Proton Pump Inhibitors

Table   Graphic  
individual studies
OutcomeTE95% CIn casesn exposedkPub. bias Congenital malformations All congenital malformations (majors, minors, majors and minors, or unspecified) Lalkin - Omeprazole (Controls unexposed NOS), 1998 Ruigomez - Omeprazole (Controls unexposed NOS), 1999 Nielsen, 1999 Källén - Omeprazole, 2001 Moretti, 2002 Diav-Citrin, 2005 Pasternak, 2010 Colvin, 2011 Matok, 2012 Choi a (Controls unexposed, sick), 2023 Broe (Controls unexposed, sick), 2025 Hongoh - Lansoprazole, 2025 121.07[1.02; 1.12]122,17659,423low Major congenital malformations Lalkin - Omeprazole (Controls unexposed NOS), 1998 Moretti, 2002 Diav-Citrin, 2005 Pasternak, 2010 Colvin, 2011 Matok, 2012 Choi a (Controls unexposed, sick), 2023 Broe (Controls unexposed, sick), 2025 Hongoh - Lansoprazole, 2025 91.07[1.03; 1.12]121,39458,383not evaluable Congenital heart defects Ruigomez - Omeprazole (Controls unexposed NOS), 1999 Källén, 2003 Matok, 2012 Choi a (Controls unexposed, sick), 2023 41.09[1.01; 1.17]50,79643,701not evaluable Cleft palate Ruigomez - Omeprazole (Controls unexposed NOS), 1999 Pasternak, 2010 Anderka, 2012 Choi a (Controls unexposed, sick), 2023 41.17[0.75; 1.83]2,84544,348not evaluable Hypospadias Källèn, 1998 Ruigomez - Omeprazole (Controls unexposed NOS), 1999 Pasternak, 2010 Anderka, 2012 Choi a (Controls unexposed, sick), 2023 51.37[0.67; 2.79]2,48624,977not evaluable Club foot / Talipes equinovarus Ruigomez - Omeprazole (Controls unexposed NOS), 1999 Pasternak, 2010 Werler, 2014 31.30[0.75; 2.25]5733,816not evaluable Congenital hydronephrosis Källèn, 1998 Ruigomez - Omeprazole (Controls unexposed NOS), 1999 Pasternak, 2010 30.60[0.27; 1.32]34,065not evaluable Atrial septal defect Källèn, 1998 Pasternak, 2010 Matok, 2012 31.28[0.90; 1.81]7715,085not evaluable Cardiac septal defects Ruigomez - Omeprazole (Controls unexposed NOS), 1999 Choi a (Controls unexposed, sick), 2023 22.33[0.36; 14.99]33,91140,679not evaluable Cleft lip with or without cleft palate Ruigomez - Omeprazole (Controls unexposed NOS), 1999 Pasternak, 2010 20.70[0.07; 7.28]13,790not evaluable Down syndrom / Trisomy 21 Källèn, 1998 Ruigomez - Omeprazole (Controls unexposed NOS), 1999 24.12[0.34; 49.29]1414not evaluable Eye defects Ruigomez - Omeprazole (Controls unexposed NOS), 1999 Choi a (Controls unexposed, sick), 2023 20.97[0.67; 1.40]2,09440,679not evaluable Hydrocephaly Munch, 2014 Choi a (Controls unexposed, sick), 2023 21.47[0.60; 3.60]1,27248,302not evaluable Limb defects Ruigomez - Omeprazole (Controls unexposed NOS), 1999 Choi a (Controls unexposed, sick), 2023 21.07[0.93; 1.22]13,71540,679not evaluable Microcephaly / Small head circumference for gestational age Ruigomez - Omeprazole (Controls unexposed NOS), 1999 Kerr, 2018 21.52[0.42; 5.56]138166not evaluable Nervous system anomalies Ruigomez - Omeprazole (Controls unexposed NOS), 1999 Choi a (Controls unexposed, sick), 2023 21.24[1.00; 1.55]4,79040,679not evaluable Polydactyly Ruigomez - Omeprazole (Controls unexposed NOS), 1999 Pasternak, 2010 20.97[0.27; 3.48]43,790not evaluable Syndactyly Ruigomez - Omeprazole (Controls unexposed NOS), 1999 Pasternak, 2010 21.28[0.04; 37.41]-3,790not evaluable Ventricular septal defect Källèn, 1998 Pasternak, 2010 Matok, 2012 31.09[0.76; 1.56]1,1975,085not evaluable Bilateral renal agenesis including Potter syndrome Ruigomez - Omeprazole (Controls unexposed NOS), 1999 13.79[0.15; 93.41]1139not evaluable Genetic syndromes and microdeletions Ruigomez - Omeprazole (Controls unexposed NOS), 1999 11.26[0.07; 23.52]4139not evaluable Hip dislocation and/or dysplasia Ruigomez - Omeprazole (Controls unexposed NOS), 1999 11.89[0.23; 15.85]7139not evaluable Patent ductus arterious Källèn, 1998 Segal, 2024 23.47[2.25; 5.36]1,885356not evaluable Abdominal wall defects Choi a (Controls unexposed, sick), 2023 12.74[1.14; 6.58]23640,540not evaluable Aortic valve atresia/stenosis Matok, 2012 11.93[0.47; 7.92]951,159not evaluable Digestive system anomalies Choi a (Controls unexposed, sick), 2023 11.25[0.99; 1.58]4,69240,540not evaluable Ear, face and neck anomalies Choi a (Controls unexposed, sick), 2023 10.68[0.29; 1.60]43740,540not evaluable Encephalocele Källèn, 1998 10.23[0.01; 5.68]1275not evaluable Genital anomalies Choi a (Controls unexposed, sick), 2023 10.96[0.69; 1.34]2,58940,540not evaluable Hypoplastic left heart (HLH/HLHS) Matok, 2012 12.99[0.39; 22.79]201,159not evaluable Limb reduction defects (LRD) Pasternak, 2010 10.40[0.05; 3.11]-3,651not evaluable Mitral valve anomalies Matok, 2012 15.57[0.69; 44.76]121,159not evaluable Oro-facial clefts Choi a (Controls unexposed, sick), 2023 10.94[0.70; 1.27]3,26940,540not evaluable Pulmonary valve atresia Matok, 2012 13.00[0.40; 22.50]311,159not evaluable Respiratory system anomalies Choi a (Controls unexposed, sick), 2023 11.77[1.12; 2.79]89140,540not evaluable Tetralogy of Fallot Matok, 2012 12.80[0.87; 8.98]921,159not evaluable Tricuspid atresia and stenosis Matok, 2012 10.86[0.12; 6.20]521,159not evaluable Urinary malformations Choi a (Controls unexposed, sick), 2023 10.97[0.83; 1.14]11,36740,540not evaluable Growth parameters and prematurity Preterm (< 37 weeks) Lalkin - Omeprazole (Controls unexposed NOS), 1998 Ruigomez - Omeprazole (Controls unexposed NOS), 1999 Nielsen, 1999 Diav-Citrin, 2005 Matok, 2012 Saleh, 2017 Breddels, 2022 Hongoh - Lansoprazole, 2025 81.25[0.97; 1.62]8,3521,400not evaluable Low birth weight (< 2500g) Nielsen, 1999 Källén - Omeprazole, 2001 Matok, 2012 Saleh, 2017 Choi b (Controls unexposed, sick), 2023 Van Gelder, 2023 Hongoh - Lansoprazole, 2025 71.02[0.78; 1.33]116,24742,505not evaluable Small for gestational age (weight) Ruigomez - Omeprazole (Controls unexposed NOS), 1999 Breddels, 2022 Van Gelder, 2023 31.17[0.91; 1.50]2139not evaluable Very preterm (28 to 32 weeks) Nielsen, 1999 Saleh, 2017 20.64[0.29; 1.40]29391not evaluable Large for gestational age (weight) Breddels, 2022 10.87[0.70; 1.08]--not evaluable Very low birth weight (< 1500g) Matok, 2012 10.17[0.02; 1.32]1,394666not evaluable Maternal consequences Preeclampsia Choi (Controls unexposed NOS), 2021 Van Gelder, 2022 Breddels, 2022 31.08[0.81; 1.44]18,71630,188not evaluable Caesarean Lalkin - Omeprazole (Controls unexposed NOS), 1998 10.97[0.48; 1.98]3891not evaluable Gestational diabetes Breddels, 2022 11.20[0.99; 1.46]--not evaluable Maternal infections 0----- Postpartum hemorrhage Saleh, 2017 10.73[0.18; 2.91]1140not evaluable Neonatal disorders Low Apgar score (< 7) (at 5 min) Matok, 2012 Breddels, 2022 20.81[0.64; 1.04]1,060-not evaluable Bone fractures / bone mineralisation anomalies Wolfe (Controls unexposed NOS), 2019 10.73[0.59; 0.90]4,47210,547not evaluable Neonatal infections Saleh, 2017 Tisseyre, 2025 20.53[0.08; 3.51]92,010466,982not evaluable Low Apgar score (< 7) (at 1 min) Matok, 2012 10.80[0.57; 1.12]6,185-not evaluable Neonatal medical care Saleh, 2017 11.22[0.57; 2.62]5340not evaluable Long term consequences Childhood asthma Andersen (Controls unexposed NOS), 2012 Hak, 2013 Mulder, 2014 Yitshak-Sade, 2016 Cea Soriano, 2016 Malaeb, 2021 Noh, 2023 71.23[1.01; 1.49]30,15642,401not evaluable Infant allergies Dehlink (Controls unexposed NOS), 2009 Mulder, 2014 Noh, 2023 31.21[0.91; 1.61]38,03139,764not evaluable Cancer (all kind) in children or adults Gudnadottir, 2025 11.11[0.79; 1.55]1,09123,910not evaluable Intrauterine deaths Late intrauterine deaths (> 22 weeks) / Stillbirths Ruigomez - Omeprazole (Controls unexposed NOS), 1999 Nielsen, 1999 Diav-Citrin, 2005 Saleh, 2017 Hongoh - Lansoprazole, 2025 51.66[0.58; 4.75]77738not evaluable Early intrauterine deaths (< 22 weeks) / Spontaneous abortions Lalkin - Omeprazole (Controls unexposed NOS), 1998 Diav-Citrin, 2005 Hongoh - Lansoprazole, 2025 31.28[0.89; 1.84]199630not evaluable Elective/induced termination of pregnancy Diav-Citrin, 2005 Hongoh - Lansoprazole, 2025 23.05[1.90; 4.91]81517not evaluable Intrauterine deaths (as a whole or unspecified) Andersen (Controls unexposed, NOS), 2013 11.03[0.90; 1.17]-3,577not evaluable Perinatal death Källén - Omeprazole, 2001 Matok, 2012 20.80[0.16; 3.98]1,3501,529not evaluable Therapeutic terminations of pregnancy Lalkin - Omeprazole (Controls unexposed NOS), 1998 11.21[0.36; 4.09]11113not evaluable Ectopic pregnancy 0----- Neuro-developmental disorders ADHD (Attention deficit hyperactivity disorder): Diagnosis Hong, 2026 11.31[1.24; 1.38]93,89429,378not evaluable ADHD (Attention deficit hyperactivity disorder): Diagnosis/Risk Hong, 2026 11.31[1.24; 1.38]93,89429,378not evaluable ASD (Autism spectrum disorder): Diagnosis Hong, 2026 11.34[1.23; 1.46]30,44029,378not evaluable ASD (Autism spectrum disorder): Diagnosis/Risk Hong, 2026 11.34[1.23; 1.46]30,44029,378not evaluable Cognitive developmental disorders/delay (> 6 years old) Hong, 2026 11.24[1.12; 1.38]24,46129,378not evaluable Neuro-developmental disorders (as a whole) Fejzo - Lansoprazole, 2015 12.00[0.87; 4.60]13825not evaluable Severe cognitive developmental delay (Mental retardation) (> 6 years old) Hong, 2026 11.24[1.12; 1.38]24,46129,378not evaluable0.0100.01.0

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