Safety of mRNA COVID-19 vaccines during pregnancy

Abstract

Pregnant people with COVID-19 are at increased risk of severe illness and death compared with non-pregnant females of reproductive age (aged 15–49 years).1Allotey J Stallings E Bonet M et al.Clinical manifestations, risk factors, and maternal and perinatal outcomes of coronavirus disease 2019 in pregnancy: living systematic review and meta-analysis.BMJ. 2020; 370m3320PubMed Google Scholar Additionally, COVID-19 during pregnancy is associated with increased risk for adverse pregnancy outcomes, such as preterm birth and stillbirth.1Allotey J Stallings E Bonet M et al.Clinical manifestations, risk factors, and maternal and perinatal outcomes of coronavirus disease 2019 in pregnancy: living systematic review and meta-analysis.BMJ. 2020; 370m3320PubMed Google Scholar When mRNA COVID-19 vaccines first became available in December, 2020, safety data in pregnancy were limited because pregnant people were excluded from pre-authorisation clinical trials.2Beigi RH Krubiner C Jamieson DJ et al.The need for inclusion of pregnant women in COVID-19 vaccine trials.Vaccine. 2021; 39: 868-870Crossref PubMed Scopus (38) Google Scholar Lack of data and safety concerns contributed to initially low uptake among pregnant people, which continues to be lower than uptake among non-pregnant females of reproductive age.3Razzaghi H Yankey D Vashist K et al.COVID-19 vaccination coverage and intent among women aged 18–49 years by pregnancy status, United States, April-November 2021.Vaccine. 2022; (published online June 13.)https://doi.org/10.1016/j.vaccine.2022.06.029Crossref PubMed Scopus (4) Google Scholar To address this issue, public health researchers from across the globe have been assessing the safety and effectiveness of COVID-19 vaccines during pregnancy. In The Lancet Infectious Diseases, Manish Sadarangani and colleagues4Sadarangani M Soe P Shulha HP et al.Safety of COVID-19 vaccines in pregnancy: a Canadian National Vaccine Safety (CANVAS) network cohort study.Lancet Infect Dis. 2022; (published online Aug 11.)https://doi.org/10.1016/S1473-3099(22)00426-1Summary Full Text Full Text PDF PubMed Scopus (5) Google Scholar report findings from the Canadian National Vaccine Safety (CANVAS) Network assessing adverse events in the week following mRNA COVID-19 vaccination among pregnant people and compare with both unvaccinated pregnant people and vaccinated non-pregnant females. In this large prospective study, the authors found that 226 (4·0%) of 5597 vaccinated pregnant people reported a significant health event (new or worsening health event sufficient to cause work or school absenteeism, medical consultation, or prevent daily activities) after dose 1 of primary series mRNA COVID-19 (mRNA-1273 [Moderna] or BNT162b2 [Pfizer BioNTech]) vaccination, with similar adverse events for both vaccines. Additionally, 227 (7·3%) of 3108 vaccinated pregnant people reported a significant health event after dose 2 of a primary series, and this did differ by vaccine type, with 147 (12·1%) of 1216 reporting a significant health event after dose 2 of mRNA-1273 and 80 (4·2%) of 1892 after dose 2 of BNT162b2. The most common significant health events following both doses in pregnant people were malaise or myalgia (66 [3·5%] of 1892 for two doses of BNT162b2 and 139 [11·4%] of 1216 for two doses of mRNA-1273) and headache or migraine (41 [2·1%] of 1892 for two doses of BNT162b2 and 103 [8·5%] of 1216 for two doses of mRNA-1273). Serious health events, defined as any event resulting in emergency department visit or hospital admission in the previous 7 days, were rare (<1·0% in all groups). The most frequently reported adverse pregnancy outcome was a combined outcome of miscarriage and stillbirth and was reported at a similar frequency in vaccinated (81 [1·4%] of 5597) and unvaccinated (seven [2·1%] of 339) pregnant people. In a multivariable analysis among those vaccinated with mRNA-1273 or BNT162b2, pregnancy was associated with reduced odds of significant adverse events reported in the week following receipt of each dose (any mRNA dose 1: aOR 0·63 [95% CI 0·55–0·72]; any mRNA dose 2: aOR 0·62 [0·54–0·71]). Additionally, pregnancy was not associated with increased risk of serious adverse events following immunisation after either dose of BNT162b2 or dose 1 of mRNA-1273, but was associated with increased risk following dose 2 of mRNA-1273 (aOR 2·3 [95% CI 1·2–4·2]). Among 1216 pregnant females who received dose 2 of mRNA-1273, 11 (0·9%) reported a serious adverse event within 7 days. These findings are consistent with and add to the growing body of evidence that COVID-19 mRNA vaccines are safe during pregnancy. In the USA, data from several vaccine safety monitoring systems, including the Vaccine Adverse Event Report System (VAERS), v-safe, the v-safe COVID-19 Vaccine Pregnancy Registry, and the Vaccine Safety Datalink, have similarly not detected any safety concerns for people who received an mRNA COVID-19 vaccine in pregnancy or for their infants.5Shimabukuro TT Kim SY Myers TR et al.Preliminary indings of mRNA COVID-19 vaccine safety in pregnant persons.N Engl J Med. 2021; 384: 2273-2282Crossref PubMed Scopus (384) Google Scholar, 6Prasad S Kalafat E Blakeway H et al.Systematic review and meta-analysis of the effectiveness and perinatal outcomes of COVID-19 vaccination in pregnancy.Nat Commun. 2022; 132414Crossref Scopus (17) Google Scholar, 7Morro PL Olson CK Clark E et al.Post-authorization surveillance of adverse events following COVID-19 vaccines in pregnant persons in the vaccine adverse event reporting system (VAERS), December 2020–October 2021.Vaccine. 2022; (published online April 12.)https://doi.org/10.1016/j.vaccine.2022.04.031Crossref Scopus (5) Google Scholar In a large study among people vaccinated early in pregnancy, reactogenicity was similar to current findings reported by Sadarangani and colleagues.5Shimabukuro TT Kim SY Myers TR et al.Preliminary indings of mRNA COVID-19 vaccine safety in pregnant persons.N Engl J Med. 2021; 384: 2273-2282Crossref PubMed Scopus (384) Google Scholar In VAERS, a passive vaccine safety monitoring system co-managed by the US Centers for Disease Control and Prevention (CDC), and the US Food and Drug Administration (FDA), no concerning patterns of negative outcomes among pregnant people or their infants were detected following COVID-19 vaccination during pregnancy, but VAERS did not have a control group.7Morro PL Olson CK Clark E et al.Post-authorization surveillance of adverse events following COVID-19 vaccines in pregnant persons in the vaccine adverse event reporting system (VAERS), December 2020–October 2021.Vaccine. 2022; (published online April 12.)https://doi.org/10.1016/j.vaccine.2022.04.031Crossref Scopus (5) Google Scholar Therefore, this finding by Sadarangani and colleagues which includes an unvaccinated pregnant control group is important. As observed by Sadarangani and colleagues, previous studies have found that COVID-19 mRNA vaccination in pregnancy is not associated with an increased risk of miscarriage or stillbirth.6Prasad S Kalafat E Blakeway H et al.Systematic review and meta-analysis of the effectiveness and perinatal outcomes of COVID-19 vaccination in pregnancy.Nat Commun. 2022; 132414Crossref Scopus (17) Google Scholar In addition to being safe in pregnancy, other studies have shown that mRNA COVID-19 vaccines are effective at reducing the risk of severe illness in pregnant people and the risk of COVID-19 hospital admission among their infants younger than 6 months.6Prasad S Kalafat E Blakeway H et al.Systematic review and meta-analysis of the effectiveness and perinatal outcomes of COVID-19 vaccination in pregnancy.Nat Commun. 2022; 132414Crossref Scopus (17) Google Scholar, 8Halasa NB Olson SM Staat MA et al.Maternal vaccination and risk of hospitalization for COVID-19 among infants.N Engl J Med. 2022; (published online June 22.)https://doi.org/10.1056/NEJMoa2204399Crossref Scopus (18) Google Scholar Protection in infants born to people vaccinated during pregnancy is particularly important because while mRNA COVID-19 vaccines were approved by the FDA on June 17, 2022, and recommended by the CDC on June 18, 2022, for children aged between 6 months and 5 years,9Fleming-Dutra KE Wallace M Moulia DL et al.Interim recommendations of the advisory committee on immunization practices for use of Moderna and Pfizer-BioNTech COVID-19 vaccines in children aged 6 months–5 years—United States, June 2022.MMWR Morb Mortal Wkly Rep. 2022; 71: 859-868Crossref PubMed Google Scholar there are not currently any vaccines available for infants younger than six months. COVID-19 vaccination among pregnant people continues to be lower than among non-pregnant females of reproductive age.3Razzaghi H Yankey D Vashist K et al.COVID-19 vaccination coverage and intent among women aged 18–49 years by pregnancy status, United States, April-November 2021.Vaccine. 2022; (published online June 13.)https://doi.org/10.1016/j.vaccine.2022.06.029Crossref PubMed Scopus (4) Google Scholar Given the risks of severe illness and adverse pregnancy outcomes, continuing to collect and disseminate data on the safety and effectiveness of COVID-19 vaccination in pregnancy and encouraging health-care providers to promote vaccination during all trimesters of pregnancy is imperative. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. We declare no competing interests. Safety of COVID-19 vaccines in pregnancy: a Canadian National Vaccine Safety (CANVAS) network cohort studyCOVID-19 mRNA vaccines have a good safety profile in pregnancy. These data can be used to appropriately inform pregnant people regarding reactogenicity of COVID-19 vaccines during pregnancy, and should be considered alongside effectiveness and immunogenicity data to make appropriate recommendations about best use of COVID-19 vaccines in pregnancy. Full-Text PDF