{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T04:29:03Z","timestamp":1792297743066,"version":"4.4.0"},"reference-count":53,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2022,6,3]],"date-time":"2022-06-03T00:00:00Z","timestamp":1654214400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2022,9]]},"abstract":"<jats:p><jats:bold>Aims:<\/jats:bold> Calcineurin inhibitors (CNIs) are often used for solid organ transplantation recipients or patients with immune\u2010mediated diseases. This systematic review and meta\u2010analysis aims to understand how CNIs affect pregnancy and neonatal outcomes.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> Electronic databases were searched for observational studies assessing pregnancy and neonatal outcomes in CNI\u2010treated patients. The pooled rate of each outcome was determined. Metaregression was conducted to identify contributing factors to the outcomes.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> We analysed 98 studies with a total of 5355 pregnancies in 4450 CNI\u2010treated patients. The pooled rates of live birth and spontaneous abortion were 82.1% (95% confidence interval [CI] 76.7\u201386.4%) and 11.7% (95% CI 8.7\u201315.5%), respectively. The rates of preterm delivery (33.2%, 95% CI 29.2\u201337.5%), low birth weight (35.8%, 95% CI 27.7\u201344.8%) and preeclampsia (13.5%, 95% CI 9.4\u201319.2%) were 3\u20134 times higher than the rates of general population. Nearly half of the CNI\u2010treated patients required caesarean delivery (43.5%, 95% CI 36.9\u201350.3%). The rates of stillbirth, neonatal and maternal death were 4.2% (95% CI 2.8\u20136.2%), 2.9% (95% CI 1.8\u20134.8%) and 2.3% (95% CI 1.3\u20134.1%), respectively. Metaregression showed that preeclampsia was significantly associated with the risks of preterm delivery and low birth weight. Older maternal age, prepregnancy hypertension and cyclosporine use increased the risk of preeclampsia.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> Given the higher mortalities in CNI\u2010treated patients and their children than the general averages, their pregnancy is considered high risk. The risks of preterm delivery and low birth weight were primarily attributed to preeclampsia. Since prepregnancy hypertension increased its risk, an appropriate preconception blood pressure management may improve their outcomes.<\/jats:p>","DOI":"10.1111\/bcp.15414","type":"journal-article","created":{"date-parts":[[2022,5,20]],"date-time":"2022-05-20T10:29:04Z","timestamp":1653042544000},"page":"3950-3961","source":"Crossref","is-referenced-by-count":28,"title":["Pregnancy and neonatal outcomes in women receiving calcineurin inhibitors: A systematic review and meta\u2010analysis"],"prefix":"10.1111","volume":"88","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0727-7638","authenticated-orcid":false,"given":"Shintaro","family":"Akiyama","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, Faculty of Medicine University of Tsukuba  Ibaraki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shadi","family":"Hamdeh","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Gastroenterology, Hepatology and Motility University of Kansas  KS USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoka","family":"Murakami","sequence":"additional","affiliation":[{"name":"Division of Renal Medicine Brigham and Women's Hospital, Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas G.","family":"Cotter","sequence":"additional","affiliation":[{"name":"Division of Digestive and Liver Diseases UT Southwestern Medical Center  Dallas TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideo","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Faculty of Medicine University of Tsukuba  Ibaraki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiichiro","family":"Tsuchiya","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Faculty of Medicine University of Tsukuba  Ibaraki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,6,3]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.04800908"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm7120552"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.14309\/ajg.0000000000001105"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.2165\/11316280\u2010000000000\u201000000"},{"key":"e_1_2_11_6_1","first-page":"103","article-title":"Report from the National Transplantation Pregnancy Registry (NTPR): outcomes of pregnancy after transplantation","author":"Armenti VT","year":"2004","journal-title":"Clin Transpl"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600\u20106143.2011.03656.x"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12882\u2010019\u20101213\u20105"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2020.11.038"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl\u20102021\u2010325317"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.5301\/jn.5000174"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40264\u2010013\u20100034\u2010x"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclinepi.2009.06.005"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/2046\u20104053\u20102\u2010111"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis\u20102020\u2010219394"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2020.08.026"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1097\/MCG.0000000000001330"},{"key":"e_1_2_11_18_1","unstructured":"WellsGA SheaB O'ConnellD et al.2000.The Newcastle\u2010Ottawa Scale (NOS) for assessing the quality of nonrandomized studies in meta\u2010analyses."},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.2147\/OTT.S90875"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclinepi.2010.07.017"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.327.7414.557"},{"key":"e_1_2_11_22_1","volume-title":"Cochrane Handbook for Systematic Reviews of Interventions, Version 5.1.0","author":"Higgins J","year":"2011"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.2307\/2533446"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.315.7109.629"},{"issue":"136","key":"e_1_2_11_25_1","first-page":"1","article-title":"Pregnancy rates for U.S. women continue to drop","author":"Curtin SC","year":"2013","journal-title":"NCHS Data Brief"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(11)61786\u20108"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(21)00682\u20106"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12978\u2010017\u20100297\u20102"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.12642"},{"key":"e_1_2_11_30_1","unstructured":"Centers for Disease Control and Prevention.Stillbirth Data and Statistics.2017.https:\/\/www.cdc.gov\/ncbddd\/stillbirth\/data.html"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1136\/jech\u20102015\u2010207013"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(10)62310\u20100"},{"key":"e_1_2_11_33_1","unstructured":"Centers for Disease Control and Prevention.Maternal and Infant Health Infant Mortality.2019.https:\/\/www.cdc.gov\/reproductivehealth\/maternalinfanthealth\/infantmortality.htm"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(05)71048\u20105"},{"key":"e_1_2_11_35_1","unstructured":"Centers for Disease Control and Prevention.FastStats Life Stages and Populations.2019.https:\/\/www.cdc.gov\/nchs\/fastats\/delivery.htm"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0148343"},{"key":"e_1_2_11_37_1","unstructured":"Centers for Disease Control and Prevention.Reproductive Health Maternal Mortality.2017.https:\/\/www.cdc.gov\/reproductivehealth\/maternal-mortality\/pregnancy-mortality-surveillance-system.htm"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(15)00838\u20107"},{"key":"e_1_2_11_39_1","unstructured":"Centers for Disease Control and Prevention.Diabetes Gestational Diabetes.2019.https:\/\/www.cdc.gov\/diabetes\/basics\/gestational.html"},{"key":"e_1_2_11_40_1","unstructured":"Centers for Disease Control and Prevention.Birth Defects Data and Statistics.2019.https:\/\/www.cdc.gov\/ncbddd\/birthdefects\/facts.html#Common"},{"key":"e_1_2_11_41_1","unstructured":"Centers for Disease Control and Prevention.National Center for Health Statistics Life Stages and Populations.2019.https:\/\/www.cdc.gov\/nchs\/fastats\/birthweight.htm"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2214\u2010109X(18)30451\u20100"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213\u20102600(13)70192\u20109"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2214\u2010109X(18)30565\u20105"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2016.11.004"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/hr.2016.126"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.88.3.1101"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1097\/HJH.0b013e32834bd1e7"},{"issue":"3","key":"e_1_2_11_49_1","first-page":"397","article-title":"Cyclosporine A in the long\u2010term management of systemic lupus erythematosus","volume":"25","author":"Germano V","year":"2011","journal-title":"J Biol Regul Homeost Agents"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1572\u20100241.2007.01718.x"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcpt.13340"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007890\u2010200203150\u201000012"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.TP.0000121196.71904.E0"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.ogx.0000150346.42901.07"}],"container-title":["British Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bcp.15414","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/bcp.15414","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bcp.15414","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,21]],"date-time":"2023-08-21T11:54:10Z","timestamp":1692618850000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/bcp.15414"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,3]]},"references-count":53,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2022,9]]}},"alternative-id":["10.1111\/bcp.15414"],"URL":"https:\/\/doi.org\/10.1111\/bcp.15414","archive":["Portico"],"relation":{},"ISSN":["0306-5251","1365-2125"],"issn-type":[{"value":"0306-5251","type":"print"},{"value":"1365-2125","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,3]]}}}