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
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
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 4 studies 0.67 [0.44;1.03] 108 1,630
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]661,39987%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: lowROB mesure: criticalROB reporting: moderate Rosenfeld, 2009Rosenfeld, 2009 0.38[0.05; 2.84]35805%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: criticalROB reporting: moderate Wing (control unexposed, sick), 1994Wing, 1994 3 0.14[0.01; 3.52]1992%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Total (4 studies) I2 = 0% 0.67[0.44; 1.03]1081,6300.05.01.0ROB: 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 unexposed, sick;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 0.67[0.44; 1.03]1081,6300%NAGianetti (control unexposed, sick), 2015 Yoshihara (control unexposed, sick), 2012 Rosenfeld, 2009 Wing (control unexposed, sick), 1994 4 case control studiescase control studies 0 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 0.73[0.34; 1.56]731,55017%NAGianetti (control unexposed, sick), 2015 Yoshihara (control unexposed, sick), 2012 Wing (control unexposed, sick), 1994 3 Tags Adjustment   - No  - No 0.68[0.16; 2.91]4223126%NAGianetti (control unexposed, sick), 2015 Rosenfeld, 2009 Wing (control unexposed, sick), 1994 3   - Yes  - Yes 0.66[0.42; 1.05]661,399 -NAYoshihara (control unexposed, sick), 2012 1 All studiesAll studies 0.67[0.44; 1.03]1081,6300%NAGianetti (control unexposed, sick), 2015 Yoshihara (control unexposed, sick), 2012 Rosenfeld, 2009 Wing (control unexposed, sick), 1994 40.05.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-3.93.51.9720.000Gianetti (control unexposed, sick), 2015Yoshihara (control unexposed, sick), 2012Rosenfeld, 2009Wing (control unexposed, sick), 1994

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 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 0.75[0.09; 5.96]791,55061%NAGianetti (control exposed to MMI), 2015 Yoshihara (control exposed to MMI), 2012 Wing (control exposed to MMI), 1994 30.510.01.0