Proton Pump Inhibitors updated on 08-09-2023

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)1.07 [1.02, 1.12]0%10 studies120,78947,198low ROB1.35 [1.17; .]
Major congenital malformations1.07 [1.02, 1.13]0%7 studies120,02046,158not evaluable ROB1.35 [1.18; .]
Congenital heart defects1.09 [1.01, 1.17]0%4 studies51,19243,701not evaluable ROB1.39 [1.12; .]
Hypospadias1.37 [0.67, 2.79]61%5 studies2,48124,977not evaluable ROB-
Cleft palate1.17 [0.75, 1.83]11%4 studies2,84544,348not evaluable ROB-
Club foot / Talipes equinovarus1.30 [0.75, 2.25]0%3 studies5733,816not evaluable ROB-
Congenital hydronephrosis0.60 [0.27, 1.32]0%3 studies34,065not evaluable ROB-
Atrial septal defect1.28 [0.90, 1.81]0%3 studies7635,085not evaluable ROB-
Cardiac septal defects2.33 [0.36, 14.99]78%2 studies33,91140,679not evaluable ROB-
Cleft lip with or without cleft palate0.70 [0.07, 7.28]50%2 studies13,790not evaluable ROB-
Down syndrom / Trisomy 214.12 [0.34, 49.29]0%2 studies1414not evaluable ROB-
Eye defects0.97 [0.67, 1.40]0%2 studies2,09440,679not evaluable ROB-
Limb defects1.07 [0.93, 1.22]0%2 studies13,71540,679not evaluable ROB-
Microcephaly / Small head circumference for gestational age1.52 [0.42, 5.56]36%2 studies138166not evaluable ROB-
Nervous system anomalies1.24 [1.00, 1.55]0%2 studies4,79040,679not evaluable ROB-
Polydactyly0.97 [0.27, 3.48]0%2 studies43,790not evaluable ROB-
Syndactyly1.28 [0.04, 37.41]59%2 studies3,790not evaluable ROB-
Ventricular septal defect1.09 [0.76, 1.56]0%3 studies1,1885,085not evaluable ROB-
Bilateral renal agenesis including Potter syndrome3.79 [0.15, 93.41]-1 study1139not evaluable ROB-
Genetic syndromes and microdeletions1.26 [0.07, 23.52]-1 study4139not evaluable ROB-
Hip dislocation and/or dysplasia1.89 [0.23, 15.85]-1 study7139not evaluable ROB-
Hydrocephaly1.47 [0.60, 3.60]78%2 studies1,27248,302not evaluable ROB-
Abdominal wall defects2.74 [1.14, 6.58]-1 study23640,540not evaluable ROB4.92 [1.54; .]
Aortic valve atresia/stenosis1.93 [0.47, 7.92]-1 study951,159not evaluable ROB-
Digestive system anomalies1.25 [0.99, 1.58]-1 study4,69240,540not evaluable ROB-
Ear, face and neck anomalies0.68 [0.29, 1.60]-1 study43740,540not evaluable ROB-
Encephalocele0.23 [0.01, 5.68]-1 study1275not evaluable ROB-
Genital anomalies0.96 [0.69, 1.34]-1 study2,58940,540not evaluable ROB-
Hypoplastic left heart (HLH/HLHS)2.99 [0.39, 22.79]-1 study201,159not evaluable ROB-
Limb reduction defects (LRD)0.40 [0.05, 3.11]-1 study3,651not evaluable ROB-
Mitral valve anomalies5.57 [0.69, 44.76]-1 study121,159not evaluable ROB-
Oro-facial clefts0.94 [0.70, 1.27]-1 study3,26940,540not evaluable ROB-
Patent ductus arterious2.09 [0.08, 51.57]-1 study1275not evaluable ROB-
Pulmonary valve atresia3.00 [0.40, 22.50]-1 study311,159not evaluable ROB-
Respiratory system anomalies1.77 [1.12, 2.79]-1 study89140,540not evaluable ROB2.94 [1.49; .]
Tetralogy of Fallot2.80 [0.87, 8.98]-1 study921,159not evaluable ROB-
Tricuspid atresia and stenosis0.86 [0.12, 6.20]-1 study521,159not evaluable ROB-
Urinary malformations0.97 [0.83, 1.14]-1 study11,36740,540not evaluable ROB-

Growth parameters and prematurity
Adverse outcome OR 95%CII2k No. casesNo. exposedpublication biasROBE-value
Preterm (< 37 weeks)1.18 [0.93, 1.51]60%8 studies8,2811,363not evaluable ROB-
Low birth weight (< 2500g)0.95 [0.90, 0.99]0%5 studies116,12842,409not evaluable ROB1.30 [.; 1.11]
Small for gestational age (weight)1.12 [0.86, 1.46]5%3 studies8998not evaluable ROB-
Very preterm (28 to 32 weeks)0.64 [0.29, 1.40]0%2 studies29391not evaluable ROB-
Extremely preterm (< 28 weeks)1.13 [0.64, 1.99]-1 study59not evaluable ROB-
Large for gestational age (weight)0.87 [0.70, 1.08]-1 studynot evaluable ROB-
Very low birth weight (< 1500g)0.17 [0.02, 1.32]-1 study1,394666not evaluable ROB-

Maternal consequences
Adverse outcome OR 95%CII2k No. casesNo. exposedpublication biasROBE-value
Preeclampsia1.08 [0.87, 1.34]76%5 studies18,91645,317not evaluable ROB-
Caesarean0.97 [0.48, 1.98]-1 study3891not evaluable ROB-
Postpartum hemorrhage0.54 [0.15, 1.91]0%2 studies1499not evaluable ROB-
Abruptio placentae (retroplacental hematoma)0.07 [0.00, 1.28]-1 study659not evaluable ROB-
Gestational diabetes1.20 [1.00, 1.44]-1 studynot evaluable ROB-
Maternal consequences (as a whole)0.24 [0.03, 2.23]-1 study559not evaluable ROB-

Neonatal disorders
Adverse outcome OR 95%CII2k No. casesNo. exposedpublication biasROBE-value
Low Apgar score (< 7) (at 5 min)0.60 [0.30, 1.23]48%3 studies1,06859not evaluable ROB-
Bone fractures / bone mineralisation anomalies0.73 [0.59, 0.90]-1 study4,47210,547not evaluable ROB2.08 [.; 1.47]
Neonatal infections0.62 [0.05, 7.91]78%2 studies2799not evaluable ROB-
Neonatal medical care1.43 [0.75, 2.75]0%2 studies6599not evaluable ROB-
Fetal distress1.18 [0.57, 2.43]-1 study5459not evaluable ROB-
Low Apgar score (< 7) (at 1 min)0.80 [0.57, 1.12]-1 study6,185not evaluable ROB-
Necrotizing enterocolitis1.38 [0.30, 6.46]-1 study759not evaluable ROB-
Neonatal death (< 28 days of life)0.76 [0.26, 2.20]-1 study1659not evaluable ROB-
Neonatal disorders (as a whole)0.91 [0.35, 2.34]-1 study2159not evaluable ROB-
Neonatal intracranial hemorrhage5.27 [0.25, 112.09]-1 study259not evaluable ROB-

Long term consequences
Adverse outcome OR 95%CII2k No. casesNo. exposedpublication biasROBE-value
Infant asthma1.23 [1.01, 1.49]91%7 studies30,15642,401not evaluable ROB1.75 [1.08; .]
Infant allergies1.21 [0.91, 1.61]94%3 studies38,03139,764not evaluable ROB-

Intrauterine deaths
Adverse outcome OR 95%CII2k No. casesNo. exposedpublication biasROBE-value
Late intrauterine deaths (> 22 weeks) / Stillbirths1.60 [0.56, 4.54]0%5 studies73700not evaluable ROB-
Early intrauterine deaths (< 22 weeks) / Spontaneous abortions1.29 [0.84, 1.97]7%2 studies114524not evaluable ROB-
Intrauterine deaths (as a whole or unspecified)1.03 [0.90, 1.17]-1 study3,577not evaluable ROB-
Perinatal death0.80 [0.16, 3.98]74%2 studies1,3501,529not evaluable ROB-
Therapeutic terminations of pregnancy1.21 [0.36, 4.09]-1 study11113not evaluable ROB-
Ectopic pregnancy--0 study-
Elective/induced termination of pregnancy2.99 [1.79, 5.00]-1 study63411not evaluable ROB5.43 [2.98; .]

Neuro-developmental disorders
Adverse outcome OR 95%CII2k No. casesNo. exposedpublication biasROBE-value
Neuro-developmental disorders (as a whole)2.00 [0.87, 4.60]-1 study13825not evaluable ROB-

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