Thiouracil, propylthiouracil, benzylthiouracil

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.
S3448
R6461
Andersen 2019 (control exposed to MMI/CMZ), 2019 Musculoskeletal system (Q65-78) early pregnancy population based cohort retrospective exposed to other treatment, sick excluded Adjustment: No 1.36 [0.81;2.29] C
excluded (control group)
26/889   34/1,574 60 889
ref
S3449
R6476
Andersen 2019 (control unexposed, disease free), 2019 Musculoskeletal system (Q65-78) early pregnancy population based cohort retrospective unexposed, disease free Adjustment: No 1.16 [0.79;1.72] C 26/889   29,260/1,159,181 29,286 889
ref
S3366
R6160
Seo (control exposed to MMI), 2018 Musculoskeletal system (Q65–Q79) 1st trimester retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: No 1.31 [0.79;2.15] C
excluded (control group)
196/9,930   17/1,120 213 9,930
ref
S3367
R6172
Seo (control unexposed, NOS), 2018 Musculoskeletal system (Q65–Q79) 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: Yes 1.21 [1.05;1.39] 196/9,930   45,188/2,872,109 45,384 9,930
ref
S3340
R5761
Andersen 2017 (control exposed to MMI/CMZ), 2017 Musculoskeletal system early pregnancy population based cohort retrospective exposed to other treatment, sick excluded Adjustment: No 1.50 [0.27;8.27] C
excluded (control group)
4/218   2/162 6 218
ref
S3339
R5744
Andersen 2017 (control unexposed, disease free), 2017 Musculoskeletal system early pregnancy population based cohort retrospective unexposed, disease free excluded Adjustment: No 0.87 [0.32;2.35] C
excluded (control group)
4/218   14,310/682,343 14,314 218
ref
S3338
R5727
Andersen 2017 (control unexposed, sick), 2017 Musculoskeletal system early pregnancy population based cohort retrospective unexposed, sick Adjustment: No 0.89 [0.31;2.53] C 4/218   32/1,551 36 218
ref
S8718
R29464
Korelitz (control exposed to MMI), 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 1.18 [0.15;9.33] C
excluded (control group)
10/915   1/108 11 915
ref
S3387
R6313
Korelitz (control exposed to MMI), 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 1.18 [0.15;9.33] C
excluded (control group)
10/915   1/108 11 915
ref
S3388
R6321
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 0.93 [0.50;1.74] C
excluded (control group)
10/915   7,432/634,858 7,442 915
ref
S3389
R6329
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 1.01 [0.50;2.05] C
excluded (exposition period)
10/915   35/3,236 45 915
ref
Total 3 studies 1.20 [1.05;1.37] 74,706 11,037
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 2019 (control unexposed, disease free), 2019Andersen 2019, 2019 1 1.16[0.79; 1.72]29,28688911%ROB confusion: seriousROB selection: moderateROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Seo (control unexposed, NOS), 2018Seo, 2018 2 1.21[1.05; 1.39]45,3849,93087%ROB confusion: criticalROB selection: moderateROB classification: lowROB missing: lowROB mesure: moderateROB reporting: moderate Andersen 2017 (control unexposed, sick), 2017Andersen 2017, 2017 3 0.89[0.31; 2.53]362182%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Total (3 studies) I2 = 0% 1.20[1.05; 1.37]74,70611,0370.25.01.0ROB: 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 1.20[1.05; 1.37]74,70611,0370%NAAndersen 2019 (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) 1.20[1.06; 1.37]74,67010,8190%NAAndersen 2019 (control unexposed, disease free), 2019 Seo (control unexposed, NOS), 2018 2 unexposed, sickunexposed, sick 0.89[0.31; 2.53]36218 -NAAndersen 2017 (control unexposed, sick), 2017 1 Tags Adjustment   - No  - No 1.13[0.78; 1.62]29,3221,1070%NAAndersen 2019 (control unexposed, disease free), 2019 Andersen 2017 (control unexposed, sick), 2017 2   - Yes  - Yes 1.21[1.05; 1.39]45,3849,930 -NASeo (control unexposed, NOS), 2018 1 All studiesAll studies 1.20[1.05; 1.37]74,70611,0370%NAAndersen 2019 (control unexposed, disease free), 2019 Seo (control unexposed, NOS), 2018 Andersen 2017 (control unexposed, sick), 2017 30.25.01.0

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 8718, 3387, 3388, 3340, 3339, 3366, 3448

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.20[1.05; 1.37]88,98411,0370%NAAndersen 2019 (control unexposed, disease free), 2019 Seo (control unexposed, NOS), 2018 Andersen 2017 (control unexposed, disease free), 2017 3 unexposed, sick controlsunexposed, sick controls 0.89[0.31; 2.53]36218 -NAAndersen 2017 (control unexposed, sick), 2017 1 exposed to other treatment, sick controlsexposed to other treatment, sick controls 1.34[0.94; 1.91]27911,0370%NAAndersen 2019 (control exposed to MMI/CMZ), 2019 Seo (control exposed to MMI), 2018 Andersen 2017 (control exposed to MMI/CMZ), 2017 30.510.01.0