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

Low birth weight (< 2500g)

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.
S18482
R78420		 Vestergaard, 2024 Low Birth Weight, <2500 grams during pregnancy (anytime or not specified) retrospective cohort unexposed, sick Adjustment: No Indications: Inflammatory Bowel disease (IBD) 0.62 [0.18;2.16] C 3/111   16/372 19 111
ref
S13740
R53536		 Reynolds, 2022 Low birth weight (<2.5 kg) throughout pregnancy retrospective cohort unexposed, sick Adjustment: Yes Indications: Systemic lupus erythematosus (SLE) 1.83 [0.74;4.53] 29/83   41/193 70 83
ref
S12218
R45543		 Mahadevan, 2021 Low Birth Weight (<2500 g) 3 months (or more) before pregnancy or during pregnancy excluded prospective cohort unexposed, sick Adjustment: Yes Indications: Inflammatory Bowel disease (IBD) 0.60 [0.30;15.00]
excluded (exposition period) 		-/242   -/379 - 242
ref
S12241
R46213		 Koslowsky, 2019 Low birth weight (< 2500 g) throughout pregnancy prospective cohort unexposed, sick Adjustment: No Indications: Inflammatory Bowel disease (IBD) 3.38 [0.15;76.51] C 2/21   0/13 2 21
ref
S12243
R53519		 Kanis, 2017 Low birth weight (<2500 g at birth) during pregnancy (anytime or not specified) prospective cohort unexposed, sick Adjustment: Yes Indications: Inflammatory Bowel disease (IBD) 0.66 [0.28;1.57] 10/108   21/293 31 108
ref
S12242
R46239		 Komoto, 2016 Low birth weight (<2500g) during pregnancy (anytime or not specified) retrospective cohort unexposed, sick Adjustment: No Indications: Inflammatory Bowel disease (IBD) 0.52 [0.05;5.13] C 1/7   7/29 8 7
ref
S13765
R53597		 Bröms (Crohn’s disease, stable disease), 2014 Low birth weight <2500 g during pregnancy (anytime or not specified) population based cohort retrospective unexposed, disease free Adjustment: Yes Indications: Inflammatory Bowel disease (IBD) 1.70 [0.88;3.30] 9/-   16,014/467,057 16,023 -
ref
S10792
R52299		 Casanova, 2013 Low birth weight 3 months (or more) before pregnancy or during pregnancy excluded retrospective cohort exposed to other treatment, sick Adjustment: No Indications: Inflammatory Bowel disease (IBD) 0.45 [0.20;1.00] C
excluded (exposition period) 		8/187   29/318 37 187
ref
S12246
R45445		 Coelho (Controls exposed to 5-ASA), 2011 Low birth weight <2500 g during pregnancy (anytime or not specified) retrospective cohort exposed to other treatment, sick excluded Adjustment: No Indications: Inflammatory Bowel disease (IBD) 2.33 [0.63;8.64] C
excluded (control group) 		7/40   4/48 11 40
ref
S12195
R45440		 Coelho (Controls unexposed, sick), 2011 Low birth weight <2500 g during pregnancy (anytime or not specified) retrospective cohort unexposed, sick Adjustment: No Indications: Inflammatory Bowel disease (IBD) 2.65 [0.51;13.88] C 7/40   2/27 9 40
ref
S8433
R27108		 Shim, 2011 Low birth weight at term (<2500 g) 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
S6258
R18035		 Cleary (Controls unexposed, NOS), 2009 Low Birth weight (<2500g) among singleton infants early pregnancy population based cohort retrospective unexposed (general population or NOS) excluded Adjustment: Yes Indications: Any or not specified 3.31 [2.47;4.32]
excluded (control group) 		46/467   37,105/1,140,988 37,151 467
ref
S12174
R45197		 Cleary (Controls unexposed, sick), 2009 Low Birth weight (<2500g) among singleton infants early pregnancy population based cohort retrospective unexposed, sick Adjustment: No Indications: Any or not specified 1.53 [1.07;2.18] 46/467   110/1,676 156 467
ref
S8427
R27091		 Goldstein, 2007 Low Birth Weight (<2500g) at least 1st trimester prospective cohort unexposed (general population or NOS) Adjustment: No Indications: Any or not specified 3.81 [2.00;7.20] 35/152   11/182 46 152
ref
S6628
R18384		 Langagergaard (Controls unexposed, NOS), 2007 Low birth weight at term (birth weight <2500 g and gestational age ≥37 weeks) throughout pregnancy population based cohort retrospective unexposed (general population or NOS) excluded Adjustment: Yes Indications: Any or not specified Matched 3.00 [0.70;12.40]
excluded (control group) 		2/48   17/1,215 19 48
ref
S6656
R18389		 Langagergaard (Controls unexposed, sick), 2007 Low birth weight at term (birth weight <2500 g and gestational age ≥37 weeks) throughout pregnancy population based cohort retrospective unexposed, sick Adjustment: Yes Indications: Any or not specified 1.70 [0.30;8.70] 2/48   4/149 6 48
ref
S13766
R53606		 Dejaco, 2005 Low birth weight (< 2500g) during pregnancy (anytime or not specified) prospective cohort unexposed, sick Adjustment: No Indications: Inflammatory Bowel disease (IBD) 0.23 [0.02;2.21] C 1/26   4/27 5 26
ref
S11066
R44834		 Francella, 2003 Low birth weight (< 2500g) throughout pregnancy retrospective cohort unexposed, sick Adjustment: No Indications: Inflammatory Bowel disease (IBD) 1.13 [0.13;10.14] C 1/14   6/94 7 14
ref
Total 13 studies 1.51 [1.04;2.19] 16,382 1,096
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 Vestergaard, 2024Vestergaard, 2024 0.62[0.18; 2.16]191117%ROB confusion: criticalROB selection: criticalROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Reynolds, 2022Reynolds, 2022 1.83[0.74; 4.53]708311%ROB confusion: seriousROB selection: unclearROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Koslowsky, 2019Koslowsky, 2019 3.38[0.15; 76.51]2211%ROB confusion: criticalROB selection: criticalROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Kanis, 2017Kanis, 2017 0.66[0.28; 1.57]3110811%ROB confusion: seriousROB selection: lowROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: unclear Komoto, 2016Komoto, 2016 0.52[0.05; 5.13]872%ROB confusion: criticalROB selection: unclearROB classification: criticalROB missing: lowROB mesure: criticalROB reporting: moderate Bröms (Crohn’s disease, stable disease), 2014Bröms, 2014 1 1.70[0.88; 3.30]16,023-15%ROB confusion: seriousROB selection: lowROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Coelho (Controls unexposed, sick), 2011Coelho, 2011 2 2.65[0.51; 13.88]9404%ROB confusion: criticalROB selection: criticalROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Shim, 2011Shim, 2011 3.97[0.08; 206.96]0191%ROB confusion: seriousROB selection: lowROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Cleary (Controls unexposed, sick), 2009Cleary, 2009 3 1.53[1.07; 2.18]15646723%ROB confusion: seriousROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Goldstein, 2007Goldstein, 2007 3.81[2.00; 7.20]4615215%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: lowROB mesure: criticalROB reporting: moderate Langagergaard (Controls unexposed, sick), 2007Langagergaard, 2007 4 1.70[0.30; 8.70]6484%ROB confusion: seriousROB selection: lowROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Dejaco, 2005Dejaco, 2005 0.23[0.02; 2.21]5262%ROB confusion: seriousROB selection: unclearROB classification: unclearROB missing: unclearROB mesure: unclearROB reporting: moderate Francella, 2003Francella, 2003 1.13[0.13; 10.14]7143%ROB confusion: criticalROB selection: unclearROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Total (13 studies) I2 = 34% 1.51[1.04; 2.19]16,3821,0960.210.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Crohn’s disease, stable disease; 2: Controls unexposed, sick; 3: Controls unexposed, sick; 4: Controls unexposed, sick;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.51[1.04; 2.19]16,3821,09634%NAVestergaard, 2024 Reynolds, 2022 Koslowsky, 2019 Kanis, 2017 Komoto, 2016 Bröms (Crohn’s disease, stable disease), 2014 Coelho (Controls unexposed, sick), 2011 Shim, 2011 Cleary (Controls unexposed, sick), 2009 Goldstein, 2007 Langagergaard (Controls unexposed, sick), 2007 Dejaco, 2005 Francella, 2003 13 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 2.56[1.16; 5.64]16,06915266%NABröms (Crohn’s disease, stable disease), 2014 Goldstein, 2007 2 unexposed, sickunexposed, sick 1.33[1.00; 1.76]3139440%NAVestergaard, 2024 Reynolds, 2022 Koslowsky, 2019 Kanis, 2017 Komoto, 2016 Coelho (Controls unexposed, sick), 2011 Shim, 2011 Cleary (Controls unexposed, sick), 2009 Langagergaard (Controls unexposed, sick), 2007 Dejaco, 2005 Francella, 2003 11 Tags Adjustment   - No  - No 1.56[0.89; 2.77]25285742%NAVestergaard, 2024 Koslowsky, 2019 Komoto, 2016 Coelho (Controls unexposed, sick), 2011 Shim, 2011 Cleary (Controls unexposed, sick), 2009 Goldstein, 2007 Dejaco, 2005 Francella, 2003 9   - Yes  - Yes 1.34[0.82; 2.21]16,13023917%NAReynolds, 2022 Kanis, 2017 Bröms (Crohn’s disease, stable disease), 2014 Langagergaard (Controls unexposed, sick), 2007 4 Indications   - Any or not specified  - Any or not specified 2.20[1.08; 4.49]20866767%NACleary (Controls unexposed, sick), 2009 Goldstein, 2007 Langagergaard (Controls unexposed, sick), 2007 3   - Inflammatory Bowel disease (IBD)  - Inflammatory Bowel disease (IBD) 1.10[0.71; 1.70]16,1043461%NAVestergaard, 2024 Koslowsky, 2019 Kanis, 2017 Komoto, 2016 Bröms (Crohn’s disease, stable disease), 2014 Coelho (Controls unexposed, sick), 2011 Shim, 2011 Dejaco, 2005 Francella, 2003 9   - Systemic lupus erythematosus (SLE)  - Systemic lupus erythematosus (SLE) 1.83[0.74; 4.53]7083 -NAReynolds, 2022 1 MatchedMatched 3.97[0.08; 206.96]-19 -NAShim, 2011 1 All studiesAll studies 1.51[1.04; 2.19]16,3821,09634%NAVestergaard, 2024 Reynolds, 2022 Koslowsky, 2019 Kanis, 2017 Komoto, 2016 Bröms (Crohn’s disease, stable disease), 2014 Coelho (Controls unexposed, sick), 2011 Shim, 2011 Cleary (Controls unexposed, sick), 2009 Goldstein, 2007 Langagergaard (Controls unexposed, sick), 2007 Dejaco, 2005 Francella, 2003 130.110.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-4.75.22.4200.000Vestergaard, 2024Reynolds, 2022Koslowsky, 2019Kanis, 2017Komoto, 2016Bröms (Crohn’s disease, stable disease), 2014Coelho (Controls unexposed, sick), 2011Shim, 2011Cleary (Controls unexposed, sick), 2009Goldstein, 2007Langagergaard (Controls unexposed, sick), 2007Dejaco, 2005Francella, 2003

Asymetry test p-value = 0.4942 (by Egger's regression)

slope=0.6136 (0.2587); intercept=-0.4137 (0.5851); t=0.7071; p=0.4942

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 6628, 6258, 12246

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 2.99[2.18; 4.10]53,23966721%NABröms (Crohn’s disease, stable disease), 2014 Cleary (Controls unexposed, NOS), 2009 Goldstein, 2007 Langagergaard (Controls unexposed, NOS), 2007 4 unexposed, sick controlsunexposed, sick controls 1.33[1.00; 1.76]3139440%NAVestergaard, 2024 Reynolds, 2022 Koslowsky, 2019 Kanis, 2017 Komoto, 2016 Coelho (Controls unexposed, sick), 2011 Shim, 2011 Cleary (Controls unexposed, sick), 2009 Langagergaard (Controls unexposed, sick), 2007 Dejaco, 2005 Francella, 2003 11 exposed to other treatment, sick controlsexposed to other treatment, sick controls 2.33[0.63; 8.64]1140 -NACoelho (Controls exposed to 5-ASA), 2011 10.510.01.0

Umbrella review (other published meta-analyses)

Published MAControlPeriodTE95% CIn exposedkI2 Mozaffari (Low birth weight)Mozaffari (Low birth weight) 0.82[0.32; 2.13]53%-Eexposed to other treatment, sickAnyduring pregnancy (anytime or not specified)studies TTT3 Mozaffari (Low birth weight)Mozaffari (Low birth weight) 1.95[0.66; 5.78]NA-U,Sunexposed, sickAnyduring pregnancy (anytime or not specified)studies TTT2 Zhang (Low birth weight)Zhang (Low birth weight) 1.05[0.74; 1.49]44%-Eexposed to other treatment, sickAnyduring pregnancy (anytime or not specified)studies TTT8 Akbari (Low birth weight (LBW))Akbari (Low birth weight (LBW)) 1.01[0.96; 1.06]0%-Wwhatever (meta-analysis)Before-Any3 months (or more) before pregnancy or during pregnancystudies TTT5 Gonzalez-Suarez (Low birth weight (LBW))Gonzalez-Suarez (Low birth weight (LBW)) 1.44[1.10; 1.88]0%-U,Sunexposed, sickAnyduring pregnancy (anytime or not specified)studies TTT5 Hutson (Low birth weight (vs disease-matched ...Hutson (Low birth weight (vs disease-matched controls (with or without on other medications))) 1.30[0.92; 1.83]0%-U,Sunexposed, sickAnyduring pregnancy (anytime or not specified)studies TTT6 Hutson (Low birth weight (vs disease-matched ...Hutson (Low birth weight (vs disease-matched controls not on other medications)) 2.06[0.56; 7.52]0%-U,Sunexposed, sickAnyduring pregnancy (anytime or not specified)studies TTT2 Hutson (Low birth weight (vs disease-matched ...Hutson (Low birth weight (vs disease-matched controls on other medications)) 1.36[0.95; 1.94]0%-Eexposed to other treatment, sickAnyduring pregnancy (anytime or not specified)studies TTT2 Hutson (Low birth weight (vs healthy or gener ...Hutson (Low birth weight (vs healthy or general population controls)) 3.13[2.44; 4.02]0%-U,GPunexposed (general population or NOS)Anyduring pregnancy (anytime or not specified)studies TTT3 metaPregmetaPreg 1.51[1.04; 2.19]34%1,096----Vestergaard, 2024 Reynolds, 2022 Koslowsky, 2019 Kanis, 2017 Komoto, 2016 Bröms (Crohn’s disease, stable disease), 2014 Coelho (Controls unexposed, sick), 2011 Shim, 2011 Cleary (Controls unexposed, sick), 2009 Goldstein, 2007 Langagergaard (Controls unexposed, sick), 2007 Dejaco, 2005 Francella, 2003 130.510.01.0