Hydroxychloroquine (All indications except Antiphospholipid Syndrom)

Table   Graphic     exposition period:

Congenital malformations
Adverse outcome OR 95%CII2k No. casesNo. exposedpublication biasROBE-value
All congenital malformations (majors, minors, majors and minors, or unspecified)1.27 [1.02, 1.59]10%15 studies60,0043,373low ROB1.86 [1.15; .]
Major congenital malformations1.26 [1.01, 1.58]11%11 studies59,9703,296low ROB1.83 [1.08; .]
Congenital heart defects1.37 [0.75, 2.49]0%3 studies2922,265not evaluable ROB-
Digestive system anomalies0.89 [0.45, 1.77]0%2 studies1112,239not evaluable ROB-
Genital anomalies2.60 [0.30, 22.70]50%2 studies1362,239not evaluable ROB-
Limb defects1.21 [0.64, 2.30]0%2 studies1062,239not evaluable ROB-
Oro-facial clefts3.70 [1.55, 8.83]-1 study162,045not evaluable ROB6.86 [2.48; .]
Urinary malformations0.98 [0.10, 10.01]61%2 studies922,239not evaluable ROB-
Microcephaly / Small head circumference for gestational age1.85 [1.07, 3.20]-1 study70212not evaluable ROB3.10 [1.34; .]
Minor congenital malformations0.87 [0.53, 1.42]-1 study93138not evaluable ROB-
Nervous system anomalies2.66 [0.11, 65.66]-1 study1194not evaluable ROB-
Atrial septal defect2.57 [0.68, 9.67]-1 studynot evaluable ROB-
Cleft palate--0 study-
Eye defects0.72 [0.04, 14.37]-1 study326not evaluable ROB-
Hypospadias--0 study-
Respiratory system anomalies1.85 [0.94, 3.64]-1 study552,045not evaluable ROB-
Ventricular septal defect3.97 [0.73, 21.68]-1 studynot evaluable ROB-

Growth parameters and prematurity
Adverse outcome OR 95%CII2k No. casesNo. exposedpublication biasROBE-value
Preterm (< 37 weeks)0.94 [0.72, 1.24]65%25 studies31,2511,913probable ROB-
Small for gestational age (weight)0.88 [0.67, 1.17]40%19 studies23,6161,467low ROB-
Low birth weight (< 2500g)0.93 [0.53, 1.61]43%5 studies11,757347not evaluable ROB-
Very preterm (28 to 32 weeks)0.37 [0.14, 0.92]0%3 studies26131not evaluable ROB4.92 [.; 1.38]
Small for gestational age (length)1.27 [0.66, 2.45]-1 study39246not evaluable ROB-
Extremely preterm (< 28 weeks)1.32 [0.48, 3.61]-1 study2149not evaluable ROB-
Very low birth weight (< 1500g)0.08 [0.00, 1.33]-1 study1138not evaluable ROB-

Maternal consequences
Adverse outcome OR 95%CII2k No. casesNo. exposedpublication biasROBE-value
Preeclampsia0.47 [0.28, 0.77]49%16 studies197710critical ROB3.71 [.; 1.94]
Caesarean0.91 [0.64, 1.29]4%4 studies278283not evaluable ROB-
Gestational diabetes0.94 [0.57, 1.55]6%3 studies10141not evaluable ROB-
Assisted deliveries (forceps, vacuum, ...)1.05 [0.52, 2.13]0%2 studies35186not evaluable ROB-
Maternal death1.43 [0.18, 11.45]0%2 studies388not evaluable ROB-
Oligohydramnios0.54 [0.15, 1.96]0%2 studies15118not evaluable ROB-
Postpartum hemorrhage2.19 [0.34, 14.03]42%2 studies2365not evaluable ROB-
Abruptio placentae (retroplacental hematoma)3.68 [0.40, 33.76]-1 study580not evaluable ROB-
Maternal infections2.67 [0.57, 12.54]-1 study741not evaluable ROB-
Maternal liver disorder / failure during pregnancy1.44 [0.03, 73.63]-1 study53not evaluable ROB-

Neonatal disorders
Adverse outcome OR 95%CII2k No. casesNo. exposedpublication biasROBE-value
Eye deficiency / Visual abnormality1.19 [0.16, 8.63]0%4 studies205not evaluable ROB-
Neonatal death (< 28 days of life)0.93 [0.22, 3.89]0%4 studies8157not evaluable ROB-
Neonatal disorders (as a whole)1.13 [0.47, 2.74]33%3 studies54253not evaluable ROB-
Fetal distress0.63 [0.33, 1.19]0%3 studies57110not evaluable ROB-
Hearing loss / Auditory deficit1.12 [0.11, 11.06]0%3 studies174not evaluable ROB-
Low Apgar score (< 7) (at 5 min)0.48 [0.17, 1.32]0%3 studies20146not evaluable ROB-
Neonatal medical care0.60 [0.35, 1.04]0%3 studies80137not evaluable ROB-
Neonatal infections0.92 [0.46, 1.83]0%2 studies50196not evaluable ROB-
Necrotizing enterocolitis3.31 [0.15, 71.54]-1 study247not evaluable ROB-
Neonatal immune dysfunction5.21 [0.23, 116.22]-1 study414not evaluable ROB-
Neonatal intracranial hemorrhage0.63 [0.01, 32.85]-1 study47not evaluable ROB-
Very low Apgar score (< 5) (at 1 min)0.89 [0.12, 6.48]-1 study472not evaluable ROB-

Long term consequences
Adverse outcome OR 95%CII2k No. casesNo. exposedpublication biasROBE-value
Child/Infant head circumference abnormalities (> 1 year)0.84 [0.32, 2.22]-1 study17173not evaluable ROB-
Child/Infant lenght abnormalities (> 1 year)0.92 [0.41, 2.07]-1 study25179not evaluable ROB-
Child/Infant weight abnormalities (> 1 year)1.43 [0.80, 2.56]-1 study58182not evaluable ROB-
Child/Infant growth abnormalities (> 1 year)0.50 [0.01, 25.63]-1 study117not evaluable ROB-

Intrauterine deaths
Adverse outcome OR 95%CII2k No. casesNo. exposedpublication biasROBE-value
Late intrauterine deaths (> 22 weeks)0.73 [0.41, 1.30]0%13 studies651,144low ROB-
Early intrauterine death (< 22 weeks)1.50 [1.10, 2.04]0%13 studies225903probable ROB2.36 [1.43; .]
Intrauterine deaths (as a whole or unspecified)1.13 [0.69, 1.85]26%6 studies240362not evaluable ROB-
Elective/induced termination of pregnancy2.42 [0.93, 6.29]0%3 studies17435not evaluable ROB-
Therapeutic terminations of pregnancy0.53 [0.02, 14.73]56%2 studies3412not evaluable ROB-
Ectopic pregnancy1.00 [0.02, 50.58]-1 study279not evaluable ROB-

Neuro-developmental disorders
Adverse outcome OR 95%CII2k No. casesNo. exposedpublication biasROBE-value
Neuro-developmental disorders (as a whole)0.47 [0.18, 1.24]0%2 studies28175not evaluable ROB-
ADHD (Attention deficit hyperactivity disorder): Diagnosis/Risk0.13 [0.01, 2.47]-1 study3149not evaluable ROB-
ADHD (Attention deficit hyperactivity disorder): Risk0.13 [0.01, 2.47]-1 study3149not evaluable ROB-
Cognitive developmental disorders/delay (3-6 years old)0.67 [0.23, 1.99]-1 study14148not evaluable ROB-
Learning disorders 0.18 [0.02, 1.53]-1 study6148not evaluable ROB-

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