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

Congenital heart defects

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.
S17723
R74778		 Meyer, 2025 Heart defects 1st trimester population based cohort retrospective unexposed, sick Adjustment: Yes Indications: Inflammatory Bowel disease (IBD) 1.28 [0.90;1.84] 38/5,223   173/28,827 211 5,223
ref
S6698
R19115		 Alami, 2017 Heart defects at least 1st trimester prospective cohort unexposed, sick Adjustment: No Indications: Any or not specified 1.15 [0.07;18.57] C 1/97   1/111 2 97
ref
S13582
R52651		 Ban (Controls unexposed, disease free), 2014 Congenital heart defects 1st trimester retrospective cohort (claims database) unexposed, disease free excluded Adjustment: No Indications: Inflammatory Bowel disease (IBD) 1.71 [0.42;6.92] C
excluded (control group) 		2/149   3,032/384,811 3,034 149
ref
S11392
R44249		 Ban (Controls unexposed, sick), 2014 Congenital heart defects 1st trimester retrospective cohort (claims database) unexposed, sick Adjustment: Yes Indications: Inflammatory Bowel disease (IBD) 1.56 [0.29;8.26] 2/149   15/1,554 17 149
ref
S6258
R18168		 Cleary (Controls unexposed, NOS), 2009 All cardiovascular malformations early pregnancy population based cohort retrospective unexposed (general population or NOS) Adjustment: Yes Indications: Any or not specified 2.02 [0.97;3.71] 10/481   12,581/1,181,450 12,591 481
ref
Total 4 studies 1.42 [1.04;1.93] 12,821 5,950
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 Meyer, 2025Meyer, 2025 1.28[0.90; 1.84]2115,22374%ROB confusion: seriousROB selection: moderateROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Alami, 2017Alami, 2017 1.15[0.07; 18.57]2971%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: lowROB mesure: unclearROB reporting: moderate Ban (Controls unexposed, sick), 2014Ban, 2014 1 1.56[0.29; 8.26]171493%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: unclearROB mesure: unclearROB reporting: moderate Cleary (Controls unexposed, NOS), 2009Cleary, 2009 2 2.02[0.97; 3.71]12,59148121%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: criticalROB reporting: moderate Total (4 studies) I2 = 0% 1.42[1.04; 1.93]12,8215,9500.55.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

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

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.42[1.04; 1.93]12,8215,9500%NAMeyer, 2025 Alami, 2017 Ban (Controls unexposed, sick), 2014 Cleary (Controls unexposed, NOS), 2009 4 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 2.02[1.03; 3.95]12,591481 -NACleary (Controls unexposed, NOS), 2009 1 unexposed, sickunexposed, sick 1.29[0.91; 1.82]2305,4690%NAMeyer, 2025 Alami, 2017 Ban (Controls unexposed, sick), 2014 3 Tags Adjustment   - No  - No 1.15[0.07; 18.57]297 -NAAlami, 2017 1   - Yes  - Yes 1.42[1.04; 1.94]12,8195,8530%NAMeyer, 2025 Ban (Controls unexposed, sick), 2014 Cleary (Controls unexposed, NOS), 2009 3 Indications   - Any or not specified  - Any or not specified 1.96[1.02; 3.76]12,5935780%NAAlami, 2017 Cleary (Controls unexposed, NOS), 2009 2   - Inflammatory Bowel disease (IBD)  - Inflammatory Bowel disease (IBD) 1.29[0.91; 1.83]2285,3720%NAMeyer, 2025 Ban (Controls unexposed, sick), 2014 2 All studiesAll studies 1.42[1.04; 1.93]12,8215,9500%NAMeyer, 2025 Alami, 2017 Ban (Controls unexposed, sick), 2014 Cleary (Controls unexposed, NOS), 2009 40.55.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-3.33.71.7050.000Meyer, 2025Alami, 2017Ban (Controls unexposed, sick), 2014Cleary (Controls unexposed, NOS), 2009

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 13582

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.96[1.07; 3.58]15,6256300%NABan (Controls unexposed, disease free), 2014 Cleary (Controls unexposed, NOS), 2009 2 unexposed, sick controlsunexposed, sick controls 1.29[0.91; 1.82]2305,4690%NAMeyer, 2025 Alami, 2017 Ban (Controls unexposed, sick), 2014 30.510.01.0