Carbimazole, Thiamazole (Methimazole)

Carbimazole embryopathy

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.
S3446
R6435		 Andersen (control unexposed, disease free), 2019 Carbimazole embryopathy (aplasia cutis, esophageal atresia, choanal atresia, and omphalocele) early pregnancy population based cohort retrospective unexposed, disease free Adjustment: Yes 20.00 [12.00;34.00] -/1,574   -/1,159,181 - 1,574
ref
S3364
R6138		 Seo (control exposed to PTU), 2018 MMI embryopathy (at least 1 of the following diagnoses: choanal atresia, esophageal atresia, omphalocele, omphalomesenteric duct anomaly, or aplasia cutis) 1st trimester retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: No 5.95 [2.43;14.58] C
excluded (control group) 		8/1,120   12/9,930 20 1,120
ref
S3365
R6150		 Seo (control unexposed, NOS), 2018 MMI embryopathy (at least 1 of the following diagnoses: choanal atresia, esophageal atresia, omphalocele, omphalomesenteric duct anomaly, or aplasia cutis) 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: Yes 9.27 [4.62;18.63] 8/1,120   2,019/2,872,109 2,027 1,120
ref
S3353
R8732		 Yoshihara (control exposed to PTU), 2012 MMI/CMZ embryopathy (at least 1 of following malfo: choanal atresia, esophageal atresia, omphalocele or aplasia cutis) 1st trimester retrospective cohort exposed to other treatment, sick excluded Adjustment: No 33.34 [1.99;559.48] C
excluded (control group) 		14/1,231   0/1,399 14 1,231
ref
S3350
R8733		 Yoshihara (control unexposed, sick), 2012 MMI/CMZ embryopathy (at least 1 of following malfo: choanal atresia, esophageal atresia, omphalocele or aplasia cutis) 1st trimester retrospective cohort unexposed, sick Adjustment: No 45.42 [2.71;762.21] C 14/1,231   0/1,906 14 1,231
ref
S3379
R8736		 Clementi, 2010 Choanal atresia or omphalocele (as a part of Carbimazole embryopathy) 1st trimester case control unexposed (general population or NOS) Adjustment: No 11.85 [6.16;22.81] C 10/160   202/36,102 212 160
ref
S3357
R8724		 Barbero, 2008 Choanal atresia (as a part of Carbimazole embryopathy) 1st trimester case control unexposed, disease free Adjustment: No 17.75 [3.49;121.40] 10/12   51/232 61 12
ref
S3396
R6344		 Di Gianantonio, 2001 MMI embryopathy (i.e., choanal atresia or esophageal atresia) 1st trimester prospective cohort unexposed, disease free Adjustment: No 27.01 [1.29;564.73] C 2/204   0/1,089 2 204
ref
Total 6 studies 14.62 [10.40;20.55] 2,316 4,301
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 Andersen (control unexposed, disease free), 2019Andersen, 2019 1 20.00[12.00; 34.00]-1,57443%ROB confusion: seriousROB selection: moderateROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Seo (control unexposed, NOS), 2018Seo, 2018 2 9.27[4.62; 18.63]2,0271,12024%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Yoshihara (control unexposed, sick), 2012Yoshihara, 2012 3 45.42[2.71; 762.21]141,2311%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: lowROB mesure: criticalROB reporting: moderate Clementi, 2010Clementi, 2010 11.85[6.16; 22.81]21216027%ROB confusion: criticalROB selection: criticalROB classification: unclearROB missing: unclearROB mesure: criticalROB reporting: critical Barbero, 2008Barbero, 2008 17.75[3.49; 121.40]61124%ROB confusion: seriousROB selection: criticalROB classification: criticalROB missing: criticalROB mesure: criticalROB reporting: moderate Di Gianantonio, 2001Di Gianantonio, 2001 27.01[1.29; 564.73]22041%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: moderateROB mesure: criticalROB reporting: moderate Total (6 studies) I2 = 0% 14.62[10.40; 20.55]2,3164,3010.9100.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: control unexposed, disease free; 2: control unexposed, NOS; 3: control unexposed, sick;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 15.42[9.11; 26.09]2,0434,12919%NAAndersen (control unexposed, disease free), 2019 Seo (control unexposed, NOS), 2018 Yoshihara (control unexposed, sick), 2012 Di Gianantonio, 2001 4 case control studiescase control studies 12.44[6.73; 22.99]2731720%NAClementi, 2010 Barbero, 2008 2 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 14.37[10.20; 20.26]2,3023,0700%NAAndersen (control unexposed, disease free), 2019 Seo (control unexposed, NOS), 2018 Clementi, 2010 Barbero, 2008 Di Gianantonio, 2001 5 unexposed, sickunexposed, sick 45.42[2.71; 762.21]141,231 -NAYoshihara (control unexposed, sick), 2012 1 Tags Adjustment   - No  - No 13.55[7.52; 24.41]2891,6070%NAYoshihara (control unexposed, sick), 2012 Clementi, 2010 Barbero, 2008 Di Gianantonio, 2001 4   - Yes  - Yes 14.12[6.67; 29.90]2,0272,69467%NAAndersen (control unexposed, disease free), 2019 Seo (control unexposed, NOS), 2018 2 All studiesAll studies 14.62[10.40; 20.55]2,3164,3010%NAAndersen (control unexposed, disease free), 2019 Seo (control unexposed, NOS), 2018 Yoshihara (control unexposed, sick), 2012 Clementi, 2010 Barbero, 2008 Di Gianantonio, 2001 60.5100.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-4.66.31.8610.000Andersen (control unexposed, disease free), 2019Seo (control unexposed, NOS), 2018Yoshihara (control unexposed, sick), 2012Clementi, 2010Barbero, 2008Di Gianantonio, 2001

Asymetry test p-value = 0.6287 (by Egger's regression)

slope=2.5350 (0.3307); intercept=0.4064 (0.7772); t=0.5228; p=0.6287

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 3353, 3364

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) Out of scale14.37[10.20; 20.26]2,3023,0700%NAAndersen (control unexposed, disease free), 2019 Seo (control unexposed, NOS), 2018 Clementi, 2010 Barbero, 2008 Di Gianantonio, 2001 5 unexposed, sick controlsunexposed, sick controls Out of scale45.42[2.71; 762.21]141,231 -NAYoshihara (control unexposed, sick), 2012 1 exposed to other treatment, sick controlsexposed to other treatment, sick controls 8.21[2.20; 30.64]342,35123%NASeo (control exposed to PTU), 2018 Yoshihara (control exposed to PTU), 2012 20.510.01.0