Thiouracil, propylthiouracil, benzylthiouracil

Limb defects

id	Study   Auto Andersen 2019 (control exposed to MMI/CMZ), 2019Andersen 2019 (control unexposed, disease free), 2019Seo (control exposed to MMI), 2018Seo (control unexposed, NOS), 2018Andersen 2017 (control exposed to MMI/CMZ), 2017Andersen 2017 (control unexposed, disease free), 2017Andersen 2017 (control unexposed, sick), 2017Korelitz (control exposed to MMI), 2013Korelitz (control exposed to MMI), 2013Korelitz (control unexposed, disease free), 2013Korelitz (control unexposed, sick), 2013	Lib. in paper	Exposition period  Auto during pregnancy (anytime or not specified)1st trimester2nd trimester3rd trimester2nd and/or 3rd trimesterthroughout pregnancyearly pregnancydays before deliverylate pregnancypreconception-onlypericonceptionalpreconceptional for kinetic reasonat least 1st trimester3 months (or more) before pregnancy or during pregnancy1st and 2nd trimester3 months or more before pregnancy or1st trimester	Study type  All studies Case control excluded Only case control	Control type    Auto unexposed (general population or NOS)unexposed, sickunexposed, disease freeexposed to other treatment, sicknot specifiedsiblingwhatever (meta-analysis)	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

Sensitivity analysis

Publication bias and p-hacking diagnosis

Sub-groups analysis using all included studies

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