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

Neuro-developmental disorders (as a whole)

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.
S13750
R53553		 Andreoli, 2022 Neurodevelopmental disorders (learning disabilities, attention deficiency and hyperactivity disorder, autism spectrum disorder) - Mean age: 17.1 years (± 9.7) during pregnancy (anytime or not specified) nested case control unexposed, sick Adjustment: No Indications: Rheumatic diseases (RD) 14.30 [1.20;171.09] C 1/3   10/296 11 3
ref
S13740
R53545		 Reynolds, 2022 Developmental delay, attention deficit disorder, special schooling or special needs throughout pregnancy retrospective cohort unexposed, sick Adjustment: No Indications: Systemic lupus erythematosus (SLE) 1.25 [0.45;3.50] C 6/87   11/197 17 87
ref
S12240
R52643		 Lazzaroni, 2020 At least one Neurodevelopmental Disorders (ADHD, Communication disorder, learning disabilities, ...) - Certified by a child neurologist or psychiatrist - At at least 6 years old during pregnancy (anytime or not specified) retrospective cohort unexposed, sick Adjustment: No Indications: Systemic lupus erythematosus (SLE) Matched 0.35 [0.07;1.70] C 2/27   12/65 14 27
ref
S7056
R21700		 Marder, 2013 Use of special educational services (special educational services (e.g., occupational or speech therapy, behavioral counseling, tutoring) - At age ≥ 2 years during pregnancy (anytime or not specified) retrospective cohort unexposed, sick Adjustment: Yes Indications: Systemic lupus erythematosus (SLE) 6.60 [1.00;43.30] 5/13   5/47 10 13
ref
Total 4 studies 2.03 [0.49;8.43] 52 130
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 Andreoli, 2022Andreoli, 2022 14.30[1.20; 171.09]11318%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Reynolds, 2022Reynolds, 2022 1.25[0.45; 3.50]178732%ROB confusion: criticalROB selection: unclearROB classification: moderateROB missing: lowROB mesure: criticalROB reporting: moderate Lazzaroni, 2020Lazzaroni, 2020 0.35[0.07; 1.70]142726%ROB confusion: seriousROB selection: unclearROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Marder, 2013Marder, 2013 6.60[1.00; 43.30]101323%ROB confusion: seriousROB selection: moderateROB classification: lowROB missing: moderateROB mesure: moderateROB reporting: moderate Total (4 studies) I2 = 66% 2.03[0.49; 8.43]521300.250.01.0ROB: 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 1.31[0.32; 5.34]4112763%NAReynolds, 2022 Lazzaroni, 2020 Marder, 2013 3 case control studiescase control studies 14.30[1.20; 171.09]113 -NAAndreoli, 2022 1 Type of controls unexposed, sickunexposed, sick 2.03[0.49; 8.43]5213066%NAAndreoli, 2022 Reynolds, 2022 Lazzaroni, 2020 Marder, 2013 4 Tags Adjustment   - No  - No 1.43[0.28; 7.27]4211768%NAAndreoli, 2022 Reynolds, 2022 Lazzaroni, 2020 3   - Yes  - Yes 6.60[1.00; 43.43]1013 -NAMarder, 2013 1 Indications   - Rheumatic diseases (RD)  - Rheumatic diseases (RD) 14.30[1.20; 171.09]113 -NAAndreoli, 2022 1   - Systemic lupus erythematosus (SLE)  - Systemic lupus erythematosus (SLE) 1.31[0.32; 5.34]4112763%NAReynolds, 2022 Lazzaroni, 2020 Marder, 2013 3 MatchedMatched 0.35[0.07; 1.70]1427 -NALazzaroni, 2020 1 All studiesAll studies 2.03[0.49; 8.43]5213066%NAAndreoli, 2022 Reynolds, 2022 Lazzaroni, 2020 Marder, 2013 40.150.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-3.23.71.5200.000Andreoli, 2022Reynolds, 2022Lazzaroni, 2020Marder, 2013

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

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed, sick controlsunexposed, sick controls 2.03[0.49; 8.43]5213066%NAAndreoli, 2022 Reynolds, 2022 Lazzaroni, 2020 Marder, 2013 40.510.01.0