{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T17:01:02Z","timestamp":1793898062393,"version":"4.8.0"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,1,30]],"date-time":"2023-01-30T00:00:00Z","timestamp":1675036800000},"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. Public Health"],"abstract":"<jats:sec><jats:title>Objectives<\/jats:title><jats:p>The low COVID-19 vaccine uptake rate among pregnant women is mainly due to safety concerns about COVID-19 vaccines due to limited safety evidence. Our goal was to evaluate the safety of COVID-19 vaccination during pregnancy with up-to-date evidence.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A comprehensive search of MEDLINE, EMBASE, the Cochrane Library, and <jats:ext-link>clinicaltrials.gov<\/jats:ext-link> was performed on April 5th, 2022, and updated on May 25th, 2022. Studies evaluating the association of COVID-19 vaccination during pregnancy with adverse maternal and neonatal outcomes were included. Two reviewers independently performed the risk of bias assessment and data extraction. Inverse variance random effect meta-analyses were performed to pool outcome data.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Forty-three observational studies were included. COVID-19 vaccination [96,384 (73.9%) BNT162b2, 30,889 (23.7%) mRNA-1273, and 3,172 (2.4%) other types] during pregnancy [23,721 (18.3%) in the first trimester, 52,778 (40.5%) in the second trimester, and 53,886 (41.2%) in the third trimester].was associated with reduced risks of stillbirth or neonatal death (OR, 0.74; 95% CI, 0.60\u20130.92). Sensitivity analysis restricted to studies in participants without COVID-19 showed that the pooled effect was not robust. COVID-19 vaccination during pregnancy was not associated with congenital anomalies (OR, 0.83; 95% CI, 0.63\u20131.08), preterm birth (OR, 0.98; 95% CI, 0.90\u20131.06), NICU admission or hospitalization (OR, 0.94; 95% CI, 0.84\u20131.04), an Apgar score at 5 min &amp;lt;7 (OR, 0.93; 95% CI, 0.86\u20131.01), low birth weight (OR, 1.00; 95% CI, 0.88\u20131.14), miscarriage (OR, 0.99; 95% CI, 0.88\u20131.11), cesarean delivery (OR, 1.07; 95% CI, 0.96\u20131.19), or postpartum hemorrhage (OR, 0.91; 95% CI, 0.81\u20131.01).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>COVID-19 vaccination during pregnancy was not associated with any of the adverse neonatal or maternal outcomes studied. Interpretation of study findings is limited by the types and timing of vaccination. The vaccinations in our study received during pregnancy were primarily mRNA vaccines administered in the second and third trimester. Future RCTs and meta-analysis are warranted to evaluate the efficacy and long-term effects of the COVID-19 vaccines.<\/jats:p><\/jats:sec><jats:sec><jats:title>Systematic review registration<\/jats:title><jats:p><jats:ext-link>https:\/\/www.crd.york.ac.uk\/prospero\/display_record.php?ID=CRD42022322525<\/jats:ext-link>, identifier: PROSPERO, CRD42022322525.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fpubh.2023.1044031","type":"journal-article","created":{"date-parts":[[2023,1,30]],"date-time":"2023-01-30T05:52:00Z","timestamp":1675057920000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":29,"title":["Associations of COVID-19 vaccination during pregnancy with adverse neonatal and maternal outcomes: A systematic review and meta-analysis"],"prefix":"10.3389","volume":"11","author":[{"given":"Cailin","family":"Ding","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yakun","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenbo","family":"Pang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yajun","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,1,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"748","DOI":"10.1097\/01.aoa.0000891692.85343.2c","article-title":"Association of SARS-CoV-2 infection with serious maternal morbidity and mortality from obstetric complications","volume":"327","author":"Metz","year":"2022","journal-title":"JAMA."},{"key":"B2","doi-asserted-by":"publisher","first-page":"m3320","DOI":"10.1136\/bmj.m3320","article-title":"Clinical manifestations, risk factors, and maternal and perinatal outcomes of coronavirus disease 2019 in pregnancy: living systematic review and meta-analysis","volume":"370","author":"Allotey","year":"2020","journal-title":"BMJ."},{"key":"B3","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1016\/j.ajog.2021.02.011","article-title":"Higher severe acute respiratory syndrome coronavirus 2 infection rate in pregnant patients","volume":"225","author":"Lokken","year":"2021","journal-title":"Am J Obstet Gynecol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1016\/j.ajog.2020.03.021","article-title":"Coronavirus disease 2019 (COVID-19) pandemic and pregnancy","volume":"222","author":"Dashraath","year":"2020","journal-title":"Am J Obstet Gynecol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1152\/physrev.00024.2020","article-title":"Pregnancy and COVID-19","volume":"101","author":"Wastnedge","year":"2021","journal-title":"Physiol REV."},{"key":"B6","doi-asserted-by":"publisher","first-page":"m2070","DOI":"10.1126\/scitranslmed.abm2070","article-title":"Pregnancy influences immune responses to SARS-CoV-2","volume":"13","author":"Ovies","year":"2021","journal-title":"Sci Transl Med."},{"key":"B7","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1056\/NEJMoa2035389","article-title":"Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine","volume":"384","author":"Baden","year":"2021","journal-title":"N Engl J Med."},{"key":"B8","doi-asserted-by":"publisher","first-page":"549","DOI":"10.15585\/mmwr.mm7115e2","article-title":"Effectiveness of COVID-19 mRNA vaccination in preventing COVID-19-associated hospitalization among adults with previous SARS-CoV-2 infection - United States, June 2021-February 2022","volume":"71","author":"Plumb","year":"2022","journal-title":"MMWR Morb Mortal Wkly Rep."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1693","DOI":"10.1038\/s41591-021-01490-8","article-title":"Effectiveness of the BNT162b2 mRNA COVID-19 vaccine in pregnancy","volume":"27","author":"Dagan","year":"2021","journal-title":"Nat Med."},{"key":"B10","doi-asserted-by":"publisher","first-page":"e007730","DOI":"10.1136\/bmjgh-2021-007730","article-title":"Global disparities in public health guidance for the use of COVID-19 vaccines in pregnancy","volume":"7","author":"Zavala","year":"2022","journal-title":"BMJ Glob Health"},{"key":"B11","doi-asserted-by":"publisher","first-page":"188","DOI":"10.2188\/jea.JE20210458","article-title":"The prevalence of COVID-19 vaccination and vaccine hesitancy in pregnant women: an internet-based cross-sectional study in Japan","volume":"32","author":"Hosokawa","year":"2022","journal-title":"J Epidemiol"},{"key":"B12","doi-asserted-by":"publisher","first-page":"504","DOI":"10.1038\/s41591-021-01666-2","article-title":"SARS-CoV-2 infection and COVID-19 vaccination rates in pregnant women in Scotland","volume":"28","author":"Stock","year":"2022","journal-title":"Nat Med."},{"key":"B13","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1186\/s12884-021-04321-3","article-title":"Women's views on accepting COVID-19 vaccination during and after pregnancy, and for their babies: a multi-methods study in the UK","volume":"22","author":"Skirrow","year":"2022","journal-title":"BMC Pregnancy Childbirth."},{"key":"B14","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1007\/s10654-021-00728-6","article-title":"COVID-19 vaccine acceptance among pregnant women and mothers of young children: results of a survey in 16 countries","volume":"36","author":"Skjefte","year":"2021","journal-title":"Eur J Epidemiol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"e92","DOI":"10.1016\/S0140-6736(20)31029-1","article-title":"Consider pregnancy in COVID-19 therapeutic drug and vaccine trials","volume":"395","author":"Whitehead","year":"2020","journal-title":"Lancet."},{"key":"B16","doi-asserted-by":"publisher","first-page":"e154834","DOI":"10.1172\/JCI154834","article-title":"Efficient maternal to neonatal transfer of antibodies against SARS-CoV-2 and BNT162b2 mRNA COVID-19 vaccine","volume":"131","author":"Beharier","year":"2021","journal-title":"J Clin Invest."},{"key":"B17","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1016\/j.ajog.2021.08.007","article-title":"COVID-19 vaccination during pregnancy: coverage and safety","volume":"226","author":"Blakeway","year":"2022","journal-title":"Am J Obstet Gynecol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"6535","DOI":"10.1016\/j.vaccine.2021.09.043","article-title":"Early exploration of COVID-19 vaccination safety and effectiveness during pregnancy: interim descriptive data from a prospective observational study","volume":"39","author":"Bleicher","year":"2021","journal-title":"Vaccine."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1698","DOI":"10.3390\/jcm11061698","article-title":"The risk of spontaneous abortion does not increase following first trimester mRNA COVID-19 vaccination","volume":"11","author":"Citu","year":"2022","journal-title":"J Clin Med."},{"key":"B20","doi-asserted-by":"publisher","first-page":"307","DOI":"10.3390\/v14020307","article-title":"Immunogenicity following administration of BNT162b2 and Ad26COV2S COVID-19 vaccines in the pregnant population during the third trimester","volume":"14","author":"Citu","year":"2022","journal-title":"Viruses."},{"key":"B21","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1186\/s12884-022-04505-5","article-title":"Safety of SARS-CoV-2 vaccination during pregnancy- obstetric outcomes from a large cohort study","volume":"22","author":"Dick","year":"2022","journal-title":"BMC Pregnancy Childbirth."},{"key":"B22","doi-asserted-by":"publisher","first-page":"1478","DOI":"10.1001\/jama.2022.4255","article-title":"Association of COVID-19 vaccination in pregnancy with adverse peripartum outcomes","volume":"327","author":"Fell","year":"2022","journal-title":"JAMA."},{"key":"B23","doi-asserted-by":"publisher","first-page":"728","DOI":"10.1001\/jama.2021.11035","article-title":"Association between BNT162b2 vaccination and incidence of SARS-CoV-2 infection in pregnant women","volume":"326","author":"Goldshtein","year":"2021","journal-title":"JAMA."},{"key":"B24","doi-asserted-by":"publisher","first-page":"470","DOI":"10.1001\/jamapediatrics.2022.0001","article-title":"Association of BNT162b2 COVID-19 vaccination during pregnancy with neonatal and early infant outcomes","volume":"176","author":"Goldshtein","year":"2022","journal-title":"JAMA Pediatr."},{"key":"B25","doi-asserted-by":"publisher","first-page":"S453","DOI":"10.1016\/j.ajog.2021.11.752","article-title":"Impact of COVID-19 disease and vaccination on the maternal fetal unit","volume":"226","author":"Kazan","year":"2022","journal-title":"Am J Obstet Gynecol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"1629","DOI":"10.1001\/jama.2021.15494","article-title":"Spontaneous abortion following COVID-19 vaccination during pregnancy","volume":"326","author":"Kharbanda","year":"2021","journal-title":"JAMA."},{"key":"B27","doi-asserted-by":"publisher","first-page":"26","DOI":"10.15585\/mmwr.mm7101e1","article-title":"Receipt of COVID-19 vaccine during pregnancy and preterm or small-for-gestational-age at birth - eight integrated health care organizations, United States, December 15, 2020-July 22, 2021","volume":"71","author":"Lipkind","year":"2022","journal-title":"MMWR Morb Mortal Wkly Rep."},{"key":"B28","doi-asserted-by":"publisher","first-page":"2008","DOI":"10.1056\/NEJMc2114466","article-title":"Covid-19 vaccination during pregnancy and first-trimester miscarriage","volume":"385","author":"Magnus","year":"2021","journal-title":"N Engl J Med."},{"key":"B29","doi-asserted-by":"publisher","first-page":"1469","DOI":"10.1001\/jama.2022.3271","article-title":"Association of SARS-CoV-2 vaccination during pregnancy with pregnancy outcomes","volume":"327","author":"Magnus","year":"2022","journal-title":"JAMA."},{"key":"B30","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1111\/1471-0528.16941","article-title":"Covid-19 vaccination during the third trimester of pregnancy: rate of vaccination and maternal and neonatal outcomes, a multicentre retrospective cohort study","volume":"129","author":"Rottenstreich","year":"2022","journal-title":"BJOG."},{"key":"B31","doi-asserted-by":"publisher","first-page":"717","DOI":"10.1001\/jamapediatrics.2022.0164","article-title":"Association of COVID-19 vaccination during early pregnancy with risk of congenital fetal anomalies","volume":"176","author":"Ruderman","year":"2022","journal-title":"JAMA Pediatr"},{"key":"B32","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1097\/AOG.0000000000004457","article-title":"Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination in pregnancy: measures of immunity and placental histopathology","volume":"138","author":"Shanes","year":"2021","journal-title":"Obstet Gynecol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"100467","DOI":"10.1016\/j.ajogmf.2021.100467","article-title":"Pregnancy and birth outcomes after SARS-CoV-2 vaccination in pregnancy","volume":"3","author":"Theiler","year":"2021","journal-title":"Am J Obstet Gynecol MFM."},{"key":"B34","doi-asserted-by":"publisher","first-page":"6037","DOI":"10.1016\/j.vaccine.2021.09.012","article-title":"Prenatal maternal COVID-19 vaccination and pregnancy outcomes","volume":"39","author":"Wainstock","year":"2021","journal-title":"Vaccine."},{"key":"B35","doi-asserted-by":"publisher","first-page":"S37","DOI":"10.1093\/cid\/ciac359","article-title":"SARS-CoV-2 infection versus vaccination in pregnancy: implications for maternal and infant immunity","volume":"75","author":"Conti","year":"2022","journal-title":"Clin Infect Dis"},{"key":"B36","doi-asserted-by":"publisher","first-page":"e157354","DOI":"10.1172\/jci.insight.157354","article-title":"Neutralizing antibody activity against SARS-CoV-2 variants in gestational age-matched mother-infant dyads after infection or vaccination","volume":"7","author":"Matsui","year":"2022","journal-title":"JCI insight"},{"key":"B37","doi-asserted-by":"publisher","first-page":"2540","DOI":"10.3390\/jcm11092540","article-title":"Obstetric and neonatal outcomes following COVID-19 vaccination in pregnancy","volume":"11","author":"Peretz-Machluf","year":"2022","journal-title":"J Clin Med"},{"key":"B38","unstructured":"2022"},{"key":"B39","doi-asserted-by":"publisher","first-page":"6015","DOI":"10.1016\/j.vaccine.2016.03.047","article-title":"Congenital anomalies: case definition and guidelines for data collection, analysis, and presentation of immunization safety data","volume":"34","author":"DeSilva","year":"2016","journal-title":"Vaccine."},{"key":"B40","doi-asserted-by":"publisher","first-page":"895","DOI":"10.15585\/mmwr.mm7024e2","article-title":"COVID-19 vaccination coverage among pregnant women during pregnancy - eight integrated Health care organizations, United States, December 14, 2020-May 8, 2021","volume":"70","author":"Razzaghi","year":"2021","journal-title":"MMWR Morb Mortal Wkly Rep."},{"key":"B41","doi-asserted-by":"publisher","first-page":"1635","DOI":"10.15585\/mmwr.mm6944e2","article-title":"Birth and infant outcomes following laboratory-confirmed SARS-CoV-2 infection in pregnancy - SET-NET, 16 jurisdictions, March 29-October 14, 2020","volume":"69","author":"Woodworth","year":"2020","journal-title":"MMWR Morb Mortal Wkly Rep."},{"key":"B42","doi-asserted-by":"publisher","first-page":"2164","DOI":"10.1016\/S0140-6736(16)31533-1","article-title":"Diversity and divergence: the dynamic burden of poor maternal health","volume":"388","author":"Graham","year":"2016","journal-title":"Lancet."},{"key":"B43","doi-asserted-by":"publisher","first-page":"1412","DOI":"10.1056\/NEJMoa2101765","article-title":"BNT162b2 mRNA Covid-19 vaccine in a nationwide mass vaccination setting","volume":"384","author":"Dagan","year":"2021","journal-title":"N Engl J Med."},{"key":"B44","volume-title":"ClinicalTrials. gov. A Study of Ad26.COV2.S in Healthy Pregnant Participants (COVID-19) (HORIZON 1)","year":""},{"key":"B45","unstructured":"ClinicalTrials. gov. Study to Evaluate the Safety, Tolerability, and Immunogenicity of SARS CoV-2 RNA Vaccine Candidate (BNT162b2) Against COVID-19 in Healthy Pregnant Women 18 Years of Age and Older. Bethesda, MD: US National Library of Medicine"},{"key":"B46","doi-asserted-by":"publisher","first-page":"S306","DOI":"10.1016\/j.ajog.2021.11.515","article-title":"Factors of COVID-19 vaccine hesitancy during pregnancy: a cross-sectional study","volume":"226","author":"Cui","year":"2022","journal-title":"Am J Obstet Gynecol."},{"key":"B47","doi-asserted-by":"publisher","first-page":"661257","DOI":"10.3389\/fpos.2021.661257","article-title":"The effect of frames on COVID-19 vaccine resistance","volume":"3","author":"Palm","year":"2021","journal-title":"Front Polit Sci."},{"key":"B48","doi-asserted-by":"publisher","first-page":"S306","DOI":"10.1016\/j.ajog.2021.11.516","article-title":"Racial differences in attitudes toward COVID-19 vaccination during pregnancy","volume":"226","author":"Binger","year":"2022","journal-title":"Am J Obstet Gynecol."},{"key":"B49","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.bpobgyn.2020.09.005","article-title":"The historical aspects of vaccination in pregnancy","volume":"76","author":"Mackin","year":"2021","journal-title":"Best Pract Res Clin Obstet Gynaecol."},{"key":"B50","unstructured":"Advice on Priority Groups for COVID-19 Vaccination"}],"container-title":["Frontiers in Public Health"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fpubh.2023.1044031\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,30]],"date-time":"2023-01-30T05:52:08Z","timestamp":1675057928000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fpubh.2023.1044031\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,30]]},"references-count":50,"alternative-id":["10.3389\/fpubh.2023.1044031"],"URL":"https:\/\/doi.org\/10.3389\/fpubh.2023.1044031","relation":{},"ISSN":["2296-2565"],"issn-type":[{"value":"2296-2565","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,30]]},"article-number":"1044031"}}