Thiouracil, propylthiouracil, benzylthiouracil

Major congenital malformations

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.
S3564
R7112
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
R7123
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
S3355
R6059
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
R6016
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
R6365
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
R5821
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
R5825
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
R5829
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
R6204
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
R6574
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
R6339
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
R6341
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 6 studies 0.70 [0.46;1.07] 180 1,640
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 Gianetti (control unexposed, sick), 2015Gianetti, 2015 1 1.99[0.35; 11.17]6526%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: lowROB mesure: criticalROB reporting: moderate Yoshihara (control unexposed, sick), 2012Yoshihara, 2012 2 0.66[0.41; 1.03]661,39984%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: lowROB mesure: criticalROB reporting: moderate Banhidy, 2011Banhidy, 2011 1.64[0.10; 26.69]7122%ROB confusion: seriousROB selection: criticalROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Rosenfeld, 2009Rosenfeld, 2009 0.38[0.05; 2.84]35804%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: criticalROB reporting: moderate Dwarakanath (control exposed to MMI), 1999Dwarakanath, 1999 3 3.46[0.12; 100.52]182%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: unclear Wing (control unexposed, sick), 1994Wing, 1994 4 0.14[0.01; 3.52]1992%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Total (6 studies) I2 = 0% 0.70[0.46; 1.07]1801,6400.010.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: control unexposed, sick; 2: control unexposed, sick; 3: control exposed to MMI; 4: control unexposed, sick;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 0.69[0.45; 1.06]1091,6380%NAGianetti (control unexposed, sick), 2015 Yoshihara (control unexposed, sick), 2012 Rosenfeld, 2009 Dwarakanath (control exposed to MMI), 1999 Wing (control unexposed, sick), 1994 5 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) 0.38[0.05; 2.84]3580 -NARosenfeld, 2009 1 unexposed, sickunexposed, sick 0.70[0.46; 1.09]1441,5520%NAGianetti (control unexposed, sick), 2015 Yoshihara (control unexposed, sick), 2012 Banhidy, 2011 Wing (control unexposed, sick), 1994 4 exposed to other treatment, sickexposed to other treatment, sick 3.46[0.12; 100.52]18 -NADwarakanath (control exposed to MMI), 1999 1 Tags Adjustment   - No  - No 0.97[0.34; 2.80]1142410%NAGianetti (control unexposed, sick), 2015 Banhidy, 2011 Rosenfeld, 2009 Dwarakanath (control exposed to MMI), 1999 Wing (control unexposed, sick), 1994 5   - Yes  - Yes 0.66[0.42; 1.05]661,399 -NAYoshihara (control unexposed, sick), 2012 1 All studiesAll studies 0.70[0.46; 1.07]1801,6400%NAGianetti (control unexposed, sick), 2015 Yoshihara (control unexposed, sick), 2012 Banhidy, 2011 Rosenfeld, 2009 Dwarakanath (control exposed to MMI), 1999 Wing (control unexposed, sick), 1994 60.010.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-4.03.72.0620.000Gianetti (control unexposed, sick), 2015Yoshihara (control unexposed, sick), 2012Banhidy, 2011Rosenfeld, 2009Dwarakanath (control exposed to MMI), 1999Wing (control unexposed, sick), 1994

Asymetry test p-value = 0.6197 (by Egger's regression)

slope=-0.4712 (0.3026); intercept=0.3080 (0.5735); t=0.5371; p=0.6197

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 3393, 3346, 3347, 3355, 3564

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) Out of scale0.38[0.05; 2.84]3580 -NARosenfeld, 2009 1 unexposed, sick controlsunexposed, sick controls 0.70[0.46; 1.09]1441,5520%NAGianetti (control unexposed, sick), 2015 Yoshihara (control unexposed, sick), 2012 Banhidy, 2011 Wing (control unexposed, sick), 1994 4 exposed to other treatment, sick controlsexposed to other treatment, sick controls 0.94[0.17; 5.31]801,55854%NAGianetti (control exposed to MMI), 2015 Yoshihara (control exposed to MMI), 2012 Dwarakanath (control exposed to MMI), 1999 Wing (control exposed to MMI), 1994 40.510.01.0