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FältnamnIndikatorerMetadata
00007045naa a2200817 4500
001oai:gup.ub.gu.se/278821
003SwePub
008240528s2019 | |||||||||||000 ||eng|
024a https://gup.ub.gu.se/publication/2788212 URI
024a https://doi.org/10.1016/s0140-6736(18)31877-42 DOI
040 a (SwePub)gu
041 a eng
042 9 SwePub
072 7a ref2 swepub-contenttype
072 7a art2 swepub-publicationtype
100a Ovadia, C.4 aut
2451 0a Association of adverse perinatal outcomes of intrahepatic cholestasis of pregnancy with biochemical markers: results of aggregate and individual patient data meta-analyses
264 1b Elsevier BV,c 2019
520 a 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 We also included unpublished data from two UK hospitals.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 mu mol/L versus four (0.28%; 0.08-0.72) of 1412 cases with total bile acids of 40-99 mu mol/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 mu mol/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 mu mol/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 (c) 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.
650 7a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Reproduktionsmedicin och gynekologi0 (SwePub)302202 hsv//swe
650 7a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Obstetrics, Gynaecology and Reproductive Medicine0 (SwePub)302202 hsv//eng
653 a bile-acid levels
653 a fetal outcomes
653 a women
653 a risk
653 a stillbirth
653 a mortality
700a Seed, P. T.4 aut
700a Sklavounos, A.4 aut
700a Geenes, V.4 aut
700a Di Illio, C.4 aut
700a Chambers, J.4 aut
700a Kohari, K.4 aut
700a Bacq, Y.4 aut
700a Bozkurt, N.4 aut
700a Brun-Furrer, R.4 aut
700a Bull, L.4 aut
700a Estiu, M. C.4 aut
700a Grymowicz, M.4 aut
700a Gunaydin, B.4 aut
700a Hague, W. M.4 aut
700a Haslinger, C.4 aut
700a Hu, Y.4 aut
700a Kawakita, T.4 aut
700a Kebapcilar, A. G.4 aut
700a Kebapcilar, L.4 aut
700a Kondrackiene, J.4 aut
700a Koster, M. P. H.4 aut
700a Kowalska-Kanka, A.4 aut
700a Kupcinskas, L.4 aut
700a Lee, R. H.4 aut
700a Locatelli, A.4 aut
700a Macias, R. I. R.4 aut
700a Marschall, Hanns-Ulrich,d 1954u Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine4 aut0 (Swepub:gu)xmarsh
700a Oudijk, M. A.4 aut
700a Raz, Y.4 aut
700a Rimon, E.4 aut
700a Shan, D.4 aut
700a Shao, Y.4 aut
700a Tribe, R.4 aut
700a Tripodi, V.4 aut
700a Abide, C. Y.4 aut
700a Yenidede, I.4 aut
700a Thornton, J. G.4 aut
700a Chappell, L. C.4 aut
700a Williamson, C.4 aut
710a Göteborgs universitetb Institutionen för medicin, avdelningen för molekylär och klinisk medicin4 org
773t The Lancetd : Elsevier BVg 393:10174, s. 899-909q 393:10174<899-909x 0140-6736
856u http://www.thelancet.com/article/S0140673618318774/pdf
8564 8u https://gup.ub.gu.se/publication/278821
8564 8u https://doi.org/10.1016/s0140-6736(18)31877-4

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