Carbimazole, Thiamazole (Methimazole)

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.
S3563
R7101		 Gianetti (control exposed to PTU), 2015 Major malformations at least 1st trimester retrospective cohort exposed to other treatment, sick excluded Adjustment: No 0.08 [0.00;1.70] C
excluded (control group) 		0/124   2/52 2 124
ref
S3562
R7090		 Gianetti (control unexposed, sick), 2015 Major malformations at least 1st trimester retrospective cohort unexposed, sick Adjustment: No 0.18 [0.01;3.35] C 0/124   4/203 4 124
ref
S3353
R5973		 Yoshihara (control exposed to PTU), 2012 Major malformations 1st trimester retrospective cohort exposed to other treatment, sick excluded Adjustment: No 2.24 [1.38;3.61] C
excluded (control group) 		50/1,231   26/1,399 76 1,231
ref
S3350
R5834		 Yoshihara (control unexposed, sick), 2012 Major malformations 1st trimester retrospective cohort unexposed, sick Adjustment: Yes 2.28 [1.54;3.33] 50/1,231   40/1,906 90 1,231
ref
S3414
R6366		 Banhidy, 2011 Congenital abnormalities at least 1st trimester case control unexposed, sick Adjustment: No 0.81 [0.14;4.55] C 2/6   69/181 71 6
ref
S3345
R5817		 Chen (control exposed to PTU), 2011 Major congenital anomalies during pregnancy (anytime or not specified) retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: No 0.78 [0.04;14.31] C
excluded (control group) 		0/73   5/630 5 73
ref
S3343
R5809		 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 1.05 [0.06;17.05] C
excluded (control group) 		0/73   92/14,150 92 73
ref
S3344
R5813		 Chen (control unexposed, sick), 2011 Major congenital anomalies during pregnancy (anytime or not specified) excluded population based cohort retrospective unexposed, sick Adjustment: No 0.94 [0.06;15.86] C
excluded (exposition period) 		0/73   15/2,127 15 73
ref
S3396
R6343		 Di Gianantonio, 2001 Major malformations 1st trimester prospective cohort unexposed, disease free Adjustment: No 1.89 [0.83;4.29] C 8/204   23/1,089 31 204
ref
S3455
R6567		 Dwarakanath (control exposed to PTU), 1999 Congenital malformations at least 1st trimester retrospective cohort exposed to other treatment, sick Adjustment: No 0.29 [0.01;8.39] C 0/8   1/8 1 8
ref
S3392
R6334		 Wing (control exposed to PTU), 1994 Major congenital anomalies, first trimester exposure 1st trimester cohort exposed to other treatment, sick excluded Adjustment: No 8.57 [0.34;215.25] C
excluded (control group) 		1/36   0/99 1 36
ref
S3391
R6337		 Wing (control unexposed, sick), 1994 Congenital anomalies, first trimester exposure 1st trimester cohort unexposed, sick Adjustment: No 1.20 [0.07;19.89] C 1/36   1/43 2 36
ref
S3362
R6113		 Khoury, 1989 Major birth defects during pregnancy (anytime or not specified) excluded case control unexposed (general population or NOS) Adjustment: No 0.41 [0.07;2.46] C
excluded (exposition period) 		2/5   4,902/7,926 4,904 5
ref
S3400
R6345		 Momotani, 1984 Major malformations of external organs 1st trimester retrospective cohort unexposed, sick Adjustment: No 0.82 [0.15;4.52] C 2/243   4/400 6 243
ref
Total 7 studies 1.78 [1.18;2.69] 205 1,852
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 0.18[0.01; 3.35]41242%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: lowROB mesure: criticalROB reporting: unclear Yoshihara (control unexposed, sick), 2012Yoshihara, 2012 2 2.28[1.54; 3.33]901,23162%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: lowROB mesure: criticalROB reporting: moderate Banhidy, 2011Banhidy, 2011 0.81[0.14; 4.55]7166%ROB confusion: seriousROB selection: criticalROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Di Gianantonio, 2001Di Gianantonio, 2001 1.89[0.83; 4.29]3120421%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: moderateROB mesure: criticalROB reporting: moderate Dwarakanath (control exposed to PTU), 1999Dwarakanath, 1999 3 0.29[0.01; 8.39]181%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: lowROB mesure: unclearROB reporting: unclear Wing (control unexposed, sick), 1994Wing, 1994 4 1.20[0.07; 19.89]2362%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Momotani, 1984Momotani, 1984 0.82[0.15; 4.52]62436%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: lowROB mesure: criticalROB reporting: moderate Total (7 studies) I2 = 8% 1.78[1.18; 2.69]2051,8520.05.01.0ROB: 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 exposed to PTU; 4: control unexposed, sick;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.85[1.20; 2.85]1341,8469%NAGianetti (control unexposed, sick), 2015 Yoshihara (control unexposed, sick), 2012 Di Gianantonio, 2001 Dwarakanath (control exposed to PTU), 1999 Wing (control unexposed, sick), 1994 Momotani, 1984 6 case control studiescase control studies 0.81[0.14; 4.55]716 -NABanhidy, 2011 1 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.89[0.83; 4.29]31204 -NADi Gianantonio, 2001 1 unexposed, sickunexposed, sick 1.41[0.68; 2.92]1731,64024%NAGianetti (control unexposed, sick), 2015 Yoshihara (control unexposed, sick), 2012 Banhidy, 2011 Wing (control unexposed, sick), 1994 Momotani, 1984 5 exposed to other treatment, sickexposed to other treatment, sick 0.29[0.01; 8.39]18 -NADwarakanath (control exposed to PTU), 1999 1 Tags Adjustment   - No  - No 1.23[0.66; 2.32]1156210%NAGianetti (control unexposed, sick), 2015 Banhidy, 2011 Di Gianantonio, 2001 Dwarakanath (control exposed to PTU), 1999 Wing (control unexposed, sick), 1994 Momotani, 1984 6   - Yes  - Yes 2.28[1.55; 3.35]901,231 -NAYoshihara (control unexposed, sick), 2012 1 All studiesAll studies 1.78[1.18; 2.69]2051,8528%NAGianetti (control unexposed, sick), 2015 Yoshihara (control unexposed, sick), 2012 Banhidy, 2011 Di Gianantonio, 2001 Dwarakanath (control exposed to PTU), 1999 Wing (control unexposed, sick), 1994 Momotani, 1984 70.05.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-4.04.62.0620.000Gianetti (control unexposed, sick), 2015Yoshihara (control unexposed, sick), 2012Banhidy, 2011Di Gianantonio, 2001Dwarakanath (control exposed to PTU), 1999Wing (control unexposed, sick), 1994Momotani, 1984

Asymetry test p-value = 0.0025 (by Egger's regression)

slope=1.1005 (0.1061); intercept=-1.3406 (0.2388); t=5.6142; p=0.0025

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 3392, 3345, 3343, 3353, 3563

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.89[0.83; 4.29]31204 -NADi Gianantonio, 2001 1 unexposed, sick controlsunexposed, sick controls 1.41[0.68; 2.92]1731,64024%NAGianetti (control unexposed, sick), 2015 Yoshihara (control unexposed, sick), 2012 Banhidy, 2011 Wing (control unexposed, sick), 1994 Momotani, 1984 5 exposed to other treatment, sick controlsexposed to other treatment, sick controls 1.06[0.19; 5.99]801,39954%NAGianetti (control exposed to PTU), 2015 Yoshihara (control exposed to PTU), 2012 Dwarakanath (control exposed to PTU), 1999 Wing (control exposed to PTU), 1994 40.510.01.0

Umbrella review (other published meta-analyses)

Published MAControlPeriodTE95% CIn exposedkI2 Li 2015b (Major congenital anomalies (all stu ...Li 2015b (Major congenital anomalies (all studies)) 1.64[1.39; 1.94]0%-Wwhatever (meta-analysis)Anyduring pregnancy (anytime or not specified)studies TTT5 Song (Major congenital malformations (MMI vs ...Song (Major congenital malformations (MMI vs Healthy control)) 2.75[0.58; 12.96]0%-U,DFunexposed, disease freeAnyduring pregnancy (anytime or not specified)studies TTT2 Song (Major congenital malformations (MMI vs PTU))Song (Major congenital malformations (MMI vs PTU)) 1.73[1.15; 2.59]11%-Eexposed to other treatment, sickAnyduring pregnancy (anytime or not specified)studies TTT4 Song (Major congenital malformations (MMI vs ...Song (Major congenital malformations (MMI vs Unexposed sick)) 1.75[1.22; 2.53]0%-U,Sunexposed, sickAnyduring pregnancy (anytime or not specified)studies TTT4 metaPregmetaPreg 1.78[1.18; 2.69]8%1,852----Gianetti (control unexposed, sick), 2015 Yoshihara (control unexposed, sick), 2012 Banhidy, 2011 Di Gianantonio, 2001 Dwarakanath (control exposed to PTU), 1999 Wing (control unexposed, sick), 1994 Momotani, 1984 70.510.01.0