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

Intrauterine deaths (as a whole or unspecified)

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
R45541		 Mahadevan, 2021 Spontaneous abortion (any gestational age) 3 months (or more) before pregnancy or during pregnancy excluded prospective cohort unexposed, sick Adjustment: Yes Indications: Inflammatory Bowel disease (IBD) 1.30 [0.40;3.80]
excluded (exposition period) 		-/242   -/379 - 242
ref
S13738
R53527		 Nguyen, 2019 Spontaneous abortion/Miscarriage (NOS) during pregnancy (anytime or not specified) prospective cohort unexposed, sick Adjustment: No Indications: Relapsing-Remitting Multiple Sclerosis (RRMS) 2.02 [0.10;39.56] C 0/4   50/763 50 4
ref
S12242
R46241		 Komoto, 2016 Spontaneous abortion (NOS) during pregnancy (anytime or not specified) retrospective cohort unexposed, sick Adjustment: No Indications: Inflammatory Bowel disease (IBD) 4.69 [0.09;258.87] C 0/7   0/31 0 7
ref
S8433
R27106		 Shim, 2011 Spontaneous abortion (NOS) throughout pregnancy retrospective cohort unexposed, sick Adjustment: No Indications: Inflammatory Bowel disease (IBD) Matched 3.97 [0.08;206.96] C 0/19   0/74 0 19
ref
S10910
R44866		 Schramm, 2006 Spontaneous abortion (all not live births) 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
S11066
R44829		 Francella, 2003 Spontaneous abortion (NOS) throughout pregnancy retrospective cohort unexposed, sick Adjustment: No Indications: Inflammatory Bowel disease (IBD) 0.19 [0.02;1.50] C 1/15   36/132 37 15
ref
Total 5 studies 0.58 [0.17;2.03] 94 59
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, 2019Nguyen, 2019 2.02[0.10; 39.56]50417%ROB confusion: criticalROB selection: lowROB classification: moderateROB missing: moderateROB mesure: moderateROB reporting: low Komoto, 2016Komoto, 2016 4.69[0.09; 258.87]079%ROB confusion: criticalROB selection: unclearROB classification: criticalROB missing: lowROB mesure: criticalROB reporting: moderate Shim, 2011Shim, 2011 3.97[0.08; 206.96]01910%ROB confusion: seriousROB selection: lowROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Schramm, 2006Schramm, 2006 0.28[0.03; 2.61]71430%ROB confusion: criticalROB selection: lowROB classification: criticalROB missing: unclearROB mesure: criticalROB reporting: moderate Francella, 2003Francella, 2003 0.19[0.02; 1.50]371534%ROB confusion: criticalROB selection: unclearROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Total (5 studies) I2 = 4% 0.58[0.17; 2.03]94590.010.01.0ROB: 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 0.58[0.17; 2.03]94594%NANguyen, 2019 Komoto, 2016 Shim, 2011 Schramm, 2006 Francella, 2003 5 case control studiescase control studies 0 Type of controls unexposed, sickunexposed, sick 0.58[0.17; 2.03]94594%NANguyen, 2019 Komoto, 2016 Shim, 2011 Schramm, 2006 Francella, 2003 5 Tags Adjustment   - No  - No 0.58[0.17; 2.03]94594%NANguyen, 2019 Komoto, 2016 Shim, 2011 Schramm, 2006 Francella, 2003 5 Indications   - Autoimmune Hepatitis (AIH)  - Autoimmune Hepatitis (AIH) 0.28[0.03; 2.61]714 -NASchramm, 2006 1   - Inflammatory Bowel disease (IBD)  - Inflammatory Bowel disease (IBD) 0.85[0.09; 8.35]374135%NAKomoto, 2016 Shim, 2011 Francella, 2003 3   - Relapsing-Remitting Multiple Sclero ...  - Relapsing-Remitting Multiple Sclerosis (RRMS) 2.02[0.10; 39.56]504 -NANguyen, 2019 1 MatchedMatched 3.97[0.08; 206.96]-19 -NAShim, 2011 1 All studiesAll studies 0.58[0.17; 2.03]94594%NANguyen, 2019 Komoto, 2016 Shim, 2011 Schramm, 2006 Francella, 2003 50.010.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-4.84.32.4550.000Nguyen, 2019Komoto, 2016Shim, 2011Schramm, 2006Francella, 2003

Asymetry test p-value = 0.0064 (by Egger's regression)

slope=-5.0163 (0.6748); intercept=3.3268 (0.4861); t=6.8431; p=0.0064

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 0.58[0.17; 2.03]94594%NANguyen, 2019 Komoto, 2016 Shim, 2011 Schramm, 2006 Francella, 2003 50.510.01.0

Umbrella review (other published meta-analyses)

Published MAControlPeriodTE95% CIn exposedkI2 Mozaffari (Spontaneous abortion)Mozaffari (Spontaneous abortion) 0.87[0.29; 2.68]NA-Eexposed to other treatment, sickAnyduring pregnancy (anytime or not specified)studies TTT2 Zhang (Spontaneous abortion)Zhang (Spontaneous abortion) 0.91[0.50; 1.65]65%-Eexposed to other treatment, sickAnyduring pregnancy (anytime or not specified)studies TTT4 Hutson (Spontaneous abortions (NOS) (vs disea ...Hutson (Spontaneous abortions (NOS) (vs disease-matched controls (with or without on other medications))) Out of scale0.48[0.21; 1.10]0%-U,Sunexposed, sickAnyduring pregnancy (anytime or not specified)studies TTT2 metaPregmetaPreg 0.58[0.17; 2.03]4%59----Nguyen, 2019 Komoto, 2016 Shim, 2011 Schramm, 2006 Francella, 2003 50.510.01.0