Hydroxychloroquine (All indications except Antiphospholipid Syndrom)

Small for gestational age (weight)

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
R52928		 Chambers (Controls unexposed, disease free), 2022 Growth deficiency at birth (weight < to the 10th centile for sex and gestational age) at least 1st trimester prospective cohort unexposed, disease free excluded Adjustment: Yes Indication HCQ: Rheumatic diseases as a whole (Systemic lupus erythematosus, Rheumatoid arthritis, Sjogren's syndrome...) Matched 2.35 [1.09;5.04]
excluded (control group) 		29/248   16/233 45 248
ref
S13649
R52944		 Chambers (Controls unexposed, sick), 2022 Growth deficiency at birth (weight < to the 10th centile for sex and gestational age) 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 [0.57;1.73] 29/248   28/239 57 248
ref
S13666
R53072		 Reynolds, 2022 Intra uterine growth retardation (IUGR) throughout pregnancy retrospective cohort unexposed, sick Adjustment: No Indication HCQ: Systemic lupus erythematosus (SLE) 0.96 [0.46;2.04] C 16/140   15/127 31 140
ref
S13676
R53140		 Andersson (Controls exposed to corticosteroides), 2021 Small for gestational age (< 10th percentile of the gestational age-specific birth weight within the source cohort) during pregnancy (anytime or not specified) population based cohort retrospective exposed to other treatment, sick excluded Adjustment: No Indication HCQ: Any or not specified Matched 0.83 [0.52;1.31]
excluded (control group) 		40/293   47/293 87 293
ref
S13677
R53144		 Andersson (Controls unexposed, NOS), 2021 Small for gestational age (< 10th percentile of the gestational age-specific birth weight within the source cohort) during pregnancy (anytime or not specified) population based cohort retrospective unexposed (general population or NOS) Adjustment: No Indication HCQ: Any or not specified Matched 1.03 [0.64;1.64] 41/298   40/298 81 298
ref
S13645
R52900		 Bérard, 2021 Small for gestational age (birthweights below the 10th percentile for newborns of the same gestational age and the same sex) during pregnancy (anytime or not specified) nested case control unexposed (general population or NOS) Adjustment: Yes Indication HCQ: Any or not specified 0.86 [0.42;1.75] 16/103   22,264/230,972 22,280 103
ref
S13769
R53867		 Canti, 2021 Intrauterine growth retardation throughout pregnancy prospective cohort unexposed, sick Adjustment: Yes Indication HCQ: Systemic lupus erythematosus (SLE) 0.15 [0.03;0.73] 4/39   8/25 12 39
ref
S13697
R53284		 Louthrenoo, 2021 Small for gestational age during pregnancy (anytime or not specified) retrospective cohort unexposed, sick Adjustment: No Indication HCQ: Systemic lupus erythematosus (SLE) 0.67 [0.20;2.20] 8/35   11/36 19 35
ref
S13707
R53368		 Abd Rahman, 2020 Intrauterine growth restriction (fetal weight < 10th percentile for gestational age) during pregnancy (anytime or not specified) retrospective cohort unexposed, sick Adjustment: No Indication HCQ: Systemic lupus erythematosus (SLE) 0.36 [0.11;1.16] 6/47   10/35 16 47
ref
S13773
R53884		 Baalbaki, 2020 Intrauterine growth restriction during pregnancy (anytime or not specified) retrospective cohort unexposed, sick Adjustment: No Indication HCQ: Systemic lupus erythematosus (SLE) 0.20 [0.02;1.98] C 1/47   3/30 4 47
ref
S13654
R53033		 Do, 2020 Intrauterine growth restriction (IUGR) during pregnancy (anytime or not specified) retrospective cohort unexposed, sick Adjustment: No Indication HCQ: Systemic lupus erythematosus (SLE) 4.98 [1.28;19.38] C 9/53   3/76 12 53
ref
S13695
R53279		 Haase, 2020 Intrauterine growth restriction during pregnancy (anytime or not specified) prospective cohort unexposed, sick Adjustment: No Indication HCQ: Systemic lupus erythematosus (SLE) 2.83 [0.25;31.75] C 2/77   1/107 3 77
ref
S13657
R53045		 Howren, 2020 Small for gestational age (less than the 10th percentile of gestational age- and sex-specific weights) during pregnancy (anytime or not specified) retrospective cohort (claims database) unexposed, sick Adjustment: Yes Indication HCQ: Rheumatic diseases as a whole (Systemic lupus erythematosus, Rheumatoid arthritis, Sjogren's syndrome...) 1.12 [0.65;1.94] 21/81   883/6,168 904 81
ref
S13713
R53409		 Mollerach, 2019 Intrauterine growth restriction throughout pregnancy retrospective cohort unexposed, sick Adjustment: No Indication HCQ: Rheumatic diseases as a whole (Systemic lupus erythematosus, Rheumatoid arthritis, Sjogren's syndrome...) 2.50 [0.37;16.70] C 2/14   3/48 5 14
ref
S13715
R53428		 Seo, 2019 Small for gestational age (birth weight less than the 10th percentile for the gestational week) throughout pregnancy retrospective cohort unexposed, sick Adjustment: No Indication HCQ: Systemic lupus erythematosus (SLE) 0.73 [0.36;1.47] C 24/72   26/64 50 72
ref
S13699
R53335		 Kroese, 2017 Small for gestational age (birth weight below the 10th percentile) during pregnancy (anytime or not specified) retrospective cohort unexposed, sick Adjustment: Yes Indication HCQ: Systemic lupus erythematosus (SLE) 2.20 [0.60;7.50] 5/20   10/68 15 20
ref
S13716
R53435		 Moroni, 2016 Small for gestational age (<10 percentile according to customized charts) during pregnancy (anytime or not specified) prospective cohort unexposed, sick Adjustment: No Indication HCQ: Systemic lupus erythematosus (SLE) 0.15 [0.03;0.77] -/37   -/31 - 37
ref
S13687
R53198		 Leroux, 2015 Antenatal diagnosis of Intrauterine growth restriction (birth weight below the10th percentile) throughout pregnancy retrospective cohort unexposed, sick Adjustment: No Indication HCQ: Systemic lupus erythematosus (SLE) 0.57 [0.15;2.22] C 3/38   10/77 13 38
ref
S13700
R53341		 Al Arfaj, 2010 Intrauterine growth retardation (IUGR) during pregnancy (anytime or not specified) retrospective cohort unexposed, sick Adjustment: No Indication HCQ: Systemic lupus erythematosus (SLE) 1.33 [0.62;2.87] C 12/40   38/156 50 40
ref
S13650
R52955		 Clowse, 2006 Small for gestational age (< 10th percentile for age) throughout pregnancy prospective cohort unexposed, sick Adjustment: No Indication HCQ: Systemic lupus erythematosus (SLE) 1.22 [0.56;2.69] C 11/47   29/145 40 47
ref
S13701
R53343		 Buchanan, 1996 Intrauterine growth retardation (IUGR) during pregnancy (anytime or not specified) retrospective cohort unexposed, sick Adjustment: No Indication HCQ: Systemic lupus erythematosus (SLE) 0.35 [0.12;1.02] C 6/31   18/44 24 31
ref
Total 19 studies 0.88 [0.67;1.17] 23,616 1,467
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 1.00[0.57; 1.73]5724810%ROB confusion: seriousROB selection: moderateROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Reynolds, 2022Reynolds, 2022 0.96[0.46; 2.04]311407%ROB confusion: criticalROB selection: unclearROB classification: moderateROB missing: lowROB mesure: criticalROB reporting: moderate Andersson (Controls unexposed, NOS), 2021Andersson, 2021 2 1.03[0.64; 1.64]8129811%ROB confusion: seriousROB selection: lowROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Bérard, 2021Bérard, 2021 0.86[0.42; 1.75]22,2801038%ROB confusion: seriousROB selection: lowROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Canti, 2021Canti, 2021 0.15[0.03; 0.73]12393%ROB confusion: seriousROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Louthrenoo, 2021Louthrenoo, 2021 0.67[0.20; 2.20]19354%ROB confusion: criticalROB selection: lowROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Abd Rahman, 2020Abd Rahman, 2020 0.36[0.11; 1.16]16474%ROB confusion: criticalROB selection: criticalROB classification: unclearROB missing: unclearROB mesure: unclearROB reporting: moderate Baalbaki, 2020Baalbaki, 2020 0.20[0.02; 1.98]4471%ROB confusion: seriousROB selection: criticalROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Do, 2020Do, 2020 4.98[1.28; 19.38]12533%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Haase, 2020Haase, 2020 2.83[0.25; 31.75]3771%ROB confusion: criticalROB selection: unclearROB classification: unclearROB missing: unclearROB mesure: unclearROB reporting: unclear Howren, 2020Howren, 2020 1.12[0.65; 1.94]9048110%ROB confusion: seriousROB selection: lowROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Mollerach, 2019Mollerach, 2019 2.50[0.37; 16.70]5142%ROB confusion: criticalROB selection: lowROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Seo, 2019Seo, 2019 0.73[0.36; 1.47]50728%ROB confusion: seriousROB selection: lowROB classification: unclearROB missing: unclearROB mesure: moderateROB reporting: moderate Kroese, 2017Kroese, 2017 2.20[0.60; 7.50]15204%ROB confusion: criticalROB selection: lowROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Moroni, 2016Moroni, 2016 0.15[0.03; 0.77]-373%ROB confusion: criticalROB selection: lowROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: critical Leroux, 2015Leroux, 2015 0.57[0.15; 2.22]13383%ROB confusion: criticalROB selection: criticalROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Al Arfaj, 2010Al Arfaj, 2010 1.33[0.62; 2.87]50407%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Clowse, 2006Clowse, 2006 1.22[0.56; 2.69]40477%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Buchanan, 1996Buchanan, 1996 0.35[0.12; 1.02]24315%ROB confusion: criticalROB selection: unclearROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Total (19 studies) I2 = 40% 0.88[0.67; 1.17]23,6161,4670.010.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Controls unexposed, sick; 2: Controls unexposed, NOS;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 0.88[0.65; 1.19]1,3361,36444%NAChambers (Controls unexposed, sick), 2022 Reynolds, 2022 Andersson (Controls unexposed, NOS), 2021 Canti, 2021 Louthrenoo, 2021 Abd Rahman, 2020 Baalbaki, 2020 Do, 2020 Haase, 2020 Howren, 2020 Mollerach, 2019 Seo, 2019 Kroese, 2017 Moroni, 2016 Leroux, 2015 Al Arfaj, 2010 Clowse, 2006 Buchanan, 1996 18 case control studiescase control studies 0.86[0.42; 1.76]22,280103 -NABérard, 2021 1 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 0.98[0.66; 1.44]22,3614010%NAAndersson (Controls unexposed, NOS), 2021 Bérard, 2021 2 unexposed, sickunexposed, sick 0.86[0.61; 1.21]1,2551,06646%NAChambers (Controls unexposed, sick), 2022 Reynolds, 2022 Canti, 2021 Louthrenoo, 2021 Abd Rahman, 2020 Baalbaki, 2020 Do, 2020 Haase, 2020 Howren, 2020 Mollerach, 2019 Seo, 2019 Kroese, 2017 Moroni, 2016 Leroux, 2015 Al Arfaj, 2010 Clowse, 2006 Buchanan, 1996 17 Tags Adjustment   - No  - No 0.87[0.63; 1.21]4051,22438%NAChambers (Controls unexposed, sick), 2022 Reynolds, 2022 Andersson (Controls unexposed, NOS), 2021 Louthrenoo, 2021 Abd Rahman, 2020 Baalbaki, 2020 Do, 2020 Haase, 2020 Mollerach, 2019 Seo, 2019 Moroni, 2016 Leroux, 2015 Al Arfaj, 2010 Clowse, 2006 Buchanan, 1996 15   - Yes  - Yes 0.88[0.43; 1.80]23,21124359%NABérard, 2021 Canti, 2021 Howren, 2020 Kroese, 2017 4 Indication HCQ   - Any or not specified  - Any or not specified 0.98[0.66; 1.44]22,3614010%NAAndersson (Controls unexposed, NOS), 2021 Bérard, 2021 2   - Rheumatic diseases as a whole (Syst ...  - Rheumatic diseases as a whole (Systemic lupus erythematosus, Rheumatoid arthritis, Sjogren's syndrome...) 1.10[0.75; 1.61]9663430%NAChambers (Controls unexposed, sick), 2022 Howren, 2020 Mollerach, 2019 3   - Systemic lupus erythematosus (SLE)  - Systemic lupus erythematosus (SLE) 0.76[0.49; 1.19]28972353%NAReynolds, 2022 Canti, 2021 Louthrenoo, 2021 Abd Rahman, 2020 Baalbaki, 2020 Do, 2020 Haase, 2020 Seo, 2019 Kroese, 2017 Moroni, 2016 Leroux, 2015 Al Arfaj, 2010 Clowse, 2006 Buchanan, 1996 14 MatchedMatched 1.02[0.71; 1.46]1385460%NAChambers (Controls unexposed, sick), 2022 Andersson (Controls unexposed, NOS), 2021 2 All studiesAll studies 0.88[0.67; 1.17]23,6161,46740%NAChambers (Controls unexposed, sick), 2022 Reynolds, 2022 Andersson (Controls unexposed, NOS), 2021 Bérard, 2021 Canti, 2021 Louthrenoo, 2021 Abd Rahman, 2020 Baalbaki, 2020 Do, 2020 Haase, 2020 Howren, 2020 Mollerach, 2019 Seo, 2019 Kroese, 2017 Moroni, 2016 Leroux, 2015 Al Arfaj, 2010 Clowse, 2006 Buchanan, 1996 190.010.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-2.92.81.4810.000Chambers (Controls unexposed, sick), 2022Reynolds, 2022Andersson (Controls unexposed, NOS), 2021Bérard, 2021Canti, 2021Louthrenoo, 2021Abd Rahman, 2020Baalbaki, 2020Do, 2020Haase, 2020Howren, 2020Mollerach, 2019Seo, 2019Kroese, 2017Moroni, 2016Leroux, 2015Al Arfaj, 2010Clowse, 2006Buchanan, 1996

Asymetry test p-value = 0.3103 (by Egger's regression)

slope=0.2174 (0.3081); intercept=-0.7333 (0.7011); t=1.0458; p=0.3103

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 13676, 13648

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.23[0.72; 2.09]22,40664952%NAChambers (Controls unexposed, disease free), 2022 Andersson (Controls unexposed, NOS), 2021 Bérard, 2021 3 unexposed, sick controlsunexposed, sick controls 0.86[0.61; 1.21]1,2551,06646%NAChambers (Controls unexposed, sick), 2022 Reynolds, 2022 Canti, 2021 Louthrenoo, 2021 Abd Rahman, 2020 Baalbaki, 2020 Do, 2020 Haase, 2020 Howren, 2020 Mollerach, 2019 Seo, 2019 Kroese, 2017 Moroni, 2016 Leroux, 2015 Al Arfaj, 2010 Clowse, 2006 Buchanan, 1996 17 exposed to other treatment, sick controlsexposed to other treatment, sick controls 0.83[0.52; 1.32]87293 -NAAndersson (Controls exposed to corticosteroides), 2021 10.510.01.0

Umbrella review (other published meta-analyses)

Published MATE95% CIn exposedkI2Control groupExposition period Duan (SLE indication)Duan (SLE indication) 0.57[0.06; 5.43]88%-unexposed, sickthroughout pregnancystudies3 metaPregmetaPreg 0.88[0.67; 1.17]40%1,467--Chambers (Controls unexposed, sick), 2022 Reynolds, 2022 Andersson (Controls unexposed, NOS), 2021 Bérard, 2021 Canti, 2021 Louthrenoo, 2021 Abd Rahman, 2020 Baalbaki, 2020 Do, 2020 Haase, 2020 Howren, 2020 Mollerach, 2019 Seo, 2019 Kroese, 2017 Moroni, 2016 Leroux, 2015 Al Arfaj, 2010 Clowse, 2006 Buchanan, 1996 190.510.01.0