Total serum bile acids or serum bile acid profile, or both, for the diagnosis of intrahepatic cholestasis of pregnancy
Appendices
Appendix 1. Preliminary search strategies
| Database | Time span | Preliminary search strategies |
| The Cochrane Hepato‐Biliary Group Controlled Trials Register | Date will be given at review stage. | (((bile or cholic or glycocholic or chenodeox*cholic or deox*cholic or lithocholic or ursodeox*cholic or glyco‐conjugated or tauro‐conjugated or glycine or taurine) and acid*) or (chol*glycine or TSBA or CA or GCA or CDCA or LCA or DCA or UDCA)) AND ((cholesta* and (hepat* or liver*)) or jaundice or (icterus gravidarum)) AND (pregnan* or obstetric* or gestation*) |
| The Cochrane Pregnancy and Childbirth Group Trials Register | Date will be given at review stage. | (((bile or cholic or glycocholic or chenodeox*cholic or deox*cholic or lithocholic or ursodeox*cholic or glyco‐conjugated or tauro‐conjugated or glycine or taurine) and acid*) or (chol*glycine or TSBA or CA or GCA or CDCA or LCA or DCA or UDCA)) AND ((cholesta* and (hepat* or liver*)) or jaundice or (icterus gravidarum)) AND (pregnan* or obstetric* or gestation*) |
| The Cochrane Hepato‐Biliary Group Diagnostic Test of Accuracy Studies Register | Date will be given at review stage. | (((bile or cholic or glycocholic or chenodeox*cholic or deox*cholic or lithocholic or ursodeox*cholic or glyco‐conjugated or tauro‐conjugated or glycine or taurine) and acid*) or (chol*glycine or TSBA or CA or GCA or CDCA or LCA or DCA or UDCA)) AND ((cholesta* and (hepat* or liver*)) or (jaundice or (icterus gravidarum)) AND (pregnan* or obstetric* or gestation*) |
| The Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library | Latest issue | #1 MeSH descriptor: [Bile Acids and Salts] explode all trees #2 ((bile or cholic or glycocholic or chenodeox*cholic or deox*cholic or lithocholic or ursodeox*cholic or glyco‐conjugated or tauro‐conjugated or glycine or taurine) and acid*) or (chol*glycine or TSBA or CA or GCA or CDCA or LCA or DCA or UDCA) |
| MEDLINE (OvidSP) | 1946 to the date of search | 1. exp "Bile Acids and Salts"/ |
| Embase (OvidSP) | 1974 to the date of search | 1. exp bile acid/ |
| Science Citation Index Expanded (Web of Science) | 1900 to the date of search | #4 #1 AND #2 AND #3 |
| CINAHL (EBSCO host) | 1981 to the date of search. | S10 S6 AND S9 S9 S8 OR S7 S8 TX pregnan* or obstetric* or gestation* S7 MW Pregnancy S6 S4 OR S5 S5 TX (cholesta* and (hepat* or liver*)) or jaundice or (icterus gravidarum) S4 MW Intrahepatic Cholestasis S3 S1 OR S2 S2 TX ((bile or cholic or glycocholic or chenodeox?cholic or deox?cholic or lithocholic or ursodeox?cholic or glyco‐conjugated or tauro‐conjugated or glycine or taurine) and acid?) or (chol?glycine or TSBA or CA or GCA or CDCA or LCA or DCA or UDCA) S1 MW Bile Acids and Salts |
| BIOSIS Previews (Web of Science) | 1969 to the date of search | #4 #1 AND #2 AND #3 |
| LILACS (VHL) | Date will be given at review stage. | 1. (tw:((tw:(cholestasis )) AND (tw:(pregnancy OR obstetric)))) OR (tw:((tw:( colestasis)) AND (tw:(gravídica OR (intrahepática AND embarazo) OR obstétrica)))) OR (tw:((tw:(ictericia)) AND (tw:(embarazo OR gravídica)))) OR (tw:((tw:(colestase)) AND (tw:(gravidez OR gestacional OR obstétrica)))) OR (tw:( (tw:(icterícia)) AND (tw:(gravidez OR colestática)))) AND (instance:"regional") AND ( db:("LILACS")) 2. (tw:(acidos biliares)) AND (tw:(embarazo OR gravidez OR obstétrica OR gestational OR gravidica)) AND (instance:"regional") AND ( db:("LILACS")) 3. (((mh:("Bile Acids and Salts")) OR (tw:(acidos biliares))) AND ((mh:("Cholestasis, Intrahepatic")) OR (tw:(cholestasis OR colestasis OR colestase OR ictericia))) AND ((mh:("Pregnancy Complications")) OR (tw:(pregnancy OR obstetric OR gravídica OR embarazo OR obstétrica OR gravidez OR gestacional)))) AND (instance:"regional") AND (db:("LILACS")) |
| SCIELO | Date will be given at review stage. | 1. ((cholestasis) AND (pregnancy OR obstetric) ) OR ((colestasis) AND (embarazo OR obstétrica) ) OR ((ictericia) AND (embarazo OR gravídica) ) OR ( (icterícia) AND (gravidez OR colestática)) OR ((colestase) AND (gravidez OR gestacional) ) 2. (bile acids) AND (pregnancy OR obstetric) 3. (acidos biliares) AND (embarazo OR gravidez OR obstétrica OR gestational OR gravidica) 4. ((cholestasis) AND (pregnancy OR obstetric) ) OR ((colestasis) AND (embarazo OR obstétrica) ) OR ((ictericia) AND (embarazo OR gravídica)) OR ((icterícia) AND (gravidez OR colestática)) OR ((colestase) AND (gravidez OR gestacional) ) OR ((bile acids) AND (pregnancy OR obstetric)) OR ((acidos biliares) AND (embarazo OR gravidez OR obstétrica OR gestational OR gravidica)) |
| TRIP, RHL, Evidence search: Health and Social Care, OpenSIGLE, NTIS | Date will be given at review stage. | 1. cholestasis AND (obstetric OR pregnancy OR pregnant OR gestation OR gestational) 2. (obstetric OR pregnancy OR pregnant OR gestation OR gestational) AND ((bile acid) OR (bile acids) OR (bile salt) OR (bile salts)) 3. cholestasis AND (obstetric OR pregnancy OR pregnant OR gestation OR gestational) AND ((bile acid) OR (bile acids) OR (bile salt) OR (bile salts)) 4. (icterus OR jaundice OR pruritus) AND (gravidarum OR pregnancy OR obstetric) 5. (cholestasis OR (bile acid) OR (bile acids) OR (bile salt) OR (bile salts)) AND (obstetric OR pregnancy OR pregnant OR gestation OR gestational) OR ((icterus OR jaundice OR pruritus) AND (gravidarum OR pregnancy OR obstetric)) |
| Chinese databases (CNKI, VIP) | Date will be given at review stage. | Search strategies in Chinese can be obtained by contacting the first review author, CM. |
Appendix 2. QUADAS‐2
| Domain | Participant selection | Index test | Reference standard | Flow and timing |
| Description | Describe methods of participant selection: describe inclusion criteria for participants (prior testing, presentation, intended use of index test, and setting): The studies that fulfil the inclusion criteria of this review should have included pregnant women recruited in any clinical setting. They should have been evaluated for personal history of skin or liver diseases, presence of pruritus during their pregnancy, and been assessed with any of the most common liver test (or tests), followed by any of the already mentioned index tests (total bile acids, cholic acid, glycocholic acid, chenodeoxycholic acid, deoxycholic acid, lithocholic acid, ursodeoxycholic acid, cholic/chenodeoxycholic acids, total glyco‐conjugated bile acids, total tauro‐conjugated bile acids, total glyco‐conjugated bile acids/total taurine‐conjugated bile acids). | Describe the index test and how it was conducted and interpreted: The index tests (total bile acids, cholic acid, glycocholic acid, chenodeoxycholic acid, deoxycholic acid, lithocholic acid, ursodeoxycholic acid, cholic/chenodeoxycholic acids, total glyco‐conjugated bile acids, total tauro‐conjugated bile acids, total glyco‐conjugated bile acids/total taurine‐conjugated bile acids) are non‐invasive laboratory serum tests performed after the first clinical evaluation of the pregnant women for the diagnosis of intrahepatic cholestasis of pregnancy. The serum concentration of the index test(s) can be assessed through different techniques. Laboratory methods and diagnostic cut‐off values could vary between studies. | Describe the reference standard and how it was conducted and interpreted: Clinical evaluation including follow‐up after delivery. The clinical evaluation is the final judgement of the clinician who takes into account the clinical assessment of suggestive signs and symptoms for intrahepatic cholestasis of pregnancy and the presence of any otherwise unexplained, persistent abnormalities of aspartate transaminase, alanine aminotransferase, or bilirubin levels until delivery. The follow‐up after delivery is the assessment of spontaneous relief of symptoms and normalisation of liver tests within 8 weeks at most. | Describe any people who did not receive the index test(s) or reference standard (or both) or who will be excluded from the 2 ×2 table (refer to flow diagram): describe the time interval and any interventions between index test(s) and reference standard: Pregnant women considered for inclusion should have undergone the reference standard and any of the index tests, singly or in combination (see Reference standards, Index tests and clinical diagnostic pathway represented in Figure 2). We will exclude participants who lack data for the 2 × 2 table. To define a time interval between our index tests and our reference standard is not relevant, as the index tests should be performed when the suspicion of intrahepatic cholestasis of pregnancy arises and the reference standard comprises the follow‐up after delivery. |
| Signalling questions: yes/no/unclear | Was a consecutive or random sample of participants enrolled? Yes: all consecutive participants or random sample of people with suspected intrahepatic cholestasis of pregnancy were enrolled in the study. No: selected participants were not included. Unclear: insufficient data were reported to permit a judgement. | Were the index test results interpreted without knowledge of the results of the reference standard? Yes: the index test results were interpreted without knowledge of the results of the reference standard. No: the index test results were not interpreted without knowledge of the results of the reference standard. Unclear: insufficient data were reported to permit a judgement. | Is the reference standard likely to classify the target condition correctly? Yes: if participants underwent a thorough clinical evaluation excluding all possible differential diagnoses and if they underwent an adequate follow‐up after delivery assessing the spontaneous relief of symptoms and normalisation of the previously found abnormal liver tests. No: clinical evaluation including the follow‐up after delivery was not able to rule out other possible differential diagnosis. Unclear: insufficient data were reported to permit a judgement. | Was there an appropriate interval between index test(s) and reference standard? This is not a relevant question to our review. |
| Was a participant‐control design avoided? Yes: participant‐control design was avoided. No: participant‐control design was not avoided. Unclear: insufficient information was reported to permit a judgement. | If a threshold was used, was it prespecified? Yes: the threshold was prespecified. No: the threshold was not prespecified. Unclear: it was not reported or not clearly described. | Were the reference standard results interpreted without knowledge of the results of the index test? Yes: clinical evaluation including the follow‐up after delivery was performed without knowledge of the results of TSBAs or any component of serum bile acid profile. No: clinical evaluation including the follow‐up after delivery was performed with knowledge of the results of TSBAs or any component of serum bile acid profile. Unclear: insufficient data were reported to permit a judgement. | Did all participants receive the reference standard? Yes: all participants underwent the reference standard, i.e. clinical evaluation including the follow‐up after delivery. No: not all participants underwent the reference standard, i.e. clinical evaluation including the follow‐up after delivery. Unclear: insufficient data were reported to permit a judgement. | |
| Did the study avoid inappropriate exclusions? Yes: the study avoided inappropriate exclusions (e.g. women having a previously assessed value of the index test(s) below a defined cut‐off). No: the study excluded participants inappropriately. Unclear: insufficient data were reported to permit a judgement. | Was the index test evaluation not part of the reference standard? Yes: the index test evaluation was not part of the reference standard. No: index test evaluation was part of the reference standard. Unclear: insufficient data were reported to permit a judgement. | Did all participants receive the same reference standard? Yes: all participants received the same reference standard (i.e. clinical evaluation including the follow‐up after delivery). No: not all participants received the same reference standard (i.e. clinical evaluation including the follow‐up after delivery). Unclear: insufficient data were reported to permit a judgement. | ||
| Were all participants included in the analysis? Yes: all participants meeting the selection criteria were included in the analysis, or data on all the selected participants were available so that a 2 × 2 table including all selected participants could be constructed. No: not all participants meeting the selection criteria were included in the analysis or the 2 × 2 table could not be constructed using data on all selected participants. Unclear: insufficient data were reported to permit a judgement. | ||||
| Risk of bias: high/low/unclear | Could the selection of participants have introduced bias? High risk of bias: yes, if the selection of participants introduced bias. Low risk of bias: no, if the selection of participants had not introduced bias. Unclear risk of bias: insufficient data were reported to permit a judgement on the risk of bias. | Could the conduct or interpretation of the index test have introduced bias? High risk of bias: if the answer to the signalling questions on the conduct or interpretation of the index test was 'no'. Low risk of bias: if the answer to the signalling questions on the conduct or interpretation of the index test was 'yes'. Unclear risk of bias: if the answers to the 2 signalling questions on the conduct or interpretation of the index test were either 'unclear' or any combination of 'unclear' with 'yes' or 'no'. | Could the reference standard, its conduct, or its interpretation have introduced bias? High risk of bias: if the answer to the signalling questions on the reference standard, its conduct, or its interpretation was 'no'. Low risk of bias: if the answer to the signalling questions on the reference standard, its conduct, or its interpretation was 'yes'. Unclear risk of bias: if the answers to the 3 signalling questions on the reference standard, its conduct, or its interpretation were either 'unclear' or any combination of 'unclear' with 'yes' or 'no'. | Could the participant flow have introduced bias? High risk of bias: if the answer to the signalling questions on flow and timing was 'no'. Low risk of bias: if the answer to the signalling questions on flow and timing was 'yes'. Unclear risk of bias: if the answers to the 4 signalling questions on flow and timing were either 'unclear' or any combination of 'unclear' with 'yes' or 'no'. |
| Concerns regarding applicability: high/low/unclear | Are there concerns that the included participants do not match the review question? High concern: there was high concern that the included participants did not match the review question. Low concern: there was low concern that the included participants did not match the review question. Unclear concern: if it was unclear. | Are there concerns that the index test, its conduct, or interpretation differ from the review question? High concern: there was high concern that the conduct or interpretation of TSBAs or any component of serum bile acid profile differed from the way likely to be used in clinical practice. Low concern: there was low concern that the conduct or interpretation of TSBAs or any component of serum bile acid profile differed from the way likely to be used in clinical practice. Unclear concern: if it was unclear. | Are there concerns that the target condition as defined by the reference standard does not match the review question? High concern: all participants did not undergo clinical evaluation including the follow‐up after delivery. Low concern: all participants underwent clinical evaluation including the follow‐up after delivery. Unclear concern: if it was unclear. | ‐ |
| TSBA: total serum bile acid. | ||||
Clinical diagnostic pathway for the diagnosis of intrahepatic cholestasis of pregnancy.
