Hydroxychloroquine (All indications except Antiphospholipid Syndrom)

Late intrauterine deaths (> 22 weeks)

id	Study   Auto Chambers (Controls unexposed, disease free), 2022Chambers (Controls unexposed, sick), 2022Canti, 2021Abd Rahman, 2020Mollerach, 2019Seo, 2019Cooper (controls exposed to TNF-I), 2014Cooper (controls unexposed, sick), 2014Diav-Citrin, 2013Al Arfaj, 2010Clowse, 2006Chakravarty, 2005Tincani, 2005Costedoat-Chalumeau, 2003Buchanan, 1996	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 specifiedwhatever (meta-analysis)	Tags	OR 95%CI	x1/n1 x0/n0	no cases	no exposed	ROB	Ref.
S13648 R52925	Chambers (Controls unexposed, disease free), 2022	Stillbirth (> 20 weeks of gestation)	at least 1st trimester	prospective cohort	unexposed, disease free excluded	Adjustment: No Indication HCQ: Rheumatic diseases as a whole (Systemic lupus erythematosus, Rheumatoid arthritis, Sjogren's syndrome...) Matched	0.33 [0.01;8.19] C excluded (control group)	0/279   1/279	1	279		ref
S13649 R52941	Chambers (Controls unexposed, sick), 2022	Stillbirth (> 20 weeks of gestation)	at least 1st trimester	prospective cohort	unexposed, sick	Adjustment: No Indication HCQ: Rheumatic diseases as a whole (Systemic lupus erythematosus, Rheumatoid arthritis, Sjogren's syndrome...) Matched	1.00 [0.02;50.58] C	0/279   0/279	0	279		ref
S13769 R53862	Canti, 2021	Intrauterine death (> 24 GW)	throughout pregnancy	prospective cohort	unexposed, sick	Adjustment: No Indication HCQ: Systemic lupus erythematosus (SLE)	0.20 [0.01;5.20] C	0/39   1/25	1	39		ref
S13707 R53365	Abd Rahman, 2020	Fetal loss >= 24 weeks	during pregnancy (anytime or not specified)	retrospective cohort	unexposed, sick	Adjustment: No Indication HCQ: Systemic lupus erythematosus (SLE)	0.72 [0.09;5.47]	2/47   2/35	4	47		ref
S13713 R53408	Mollerach, 2019	Fetal death (NOS)	throughout pregnancy	retrospective cohort	unexposed, sick	Adjustment: No Indication HCQ: Rheumatic diseases as a whole (Systemic lupus erythematosus, Rheumatoid arthritis, Sjogren's syndrome...)	1.15 [0.04;29.83] C	0/14   1/48	1	14		ref
S13715 R53419	Seo, 2019	Stillbirth (after 20 weeks’ gestation)	throughout pregnancy	retrospective cohort	unexposed, sick	Adjustment: No Indication HCQ: Systemic lupus erythematosus (SLE)	1.19 [0.26;5.52] C	4/80   3/71	7	80		ref
S13651 R52960	Cooper (controls exposed to TNF-I), 2014	Fetal death (mean 34.5 weeks)	1st trimester	retrospective cohort (claims database)	exposed to other treatment, sick excluded	Adjustment: No Indication HCQ: Rheumatic diseases as a whole (Systemic lupus erythematosus, Rheumatoid arthritis, Sjogren's syndrome...)	1.45 [0.07;30.63] C excluded (control group)	2/194   0/56	2	194		ref
S13652 R52990	Cooper (controls unexposed, sick), 2014	Fetal death (mean 34.5 weeks)	1st trimester	retrospective cohort (claims database)	unexposed, sick	Adjustment: Yes Indication HCQ: Rheumatic diseases as a whole (Systemic lupus erythematosus, Rheumatoid arthritis, Sjogren's syndrome...)	0.35 [0.05;2.44]	2/194   4/171	6	194		ref
S13679 R53156	Diav-Citrin, 2013	Stillbirth	at least 1st trimester	prospective cohort	unexposed (general population or NOS)	Adjustment: No Indication HCQ: Rheumatic diseases as a whole (Systemic lupus erythematosus, Rheumatoid arthritis, Sjogren's syndrome...)	0.99 [0.11;8.93] C	1/115   4/455	5	115		ref
S13700 R53338	Al Arfaj, 2010	Stillbirth (> 24 weeks of gestation)	during pregnancy (anytime or not specified)	retrospective cohort	unexposed, sick	Adjustment: No Indication HCQ: Systemic lupus erythematosus (SLE)	0.28 [0.04;2.23] C	1/69   11/222	12	69		ref
S13650 R52952	Clowse, 2006	Stillbirth (pregnancy loss after 20 weeks)	throughout pregnancy	prospective cohort	unexposed, sick	Adjustment: No Indication HCQ: Systemic lupus erythematosus (SLE)	0.72 [0.20;2.65] C	3/49   13/157	16	49		ref
S13702 R53357	Chakravarty, 2005	Second or third trimester pregnancy losses	during pregnancy (anytime or not specified)	retrospective cohort	unexposed, sick	Adjustment: No Indication HCQ: Systemic lupus erythematosus (SLE)	3.96 [0.07;209.57] C	0/13   0/50	0	13		ref
S13671 R53115	Tincani, 2005	Fetal deaths	during pregnancy (anytime or not specified)	prospective cohort	unexposed, sick	Adjustment: No Indication HCQ: Connective tissue diseases (CTD)	5.41 [0.26;114.53] C	2/76   0/80	2	76		ref
S13653 R53020	Costedoat-Chalumeau, 2003	Fetal death (after 20 weeks’ gestation)	throughout pregnancy	prospective cohort	unexposed, sick	Adjustment: No Indication HCQ: Any or not specified	0.26 [0.02;2.89] C	1/133   2/70	3	133		ref
S13701 R53346	Buchanan, 1996	Fetal death (>= 12 weeks gestation)	during pregnancy (anytime or not specified)	retrospective cohort	unexposed, sick	Adjustment: No Indication HCQ: Systemic lupus erythematosus (SLE)	0.87 [0.20;3.91] C	3/36   5/53	8	36		ref
					Total	13 studies	0.73 [0.41;1.30]		65	1,144
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 13651, 13648

Umbrella review (other published meta-analyses)