Carbimazole, Thiamazole (Methimazole)

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.
S8483
R27807		 Yoshihara (Controls exposed to PTU), 2021 Birth defects 1st trimester retrospective cohort exposed to other treatment, sick excluded Adjustment: No 0.37 [0.02;6.28] C
excluded (control group) 		0/23   30/541 30 23
ref
S8482
R27785		 Yoshihara (Controls unexposed, sick), 2021 Birth defects 1st trimester retrospective cohort unexposed, sick Adjustment: No 0.36 [0.02;6.12] C 0/23   27/475 27 23
ref
S3447
R6436		 Andersen (control exposed to PTU), 2019 All birth defects (ICD-10: Q00-99) early pregnancy population based cohort retrospective exposed to other treatment, sick excluded Adjustment: No 1.17 [0.87;1.56] C
excluded (control group) 		151/1,574   74/889 225 1,574
ref
S3446
R6421		 Andersen (control unexposed, disease free), 2019 All birth defects (ICD-10: Q00-99) early pregnancy population based cohort retrospective unexposed, disease free Adjustment: Yes 1.41 [1.19;1.67] 151/1,574   77,791/1,159,181 77,942 1,574
ref
S3364
R6127		 Seo (control exposed to PTU), 2018 Overall congenital malformations (Q00 to Q99) 1st trimester retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: No 1.17 [0.93;1.47] C
excluded (control group) 		91/1,120   699/9,930 790 1,120
ref
S3365
R6139		 Seo (control unexposed, NOS), 2018 Overall congenital malformations (Q00 to Q99) 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: Yes 1.31 [1.06;1.63] 91/1,120   170,716/2,872,109 170,807 1,120
ref
S3337
R5700		 Andersen 2017 (control exposed to PTU), 2017 Birth defects (ICD­10: Q00-­Q99) early pregnancy population based cohort retrospective exposed to other treatment, sick excluded Adjustment: No 1.06 [0.47;2.40] C
excluded (control group) 		11/162   14/218 25 162
ref
S3335
R5665		 Andersen 2017 (control unexposed, disease free), 2017 Birth defects (ICD­10: Q00-Q99) early pregnancy population based cohort retrospective unexposed, disease free excluded Adjustment: Yes 0.72 [0.37;1.41]
excluded (control group) 		11/162   54,827/682,343 54,838 162
ref
S3336
R5679		 Andersen 2017 (control unexposed, sick), 2017 Birth defects (ICD­10: Q00-­Q99) early pregnancy population based cohort retrospective unexposed, sick Adjustment: No 0.76 [0.40;1.43] C 11/162   136/1,551 147 162
ref
S3421
R6369		 Hawken (control exposed to PTU), 2016 Malformations 1st trimester retrospective cohort exposed to other treatment, sick Adjustment: No 7.76 [0.38;158.69] C 4/19   0/13 4 19
ref
S3563
R11293		 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
R11294		 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
S3376
R6250		 Lo (control exposed to PTU), 2015 Congenital anomalies (ICD-9) during pregnancy (anytime or not specified) retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: No 1.13 [0.14;8.86] C
excluded (control group) 		1/30   15/507 16 30
ref
S3372
R6194		 Lo (control unexposed, sick), 2015 Congenital anomalies (ICD-9) during pregnancy (anytime or not specified) excluded retrospective cohort (claims database) unexposed, sick Adjustment: No 0.74 [0.10;5.55] C
excluded (exposition period) 		1/30   52/1,171 53 30
ref
S3386
R6306		 Korelitz (control exposed to PTU), 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 0.76 [0.32;1.79] C
excluded (control group) 		6/108   66/915 72 108
ref
S3384
R6290		 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 0.93 [0.41;2.11]
excluded (control group) 		6/108   37,351/634,858 37,357 108
ref
S3385
R6298		 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 0.87 [0.38;2.01] C
excluded (exposition period) 		6/108   205/3,236 211 108
ref
S3353
R11299		 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
R11300		 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
R35109		 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
R11288		 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
R11289		 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
R11290		 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
S3426
R6371		 Azizi, 2002 Congenital malformations throughout pregnancy retrospective cohort unexposed (general population or NOS) Adjustment: No Matched 1.31 [0.03;68.65] C 0/23   0/30 0 23
ref
S3396
R11291		 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
R11292		 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
R11297		 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
R11298		 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
R11295		 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
R11296		 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 13 studies 1.40 [1.14;1.72] 249,132 4,773
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 0.36[0.02; 6.12]27231%ROB confusion: criticalROB selection: moderateROB classification: unclearROB missing: unclearROB mesure: criticalROB reporting: moderate Andersen (control unexposed, disease free), 2019Andersen, 2019 2 1.41[1.19; 1.67]77,9421,57434%ROB confusion: seriousROB selection: moderateROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Seo (control unexposed, NOS), 2018Seo, 2018 3 1.31[1.06; 1.63]170,8071,12030%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Andersen 2017 (control unexposed, sick), 2017Andersen 2017, 2017 4 0.76[0.40; 1.43]1471628%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Hawken (control exposed to PTU), 2016Hawken, 2016 5 7.76[0.38; 158.69]4190%ROB confusion: criticalROB selection: criticalROB classification: unclearROB missing: lowROB mesure: criticalROB reporting: unclear Gianetti (control unexposed, sick), 2015Gianetti, 2015 6 0.18[0.01; 3.35]41240%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: lowROB mesure: criticalROB reporting: unclear Yoshihara (control unexposed, sick), 2012Yoshihara, 2012 7 2.28[1.54; 3.33]901,23117%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: lowROB mesure: criticalROB reporting: moderate Banhidy, 2011Banhidy, 2011 0.81[0.14; 4.55]7161%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Azizi, 2002Azizi, 2002 1.31[0.03; 68.65]0230%ROB confusion: criticalROB selection: moderateROB classification: unclearROB missing: lowROB mesure: moderateROB reporting: moderate Di Gianantonio, 2001Di Gianantonio, 2001 1.89[0.83; 4.29]312046%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: moderateROB mesure: criticalROB reporting: moderate Dwarakanath (control exposed to PTU), 1999Dwarakanath, 1999 8 0.29[0.01; 8.39]180%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: lowROB mesure: unclearROB reporting: unclear Wing (control unexposed, sick), 1994Wing, 1994 9 1.20[0.07; 19.89]2361%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Momotani, 1984Momotani, 1984 0.82[0.15; 4.52]62431%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: lowROB mesure: criticalROB reporting: moderate Total (13 studies) I2 = 26% 1.40[1.14; 1.72]249,1324,7730.020.01.0ROB: 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 PTU; 6: control unexposed, sick; 7: control unexposed, sick; 8: control exposed to PTU; 9: control unexposed, sick;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.41[1.13; 1.75]249,0614,76731%NAYoshihara (Controls unexposed, sick), 2021 Andersen (control unexposed, disease free), 2019 Seo (control unexposed, NOS), 2018 Andersen 2017 (control unexposed, sick), 2017 Hawken (control exposed to PTU), 2016 Gianetti (control unexposed, sick), 2015 Yoshihara (control unexposed, sick), 2012 Azizi, 2002 Di Gianantonio, 2001 Dwarakanath (control exposed to PTU), 1999 Wing (control unexposed, sick), 1994 Momotani, 1984 12 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) 1.38[1.21; 1.58]248,7802,9210%NAAndersen (control unexposed, disease free), 2019 Seo (control unexposed, NOS), 2018 Azizi, 2002 Di Gianantonio, 2001 4 unexposed, sickunexposed, sick 1.02[0.51; 2.05]3471,82554%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 Momotani, 1984 7 exposed to other treatment, sickexposed to other treatment, sick 1.64[0.07; 40.94]52751%NAHawken (control exposed to PTU), 2016 Dwarakanath (control exposed to PTU), 1999 2 Tags Adjustment   - No  - No 0.99[0.64; 1.53]2938480%NAYoshihara (Controls unexposed, sick), 2021 Andersen 2017 (control unexposed, sick), 2017 Hawken (control exposed to PTU), 2016 Gianetti (control unexposed, sick), 2015 Banhidy, 2011 Azizi, 2002 Di Gianantonio, 2001 Dwarakanath (control exposed to PTU), 1999 Wing (control unexposed, sick), 1994 Momotani, 1984 10   - Yes  - Yes 1.53[1.20; 1.96]248,8393,92568%NAAndersen (control unexposed, disease free), 2019 Seo (control unexposed, NOS), 2018 Yoshihara (control unexposed, sick), 2012 3 MatchedMatched 1.31[0.03; 68.65]-23 -NAAzizi, 2002 1 All studiesAll studies 1.40[1.14; 1.72]249,1324,77326%NAYoshihara (Controls unexposed, sick), 2021 Andersen (control unexposed, disease free), 2019 Seo (control unexposed, NOS), 2018 Andersen 2017 (control unexposed, sick), 2017 Hawken (control exposed to PTU), 2016 Gianetti (control unexposed, sick), 2015 Yoshihara (control unexposed, sick), 2012 Banhidy, 2011 Azizi, 2002 Di Gianantonio, 2001 Dwarakanath (control exposed to PTU), 1999 Wing (control unexposed, sick), 1994 Momotani, 1984 130.020.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-4.75.12.4230.000Yoshihara (Controls unexposed, sick), 2021Andersen (control unexposed, disease free), 2019Seo (control unexposed, NOS), 2018Andersen 2017 (control unexposed, sick), 2017Hawken (control exposed to PTU), 2016Gianetti (control unexposed, sick), 2015Yoshihara (control unexposed, sick), 2012Banhidy, 2011Azizi, 2002Di Gianantonio, 2001Dwarakanath (control exposed to PTU), 1999Wing (control unexposed, sick), 1994Momotani, 1984

Asymetry test p-value = 0.3994 (by Egger's regression)

slope=0.3932 (0.0941); intercept=-0.3708 (0.4230); t=0.8766; p=0.3994

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 3392, 3345, 3343, 3353, 3386, 3384, 3563, 3376, 3337, 3335, 3364, 3447, 8483

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.34[1.16; 1.55]303,6183,0839%NAAndersen (control unexposed, disease free), 2019 Seo (control unexposed, NOS), 2018 Andersen 2017 (control unexposed, disease free), 2017 Azizi, 2002 Di Gianantonio, 2001 5 unexposed, sick controlsunexposed, sick controls 1.02[0.51; 2.05]3471,82554%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 Momotani, 1984 7 exposed to other treatment, sick controlsexposed to other treatment, sick controls 1.30[0.95; 1.78]1,1544,29741%NAYoshihara (Controls exposed to PTU), 2021 Andersen (control exposed to PTU), 2019 Seo (control exposed to PTU), 2018 Andersen 2017 (control exposed to PTU), 2017 Hawken (control exposed to PTU), 2016 Gianetti (control exposed to PTU), 2015 Yoshihara (control exposed to PTU), 2012 Dwarakanath (control exposed to PTU), 1999 Wing (control exposed to PTU), 1994 90.510.01.0

Umbrella review (other published meta-analyses)

Published MAControlPeriodTE95% CIn exposedkI2 Morales (Birth defects (compared to all unexp ...Morales (Birth defects (compared to all unexposed women - all studies)) 1.64[1.39; 1.92]35%-U,GPunexposed (general population or NOS)Anyduring pregnancy (anytime or not specified)studies TTT7 Morales (Birth defects (compared to all unexp ...Morales (Birth defects (compared to all unexposed women - only adjusted studies)) 1.28[1.06; 1.54]33%-U,GPunexposed (general population or NOS)Anyduring pregnancy (anytime or not specified)studies TTT4 Morales (Birth defects (compared to all unexp ...Morales (Birth defects (compared to all unexposed women - only adjusted studies)) 1.29[1.05; 1.59]-U,GPunexposed (general population or NOS)T11st trimesterstudies TTT3 Li 2015b (Congenital anomalies (all studies))Li 2015b (Congenital anomalies (all studies)) 1.64[1.39; 1.92]35%-Wwhatever (meta-analysis)Anyduring pregnancy (anytime or not specified)studies TTT7 Li 2015a (Congenital malformations (MMI vs PTU))Li 2015a (Congenital malformations (MMI vs PTU)) 1.37[1.04; 1.79]42%-Eexposed to other treatment, sickAnyduring pregnancy (anytime or not specified)studies TTT5 Li 2015a (Congenital malformations (MMI vs un ...Li 2015a (Congenital malformations (MMI vs unexposed sick)) 1.71[1.39; 2.10]0%-U,Sunexposed, sickAnyduring pregnancy (anytime or not specified)studies TTT5 Song (Neonatal congenital malformations (MMI ...Song (Neonatal congenital malformations (MMI vs Healthy control)) 1.61[1.32; 1.97]1%-U,DFunexposed, disease freeAnyduring pregnancy (anytime or not specified)studies TTT4 Song (Neonatal congenital malformations (MMI ...Song (Neonatal congenital malformations (MMI vs Unexposed sick)) 1.88[1.33; 2.65]41%-U,Sunexposed, sickAnyduring pregnancy (anytime or not specified)studies TTT6 Song (Neonatal congenital malformations (MMI ...Song (Neonatal congenital malformations (MMI vs Unexposed sick)) 1.72[1.41; 2.09]40%-U,Sunexposed, sickAnyduring pregnancy (anytime or not specified)studies TTT8 metaPregmetaPreg 1.40[1.14; 1.72]26%4,773----Yoshihara (Controls unexposed, sick), 2021 Andersen (control unexposed, disease free), 2019 Seo (control unexposed, NOS), 2018 Andersen 2017 (control unexposed, sick), 2017 Hawken (control exposed to PTU), 2016 Gianetti (control unexposed, sick), 2015 Yoshihara (control unexposed, sick), 2012 Banhidy, 2011 Azizi, 2002 Di Gianantonio, 2001 Dwarakanath (control exposed to PTU), 1999 Wing (control unexposed, sick), 1994 Momotani, 1984 130.510.01.0