Carbimazole, Thiamazole (Methimazole)

Limb defects

R analysis

id	Study	Lib. in paper	Exposition period	Study type All studies Case control excluded Only case control	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

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

Sensitivity analysis

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

S3447 R6446	Andersen (control exposed to PTU), 2019	Musculoskeletal system (Q65-78) (80)	early pregnancy	exposed to other treatment, sick	0.73 [0.44;1.23]	34/1574 26/889
S3446 R6431	Andersen (control unexposed, disease free), 2019	Musculoskeletal system (Q65-78) (80)	early pregnancy	unexposed, disease free	0.85 [0.61;1.20]	34/1574 29260/1159181
S3364 R6136	Seo (control exposed to PTU), 2018	Musculoskeletal system (Q65–Q79) (80)	1st trimester	exposed to other treatment, sick	0.77 [0.46;1.26]	17/1120 196/9930
S3365 R6148	Seo (control unexposed, NOS), 2018	Musculoskeletal system (Q65–Q79) (80)	1st trimester	unexposed (general population or NOS)	0.89 [0.55;1.44]	17/1120 45188/2872109
S3337 R5710	Andersen 2017 (control exposed to PTU), 2017	Musculoskeletal system (80)	early pregnancy	exposed to other treatment, sick	0.67 [0.12;3.70]	2/162 4/218
S3335 R5675	Andersen 2017 (control unexposed, disease free), 2017	Musculoskeletal system (80)	early pregnancy	unexposed, disease free	0.58 [0.14;2.35]	2/162 14310/682343
S3336 R5689	Andersen 2017 (control unexposed, sick), 2017	Musculoskeletal system (80)	early pregnancy	unexposed, sick	0.59 [0.14;2.50]	2/162 32/1551
S3386 R6305	Korelitz (control exposed to PTU), 2013	Certain congenital musculoskeletal deformities (80)	3 months (or more) before pregnancy or during pregnancy	exposed to other treatment, sick	0.85 [0.11;6.67]	1/108 10/915
S3384 R6289	Korelitz (control unexposed, disease free), 2013	Certain congenital musculoskeletal deformities (80)	3 months (or more) before pregnancy or during pregnancy	unexposed, disease free	0.79 [0.11;5.65]	1/108 7432/634858
S3385 R6297	Korelitz (control unexposed, sick), 2013	Certain congenital musculoskeletal deformities (80)	3 months (or more) before pregnancy or during pregnancy	unexposed, sick	0.85 [0.12;6.30]	1/108 35/3236