Proton Pump Inhibitors

Table   Graphic     exposition period:

Congenital malformations
Adverse outcome OR 95%CII2k No. casesNo. exposedpublication biasROB
All congenital malformations (majors, minors, majors and minors, or unspecified)1.07 [1.02, 1.12]0%10 studies120,80247,198low ROB
Major congenital malformations1.07 [1.02, 1.13]0%7 studies120,02046,158not evaluable ROB
Congenital heart defects1.09 [1.01, 1.17]0%4 studies51,19243,701not evaluable ROB
Hypospadias1.37 [0.67, 2.79]61%5 studies2,48624,977not 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 studies7715,085not 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 studies1,1975,085not 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 ROB
Respiratory system anomalies1.77 [1.12, 2.79]-1 study89140,540not evaluable ROB
17 non statistically significant endpoints reported in only one study

Growth parameters and prematurity
Adverse outcome OR 95%CII2k No. casesNo. exposedpublication biasROB
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 ROB
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
3 non statistically significant endpoints reported in only one study

Maternal consequences
Adverse outcome OR 95%CII2k No. casesNo. exposedpublication biasROB
Preeclampsia1.08 [0.87, 1.34]76%5 studies18,98245,317not evaluable ROB
Postpartum hemorrhage0.54 [0.15, 1.91]0%2 studies1499not evaluable ROB
4 non statistically significant endpoints reported in only one study

Neonatal disorders
Adverse outcome OR 95%CII2k No. casesNo. exposedpublication biasROB
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 ROB
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
6 non statistically significant endpoints reported in only one study

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

Intrauterine deaths
Adverse outcome OR 95%CII2k No. casesNo. exposedpublication biasROB
Late intrauterine deaths (> 22 weeks)1.60 [0.56, 4.54]0%5 studies73700not evaluable ROB
Early intrauterine death (< 22 weeks)1.29 [0.84, 1.97]7%2 studies114524not evaluable ROB
Perinatal death0.80 [0.16, 3.98]74%2 studies1,3501,529not evaluable ROB
Ectopic pregnancy--0 study
Elective/induced termination of pregnancy2.99 [1.79, 5.00]-1 study63411not evaluable ROB
2 non statistically significant endpoints reported in only one study

Neuro-developmental disorders
Adverse outcome OR 95%CII2k No. casesNo. exposedpublication biasROB
1 non statistically significant endpoints reported in only one study