were found to be statistically significantly lower, and the need for neonatal intensive care unit (NICU) increased significantly (p<0.05). ROC curve showed that AUC values of maternal, obstetric fetal and adverse outcomes were 0.67, 0.74, 0.71 and 0.80, respectively. Conclusion: Preterm birth, meconium-stained amniotic fluid, neonatal respiratory distress syndrome (RDS), admission to NICU, and neonatal death were found to be statistically significantly higher in cases with a diagnosis of ICP with SBA > 40 umol/L. In particular, the significant increase in adverse pregnancy outcomes above certain SBA levels may guide clinicians to achieve better clinical outcomes in the management of pregnancies complicated by ICP.

Keywords

• fasting serum bile acid
• intrahepatic cholestasis of pregnancy
• meconium-stained amniotic fluid
• preterm birth
• stillbirth.

İntrahepatik gebelik kolestazı olan hastalarda safra asidi düzeyleri ile olumsuz gebelik sonuçları arasındaki ilişki: 120 vakanın retrospektif analizi

Abstract

Amaç: Literatürde birçok çalışmada intrahepatik gebelik kolestazı (İGK) tanılı kadınlarda serum açlık safra asidi (ASA) düzeylerinin 40 umol/L üzerinde iken olumsuz perinatal sonuçları öngörmede daha iyi olduğu gösterilmiştir. Çalışmamızda, İGK tanısı alan hastalarda, serum ASA düzeylerine göre (10-40 ve >40 mmol/L) oluşturulan gruplar arasında hastalık şiddeti ile olumsuz perinatal sonuçlar arasındaki ilişkiyi ölçmeyi amaçladık. Gereç ve Yöntemler: 1 Eylül 2019 - 31 Aralık 2020 tarihleri arasında hastanemizde yapılan bu retrospektif çalışmaya İGK tanısı alan 120 hasta dahil edildi. Obstetrik sonuçlar, maternal ve fetal komplikasyonlar analiz edildi. Bulgular: Serum ASA düzeyleri 10-40 umol/L aralığında olan 88 olgu ile 40 umol/L’nin üzerinde olan 32 olgu karşılaştırıldı. Maternal ve fetal komplikasyon oranları, açlık safra asidi düzeyi >40 umol/L olan grupta anlamlı olarak artmış saptandı (p<0.01). Serum ASA >40 umol/L olan grupta 1. dk ve 5.dk Apgar skorları istatistiksel olarak anlamlı oranda düşük saptanmış olup, yenidoğan yoğun bakım (YDYB) ihtiyacı da anlamlı olarak artmış bulundu (p<0.05). ROC eğrisi, maternal, obstetrik, fetal ve olumsuz sonuçların AUC değerlerinin sırasıyla 0.67, 0.74, 0.71 ve 0.80 olduğunu gösterdi. Sonuç: ASA > 40 umol/L olan İGK tanılı olgularda preterm doğum, mekonyumlu amniyon, neonatal respiratuar distres sendromu (RDS), YDYB ihtiyacı ve neonatal ölümü içeren gebelik olumsuz sonuçları istatistiksel olarak anlamlı düzeyde yüksek saptandı. Özellikle olumsuz gebelik sonuçlarının belirli ASA değerlerinin üzerinde anlamlı olarak yükselmesi, klinisyenleri İGK ile komplike olan gebeliklerin yönetiminde daha iyi klinik sonuçlar elde etmek açısından yönlendirebilir.

Keywords

• açlık safra asidi
• intrahepatik gebelik kolestazı
• mekonyumlu amniyon
• preterm doğum
• ölü doğum

References

1. [1] Lee RH, Mara G, Metz TD, Pettker CM: Society for Maternal-Fetal Medicine Consult Series #53: Intrahepatic cholestasis of pregnancy: Replaces Consult #13, April 2011. Am J Obstet Gynecol 2021;224(2): B2-b9.
2. [2] McIlvride S, Dixon PH, Williamson C: Bile acids and gestation. Mol Aspects Med 2017;56: 90-100.
3. [3] Fan HM, Mitchell AL, Williamson C: ENDOCRINOLOGY IN PREGNANCY: Metabolic impact of bile acids in gestation. Eur J Endocrinol 2021;184(3): R69-r83.
4. [4] Williamson C, Hems LM, Goulis DG, Walker I, Chambers J, Donaldson O, et al.: Clinical outcome in a series of cases of obstetric cholestasis identified via a patient support group. Bjog 2004;111(7): 676-681.
5. [5] Di Mascio D, Quist-Nelson J, Riegel M, George B, Saccone G, Brun R, et al.: Perinatal death by bile acid levels in intrahepatic cholestasis of pregnancy: a systematic review. J Matern Fetal Neonatal Med 2021;34(21): 3614-3622.
6. [6] Geenes V, Chappell LC, Seed PT, Steer PJ, Knight M, Williamson C: Association of severe intrahepatic cholestasis of pregnancy with adverse pregnancy outcomes: a prospective population-based case-control study. Hepatology (Baltimore, Md) 2014;59(4): 1482-1491.
7. [7] 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: 80-85.
8. [8] Cui D, Zhong Y, Zhang L, Du H: Bile acid levels and risk of adverse perinatal outcomes in intrahepatic cholestasis of pregnancy: A meta-analysis. J Obstet Gynaecol Res 2017;43(9): 1411-1420.

9. [9] Ovadia C, Seed PT, Sklavounos A, Geenes V, Di Ilio C, Chambers J, et al.: Association of adverse perinatal outcomes of intrahepatic cholestasis of pregnancy with biochemical markers: results of aggregate and individual patient data meta-analyses. Lancet 2019;393(10174): 899-909.
10. [10] Kawakita T, Parikh LI, Ramsey PS, Huang CC, Zeymo A, Fernandez M, et al.: Predictors of adverse neonatal outcomes in intrahepatic cholestasis of pregnancy. Am J Obstet Gynecol 2015;213(4): 570.e571-578.
11. [11] Glantz A, Marschall HU, Mattsson LA: Intrahepatic cholestasis of pregnancy: Relationships between bile acid levels and fetal complication rates. Hepatology 2004;40(2): 467-474.
12. [12] Arafa A, Dong JY: Association between intrahepatic cholestasis of pregnancy and risk of gestational diabetes and preeclampsia: a systematic review and meta-analysis. Hypertens Pregnancy 2020;39(3): 354-360.
13. [13] Fleminger J, Seed PT, Smith A, Juszczak E, Dixon PH, Chambers J, et al.: Ursodeoxycholic acid in intrahepatic cholestasis of pregnancy: a secondary analysis of the PITCHES trial. Bjog 2021;128(6): 1066-1075.
14. [14] Bacq Y, Sapey T, Bréchot MC, Pierre F, Fignon A, Dubois F: Intrahepatic cholestasis of pregnancy: a French prospective study. Hepatology 1997;26(2): 358-364.
15. [15] Brouwers L, Koster MP, Page-Christiaens GC, Kemperman H, Boon J, Evers IM, et al.: Intrahepatic cholestasis of pregnancy: maternal and fetal outcomes associated with elevated bile acid levels. Am J Obstet Gynecol 2015;212(1): 100.e101-107.
16. [16] Yule CS, Holcomb DS, Kraus AC, Brown CEL, McIntire DD, Nelson DB: Cholestasis: A Prospective Study of Perinatal Outcomes and Time to Symptom Improvement. Am J Perinatol 2021;38(5): 414-420.