Hydroxychloroquine (All indications except Antiphospholipid Syndrom)

Early intrauterine death (< 22 weeks)

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.
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

StudyTE95% CIn casesn exposedweightROBABCDEF Chambers (Controls unexposed, sick), 2022Chambers, 2022 1 1.09[0.41; 2.91]1619310%ROB confusion: seriousROB selection: moderateROB classification: moderateROB missing: lowROB mesure: criticalROB reporting: moderate Canti, 2021Canti, 2021 0.96[0.25; 3.75]10455%ROB confusion: seriousROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Abd Rahman, 2020Abd Rahman, 2020 1.08[0.37; 3.19]17478%ROB confusion: criticalROB selection: criticalROB classification: unclearROB missing: unclearROB mesure: unclearROB reporting: moderate Mollerach, 2019Mollerach, 2019 3.83[0.49; 30.09]4142%ROB confusion: criticalROB selection: lowROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Seo, 2019Seo, 2019 0.88[0.21; 3.66]8805%ROB confusion: seriousROB selection: lowROB classification: unclearROB missing: unclearROB mesure: moderateROB reporting: moderate Kroese, 2017Kroese, 2017 1.50[0.30; 9.00]19303%ROB confusion: criticalROB selection: lowROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Diav-Citrin, 2013Diav-Citrin, 2013 1.35[0.61; 2.97]3711515%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: lowROB mesure: criticalROB reporting: moderate Al Arfaj, 2010Al Arfaj, 2010 2.42[1.32; 4.46]616926%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Clowse, 2006Clowse, 2006 3.45[1.10; 10.80]13527%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Chakravarty, 2005Chakravarty, 2005 0.27[0.01; 5.09]6131%ROB confusion: criticalROB selection: lowROB classification: criticalROB missing: lowROB mesure: criticalROB reporting: moderate Tincani, 2005Tincani, 2005 1.05[0.21; 5.39]6764%ROB confusion: criticalROB selection: unclearROB classification: unclearROB missing: unclearROB mesure: moderateROB reporting: unclear Costedoat-Chalumeau, 2003Costedoat-Chalumeau, 2003 1.14[0.44; 2.95]2213311%ROB confusion: criticalROB selection: unclearROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Buchanan, 1996Buchanan, 1996 0.72[0.12; 4.16]6363%ROB confusion: criticalROB selection: unclearROB classification: criticalROB missing: unclearROB mesure: criticalROB reporting: moderate Total (13 studies) I2 = 0% 1.50[1.10; 2.04]2259030.210.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Controls unexposed, sick;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.50[1.10; 2.04]2259030%NAChambers (Controls unexposed, sick), 2022 Canti, 2021 Abd Rahman, 2020 Mollerach, 2019 Seo, 2019 Kroese, 2017 Diav-Citrin, 2013 Al Arfaj, 2010 Clowse, 2006 Chakravarty, 2005 Tincani, 2005 Costedoat-Chalumeau, 2003 Buchanan, 1996 13 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.35[0.61; 2.98]37115 -NADiav-Citrin, 2013 1 unexposed, sickunexposed, sick 1.53[1.09; 2.14]1887880%NAChambers (Controls unexposed, sick), 2022 Canti, 2021 Abd Rahman, 2020 Mollerach, 2019 Seo, 2019 Kroese, 2017 Al Arfaj, 2010 Clowse, 2006 Chakravarty, 2005 Tincani, 2005 Costedoat-Chalumeau, 2003 Buchanan, 1996 12 Tags Adjustment   - No  - No 1.53[1.09; 2.15]1697580%NAChambers (Controls unexposed, sick), 2022 Canti, 2021 Abd Rahman, 2020 Mollerach, 2019 Seo, 2019 Al Arfaj, 2010 Clowse, 2006 Chakravarty, 2005 Tincani, 2005 Costedoat-Chalumeau, 2003 Buchanan, 1996 11   - Yes  - Yes 1.38[0.67; 2.82]561450%NAKroese, 2017 Diav-Citrin, 2013 2 Indication HCQ   - Any or not specified  - Any or not specified 1.14[0.44; 2.95]22133 -NACostedoat-Chalumeau, 2003 1   - Connective tissue diseases (CTD)  - Connective tissue diseases (CTD) 1.05[0.21; 5.39]676 -NATincani, 2005 1   - Rheumatic diseases as a whole (Syst ...  - Rheumatic diseases as a whole (Systemic lupus erythematosus, Rheumatoid arthritis, Sjogren's syndrome...) 1.36[0.75; 2.45]573220%NAChambers (Controls unexposed, sick), 2022 Mollerach, 2019 Diav-Citrin, 2013 3   - Systemic lupus erythematosus (SLE)  - Systemic lupus erythematosus (SLE) 1.64[1.07; 2.51]1403725%NACanti, 2021 Abd Rahman, 2020 Seo, 2019 Kroese, 2017 Al Arfaj, 2010 Clowse, 2006 Chakravarty, 2005 Buchanan, 1996 8 MatchedMatched 1.09[0.41; 2.90]16193 -NAChambers (Controls unexposed, sick), 2022 1 All studiesAll studies 1.50[1.10; 2.04]2259030%NAChambers (Controls unexposed, sick), 2022 Canti, 2021 Abd Rahman, 2020 Mollerach, 2019 Seo, 2019 Kroese, 2017 Diav-Citrin, 2013 Al Arfaj, 2010 Clowse, 2006 Chakravarty, 2005 Tincani, 2005 Costedoat-Chalumeau, 2003 Buchanan, 1996 130.110.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-3.53.91.8030.000Chambers (Controls unexposed, sick), 2022Canti, 2021Abd Rahman, 2020Mollerach, 2019Seo, 2019Kroese, 2017Diav-Citrin, 2013Al Arfaj, 2010Clowse, 2006Chakravarty, 2005Tincani, 2005Costedoat-Chalumeau, 2003Buchanan, 1996

Asymetry test p-value = 0.1113 (by Egger's regression)

slope=0.9541 (0.3427); intercept=-1.0445 (0.6033); t=1.7314; p=0.1113

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 13648

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.09[0.58; 2.04]523080%NAChambers (Controls unexposed, disease free), 2022 Diav-Citrin, 2013 2 unexposed, sick controlsunexposed, sick controls 1.53[1.09; 2.14]1887880%NAChambers (Controls unexposed, sick), 2022 Canti, 2021 Abd Rahman, 2020 Mollerach, 2019 Seo, 2019 Kroese, 2017 Al Arfaj, 2010 Clowse, 2006 Chakravarty, 2005 Tincani, 2005 Costedoat-Chalumeau, 2003 Buchanan, 1996 120.510.01.0

Umbrella review (other published meta-analyses)

Published MAControlPeriodTE95% CIn exposedkI2 Duan (SLE indication) (Premature rupture of m ...Duan (SLE indication) (Premature rupture of membranes) 0.58[0.24; 1.39]0%-U,Sunexposed, sickAllthroughout pregnancystudies TTT2 Duan (SLE indication) (Spontaneous abortion)Duan (SLE indication) (Spontaneous abortion) 1.77[0.96; 3.26]35%-U,Sunexposed, sickAllthroughout pregnancystudies TTT5 Kaplan (All indications) (Spontaneous abortion)Kaplan (All indications) (Spontaneous abortion) 1.85[1.10; 3.13]13%-Wwhatever (meta-analysis)T1+at least 1st trimesterstudies TTT4 Kaplan (All indications) (Spontaneous abortio ...Kaplan (All indications) (Spontaneous abortion (after exclusion of pregnant women with antiphospholipid syndrome)) 1.77[1.09; 2.88]0%-Wwhatever (meta-analysis)T1+at least 1st trimesterstudies TTT4 Sperber (Autoimmune diseases) (Spontaneous ab ...Sperber (Autoimmune diseases) (Spontaneous abortions (< 20 weeks of gestation)) 0.92[0.49; 1.72]0%-Wwhatever (meta-analysis)Anyduring pregnancy (anytime or not specified)studies TTT4 metaPregmetaPreg 1.50[1.10; 2.04]0%903----Chambers (Controls unexposed, sick), 2022 Canti, 2021 Abd Rahman, 2020 Mollerach, 2019 Seo, 2019 Kroese, 2017 Diav-Citrin, 2013 Al Arfaj, 2010 Clowse, 2006 Chakravarty, 2005 Tincani, 2005 Costedoat-Chalumeau, 2003 Buchanan, 1996 130.510.01.0