Association of adverse perinatal outcomes of intrahepatic cholestasis of pregnancy with biochemical markers: results of aggregate and individual patient data meta-analyses.

Autor:	Ovadia C; Department of Women and Children's Health, King's College London, London, UK., Seed PT; Department of Women and Children's Health, King's College London, London, UK., Sklavounos A; Department of Women and Children's Health, King's College London, London, UK., Geenes V; Department of Women and Children's Health, King's College London, London, UK., Di Ilio C; Department of Women and Children's Health, King's College London, London, UK., Chambers J; Department of Women and Children's Health, King's College London, London, UK; Women's Health Research Centre, Imperial College London, London, UK., Kohari K; Department of Obstetrics, Gynecology and Reproductive Sciences, Yale School of Medicine, New Haven, CT, USA., Bacq Y; Department of Hepatology and Gastroenterology, University Hospital of Tours, Tours, France., Bozkurt N; Department of Obstetrics and Gynecology, Gazi University School of Medicine, Ankara, Turkey., Brun-Furrer R; Division of Obstetrics, University Hospital of Zurich, Zurich, Switzerland., Bull L; Department of Medicine and Institute for Human Genetics, University of California, San Francisco, CA, USA., Estiú MC; Ramón Sardá Mother's and Children's Hospital, Buenos Aires, Argentina., Grymowicz M; Department of Gynecological Endocrinology, Warsaw Medical University, Warsaw, Poland., Gunaydin B; Department of Anesthesiology and Reanimation, Gazi University School of Medicine, Ankara, Turkey., Hague WM; Robinson Research Institute, University of Adelaide, Adelaide, SA, Australia., Haslinger C; Division of Obstetrics, University Hospital of Zurich, Zurich, Switzerland., Hu Y; Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China., Kawakita T; Department of Obstetrics and Gynecology, MedStar Washington Hospital Center, Washington, DC, USA., Kebapcilar AG; Department of Gynecology and Obstetrics, Selcuk University, Konya, Turkey., Kebapcilar L; Internal Medicine, Selcuk University, Konya, Turkey., Kondrackienė J; Department of Gastroenterology, Lithuanian University of Health Sciences, Kaunas, Lithuania., Koster MPH; Department of Obstetrics and Gynaecology, Erasmus MC, Rotterdam, Netherlands., Kowalska-Kańka A; Obstetrics and Gynaecology Clinic, Institute of Mother and Child, Warsaw, Poland., Kupčinskas L; Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania., Lee RH; Obstetrics and Gynecology, Keck School of Medicine University of Southern California, Los Angeles, CA, USA., Locatelli A; Department of Obstetrics and Gynecology, University of Milano-Bicocca, Monza, Italy., Macias RIR; National Institute for the Study of Liver and Gastrointestinal Diseases, Institute of Biomedical Research of Salamanca, University of Salamanca, Salamanca, Spain., Marschall HU; Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden., Oudijk MA; Department of Obstetrics, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, Netherlands., Raz Y; Department of Obstetrics and Gynecology, Tel Aviv Medical Center, Sackler Faculty of Medicine, Tel Aviv, Israel., Rimon E; Department of Obstetrics and Gynecology, Tel Aviv Medical Center, Sackler Faculty of Medicine, Tel Aviv, Israel., Shan D; Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China., Shao Y; Department of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China., Tribe R; Department of Women and Children's Health, King's College London, London, UK., Tripodi V; School of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina., Yayla Abide C; Clinic of Obstetrics and Gynecology, Zeynep Kamil Women and Children's Health Training and Research Hospital, University of Health Sciences, Istanbul, Turkey., Yenidede I; Clinic of Obstetrics and Gynecology, Zeynep Kamil Women and Children's Health Training and Research Hospital, University of Health Sciences, Istanbul, Turkey., Thornton JG; Division of Child Health, Obstetrics and Gynaecology, University of Nottingham, Nottingham, UK., Chappell LC; Department of Women and Children's Health, King's College London, London, UK., Williamson C; Department of Women and Children's Health, King's College London, London, UK. Electronic address: catherine.williamson@kcl.ac.uk.
Jazyk:	angličtina
Zdroj:	Lancet (London, England) [Lancet] 2019 Mar 02; Vol. 393 (10174), pp. 899-909. Date of Electronic Publication: 2019 Feb 14.
DOI:	10.1016/S0140-6736(18)31877-4
Abstrakt:	Background: Intrahepatic cholestasis of pregnancy is associated with adverse perinatal outcomes, but the association with the concentration of specific biochemical markers is unclear. We aimed to quantify the adverse perinatal effects of intrahepatic cholestasis of pregnancy in women with increased serum bile acid concentrations and determine whether elevated bile acid concentrations were associated with the risk of stillbirth and preterm birth. Methods: We did a systematic review by searching PubMed, Web of Science, and Embase databases for studies published from database inception to June 1, 2018, reporting perinatal outcomes for women with intrahepatic cholestasis of pregnancy when serum bile acid concentrations were available. Inclusion criteria were studies defining intrahepatic cholestasis of pregnancy based upon pruritus and elevated serum bile acid concentrations, with or without raised liver aminotransferase concentrations. Eligible studies were case-control, cohort, and population-based studies, and randomised controlled trials, with at least 30 participants, and that reported bile acid concentrations and perinatal outcomes. Studies at potential higher risk of reporter bias were excluded, including case reports, studies not comprising cohorts, or successive cases seen in a unit; we also excluded studies with high risk of bias from groups selected (eg, a subgroup of babies with poor outcomes were explicitly excluded), conference abstracts, and Letters to the Editor without clear peer review. We also included unpublished data from two UK hospitals. We did a random effects meta-analysis to determine risk of adverse perinatal outcomes. Aggregate data for maternal and perinatal outcomes were extracted from case-control studies, and individual patient data (IPD) were requested from study authors for all types of study (as no control group was required for the IPD analysis) to assess associations between biochemical markers and adverse outcomes using logistic and stepwise logistic regression. This study is registered with PROSPERO, number CRD42017069134. Findings: We assessed 109 full-text articles, of which 23 studies were eligible for the aggregate data meta-analysis (5557 intrahepatic cholestasis of pregnancy cases and 165 136 controls), and 27 provided IPD (5269 intrahepatic cholestasis of pregnancy cases). Stillbirth occurred in 45 (0·83%) of 4936 intrahepatic cholestasis of pregnancy cases and 519 (0·32%) of 163 947 control pregnancies (odds ratio [OR] 1·46 [95% CI 0·73-2·89]; I 2 =59·8%). In singleton pregnancies, stillbirth was associated with maximum total bile acid concentration (area under the receiver operating characteristic curve [ROC AUC]) 0·83 [95% CI 0·74-0·92]), but not alanine aminotransferase (ROC AUC 0·46 [0·35-0·57]). For singleton pregnancies, the prevalence of stillbirth was three (0·13%; 95% CI 0·02-0·38) of 2310 intrahepatic cholestasis of pregnancy cases in women with serum total bile acids of less than 40 μmol/L versus four (0·28%; 0·08-0·72) of 1412 cases with total bile acids of 40-99 μmol/L (hazard ratio [HR] 2·35 [95% CI 0·52-10·50]; p=0·26), and versus 18 (3·44%; 2·05-5·37) of 524 cases for bile acids of 100 μmol/L or more (HR 30·50 [8·83-105·30]; p<0·0001). Interpretation: The risk of stillbirth is increased in women with intrahepatic cholestasis of pregnancy and singleton pregnancies when serum bile acids concentrations are of 100 μmol/L or more. Because most women with intrahepatic cholestasis of pregnancy have bile acids below this concentration, they can probably be reassured that the risk of stillbirth is similar to that of pregnant women in the general population, provided repeat bile acid testing is done until delivery. Funding: Tommy's, ICP Support, UK National Institute of Health Research, Wellcome Trust, and Genesis Research Trust. (Copyright © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)
Databáze:	MEDLINE
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