{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T17:43:28Z","timestamp":1793727808125,"version":"4.6.1"},"reference-count":29,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2021,4,13]],"date-time":"2021-04-13T00:00:00Z","timestamp":1618272000000},"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":["Diabetes Metabolism Res"],"published-print":{"date-parts":[[2021,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>To evaluate the risk of adverse fetal outcomes after exposure to angiotensin converting enzyme inhibitors (ACE\u2010Is) or angiotensin receptor blockers (ARBs) in first trimester of pregnancy, by conducting a systematic review and meta\u2010analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>A systematic literature search was conducted using Medline, Embase, Cochrane and PubMed from inception to 25 November 2019. Studies were included if they evaluated pregnancies exposed to ACE\u2010Is or ARBs, reported fetal outcomes, and compared these outcomes with a control group. Pooled odds ratios (ORs) were estimated using inverse variance\u2010weighted random effects model. The protocol was registered with the PROSPERO International Prospective Register of Systematic Reviews (CRD42020160566).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Studies reporting on 6234 pregnancies exposed to ACE\u2010Is or ARBs, 4104 pregnancies exposed to other oral antihypertensives, and 1,872,733 pregnancies without exposure were included in the meta\u2010analysis. ACE\u2010I or ARB exposed pregnancies, compared to non\u2010exposed controls, had higher risk of major congenital malformations (OR 1.82; 95% confidence interval [CI]: 1.42\u20132.34), cardiovascular malformations (OR 2.50; 95% CI: 1.62\u20133.87) and stillbirths (OR 1.75; 95% CI: 1.21\u20132.53). There was no difference in congenital malformations observed between pregnancies exposed to other antihypertensives compared to non\u2010exposed controls (OR 0.96; 95% CI: 0.69\u20131.33).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Women exposed to ACE\u2010Is or ARBs during early pregnancy had higher risk of adverse fetal outcomes, including malformations and stillbirths, than non\u2010exposed controls. This increased risk was independent of underlying maternal hypertension, as those exposed to other antihypertensives did not exhibit a higher risk than healthy controls. Women planning for pregnancy using these medications, including those with diabetic nephropathy, should be counselled appropriately.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/dmrr.3453","type":"journal-article","created":{"date-parts":[[2021,3,29]],"date-time":"2021-03-29T04:59:03Z","timestamp":1616993943000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Increased risk of major congenital malformations in early pregnancy use of angiotensin\u2010converting\u2010enzyme inhibitors and angiotensin\u2010receptor\u2010blockers: a meta\u2010analysis"],"prefix":"10.1002","volume":"37","author":[{"given":"Jennifer","family":"Fu","sequence":"first","affiliation":[{"name":"Department of Medicine University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Tomlinson","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Toronto  Toronto Ontario Canada"},{"name":"University Health Network  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8561-7584","authenticated-orcid":false,"given":"Denice S.","family":"Feig","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Toronto  Toronto Ontario Canada"},{"name":"Leadership Sinai Centre for Diabetes Mount Sinai Hospital Sinai Health System Toronto Ontario Canada"},{"name":"Lunenfeld\u2010Tanenbaum Research Institute  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,4,13]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cjca.2018.02.022"},{"issue":"1","key":"e_1_2_11_3_1","first-page":"S1","article-title":"\u201cChapter 29: Chronic kidney disease in diabetes.\u201d Diabetes Canada 2018 clinical practice guidelines for the prevention and management of diabetes in Canada","volume":"42","author":"McFarlane P","year":"2018","journal-title":"Can J Diabetes"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.3109\/01443615.2011.579197"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa055202"},{"issue":"1","key":"e_1_2_11_6_1","first-page":"S1","article-title":"\u201cChapter 36: Diabetes and pregnancy.\u201d Diabetes Canada 2018 clinical practice guidelines for the prevention and management of diabetes in Canada","volume":"42","author":"Feig DS","year":"2018","journal-title":"Can J Diabetes"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.d5931"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/phar.1212"},{"key":"e_1_2_11_9_1","first-page":"129","article-title":"The use of angiotensin converting enzyme inhibitors during the first trimester of pregnancy","volume":"2","author":"Colvin L","year":"2014","journal-title":"J\u00a0Pharmacovigil"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/AOG.0000000000001775"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preghy.2018.04.022"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1467-9876.2005.00489.x"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.1009"},{"issue":"3","key":"e_1_2_11_14_1","first-page":"40","article-title":"Meta: an R package for meta\u2010analysis","volume":"7","author":"Schwarzer G","year":"2007","journal-title":"R News"},{"key":"e_1_2_11_15_1","volume-title":"A Language and Environment for Statistical Computing","author":"R Core Team. 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