{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T13:31:46Z","timestamp":1790688706893,"version":"4.1.0"},"reference-count":63,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2020,1,7]],"date-time":"2020-01-07T00:00:00Z","timestamp":1578355200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aliment Pharmacol Ther"],"published-print":{"date-parts":[[2020,2]]},"abstract":"<jats:title>Summary<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>There have been safety concerns considering long\u2010term proton pump inhibitor (PPI) use, also during pregnancy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>To assess the risk of adverse neonatal outcomes associated with maternal intake of PPIs by means of systematic review and meta\u2010analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The systematic search included PubMed, Web of Science, Cochrane Database and Embase (inception until June 2019). All studies reporting \u22651 adverse pregnancy outcome comparing PPI users to non\u2010users. Histamine\u20102 receptor antagonists (H2RA) were also compared to both non\u2010users and PPI users. Outcomes included congenital malformations, abortion, stillbirth, neonatal death, preterm birth, small for gestational age and low birth weight. Pooled odds ratios (OR) and 95% confidence intervals (CI) were obtained by random\u2010effects modelling. PROSPERO study\u2010protocol: CRD42018103320.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In total, 26 observational studies (20 cohort, 6 case\u2010control studies) were identified, of which 19 assessed PPIs and 12 H2RA. PPI use was associated with an increased risk of congenital malformations (OR\u00a01.28, 95% CI 1.09\u20101.52), especially in case\u2010control studies (OR 2.04, 1.46\u20102.86). No associations were found between H2RA and congenital malformations. No significant associations were found between PPI use and abortions, stillbirth, neonatal death, preterm birth and low\u2010birth weight, although H2RA use may be associated with an increased risk of preterm birth (OR 1.25, 95% CI 1.02\u20101.56). Although statistical heterogeneity and the risk of bias were overall low, clinical heterogeneity, information and selection bias may be present in the individual studies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This meta\u2010analysis suggests an association between maternal PPI use and congenital malformations in humans, yet power was insufficient to assess specific malformations and drugs.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/apt.15610","type":"journal-article","created":{"date-parts":[[2020,1,7]],"date-time":"2020-01-07T07:10:46Z","timestamp":1578381046000},"page":"410-420","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":53,"title":["Systematic review with meta\u2010analysis: the risks of proton pump inhibitors during pregnancy"],"prefix":"10.1111","volume":"51","author":[{"given":"Cheng Mei","family":"Li","sequence":"first","affiliation":[{"name":"Centre for Translational Microbiome Research Department of Microbiology, Tumor and Cell Biology Karolinska Institutet Stockholm Sweden"},{"name":"Science for Life Laboratory Stockholm Sweden"},{"name":"Shanghai Children's Hospital Shanghai Jiao Tong University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Zhernakova","sequence":"additional","affiliation":[{"name":"Department of Genetics University of Groningen University Medical Center Groningen Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Engstrand","sequence":"additional","affiliation":[{"name":"Centre for Translational Microbiome Research Department of Microbiology, Tumor and Cell Biology Karolinska Institutet Stockholm Sweden"},{"name":"Science for Life Laboratory Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cisca","family":"Wijmenga","sequence":"additional","affiliation":[{"name":"Department of Genetics University of Groningen University Medical Center Groningen Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0137-447X","authenticated-orcid":false,"given":"Nele","family":"Brusselaers","sequence":"additional","affiliation":[{"name":"Centre for Translational Microbiome Research Department of Microbiology, Tumor and Cell Biology Karolinska Institutet Stockholm Sweden"},{"name":"Science for Life Laboratory Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,1,7]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2017-017739"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1177\/1756284818777943"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.4292\/wjgpt.v8.i3.180"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1177\/1756283X16650156"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.l1580"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2017-315629"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1159\/000495705"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gtc.2019.04.002"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1080\/19490976.2017.1284732"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aad3369"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1015863018105"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2009.122"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMe1009631"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2017-0889"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12539-019-00335-w"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-008-0587-1"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpg.2007.06.002"},{"key":"e_1_2_7_19_1","unstructured":"Administration FDA.Regulations.1980;44:37434\u201037467."},{"key":"e_1_2_7_20_1","unstructured":"Omeprazole pregnancy and breastfeeding warnings(Medically reviewed June 25 2018).2018.https:\/\/www.drugs.com\/pregnancy\/omeprazole.html. 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