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

Early intrauterine deaths (< 22 weeks) / Spontaneous abortions

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.
S12218
R45536		 Mahadevan, 2021 Spontaneous abortion (gestational age <140 days = 20 weeks) 3 months (or more) before pregnancy or during pregnancy excluded prospective cohort unexposed, sick Adjustment: Yes Indications: Inflammatory Bowel disease (IBD) 0.96 [0.28;3.33]
excluded (exposition period) 		-/242   -/379 - 242
ref
S6698
R52661		 Alami, 2017 Miscarriage, < 22 GW at least 1st trimester prospective cohort unexposed, sick Adjustment: No Indications: Any or not specified 1.39 [0.36;5.34] C 5/101   4/111 9 101
ref
S12243
R46249		 Kanis, 2017 Spontaneous abortion (< 24 wk of gestation) during pregnancy (anytime or not specified) prospective cohort unexposed, sick Adjustment: Yes Indications: Inflammatory Bowel disease (IBD) 1.26 [0.73;2.20] 35/146   43/263 78 146
ref
S10792
R44837		 Casanova, 2013 Spontaneous abortion (NOS) 3 months (or more) before pregnancy or during pregnancy excluded retrospective cohort exposed to other treatment, sick Adjustment: No Indications: Inflammatory Bowel disease (IBD) 0.67 [0.36;1.23] C
excluded (exposition period) 		16/187   39/318 55 187
ref
S10910
R53481		 Schramm, 2006 Spontaneous abortions (before 20 weeks of gestation) during pregnancy (anytime or not specified) retrospective cohort unexposed, sick Adjustment: No Indications: Autoimmune Hepatitis (AIH) 0.28 [0.03;2.61] C 1/14   6/28 7 14
ref
S13766
R53603		 Dejaco, 2005 Abortions during pregnancy (anytime or not specified) prospective cohort unexposed, sick Adjustment: No Indications: Inflammatory Bowel disease (IBD) 0.91 [0.29;2.87] C 7/33   8/35 15 33
ref
S13739
R53529		 Tennenbaum, 1999 Spontaneous abortion during pregnancy (anytime or not specified) retrospective cohort unexposed, sick Adjustment: No Indications: Inflammatory Bowel disease (IBD) 0.60 [0.03;12.50] C 0/12   3/52 3 12
ref
Total 5 studies 1.12 [0.71;1.76] 112 306
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 Alami, 2017Alami, 2017 1.39[0.36; 5.34]910111%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: lowROB mesure: unclearROB reporting: moderate Kanis, 2017Kanis, 2017 1.26[0.73; 2.20]7814667%ROB confusion: seriousROB selection: lowROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: unclear Schramm, 2006Schramm, 2006 0.28[0.03; 2.61]7144%ROB confusion: criticalROB selection: lowROB classification: criticalROB missing: unclearROB mesure: criticalROB reporting: moderate Dejaco, 2005Dejaco, 2005 0.91[0.29; 2.87]153315%ROB confusion: seriousROB selection: unclearROB classification: unclearROB missing: unclearROB mesure: unclearROB reporting: moderate Tennenbaum, 1999Tennenbaum, 1999 0.60[0.03; 12.50]3122%ROB confusion: criticalROB selection: criticalROB classification: criticalROB missing: lowROB mesure: criticalROB reporting: moderate Total (5 studies) I2 = 0% 1.12[0.71; 1.76]1123060.25.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.12[0.71; 1.76]1123060%NAAlami, 2017 Kanis, 2017 Schramm, 2006 Dejaco, 2005 Tennenbaum, 1999 5 case control studiescase control studies 0 Type of controls unexposed, sickunexposed, sick 1.12[0.71; 1.76]1123060%NAAlami, 2017 Kanis, 2017 Schramm, 2006 Dejaco, 2005 Tennenbaum, 1999 5 Tags Adjustment   - No  - No 0.88[0.40; 1.94]341600%NAAlami, 2017 Schramm, 2006 Dejaco, 2005 Tennenbaum, 1999 4   - Yes  - Yes 1.26[0.73; 2.19]78146 -NAKanis, 2017 1 Indications   - Any or not specified  - Any or not specified 1.39[0.36; 5.34]9101 -NAAlami, 2017 1   - Autoimmune Hepatitis (AIH)  - Autoimmune Hepatitis (AIH) 0.28[0.03; 2.61]714 -NASchramm, 2006 1   - Inflammatory Bowel disease (IBD)  - Inflammatory Bowel disease (IBD) 1.16[0.71; 1.90]961910%NAKanis, 2017 Dejaco, 2005 Tennenbaum, 1999 3 All studiesAll studies 1.12[0.71; 1.76]1123060%NAAlami, 2017 Kanis, 2017 Schramm, 2006 Dejaco, 2005 Tennenbaum, 1999 50.15.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-3.63.81.8560.000Alami, 2017Kanis, 2017Schramm, 2006Dejaco, 2005Tennenbaum, 1999

Asymetry test p-value = 0.1563 (by Egger's regression)

slope=0.5032 (0.2434); intercept=-0.8900 (0.4727); t=1.8827; p=0.1563

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed, sick controlsunexposed, sick controls 1.12[0.71; 1.76]1123060%NAAlami, 2017 Kanis, 2017 Schramm, 2006 Dejaco, 2005 Tennenbaum, 1999 50.510.01.0