Hydroxychloroquine (All indications except Antiphospholipid Syndrom)

Early intrauterine death (< 22 weeks)

id	Study   Auto Chambers (Controls unexposed, disease free), 2022Chambers (Controls unexposed, sick), 2022Canti, 2021Abd Rahman, 2020Mollerach, 2019Seo, 2019Kroese, 2017Diav-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 R52922	Chambers (Controls unexposed, disease free), 2022	Spontaneous abortions (<20.0 gestational weeks)	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	0.77 [0.28;2.14] excluded (control group)	8/193   7/196	15	193		ref
S13649 R52938	Chambers (Controls unexposed, sick), 2022	Spontaneous abortions (<20.0 gestational weeks)	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	1.09 [0.41;2.91]	8/193   8/211	16	193		ref
S13769 R53861	Canti, 2021	Early miscarriage (< 24 GW)	throughout pregnancy	prospective cohort	unexposed, sick	Adjustment: No Indication HCQ: Systemic lupus erythematosus (SLE)	0.96 [0.25;3.75] C	6/45   4/29	10	45		ref
S13707 R53367	Abd Rahman, 2020	Miscarriage (< 24 weeks)	during pregnancy (anytime or not specified)	retrospective cohort	unexposed, sick	Adjustment: No Indication HCQ: Systemic lupus erythematosus (SLE)	1.08 [0.37;3.19] C	10/47   7/35	17	47		ref
S13713 R53407	Mollerach, 2019	Abortion	throughout pregnancy	retrospective cohort	unexposed, sick	Adjustment: No Indication HCQ: Rheumatic diseases as a whole (Systemic lupus erythematosus, Rheumatoid arthritis, Sjogren's syndrome...)	3.83 [0.49;30.09] C	2/14   2/48	4	14		ref
S13715 R53418	Seo, 2019	Spontaneous abortion (before 20 weeks’ gestation)	throughout pregnancy	retrospective cohort	unexposed, sick	Adjustment: No Indication HCQ: Systemic lupus erythematosus (SLE)	0.88 [0.21;3.66] C	4/80   4/71	8	80		ref
S13699 R53331	Kroese, 2017	Early spontaneous abortion (<10 weeks of gestation)	during pregnancy (anytime or not specified)	retrospective cohort	unexposed, sick	Adjustment: Yes Indication HCQ: Systemic lupus erythematosus (SLE)	1.50 [0.30;9.00]	9/30   10/80	19	30		ref
S13679 R53148	Diav-Citrin, 2013	Miscarriage	at least 1st trimester	prospective cohort	unexposed (general population or NOS)	Adjustment: Yes Indication HCQ: Rheumatic diseases as a whole (Systemic lupus erythematosus, Rheumatoid arthritis, Sjogren's syndrome...)	1.35 [0.61;2.97]	13/115   24/455	37	115		ref
S13700 R53337	Al Arfaj, 2010	Miscarriage	during pregnancy (anytime or not specified)	retrospective cohort	unexposed, sick	Adjustment: No Indication HCQ: Systemic lupus erythematosus (SLE)	2.42 [1.32;4.46] C	23/69   38/222	61	69		ref
S13650 R52951	Clowse, 2006	Miscarriage (prior to 20 weeks’ gestation)	throughout pregnancy	prospective cohort	unexposed, sick	Adjustment: No Indication HCQ: Systemic lupus erythematosus (SLE)	3.45 [1.10;10.80] C	7/52   6/139	13	52		ref
S13702 R53356	Chakravarty, 2005	Spontaneous abortion during the first trimester	during pregnancy (anytime or not specified)	retrospective cohort	unexposed, sick	Adjustment: No Indication HCQ: Systemic lupus erythematosus (SLE)	0.27 [0.01;5.09] C	0/13   6/50	6	13		ref
S13671 R53113	Tincani, 2005	Spontaneous abortion (NOS)	during pregnancy (anytime or not specified)	prospective cohort	unexposed, sick	Adjustment: No Indication HCQ: Connective tissue diseases (CTD)	1.05 [0.21;5.39] C	3/76   3/80	6	76		ref
S13653 R53019	Costedoat-Chalumeau, 2003	Spontaneous abortion (prior to 20 weeks’ gestation)	throughout pregnancy	prospective cohort	unexposed, sick	Adjustment: No Indication HCQ: Any or not specified	1.14 [0.44;2.95] C	15/133   7/70	22	133		ref
S13701 R53345	Buchanan, 1996	Spontaneous abortion (< 12 weeks gestation)	during pregnancy (anytime or not specified)	retrospective cohort	unexposed, sick	Adjustment: No Indication HCQ: Systemic lupus erythematosus (SLE)	0.72 [0.12;4.16] C	2/36   4/53	6	36		ref
					Total	13 studies	1.50 [1.10;2.04]		225	903
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 13648

Umbrella review (other published meta-analyses)