Thiouracil, propylthiouracil, benzylthiouracil

All congenital malformations (majors, minors, majors and minors, 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.
S8484
R27829
Yoshihara (Controls exposed to MMI), 2021 Birth defects 1st trimester retrospective cohort exposed to other treatment, sick excluded Adjustment: No 2.69 [0.16;45.39] C
excluded (control group)
30/541   0/23 30 541
ref
S8481
R27763
Yoshihara (Controls unexposed, sick), 2021 Birth defects 1st trimester retrospective cohort unexposed, sick Adjustment: No 0.97 [0.57;1.66] C 30/541   27/475 57 541
ref
S3448
R6451
Andersen 2019 (control exposed to MMI/CMZ), 2019 All birth defects (ICD-10: Q00-99) early pregnancy population based cohort retrospective exposed to other treatment, sick excluded Adjustment: No 0.86 [0.64;1.14] C
excluded (control group)
74/889   151/1,574 225 889
ref
S3449
R6466
Andersen 2019 (control unexposed, disease free), 2019 All birth defects (ICD-10: Q00-99) early pregnancy population based cohort retrospective unexposed, disease free Adjustment: Yes 1.17 [0.91;1.49] 74/889   77,791/1,159,181 77,865 889
ref
S3366
R6151
Seo (control exposed to MMI), 2018 Overall congenital malformations (Q00 to Q99) 1st trimester retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: No 0.86 [0.68;1.08] C
excluded (control group)
699/9,930   91/1,120 790 9,930
ref
S3367
R6163
Seo (control unexposed, NOS), 2018 Overall congenital malformations (Q00 to Q99) 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: Yes 1.16 [1.07;1.25] 699/9,930   170,716/2,872,109 171,415 9,930
ref
S3340
R5751
Andersen 2017 (control exposed to MMI/CMZ), 2017 Birth defects (ICD­10: Q00-­Q99) early pregnancy population based cohort retrospective exposed to other treatment, sick excluded Adjustment: No 0.94 [0.42;2.13] C
excluded (control group)
14/218   11/162 25 218
ref
S3339
R5734
Andersen 2017 (control unexposed, disease free), 2017 Birth defects (ICD­10: Q00-Q99) early pregnancy population based cohort retrospective unexposed, disease free excluded Adjustment: Yes 0.89 [0.52;1.54]
excluded (control group)
14/218   54,827/682,343 54,841 218
ref
S3338
R5717
Andersen 2017 (control unexposed, sick), 2017 Birth defects (ICD­10: Q00-Q99) early pregnancy population based cohort retrospective unexposed, sick Adjustment: No 0.71 [0.40;1.26] C 14/218   136/1,551 150 218
ref
S3422
R6370
Hawken (control exposed to MMI), 2016 Malformations 1st trimester retrospective cohort exposed to other treatment, sick Adjustment: No 0.11 [0.01;2.29] C 0/13   4/17 4 13
ref
S3564
R11278
Gianetti (control exposed to MMI), 2015 Major malformations at least 1st trimester retrospective cohort exposed to other treatment, sick excluded Adjustment: No 12.47 [0.59;264.54] C
excluded (control group)
2/52   0/124 2 52
ref
S3565
R11279
Gianetti (control unexposed, sick), 2015 Major malformations throughout pregnancy retrospective cohort unexposed, sick Adjustment: No 1.99 [0.35;11.17] C 2/52   4/203 6 52
ref
S3377
R6251
Lo (control exposed to MMI), 2015 Congenital anomalies (ICD-9) during pregnancy (anytime or not specified) retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: No 0.88 [0.11;6.93] C
excluded (control group)
15/507   1/30 16 507
ref
S3371
R6193
Lo (control unexposed, sick), 2015 Congenital anomalies (ICD-9) during pregnancy (anytime or not specified) excluded retrospective cohort (claims database) unexposed, sick Adjustment: No 0.66 [0.37;1.18] C
excluded (exposition period)
15/507   52/1,171 67 507
ref
S3387
R6314
Korelitz (control exposed to MMI), 2013 Any congenital defect 3 months (or more) before pregnancy or during pregnancy retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: No 1.32 [0.56;3.12] C
excluded (control group)
66/915   6/108 72 915
ref
S8718
R29465
Korelitz (control exposed to MMI), 2013 Any congenital defect 3 months (or more) before pregnancy or during pregnancy retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: No 1.32 [0.56;3.12] C
excluded (control group)
66/915   6/108 72 915
ref
S3388
R6322
Korelitz (control unexposed, disease free), 2013 Any congenital defect 3 months (or more) before pregnancy or during pregnancy retrospective cohort (claims database) unexposed, disease free excluded Adjustment: Yes 1.22 [0.95;1.57]
excluded (control group)
66/915   37,351/634,858 37,417 915
ref
S3389
R6330
Korelitz (control unexposed, sick), 2013 Any congenital defect 3 months (or more) before pregnancy or during pregnancy excluded retrospective cohort (claims database) unexposed, sick Adjustment: No 1.15 [0.86;1.53] C
excluded (exposition period)
66/915   205/3,236 271 915
ref
S3355
R11283
Yoshihara (control exposed to MMI), 2012 Major malformations 1st trimester retrospective cohort exposed to other treatment, sick excluded Adjustment: No 0.45 [0.28;0.72] C
excluded (control group)
26/1,399   50/1,231 76 1,399
ref
S3354
R11284
Yoshihara (control unexposed, sick), 2012 Major malformations 1st trimester retrospective cohort unexposed, sick Adjustment: Yes 0.66 [0.41;1.03] 26/1,399   40/1,906 66 1,399
ref
S3415
R35108
Banhidy, 2011 Congenital abnormalities throughout pregnancy case control unexposed, sick Adjustment: No 1.64 [0.10;26.69] C 1/2   70/185 71 2
ref
S3346
R11274
Chen (Control exposed to MMI), 2011 Major congenital anomalies during pregnancy (anytime or not specified) retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: No 1.28 [0.07;23.33] C
excluded (control group)
5/630   0/73 5 630
ref
S3347
R11275
Chen (control unexposed, disease free), 2011 Major congenital anomalies during pregnancy (anytime or not specified) retrospective cohort (claims database) unexposed, disease free excluded Adjustment: No 1.22 [0.50;3.02] C
excluded (control group)
5/630   92/14,150 97 630
ref
S3348
R11276
Chen (control unexposed, sick), 2011 Major congenital anomalies during pregnancy (anytime or not specified) excluded population based cohort retrospective unexposed, sick Adjustment: Yes 1.10 [0.40;3.06]
excluded (exposition period)
5/630   15/2,127 20 630
ref
S3374
R11280
Rosenfeld, 2009 Major birth defects 1st trimester prospective cohort unexposed (general population or NOS) Adjustment: No 0.38 [0.05;2.84] C 1/80   34/1,066 35 80
ref
S3456
R11277
Dwarakanath (control exposed to MMI), 1999 Congenital malformations at least 1st trimester retrospective cohort exposed to other treatment, sick Adjustment: No 3.46 [0.12;100.52] C 1/8   0/8 1 8
ref
S3393
R11281
Wing (control exposed to MMI), 1994 Major congenital anomalies, first trimester exposure 1st trimester cohort exposed to other treatment, sick excluded Adjustment: No 0.12 [0.00;2.93] C
excluded (control group)
0/99   1/36 1 99
ref
S3394
R11282
Wing (control unexposed, sick), 1994 Congenital anomalies, first trimester exposure 1st trimester cohort unexposed, sick Adjustment: No 0.14 [0.01;3.52] C 0/99   1/43 1 99
ref
Total 11 studies 1.01 [0.83;1.22] 249,671 13,231
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 Yoshihara (Controls unexposed, sick), 2021Yoshihara, 2021 1 0.97[0.57; 1.66]5754110%ROB confusion: criticalROB selection: moderateROB classification: unclearROB missing: unclearROB mesure: criticalROB reporting: moderate Andersen 2019 (control unexposed, disease free), 2019Andersen 2019, 2019 2 1.17[0.91; 1.49]77,86588925%ROB confusion: seriousROB selection: moderateROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Seo (control unexposed, NOS), 2018Seo, 2018 3 1.16[1.07; 1.25]171,4159,93040%ROB confusion: criticalROB selection: moderateROB classification: lowROB missing: lowROB mesure: moderateROB reporting: moderate Andersen 2017 (control unexposed, sick), 2017Andersen 2017, 2017 4 0.71[0.40; 1.26]1502189%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Hawken (control exposed to MMI), 2016Hawken, 2016 5 0.11[0.01; 2.29]4130%ROB confusion: criticalROB selection: criticalROB classification: unclearROB missing: lowROB mesure: criticalROB reporting: unclear Gianetti (control unexposed, sick), 2015Gianetti, 2015 6 1.99[0.35; 11.17]6521%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: lowROB mesure: criticalROB reporting: moderate Yoshihara (control unexposed, sick), 2012Yoshihara, 2012 7 0.66[0.41; 1.03]661,39912%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: lowROB mesure: criticalROB reporting: moderate Banhidy, 2011Banhidy, 2011 1.64[0.10; 26.69]7120%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Rosenfeld, 2009Rosenfeld, 2009 0.38[0.05; 2.84]35801%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: criticalROB reporting: moderate Dwarakanath (control exposed to MMI), 1999Dwarakanath, 1999 8 3.46[0.12; 100.52]180%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: lowROB mesure: unclearROB reporting: unclear Wing (control unexposed, sick), 1994Wing, 1994 9 0.14[0.01; 3.52]1990%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Total (11 studies) I2 = 31% 1.01[0.83; 1.22]249,67113,2310.010.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Controls unexposed, sick; 2: control unexposed, disease free; 3: control unexposed, NOS; 4: control unexposed, sick; 5: control exposed to MMI; 6: control unexposed, sick; 7: control unexposed, sick; 8: control exposed to MMI; 9: control unexposed, sick;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 0.99[0.81; 1.22]249,60013,22937%NAYoshihara (Controls unexposed, sick), 2021 Andersen 2019 (control unexposed, disease free), 2019 Seo (control unexposed, NOS), 2018 Andersen 2017 (control unexposed, sick), 2017 Hawken (control exposed to MMI), 2016 Gianetti (control unexposed, sick), 2015 Yoshihara (control unexposed, sick), 2012 Rosenfeld, 2009 Dwarakanath (control exposed to MMI), 1999 Wing (control unexposed, sick), 1994 10 case control studiescase control studies 1.64[0.10; 26.69]712 -NABanhidy, 2011 1 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.16[1.08; 1.25]249,31510,8990%NAAndersen 2019 (control unexposed, disease free), 2019 Seo (control unexposed, NOS), 2018 Rosenfeld, 2009 3 unexposed, sickunexposed, sick 0.78[0.58; 1.04]3512,3110%NAYoshihara (Controls unexposed, sick), 2021 Andersen 2017 (control unexposed, sick), 2017 Gianetti (control unexposed, sick), 2015 Yoshihara (control unexposed, sick), 2012 Banhidy, 2011 Wing (control unexposed, sick), 1994 6 exposed to other treatment, sickexposed to other treatment, sick 0.57[0.02; 16.53]52155%NAHawken (control exposed to MMI), 2016 Dwarakanath (control exposed to MMI), 1999 2 Tags Adjustment   - No  - No 0.83[0.58; 1.20]3251,0130%NAYoshihara (Controls unexposed, sick), 2021 Andersen 2017 (control unexposed, sick), 2017 Hawken (control exposed to MMI), 2016 Gianetti (control unexposed, sick), 2015 Banhidy, 2011 Rosenfeld, 2009 Dwarakanath (control exposed to MMI), 1999 Wing (control unexposed, sick), 1994 8   - Yes  - Yes 1.06[0.85; 1.33]249,34612,21864%NAAndersen 2019 (control unexposed, disease free), 2019 Seo (control unexposed, NOS), 2018 Yoshihara (control unexposed, sick), 2012 3 All studiesAll studies 1.01[0.83; 1.22]249,67113,23131%NAYoshihara (Controls unexposed, sick), 2021 Andersen 2019 (control unexposed, disease free), 2019 Seo (control unexposed, NOS), 2018 Andersen 2017 (control unexposed, sick), 2017 Hawken (control exposed to MMI), 2016 Gianetti (control unexposed, sick), 2015 Yoshihara (control unexposed, sick), 2012 Banhidy, 2011 Rosenfeld, 2009 Dwarakanath (control exposed to MMI), 1999 Wing (control unexposed, sick), 1994 110.010.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-4.04.02.0620.000Yoshihara (Controls unexposed, sick), 2021Andersen 2019 (control unexposed, disease free), 2019Seo (control unexposed, NOS), 2018Andersen 2017 (control unexposed, sick), 2017Hawken (control exposed to MMI), 2016Gianetti (control unexposed, sick), 2015Yoshihara (control unexposed, sick), 2012Banhidy, 2011Rosenfeld, 2009Dwarakanath (control exposed to MMI), 1999Wing (control unexposed, sick), 1994

Asymetry test p-value = 0.0835 (by Egger's regression)

slope=0.1714 (0.0463); intercept=-0.7423 (0.3814); t=1.9460; p=0.0835

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 3393, 3346, 3347, 3355, 8718, 3387, 3388, 3564, 3377, 3340, 3339, 3366, 3448, 8484

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.15[1.07; 1.24]304,15611,1170%NAAndersen 2019 (control unexposed, disease free), 2019 Seo (control unexposed, NOS), 2018 Andersen 2017 (control unexposed, disease free), 2017 Rosenfeld, 2009 4 unexposed, sick controlsunexposed, sick controls 0.78[0.58; 1.04]3512,3110%NAYoshihara (Controls unexposed, sick), 2021 Andersen 2017 (control unexposed, sick), 2017 Gianetti (control unexposed, sick), 2015 Yoshihara (control unexposed, sick), 2012 Banhidy, 2011 Wing (control unexposed, sick), 1994 6 exposed to other treatment, sick controlsexposed to other treatment, sick controls 0.77[0.56; 1.05]1,15413,14942%NAYoshihara (Controls exposed to MMI), 2021 Andersen 2019 (control exposed to MMI/CMZ), 2019 Seo (control exposed to MMI), 2018 Andersen 2017 (control exposed to MMI/CMZ), 2017 Hawken (control exposed to MMI), 2016 Gianetti (control exposed to MMI), 2015 Yoshihara (control exposed to MMI), 2012 Dwarakanath (control exposed to MMI), 1999 Wing (control exposed to MMI), 1994 90.510.01.0