Hydroxychloroquine (All indications except Antiphospholipid Syndrom)

Table   Graphic  
individual studies
OutcomeTE95% CIn casesn exposedkPub. bias Congenital malformations All congenital malformations (majors, minors, majors and minors, or unspecified) Costedoat-Chalumeau, 2003 Clowse, 2006 Vroom (controls exposed to sulfasalazine), 2009 Colvin, 2010 Diav-Citrin, 2013 Cooper (controls unexposed, sick), 2014 Langen, 2014 Leroux, 2015 Howren, 2020 Howley - BDS study, 2021 Howley - NBDPS study, 2021 Huybrechts (Controls unexposed, sick), 2021 Bérard, 2021 Andersson (Controls unexposed, NOS), 2021 Reynolds, 2022 Chambers (Controls unexposed, sick), 2022 161.27[1.05; 1.53]91,4723,391low Major congenital malformations Costedoat-Chalumeau, 2003 Clowse, 2006 Colvin, 2010 Diav-Citrin, 2013 Cooper (controls unexposed, sick), 2014 Huybrechts (Controls unexposed, sick), 2021 Andersson (Controls unexposed, NOS), 2021 Bérard, 2021 Howley - BDS study, 2021 Howley - NBDPS study, 2021 Reynolds, 2022 Chambers (Controls unexposed, sick), 2022 121.26[1.06; 1.50]91,4383,314low Congenital heart defects Vroom (controls exposed to sulfasalazine), 2009 Cooper (controls unexposed, sick), 2014 Huybrechts (Controls unexposed, sick), 2021 31.37[0.75; 2.49]2922,265not evaluable Digestive system anomalies Cooper (controls unexposed, sick), 2014 Huybrechts (Controls unexposed, sick), 2021 20.89[0.45; 1.77]1112,239not evaluable Genital anomalies Cooper (controls unexposed, sick), 2014 Huybrechts (Controls unexposed, sick), 2021 22.60[0.30; 22.70]1362,239not evaluable Limb defects Cooper (controls unexposed, sick), 2014 Huybrechts (Controls unexposed, sick), 2021 21.21[0.64; 2.30]1062,239not evaluable Oro-facial clefts Huybrechts (Controls unexposed, sick), 2021 13.70[1.55; 8.83]162,045not evaluable Urinary malformations Cooper (controls unexposed, sick), 2014 Huybrechts (Controls unexposed, sick), 2021 20.98[0.10; 10.01]922,239not evaluable Microcephaly / Small head circumference for gestational age Chambers (Controls unexposed, sick), 2022 11.85[1.07; 3.20]70212not evaluable Minor congenital malformations Chambers (Controls unexposed, sick), 2022 10.87[0.53; 1.42]93138not evaluable Nervous system anomalies Cooper (controls unexposed, sick), 2014 12.66[0.11; 65.66]1194not evaluable Atrial septal defect Howley - BDS study, 2021 12.57[0.68; 9.67]--not evaluable Cleft palate 0----- Eye defects Vroom (controls exposed to sulfasalazine), 2009 10.72[0.04; 14.37]326not evaluable Hypospadias 0----- Respiratory system anomalies Huybrechts (Controls unexposed, sick), 2021 11.85[0.94; 3.64]552,045not evaluable Ventricular septal defect Howley - BDS study, 2021 13.97[0.73; 21.68]--not evaluable Growth parameters and prematurity Preterm (< 37 weeks) Buchanan, 1996 Costedoat-Chalumeau, 2003 Tincani, 2005 Chakravarty, 2005 Clowse, 2006 Vroom (controls unexposed, disease free), 2009 Al Arfaj, 2010 Diav-Citrin, 2013 Cooper (controls unexposed, sick), 2014 Leroux, 2015 Kroese, 2017 Mollerach, 2019 Seo, 2019 Abd Rahman, 2020 Do, 2020 Haase, 2020 Baalbaki, 2020 Louthrenoo, 2021 Canti, 2021 Bérard, 2021 Liu, 2021 Andersson (Controls unexposed, NOS), 2021 Reynolds, 2022 Tang, 2022 Chambers (Controls unexposed, sick), 2022 250.94[0.72; 1.24]31,2511,913probable Small for gestational age (weight) Buchanan, 1996 Clowse, 2006 Al Arfaj, 2010 Leroux, 2015 Moroni, 2016 Kroese, 2017 Mollerach, 2019 Seo, 2019 Do, 2020 Howren, 2020 Abd Rahman, 2020 Haase, 2020 Baalbaki, 2020 Andersson (Controls unexposed, NOS), 2021 Bérard, 2021 Louthrenoo, 2021 Canti, 2021 Reynolds, 2022 Chambers (Controls unexposed, sick), 2022 190.88[0.67; 1.17]23,6161,467low Low birth weight (< 2500g) Leroux, 2015 Louthrenoo, 2021 Bérard, 2021 Reynolds, 2022 Tang, 2022 50.93[0.53; 1.61]11,757347not evaluable Very preterm (28 to 32 weeks) Leroux, 2015 Kroese, 2017 Seo, 2019 30.37[0.14; 0.92]26131not evaluable Small for gestational age (length) Chambers (Controls unexposed, sick), 2022 11.27[0.66; 2.45]39246not evaluable Extremely preterm (< 28 weeks) Clowse, 2006 11.32[0.48; 3.61]2149not evaluable Very low birth weight (< 1500g) Leroux, 2015 10.08[0.00; 1.33]1138not evaluable Maternal consequences Preeclampsia Buchanan, 1996 Levy, 2001 Chakravarty, 2005 Leroux, 2015 Mollerach, 2019 Seo, 2019 Abd Rahman, 2020 Kiatkongchuchai, 2020 Baalbaki, 2020 Do, 2020 Haase, 2021 Canti, 2021 Louthrenoo, 2021 Liu, 2021 Tang, 2022 Reynolds, 2022 160.47[0.28; 0.77]197710critical Caesarean Seo, 2019 Abd Rahman, 2020 Reynolds, 2022 Tang, 2022 40.91[0.64; 1.29]278283not evaluable Gestational diabetes Seo, 2019 Mollerach, 2019 Abd Rahman, 2020 30.94[0.57; 1.55]10141not evaluable Assisted deliveries (forceps, vacuum, ...) Abd Rahman, 2020 Reynolds, 2022 21.05[0.52; 2.13]35186not evaluable Maternal death Leroux, 2015 Baalbaki, 2020 21.43[0.18; 11.45]388not evaluable Oligohydramnios Leroux, 2015 Seo, 2019 20.54[0.15; 1.96]15118not evaluable Postpartum hemorrhage Liu, 2021 Tang, 2022 22.19[0.34; 14.03]2365not evaluable Abruptio placentae (retroplacental hematoma) Seo, 2019 13.68[0.40; 33.76]580not evaluable Maternal infections Leroux, 2015 12.67[0.57; 12.54]741not evaluable Maternal liver disorder / failure during pregnancy Do, 2020 11.44[0.03; 73.63]-53not evaluable Neonatal disorders Eye deficiency / Visual abnormality Buchanan, 1996 Levy, 2001 Costedoat-Chalumeau, 2003 Clowse, 2006 41.19[0.16; 8.63]-205not evaluable Neonatal death (< 28 days of life) Buchanan, 1996 Levy, 2001 Al Arfaj, 2010 Baalbaki, 2020 40.93[0.22; 3.89]8157not evaluable Neonatal disorders (as a whole) Cooper (controls unexposed, sick), 2014 Mollerach, 2019 Baalbaki, 2020 31.13[0.47; 2.74]54253not evaluable Fetal distress Buchanan, 1996 Canti, 2021 Liu, 2021 30.63[0.33; 1.19]57110not evaluable Hearing loss / Auditory deficit Levy, 2001 Costedoat-Chalumeau, 2003 Clowse, 2006 31.12[0.11; 11.06]-174not evaluable Low Apgar score (< 7) (at 5 min) Leroux, 2015 Seo, 2019 Abd Rahman, 2020 30.48[0.17; 1.32]20146not evaluable Neonatal infections Baalbaki, 2020 Reynolds, 2022 20.92[0.46; 1.83]50196not evaluable Neonatal medical care Do, 2020 Baalbaki, 2020 20.61[0.34; 1.11]71100not evaluable Necrotizing enterocolitis Baalbaki, 2020 13.31[0.15; 71.54]247not evaluable Neonatal immune dysfunction Cimaz, 2007 15.21[0.23; 116.22]414not evaluable Neonatal intracranial hemorrhage Baalbaki, 2020 10.63[0.01; 32.85]-47not evaluable Very low Apgar score (< 5) (at 1 min) Seo, 2019 10.89[0.12; 6.48]472not evaluable Long term consequences Child/Infant head circumference abnormalities (> 1 year) Chambers (Controls unexposed, sick), 2022 10.84[0.32; 2.22]17173not evaluable Child/Infant lenght abnormalities (> 1 year) Chambers (Controls unexposed, sick), 2022 10.92[0.41; 2.07]25179not evaluable Child/Infant weight abnormalities (> 1 year) Chambers (Controls unexposed, sick), 2022 11.43[0.80; 2.56]58182not evaluable Child/Infant growth abnormalities (> 1 year) Costedoat-Chalumeau, 2003 10.50[0.01; 25.63]-117not evaluable Intrauterine deaths Late intrauterine deaths (> 22 weeks) Buchanan, 1996 Costedoat-Chalumeau, 2003 Tincani, 2005 Chakravarty, 2005 Clowse, 2006 Al Arfaj, 2010 Diav-Citrin, 2013 Cooper (controls unexposed, sick), 2014 Seo, 2019 Mollerach, 2019 Abd Rahman, 2020 Canti, 2021 Chambers (Controls unexposed, sick), 2022 130.73[0.41; 1.30]651,144low Early intrauterine death (< 22 weeks) Buchanan, 1996 Costedoat-Chalumeau, 2003 Tincani, 2005 Chakravarty, 2005 Clowse, 2006 Al Arfaj, 2010 Diav-Citrin, 2013 Kroese, 2017 Seo, 2019 Mollerach, 2019 Abd Rahman, 2020 Canti, 2021 Chambers (Controls unexposed, sick), 2022 131.50[1.10; 2.04]225903probable Intrauterine deaths (as a whole or unspecified) Costedoat-Chalumeau, 2003 Frassi, 2004 Vroom (controls exposed to sulfasalazine), 2009 Leroux, 2015 Kroese, 2017 Louthrenoo, 2021 61.13[0.69; 1.85]240362not evaluable Elective/induced termination of pregnancy Diav-Citrin, 2013 Leroux, 2015 Chambers (Controls unexposed, sick), 2022 32.42[0.93; 6.29]17435not evaluable Therapeutic terminations of pregnancy Costedoat-Chalumeau, 2003 Chambers (Controls unexposed, sick), 2022 20.53[0.02; 14.73]3412not evaluable Ectopic pregnancy Chambers (Controls unexposed, sick), 2022 11.00[0.02; 50.58]-279not evaluable Neuro-developmental disorders Neuro-developmental disorders (as a whole) Reynolds, 2022 Andreoli, 2022 20.47[0.18; 1.23]28175not evaluable ADHD (Attention deficit hyperactivity disorder): Diagnosis/Risk Reynolds, 2022 10.13[0.01; 2.47]3149not evaluable ADHD (Attention deficit hyperactivity disorder): Risk Reynolds, 2022 10.13[0.01; 2.47]3149not evaluable Cognitive developmental disorders/delay (3-6 years old) Reynolds, 2022 10.67[0.23; 1.99]14148not evaluable Learning disorders Reynolds, 2022 10.18[0.02; 1.53]6148not evaluable0.0100.01.0

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