Carbimazole, Thiamazole (Methimazole)

Limb defects

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.
S3447
R6446
Andersen (control exposed to PTU), 2019 Musculoskeletal system (Q65-78) early pregnancy population based cohort retrospective exposed to other treatment, sick excluded Adjustment: No 0.73 [0.44;1.23] C
excluded (control group)
34/1,574   26/889 60 1,574
ref
S3446
R6431
Andersen (control unexposed, disease free), 2019 Musculoskeletal system (Q65-78) early pregnancy population based cohort retrospective unexposed, disease free Adjustment: No 0.85 [0.61;1.20] C 34/1,574   29,260/1,159,181 29,294 1,574
ref
S3364
R6136
Seo (control exposed to PTU), 2018 Musculoskeletal system (Q65–Q79) 1st trimester retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: No 0.77 [0.46;1.26] C
excluded (control group)
17/1,120   196/9,930 213 1,120
ref
S3365
R6148
Seo (control unexposed, NOS), 2018 Musculoskeletal system (Q65–Q79) 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: Yes 0.89 [0.55;1.44] 17/1,120   45,188/2,872,109 45,205 1,120
ref
S3337
R5710
Andersen 2017 (control exposed to PTU), 2017 Musculoskeletal system early pregnancy population based cohort retrospective exposed to other treatment, sick excluded Adjustment: No 0.67 [0.12;3.70] C
excluded (control group)
2/162   4/218 6 162
ref
S3335
R5675
Andersen 2017 (control unexposed, disease free), 2017 Musculoskeletal system early pregnancy population based cohort retrospective unexposed, disease free excluded Adjustment: No 0.58 [0.14;2.35] C
excluded (control group)
2/162   14,310/682,343 14,312 162
ref
S3336
R5689
Andersen 2017 (control unexposed, sick), 2017 Musculoskeletal system early pregnancy population based cohort retrospective unexposed, sick Adjustment: No 0.59 [0.14;2.50] C 2/162   32/1,551 34 162
ref
S3386
R6305
Korelitz (control exposed to PTU), 2013 Certain congenital musculoskeletal deformities 3 months (or more) before pregnancy or during pregnancy retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: No 0.85 [0.11;6.67] C
excluded (control group)
1/108   10/915 11 108
ref
S3384
R6289
Korelitz (control unexposed, disease free), 2013 Certain congenital musculoskeletal deformities 3 months (or more) before pregnancy or during pregnancy retrospective cohort (claims database) unexposed, disease free excluded Adjustment: No 0.79 [0.11;5.65] C
excluded (control group)
1/108   7,432/634,858 7,433 108
ref
S3385
R6297
Korelitz (control unexposed, sick), 2013 Certain congenital musculoskeletal deformities 3 months (or more) before pregnancy or during pregnancy excluded retrospective cohort (claims database) unexposed, sick Adjustment: No 0.85 [0.12;6.30] C
excluded (exposition period)
1/108   35/3,236 36 108
ref
Total 3 studies 0.85 [0.65;1.12] 74,533 2,856
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 0.85[0.61; 1.20]29,2941,57464%ROB confusion: seriousROB selection: moderateROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Seo (control unexposed, NOS), 2018Seo, 2018 2 0.89[0.55; 1.44]45,2051,12032%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Andersen 2017 (control unexposed, sick), 2017Andersen 2017, 2017 3 0.59[0.14; 2.50]341624%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Total (3 studies) I2 = 0% 0.85[0.65; 1.12]74,5332,8560.22.01.0ROB: 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 0.85[0.65; 1.12]74,5332,8560%NAAndersen (control unexposed, disease free), 2019 Seo (control unexposed, NOS), 2018 Andersen 2017 (control unexposed, sick), 2017 3 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 0.86[0.66; 1.14]74,4992,6940%NAAndersen (control unexposed, disease free), 2019 Seo (control unexposed, NOS), 2018 2 unexposed, sickunexposed, sick 0.59[0.14; 2.50]34162 -NAAndersen 2017 (control unexposed, sick), 2017 1 Tags Adjustment   - No  - No 0.84[0.60; 1.16]29,3281,7360%NAAndersen (control unexposed, disease free), 2019 Andersen 2017 (control unexposed, sick), 2017 2   - Yes  - Yes 0.89[0.55; 1.44]45,2051,120 -NASeo (control unexposed, NOS), 2018 1 All studiesAll studies 0.85[0.65; 1.12]74,5332,8560%NAAndersen (control unexposed, disease free), 2019 Seo (control unexposed, NOS), 2018 Andersen 2017 (control unexposed, sick), 2017 30.210.01.0

Publication bias and p-hacking diagnosis

funnel plot

Funnel plot not drawn. Less than 3 points.

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

not enought points

p values plot

Funnel plot not drawn. Less than 3 points.

Sub-groups analysis using all included studies

excluded 3386, 3384, 3337, 3335, 3364, 3447

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 0.85[0.65; 1.12]88,8112,8560%NAAndersen (control unexposed, disease free), 2019 Seo (control unexposed, NOS), 2018 Andersen 2017 (control unexposed, disease free), 2017 3 unexposed, sick controlsunexposed, sick controls 0.59[0.14; 2.50]34162 -NAAndersen 2017 (control unexposed, sick), 2017 1 exposed to other treatment, sick controlsexposed to other treatment, sick controls 0.75[0.52; 1.06]2792,8560%NAAndersen (control exposed to PTU), 2019 Seo (control exposed to PTU), 2018 Andersen 2017 (control exposed to PTU), 2017 30.510.01.0