Thiopurines (Azathioprine, Mercaptopurin) updated on 07-28-2025

Maternal liver disorder / failure during pregnancy or Intrahepatic cholestasis of pregnancy

R analysis
id Study   Lib. in paper Exposition period    Study type 
 Control type 
 
Tags OR 95%CI x1/n1 x0/n0 no cases no exposed ROB Ref.
S18484
R78389		 Nguyen_IBD (Controls exposed to TNFi), 2025 Intrahepatic cholestasis of pregnancy (maternal ICD-10 code O26.6) during pregnancy (anytime or not specified) population based cohort retrospective exposed to other treatment, sick excluded Adjustment: Yes Indications: Inflammatory Bowel disease (IBD) 11.33 [3.58;35.88]
excluded (control group) 		-/714   3/357 - 714
ref
S18478
R78386		 Nguyen_IBD (Controls unexposed, sick), 2025 Intrahepatic cholestasis of pregnancy (maternal ICD-10 code O26.6) during pregnancy (anytime or not specified) population based cohort retrospective unexposed, sick Adjustment: Yes Indications: Inflammatory Bowel disease (IBD) 7.78 [5.41;11.17] 140/1,924   36/3,848 176 1,924
ref
S18486
R78395		 Nguyen_SLE (Controls exposed to TNFi), 2025 Intrahepatic cholestasis of pregnancy (maternal ICD-10 code O26.6) during pregnancy (anytime or not specified) population based cohort retrospective exposed to other treatment, sick excluded Adjustment: Yes Indications: Systemic lupus erythematosus (SLE) 3.89 [1.68;8.99]
excluded (control group) 		27/-   -/- - -
ref
S18485
R78392		 Nguyen_SLE (Controls unexposed, sick), 2025 Intrahepatic cholestasis of pregnancy (maternal ICD-10 code O26.6) during pregnancy (anytime or not specified) population based cohort retrospective unexposed, sick Adjustment: Yes Indications: Systemic lupus erythematosus (SLE) 3.06 [1.36;6.90] 14/297   11/594 25 297
ref
S18480
R78604		 Selinger (Controls unexposed, disease free), 2023 Intrahepatic cholestasis of pregnancy (ICP) (total serum bile acids TSBAs ≥14 μmol/L) throughout pregnancy retrospective cohort unexposed, disease free excluded Adjustment: No Indications: Inflammatory Bowel disease (IBD) Matched 7.55 [2.52;22.57]
excluded (control group) 		10/111   5/386 15 111
ref
S18494
R78605		 Selinger (Controls unexposed, sick), 2023 Intrahepatic cholestasis of pregnancy (ICP) (total serum bile acids TSBAs ≥14 μmol/L) throughout pregnancy retrospective cohort unexposed, sick Adjustment: No Indications: Inflammatory Bowel disease (IBD) 5.34 [1.78;16.02] 10/111   5/275 15 111
ref
S12244
R78385		 Kanis, 2021 Intrahepatic cholestasis of pregnancy (ICP) throughout pregnancy retrospective cohort unexposed, sick Adjustment: No Indications: Inflammatory Bowel disease (IBD) 7.29 [1.95;27.15] C 9/240   3/564 12 240
ref
Total 4 studies 5.90 [3.69;9.43] 228 2,572
x1: number of endpoints among exposed, n1: number of exposed; x0: number of endpoints among non exposed, n0: number of non exposed; C: calculated odds ratio from numbers of events and effectives

Forest plot

StudyTE95% CIn casesn exposedweightROBABCDEF Nguyen_IBD (Controls unexposed, sick), 2025Nguyen_IBD, 2025 1 7.78[5.41; 11.17]1761,92451%ROB confusion: moderateROB selection: lowROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Nguyen_SLE (Controls unexposed, sick), 2025Nguyen_SLE, 2025 2 3.06[1.36; 6.90]2529723%ROB confusion: moderateROB selection: lowROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Selinger (Controls unexposed, sick), 2023Selinger, 2023 3 5.34[1.78; 16.02]1511115%ROB confusion: seriousROB selection: lowROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Kanis, 2021Kanis, 2021 7.29[1.95; 27.15]1224011%ROB confusion: criticalROB selection: criticalROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Total (4 studies) I2 = 32% 5.90[3.69; 9.43]2282,5720.920.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Controls unexposed, sick; 2: Controls unexposed, sick; 3: Controls unexposed, sick;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 5.90[3.69; 9.43]2282,57232%NANguyen_IBD (Controls unexposed, sick), 2025 Nguyen_SLE (Controls unexposed, sick), 2025 Selinger (Controls unexposed, sick), 2023 Kanis, 2021 4 case control studiescase control studies 0 Type of controls unexposed, sickunexposed, sick 5.90[3.69; 9.43]2282,57232%NANguyen_IBD (Controls unexposed, sick), 2025 Nguyen_SLE (Controls unexposed, sick), 2025 Selinger (Controls unexposed, sick), 2023 Kanis, 2021 4 Tags Adjustment   - No  - No 6.07[2.61; 14.10]273510%NASelinger (Controls unexposed, sick), 2023 Kanis, 2021 2   - Yes  - Yes 5.25[2.13; 12.96]2012,22176%NANguyen_IBD (Controls unexposed, sick), 2025 Nguyen_SLE (Controls unexposed, sick), 2025 2 Indications   - Inflammatory Bowel disease (IBD)  - Inflammatory Bowel disease (IBD) 7.48[5.36; 10.44]2032,2750%NANguyen_IBD (Controls unexposed, sick), 2025 Selinger (Controls unexposed, sick), 2023 Kanis, 2021 3   - Systemic lupus erythematosus (SLE)  - Systemic lupus erythematosus (SLE) 3.06[1.36; 6.89]25297 -NANguyen_SLE (Controls unexposed, sick), 2025 1 All studiesAll studies 5.90[3.69; 9.43]2282,57232%NANguyen_IBD (Controls unexposed, sick), 2025 Nguyen_SLE (Controls unexposed, sick), 2025 Selinger (Controls unexposed, sick), 2023 Kanis, 2021 40.520.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-2.53.40.8050.000Nguyen_IBD (Controls unexposed, sick), 2025Nguyen_SLE (Controls unexposed, sick), 2025Selinger (Controls unexposed, sick), 2023Kanis, 2021

Asymetry test p-value = NaN (by Egger's regression)

not enought points

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 18480, 18484, 18486

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 7.55[2.52; 22.60]15111 -NASelinger (Controls unexposed, disease free), 2023 1 unexposed, sick controlsunexposed, sick controls 5.90[3.69; 9.43]2282,57232%NANguyen_IBD (Controls unexposed, sick), 2025 Nguyen_SLE (Controls unexposed, sick), 2025 Selinger (Controls unexposed, sick), 2023 Kanis, 2021 4 exposed to other treatment, sick controlsexposed to other treatment, sick controls 6.15[2.18; 17.35]1871454%NANguyen_IBD (Controls exposed to TNFi), 2025 Nguyen_SLE (Controls exposed to TNFi), 2025 20.510.01.0

Umbrella review (other published meta-analyses)

Published MAControlPeriodTE95% CIn exposedkI2 Joudaki (Intrahepatic cholestasis of pregnanc ...Joudaki (Intrahepatic cholestasis of pregnancy (ICP)) 6.65[3.10; 14.25]0%-Wwhatever (meta-analysis)Anyduring pregnancy (anytime or not specified)studies TTT3 metaPregmetaPreg 5.90[3.69; 9.43]32%2,572----Nguyen_IBD (Controls unexposed, sick), 2025 Nguyen_SLE (Controls unexposed, sick), 2025 Selinger (Controls unexposed, sick), 2023 Kanis, 2021 40.510.01.0