{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T22:01:31Z","timestamp":1783116091155,"version":"3.54.6"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,5,9]],"date-time":"2023-05-09T00:00:00Z","timestamp":1683590400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p><jats:bold>Objective:<\/jats:bold> To evaluate whether periconceptional or pregnancy exposure of human papillomavirus (HPV) vaccination would increase the risk of adverse pregnancy outcomes.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> The PubMed, Web of Science, Embase, the Cochrane Library of clinical trials were searched from inception to March 2023. We computed relative risk (RR) and 95% confidence intervals (CIs) and prediction intervals (PIs) regarding the association between HPV vaccination in periconceptional period or during pregnancy and the risks of adverse pregnancy outcomes by using R software Version 4.1.2 and STATA Version 12.0. A trial sequential analysis (TSA) was performed with TSA v0.9.5.10 Beta software.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> Four randomized controlled trials (RCTs) and eight cohort studies were included in this meta-analysis. Analysis of RCTs showed that HPV vaccination in periconceptional period or during pregnancy did not increase the risks of spontaneous abortion (RR = 1.152, 95% CI: 0.909\u20131.460, 95% PI: 0.442\u20133.000), birth defects (RR = 1.171, 95% CI: 0.802\u20131.709, 95% PI: 0.320\u20134.342), stillbirth (RR = 1.053, 95% CI: 0.616\u20131.800, 95% PI: 0.318\u20133.540), preterm birth (RR = 0.940, 95% CI: 0.670\u20131.318) and ectopic pregnancy (RR = 0.807, 95% CI: 0.353\u20131.842, 95% PI: 0.128\u20135.335). In cohort studies, periconceptional or pregnancy exposures of HPV vaccine were not associated with the increased risk of spontaneous abortion (RR = 0.987, 95% CI: 0.854\u20131.140, 95% PI: 0.652\u20131.493), birth defects (RR = 0.960, 95% CI: 0.697\u20131.322, 95% PI: 0.371\u20132.480), stillbirth (RR = 1.033, 95% CI: 0.651\u20131.639, 95% PI: 0.052\u201321.064), small size for gestational age (SGA) (RR = 0.971, 95% CI: 0.873\u20131.081, 95% PI: 0.657\u20131.462) and preterm birth (RR = 0.977, 95% CI: 0.874\u20131.092, 95% PI: 0.651\u20131.444).<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> HPV vaccine exposures in periconceptional period or during pregnancy did not increase the risks of adverse pregnancy outcomes, including spontaneous abortion, birth defects, stillbirth, SGA, preterm birth and ectopic pregnancy.<\/jats:p><jats:p><jats:bold>Systematic Review Registration:<\/jats:bold><jats:ext-link>https:\/\/www.crd.york.ac.uk\/prospero\/<\/jats:ext-link>, identifier CRD42023399777.<\/jats:p>","DOI":"10.3389\/fphar.2023.1181919","type":"journal-article","created":{"date-parts":[[2023,5,9]],"date-time":"2023-05-09T05:29:37Z","timestamp":1683610177000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["Association of periconceptional or pregnancy exposure of HPV vaccination and adverse pregnancy outcomes: a systematic review and meta-analysis with trial sequential analysis"],"prefix":"10.3389","volume":"14","author":[{"given":"Xiaoli","family":"Yan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyu","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ge","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,5,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"466","DOI":"10.1002\/pds.3554","article-title":"Pooled analysis of large and long-term safety data from the human papillomavirus-16\/18-AS04-adjuvanted vaccine clinical trial programme","volume":"23","author":"Angelo","year":"2014","journal-title":"Pharmacoepidemiol Drug Saf."},{"key":"B2","doi-asserted-by":"publisher","first-page":"6884","DOI":"10.1016\/j.vaccine.2015.07.024","article-title":"Risk of spontaneous abortion and other pregnancy outcomes in 15-25 year old women exposed to human papillomavirus-16\/18 AS04-adjuvanted vaccine in the United Kingdom","volume":"33","author":"Baril","year":"2015","journal-title":"Vaccine"},{"key":"B3","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1586\/14760584.2014.867236","article-title":"Is administration of the HPV vaccine during pregnancy feasible in the future?","volume":"13","author":"Berenson","year":"2014","journal-title":"Expert Rev. 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