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

Preterm (< 37 weeks)

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
R78416		 Vestergaard, 2024 Preterm Birth < 38 Gestational Weeks during pregnancy (anytime or not specified) retrospective cohort unexposed, sick Adjustment: No Indications: Inflammatory Bowel disease (IBD) 1.18 [0.49;2.88] C 7/111   20/372 27 111
ref
S18477
R78396		 Yeaman (Controls mainly exposed to biologics), 2023 Preterm delivery (<37 weeks of gestation) during pregnancy (anytime or not specified) prospective cohort exposed to other treatment, sick excluded Adjustment: No Indications: Inflammatory Bowel disease (IBD) 0.66 [0.16;2.70] C
excluded (control group) 		3/19   11/50 14 19
ref
S18487
R78405		 Yeaman (Controls unexposed, disease free), 2023 Preterm delivery (<37 weeks of gestation) during pregnancy (anytime or not specified) prospective cohort unexposed, disease free Adjustment: No Indications: Inflammatory Bowel disease (IBD) 1.55 [0.31;7.75] C 3/19   4/37 7 19
ref
S13740
R53534		 Reynolds, 2022 Pre-term delivery at <38 weeks throughout pregnancy retrospective cohort unexposed, sick Adjustment: No Indications: Systemic lupus erythematosus (SLE) 2.38 [1.41;4.01] C 44/86   59/193 103 86
ref
S12244
R46201		 Kanis, 2021 Preterm (< 37 weeks) throughout pregnancy retrospective cohort unexposed, sick Adjustment: Yes Indications: Inflammatory Bowel disease (IBD) 1.16 [0.71;1.88] 33/240   61/564 94 240
ref
S12218
R45542		 Mahadevan, 2021 Preterm Birth (<37 weeks) 3 months (or more) before pregnancy or during pregnancy excluded prospective cohort unexposed, sick Adjustment: Yes Indications: Inflammatory Bowel disease (IBD) 1.40 [0.80;2.60]
excluded (exposition period) 		-/242   -/379 - 242
ref
S13576
R52616		 Meyer b (Controls exposed to Anti-TNF), 2021 Preterm (< 37 weeks) during pregnancy (anytime or not specified) retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: Yes Indications: Inflammatory Bowel disease (IBD) 1.85 [1.52;2.22]
excluded (control group) 		436/3,554   282/3,525 718 3,554
ref
S13454
R51826		 Meyer b (Controls unexposed, sick), 2021 Preterm (< 37 weeks) during pregnancy (anytime or not specified) retrospective cohort (claims database) unexposed, sick Adjustment: Yes Indications: Inflammatory Bowel disease (IBD) 1.78 [1.57;2.02] 436/3,554   1,405/19,811 1,841 3,554
ref
S12240
R46209		 Lazzaroni, 2020 Preterm delivery (<37 weeks) during pregnancy (anytime or not specified) retrospective cohort unexposed, sick Adjustment: No Indications: Systemic lupus erythematosus (SLE) Matched 1.19 [0.44;3.21] C 8/27   17/65 25 27
ref
S12241
R46212		 Koslowsky, 2019 Preterm birth (< 37 weeks) throughout pregnancy prospective cohort unexposed, sick Adjustment: No Indications: Inflammatory Bowel disease (IBD) 5.00 [0.24;105.67] C 3/21   0/13 3 21
ref
S13738
R53526		 Nguyen, 2019 Pre-term (<37 weeks) during pregnancy (anytime or not specified) prospective cohort unexposed, sick Adjustment: No Indications: Relapsing-Remitting Multiple Sclerosis (RRMS) 0.92 [0.10;8.93] C 1/4   182/686 183 4
ref
S12197
R53602		 Bröms, 2016 Preterm birth (delivery before 37 weeks’ of gestation) throughout pregnancy nested case control unexposed, sick Adjustment: Yes Indications: Inflammatory Bowel disease (IBD) 2.15 [1.25;3.72] 46/73   175/385 221 73
ref
S12242
R46238		 Komoto, 2016 Premature birth (<35 weeks) during pregnancy (anytime or not specified) retrospective cohort unexposed, sick Adjustment: No Indications: Inflammatory Bowel disease (IBD) 2.25 [0.17;29.06] C 1/7   2/29 3 7
ref
S10792
R52287		 Casanova, 2013 Preterm delivery 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
R45444		 Coelho (Controls exposed to 5-ASA), 2011 Preterm birth (<37 weeks) during pregnancy (anytime or not specified) retrospective cohort exposed to other treatment, sick excluded Adjustment: No Indications: Inflammatory Bowel disease (IBD) 2.33 [0.76;7.12] C
excluded (control group) 		10/40   6/48 16 40
ref
S12195
R45439		 Coelho (Controls unexposed, sick), 2011 Preterm birth (<37 weeks) during pregnancy (anytime or not specified) retrospective cohort unexposed, sick Adjustment: No Indications: Inflammatory Bowel disease (IBD) 1.92 [0.53;6.90] C 10/40   4/27 14 40
ref
S8433
R27107		 Shim, 2011 Preterm birth (< 37 weeks gestation) throughout pregnancy retrospective cohort unexposed, sick Adjustment: No Indications: Inflammatory Bowel disease (IBD) Matched 2.28 [0.67;7.73] 5/19   10/74 15 19
ref
S6258
R18034		 Cleary (Controls unexposed, NOS), 2009 Preterm (<37 completed weeks) among singleton infants early pregnancy population based cohort retrospective unexposed (general population or NOS) excluded Adjustment: Yes Indications: Any or not specified 3.56 [2.81;4.50]
excluded (control group) 		74/469   57,946/1,144,591 58,020 469
ref
S12174
R45196		 Cleary (Controls unexposed, sick), 2009 Preterm (<37 completed weeks) among singleton infants early pregnancy population based cohort retrospective unexposed, sick Adjustment: No Indications: Any or not specified 1.66 [1.23;2.23] 74/469   172/1,683 246 469
ref
S8427
R27090		 Goldstein, 2007 Preterm births (< 37 weeks) at least 1st trimester prospective cohort unexposed (general population or NOS) Adjustment: No Indications: Any or not specified 4.09 [2.00;8.06] 33/154   10/191 43 154
ref
S6628
R18381		 Langagergaard (Controls unexposed, NOS), 2007 Preterm birth (gestational age < 37 weeks) throughout pregnancy population based cohort retrospective unexposed (general population or NOS) excluded Adjustment: Yes Indications: Any or not specified Matched 5.60 [3.50;9.10]
excluded (control group) 		17/65   59/1,274 76 65
ref
S6656
R18386		 Langagergaard (Controls unexposed, sick), 2007 Preterm birth (gestational age < 37 weeks) throughout pregnancy population based cohort retrospective unexposed, sick Adjustment: Yes Indications: Any or not specified 1.90 [1.10;3.30] 17/65   25/174 42 65
ref
S10910
R44867		 Schramm, 2006 Preterm deliveries (<36 weeks) during pregnancy (anytime or not specified) retrospective cohort unexposed, sick Adjustment: No Indications: Autoimmune Hepatitis (AIH) 3.33 [0.63;17.65] C 4/14   3/28 7 14
ref
S13766
R53605		 Dejaco, 2005 Preterm (< 37 weeks) during pregnancy (anytime or not specified) prospective cohort unexposed, sick Adjustment: No Indications: Inflammatory Bowel disease (IBD) 0.57 [0.12;2.69] C 3/26   5/27 8 26
ref
S11066
R44830		 Francella, 2003 Preterm (gestational age < 37 weeks) throughout pregnancy retrospective cohort unexposed, sick Adjustment: No Indications: Inflammatory Bowel disease (IBD) 4.97 [1.24;20.00] C 4/14   7/94 11 14
ref
Total 18 studies 1.80 [1.60;2.02] 2,893 4,943
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 1.18[0.49; 2.88]271112%ROB confusion: criticalROB selection: criticalROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Yeaman (Controls unexposed, disease free), 2023Yeaman, 2023 1 1.55[0.31; 7.75]7191%ROB confusion: seriousROB selection: lowROB classification: moderateROB missing: unclearROB mesure: lowROB reporting: moderate Reynolds, 2022Reynolds, 2022 2.38[1.41; 4.01]103865%ROB confusion: criticalROB selection: unclearROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Kanis, 2021Kanis, 2021 1.16[0.71; 1.88]942406%ROB confusion: seriousROB selection: criticalROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Meyer b (Controls unexposed, sick), 2021Meyer b, 2021 2 1.78[1.57; 2.02]1,8413,55456%ROB confusion: seriousROB selection: lowROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Lazzaroni, 2020Lazzaroni, 2020 1.19[0.44; 3.21]25271%ROB confusion: seriousROB selection: unclearROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Koslowsky, 2019Koslowsky, 2019 5.00[0.24; 105.67]3210%ROB confusion: criticalROB selection: criticalROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Nguyen, 2019Nguyen, 2019 0.92[0.10; 8.93]18340%ROB confusion: criticalROB selection: lowROB classification: moderateROB missing: moderateROB mesure: moderateROB reporting: low Bröms, 2016Bröms, 2016 2.15[1.25; 3.72]221735%ROB confusion: moderateROB selection: lowROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Komoto, 2016Komoto, 2016 2.25[0.17; 29.06]370%ROB confusion: criticalROB selection: unclearROB classification: criticalROB missing: lowROB mesure: criticalROB reporting: moderate Coelho (Controls unexposed, sick), 2011Coelho, 2011 3 1.92[0.53; 6.90]14401%ROB confusion: criticalROB selection: criticalROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Shim, 2011Shim, 2011 2.28[0.67; 7.73]15191%ROB confusion: seriousROB selection: lowROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Cleary (Controls unexposed, sick), 2009Cleary, 2009 4 1.66[1.23; 2.23]24646914%ROB confusion: seriousROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Goldstein, 2007Goldstein, 2007 4.09[2.00; 8.06]431543%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: lowROB mesure: criticalROB reporting: moderate Langagergaard (Controls unexposed, sick), 2007Langagergaard, 2007 5 1.90[1.10; 3.30]42654%ROB confusion: seriousROB selection: lowROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Schramm, 2006Schramm, 2006 3.33[0.63; 17.65]7140%ROB confusion: criticalROB selection: lowROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Dejaco, 2005Dejaco, 2005 0.57[0.12; 2.69]8261%ROB confusion: seriousROB selection: unclearROB classification: unclearROB missing: unclearROB mesure: unclearROB reporting: moderate Francella, 2003Francella, 2003 4.97[1.24; 20.00]11141%ROB confusion: criticalROB selection: unclearROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Total (18 studies) I2 = 3% 1.80[1.60; 2.02]2,8934,9430.210.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Controls unexposed, disease free; 2: Controls unexposed, sick; 3: Controls unexposed, sick; 4: Controls unexposed, sick; 5: Controls unexposed, sick;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.78[1.56; 2.04]2,6724,8706%NAVestergaard, 2024 Yeaman (Controls unexposed, disease free), 2023 Reynolds, 2022 Kanis, 2021 Meyer b (Controls unexposed, sick), 2021 Lazzaroni, 2020 Koslowsky, 2019 Nguyen, 2019 Komoto, 2016 Coelho (Controls unexposed, sick), 2011 Shim, 2011 Cleary (Controls unexposed, sick), 2009 Goldstein, 2007 Langagergaard (Controls unexposed, sick), 2007 Schramm, 2006 Dejaco, 2005 Francella, 2003 17 case control studiescase control studies 2.15[1.25; 3.71]22173 -NABröms, 2016 1 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 3.34[1.54; 7.24]5017315%NAYeaman (Controls unexposed, disease free), 2023 Goldstein, 2007 2 unexposed, sickunexposed, sick 1.76[1.59; 1.95]2,8434,7700%NAVestergaard, 2024 Reynolds, 2022 Kanis, 2021 Meyer b (Controls unexposed, sick), 2021 Lazzaroni, 2020 Koslowsky, 2019 Nguyen, 2019 Bröms, 2016 Komoto, 2016 Coelho (Controls unexposed, sick), 2011 Shim, 2011 Cleary (Controls unexposed, sick), 2009 Langagergaard (Controls unexposed, sick), 2007 Schramm, 2006 Dejaco, 2005 Francella, 2003 16 Tags Adjustment   - No  - No 1.93[1.53; 2.44]6951,0114%NAVestergaard, 2024 Yeaman (Controls unexposed, disease free), 2023 Reynolds, 2022 Lazzaroni, 2020 Koslowsky, 2019 Nguyen, 2019 Komoto, 2016 Coelho (Controls unexposed, sick), 2011 Shim, 2011 Cleary (Controls unexposed, sick), 2009 Goldstein, 2007 Schramm, 2006 Dejaco, 2005 Francella, 2003 14   - Yes  - Yes 1.74[1.47; 2.05]2,1983,93213%NAKanis, 2021 Meyer b (Controls unexposed, sick), 2021 Bröms, 2016 Langagergaard (Controls unexposed, sick), 2007 4 Indications   - Any or not specified  - Any or not specified 2.17[1.35; 3.48]33168863%NACleary (Controls unexposed, sick), 2009 Goldstein, 2007 Langagergaard (Controls unexposed, sick), 2007 3   - Autoimmune Hepatitis (AIH)  - Autoimmune Hepatitis (AIH) 3.33[0.63; 17.65]714 -NASchramm, 2006 1   - Inflammatory Bowel disease (IBD)  - Inflammatory Bowel disease (IBD) 1.75[1.56; 1.96]2,2444,1240%NAVestergaard, 2024 Yeaman (Controls unexposed, disease free), 2023 Kanis, 2021 Meyer b (Controls unexposed, sick), 2021 Koslowsky, 2019 Bröms, 2016 Komoto, 2016 Coelho (Controls unexposed, sick), 2011 Shim, 2011 Dejaco, 2005 Francella, 2003 11   - Relapsing-Remitting Multiple Sclero ...  - Relapsing-Remitting Multiple Sclerosis (RRMS) 0.92[0.10; 8.93]1834 -NANguyen, 2019 1   - Systemic lupus erythematosus (SLE)  - Systemic lupus erythematosus (SLE) 1.92[1.03; 3.60]12811332%NAReynolds, 2022 Lazzaroni, 2020 2 MatchedMatched 1.54[0.71; 3.33]40460%NALazzaroni, 2020 Shim, 2011 2 All studiesAll studies 1.80[1.60; 2.02]2,8934,9433%NAVestergaard, 2024 Yeaman (Controls unexposed, disease free), 2023 Reynolds, 2022 Kanis, 2021 Meyer b (Controls unexposed, sick), 2021 Lazzaroni, 2020 Koslowsky, 2019 Nguyen, 2019 Bröms, 2016 Komoto, 2016 Coelho (Controls unexposed, sick), 2011 Shim, 2011 Cleary (Controls unexposed, sick), 2009 Goldstein, 2007 Langagergaard (Controls unexposed, sick), 2007 Schramm, 2006 Dejaco, 2005 Francella, 2003 180.210.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-3.74.21.8680.000Vestergaard, 2024Yeaman (Controls unexposed, disease free), 2023Reynolds, 2022Kanis, 2021Meyer b (Controls unexposed, sick), 2021Lazzaroni, 2020Koslowsky, 2019Nguyen, 2019Bröms, 2016Komoto, 2016Coelho (Controls unexposed, sick), 2011Shim, 2011Cleary (Controls unexposed, sick), 2009Goldstein, 2007Langagergaard (Controls unexposed, sick), 2007Schramm, 2006Dejaco, 2005Francella, 2003

Asymetry test p-value = 0.6522 (by Egger's regression)

slope=0.5603 (0.0724); intercept=0.1509 (0.3286); t=0.4593; p=0.6522

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 6628, 6258, 12246, 13576, 18477

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 3.98[2.98; 5.34]58,14670726%NAYeaman (Controls unexposed, disease free), 2023 Cleary (Controls unexposed, NOS), 2009 Goldstein, 2007 Langagergaard (Controls unexposed, NOS), 2007 4 unexposed, sick controlsunexposed, sick controls 1.76[1.59; 1.95]2,8434,7700%NAVestergaard, 2024 Reynolds, 2022 Kanis, 2021 Meyer b (Controls unexposed, sick), 2021 Lazzaroni, 2020 Koslowsky, 2019 Nguyen, 2019 Bröms, 2016 Komoto, 2016 Coelho (Controls unexposed, sick), 2011 Shim, 2011 Cleary (Controls unexposed, sick), 2009 Langagergaard (Controls unexposed, sick), 2007 Schramm, 2006 Dejaco, 2005 Francella, 2003 16 exposed to other treatment, sick controlsexposed to other treatment, sick controls 1.79[1.31; 2.45]7483,6139%NAYeaman (Controls mainly exposed to biologics), 2023 Meyer b (Controls exposed to Anti-TNF), 2021 Coelho (Controls exposed to 5-ASA), 2011 30.510.01.0

Umbrella review (other published meta-analyses)

Published MAControlPeriodTE95% CIn exposedkI2 Mozaffari (Prematurity)Mozaffari (Prematurity) 1.07[0.42; 2.70]69%-Eexposed to other treatment, sickAnyduring pregnancy (anytime or not specified)studies TTT3 Mozaffari (Prematurity)Mozaffari (Prematurity) 2.65[0.85; 8.30]NA-U,Sunexposed, sickAnyduring pregnancy (anytime or not specified)studies TTT2 Hutson (Prematurity (vs disease-matched contr ...Hutson (Prematurity (vs disease-matched controls (with or without on other medications))) 1.67[1.17; 2.37]28%-U,Sunexposed, sickAnyduring pregnancy (anytime or not specified)studies TTT6 Hutson (Prematurity (vs disease-matched contr ...Hutson (Prematurity (vs disease-matched controls not on other medications)) 2.49[0.92; 6.75]57%-U,Sunexposed, sickAnyduring pregnancy (anytime or not specified)studies TTT2 Hutson (Prematurity (vs disease-matched contr ...Hutson (Prematurity (vs disease-matched controls on other medications)) 1.49[1.13; 1.96]0%-Eexposed to other treatment, sickAnyduring pregnancy (anytime or not specified)studies TTT2 Hutson (Prematurity (vs healthy or general po ...Hutson (Prematurity (vs healthy or general population controls)) 3.97[2.65; 5.94]62%-U,GPunexposed (general population or NOS)Anyduring pregnancy (anytime or not specified)studies TTT3 Akbari (Preterm birth)Akbari (Preterm birth) 1.67[1.26; 2.20]0%-Wwhatever (meta-analysis)Before-Any3 months (or more) before pregnancy or during pregnancystudies TTT5 Zhang (Preterm Birth)Zhang (Preterm Birth) 1.34[1.00; 1.79]41%-Eexposed to other treatment, sickAnyduring pregnancy (anytime or not specified)studies TTT8 metaPregmetaPreg 1.80[1.60; 2.02]3%4,943----Vestergaard, 2024 Yeaman (Controls unexposed, disease free), 2023 Reynolds, 2022 Kanis, 2021 Meyer b (Controls unexposed, sick), 2021 Lazzaroni, 2020 Koslowsky, 2019 Nguyen, 2019 Bröms, 2016 Komoto, 2016 Coelho (Controls unexposed, sick), 2011 Shim, 2011 Cleary (Controls unexposed, sick), 2009 Goldstein, 2007 Langagergaard (Controls unexposed, sick), 2007 Schramm, 2006 Dejaco, 2005 Francella, 2003 180.510.01.0