The most common AE were systemic events, with spontaneous abortion being the most frequent type of event (2.37%) and with differences in the frequency found for the different types of vaccines available.
This is a republication of an excerpt version of the paper “Adverse events of COVID-19 vaccines in pregnant and postpartum women in Brazil: A cross-sectional study”, with the title above. The post is preceded by an Executive Summary, by the Editor of the Site.
health transformation institute
pandemic response transformation unit
Joaquim Cardoso MSc
Senior Advisor and
Chief Researcher and Editor
January 16, 2023
- This cross-sectional study aimed to describe the adverse events (AE) of COVID-19 vaccines in pregnant and postpartum women in Brazil during the early stage of the vaccination campaign.
- Data was collected from the Brazilian surveillance information system from April to August 2021 and included information on 4 different COVID-19 vaccines (Sinovac/Butantan, Pfizer/BioNTech, AstraZeneca, and Janssen).
- The study found that there were 3,333 AE reported for the study population with an AE incidence rate of 309.4/100,000 doses.
- The Sinovac/Butantan vaccine had the lowest incidence of AE. The majority of AE were systemic events
- The overall incidence of AE found for this population was 309.4/ 100,000 doses.
- The most common AE were systemic events, with spontaneous abortion being the most frequent type of event (2.37%) and with differences in the frequency found for the different types of vaccines available.
- The study concludes that while there is a lack of evidence regarding the safety of these vaccines in the maternal population, the findings are in accordance with the available literature for other studies that assessed safety of COVID-19 in different populations groups.
- However, further studies with longer observation times are needed to provide more evidence on the safety of these vaccines in this population.
- By the fact that pregnant and postpartum women are currently using COVID-19 vaccines, ensure their safety is critical.
- So, more safety evidence is crucial to include this new technology to their vaccine’s calendar and to develop public policies regarding the support and training of Health Care Personnel.
- This study aims to describe the adverse events (AE) of COVID-19 vaccines in pregnant and postpartum women in the early stage of vaccination campaign in Brazil.
- An observational cross-sectional study using data from the Brazilian surveillance information system to characterize the AE of COVID-19 vaccines (Sinovac/Butantan, Pfizer/BioNTech, AstraZeneca and Janssen) in Brazilian pregnant and postpartum women from April to August 2021.
- Frequency and incidence rate of AE for COVID-19 vaccines were assessed.
- 3,333 AE following immunization were reported for the study population. AE incidence was 309.4/100,000 doses (95% CI 297.23, 321.51).
- Within the vaccines available, Sinovac/Butantan had the lowest incidence (74.08/100,000 doses; 95% CI 63.47, 84.69).
- Systemic events were the most frequent notified (82.07%), followed by local (11.93%) and maternal (4.74%), being most of them classified as non-severe (90.65%).
- Our results corroborate the recommendation of vaccination for these groups.
- Even though, further studies appraising a longer observation time are still needed to provide a broader safety aspect for the vaccines currently under use for this population.
Received: August 5, 2022; Accepted: December 26, 2022; Published: January 13, 2023
Funding: This study was funded by Sinovac Life Sciences. The funder had no role in study design, data collection, analysis and preparation of the manuscript. They were all provided by IQVIA Brazil.
Adverse events of COVID-19 vaccines in pregnant and postpartum women in Brazil: A cross-sectional study [excerpt]
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The Coronavirus disease 2019 (COVID-19) has been shown to be less lethal than previous coronavirus diseases, although it is highly contagious. Also, a higher risk of severe disease has been associated with aging and comorbidities [ 1]. Equally important increased risk has been noted in pregnant and postpartum women, making them particularly vulnerable to COVID-19 [ 1]. Studies have shown that, when compared to non-pregnant, pregnant women might develop more severe symptoms, being at increased risk of requiring hospitalization in intensive care unit, along with invasive ventilation, extra corporeal membrane oxygenation and mortality [ 2, 3]. In Brazil, more than 18 thousand cases of severe acute respiratory syndrome (SARS) by COVID-19 were recorded in pregnant and postpartum women, resulting in almost 1,500 deaths by June 2021 [ 4]. Likewise, a 20% increase in maternal mortality rate was observed in 2020 [ 4].
Currently, studies have shown no difference or low incidence of adverse event following immunization (AEFI) of COVID-19 when comparing pregnant and non-pregnant women [ 5– 7]. However, in the beginning of the vaccination campaign, few evidence regarding the safety and efficacy of the vaccines in this population were available, since they were not in included in initial studies of COVID-19 vaccines [ 8]. Even though, considering their higher susceptibility to COVID-19, vaccination for this group has been conducted by assessing risks and benefits [ 9]. COVID-19 immunization started on January 2021 in Brazil and, in March 2021, pregnant and postpartum women with comorbidities were defined as priority group [ 10]. In April 2021, Ministry of Health (MoH) recommended that this subgroup should be vaccinated, as long as a careful assessment was carried out with the physician, regardless of the gestational age [ 10]. Due to adverse events experience by this subgroup, in May 2021 vaccination was changed again only for those women with comorbidity, and, in July 2021, changed to include the entire maternal population [ 10]. Four COVID-19 vaccines were initially recommended-Sinovac/Butantan, Janssen, AstraZeneca and Pfizer/BioNTech, although after May 2021 there was a recommendation to remain only Sinovac/Butantan and Pfizer/BioNTech vaccines for this group [ 11, 12].
By November 2021, about 1,7 million doses have been administered in this group, with an estimative to vaccinate more than 2,5 million pregnant and postpartum women in the country [ 11, 13]. Post authorization safety studies are a way to provide more evidence for this population. However, up to now, there are few publications regarding the safety profile of those vaccines for pregnant and postpartum women from real world evidence perspective, considering pharmacovigilance systems as main source of information, especially for low and middle-income countries (LMIC), such as Brazil [ 14]. In that way, differently from published studies from high-income countries that evaluated safety and effectiveness of the vaccines [ 5– 7], this study aims to describe the incidence of adverse events (AE) reported by pregnant and postpartum women after receiving vaccines approved for use in the early stage of vaccination campaign (April 2021 to August 2021) in Brazil.
Methods, Results and Other Sections
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In the COVID-19 pandemic reality, despite the recognition of the need for inclusion of pregnant and postpartum women in clinical trials, the speed at which the COVID-19 vaccines were developed, and trials conducted precluded inclusion of them [ 25]. In that sense, post authorization safety studies are a way to provide more evidence for this population.
Using surveillance data, we found more than 3,000 events notifications by pregnant and postpartum women after receiving at least one dose of a COVID-19 vaccine in the early stage of the campaign in Brazil. AE were the most common, although for some vaccines IE were more frequent-which may reflect the changes in recommendation to vaccinate this group disposed by the Brazilian MoH [ 11, 26].
Concerning the frequency of AE, the distribution according to the age and race/ethnicity was similar within all vaccines available. However, in a regional perspective, it differed as each region/state could have differences in the cold chain distribution strategies [ 11]. Among the maternal population, pregnant women were responsible for most of the notifications reported in the period.
The overall incidence of AE found for this population was 309.4/ 100,000 doses. Although there is a lack of evidence regarding the safety of these vaccines in the maternal population, our findings are in accordance with the available literature for other studies that assessed safety of COVID-19 in different populations groups. An epidemiological bulletin from the Brazilian MoH from January to February of 2021 showed a 350.9 AEFI notifications/ 100,000 doses of vaccines early administered in the Brazilian population [ 27]. Another study conducted in Minas Gerais state that assessed safety of COVID-19 vaccines from January to March 2021 found an incidence rate of 777.12 AEFI per 100,000 doses applied, with 97% of them classified as non-severe AE [ 28].
In relation to the magnitude of our findings when compared to other vaccines recommended to pregnant and postpartum women in Brazil, a study from Silveira IO et al, assessing adverse events from the SI-EAPV database from 2015 to 2019 in Minas Gerais state, found an overall incidence of 76.9 AEFI notifications/100,000 doses [ 29]. Findings related to race/ ethnicity, type of event and case evolution were also similar to the patterns found in our results [ 29].
As for the systemic events found in our study, the most frequent types follow a similar pattern described by Gattás VL, et al in relation to the ones found for influenza vaccine, which is recommended for any gestational age in Brazil, as COVID-19 vaccines are [ 30]. Although we have not compared pregnant to non-pregnant women, there are studies suggesting that the physiologic changes in pregnancy seems to not materially affect non-maternal events [ 31, 32].
Additionally, our study describes with more emphasis systemic events classified as maternal, showing an incidence of 14.56 AE notifications/ 100,000 doses, of which spontaneous abortion was the most frequent type of event (2.37%) and with differences in the frequency found for the different types of vaccines available. An estimative of 44 abortions per 1,000 women of reproductive age was found in 2014 in Latin America [ 33]. Brazilian data up to 2015 showed that, among all deaths declared as having an underlying cause of abortion, spontaneous accounted for 14.9% in the country [ 34]. Meanwhile, spontaneous abortion incidence in the literature varies from 6.5% to 21% of pregnancies, and it is recognized as one of the most common complications during a pregnancy [ 35– 37]. In addition, a study assessing safety of mRNA COVID-19 vaccines in pregnant population in the United States assessed by the V-Safe pregnancy registry system found an overall frequency of spontaneous abortion of 12.6% among pregnant women who received a COVID-19 vaccines [ 31]. Cardoso BB et al [ 34], however, argues that data on abortion and its complications may be incomplete in Brazil, since the hospitalizations occurred due to an abortion is only one data source to estimate the total number of abortions in the country [ 34].
When comparing the different vaccines administered in this population in Brazil, we found that Sinovac/Butantan and Pfizer/BioNTech vaccines had the lowest IR of AE, which is in line with MoH recommendations to only administer them in pregnant and postpartum woman [ 11, 20].
Our study has some limitations. The AEFI notifications used in this study are subject to limitations of passive surveillance system. This means that each health level routinely and periodically sends information about the events subject to surveillance at the immediately superior. In the same way, the classifications in the database might be susceptible to the interpretation of the person filling out the system, implying in the possibility of lack of uniformity in reporting the characteristics of the event and in the place where the information is filled in the form of the surveillance system. Although these systems generate valuable information regarding the description of the occurrence of adverse events, they usually do not allow establishing causality between the occurrence of AEFI and the vaccine [ 14, 38– 40]. In that sense, our study is unable to evaluate AE outcomes that might occur in association with exposures earlier in pregnancy or postpartum period.
Furthermore, the definition of postpartum women varied in the data sources used-which may underestimate the incidence in this population. In the same direction, the Brazilian obstetric observatory for COVID-19 has been showing that there are inconsistencies in the vaccination information fulfilling, since they found pregnant and postpartum women of male sex, and AEFI notified for COVID-19 vaccines administered previous to the vaccination campaign start and over 55 years old [ 4].
Another potential limitation of our analyses is the underreporting of AE. Coverage in Brazil is done on an administrative basis considering applied doses and not actual doses [ 41]. Also, SIEAPV is a passive surveillance system. Underreporting can occur due to difficulties in the conclusion of cases investigations and in adherence of the population to notify the events. In that sense, mild to moderate events might be more underreported than severe that required hospitalization or more intensive care. On the other hand, each of the four vaccines were available in different moments (Sinovac/Butantan and AstraZeneca since January, Pfizer/BioNTech since May and Janssen since July 2021) [ 11]. The Janssen vaccine was first provided to the population when there was already the recommendation not to vaccinate pregnant and postpartum women with viral vector vaccines, which led to a small number of doses administered in this population, hence, a low number of notifications up to the cut-off period of this study. In the same sense, Sinovac/Butantan and AstraZeneca vaccines were available in the beginning of the campaign, when only women with comorbidities were being vaccinated [ 11]. Also, some of the AE presented in this study might be still under investigation during the study period and might not have a final classification. Besides, because many AE were noticed, there is the possibility that some of them were not related to vaccination but to conditions related to the women with other comorbidities vaccinated during the start of the campaign in Brazil. These pre-existed conditions can elevate the incidence of fetal death, preterm labor, and abortions. Even though, vaccination was still recommended [ 10, 42].
Nevertheless, our study allows a better understand of COVID-19 vaccines safety profile under a vaccination campaign placed during a pandemic setting in a LMIC as Brazil. We found a similar pattern of AE as stated in other studies, with even better results for non-viral vector vaccines, corroborating that vaccination of this groups should continue as a priority. Additionally, it shows the importance of a structured calendar for this population and training for all Health Care Personnel involved in the immunization, assuring more safety for pregnant and postpartum women [ 43, 44].
Considering that it was conducted in the beginning of vaccination campaign in Brazil, further studies appraising a longer time for a better understanding adverse events incidence in relation to second and booster doses and the component of vaccine interchangeability are still needed to provide a broader safety aspect for the vaccines currently under use for this population.
We thank Yaping Qiao, Xing Meng and Weidong Yin for their contribution in the review and discussion of the study findings.
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Originally published at https://journals.plos.org.
About the authors & affiliations
Dimas Tadeu CovasID 1 *,
Ariane de Jesus Lopes de Abreu 2¤ ,
Carolina Zampirolli Dias 2 ,
Rafaela Vansan Ferreira 2 ,
Ramon Gonc¸alves Pereira 2 ,
Guilherme Silva Julian 2¤
1 Butantan Institute, São Paulo, Brazil,
2 IQVIA Brazil, São Paulo, Brazil
Covas DT, de Jesus Lopes de Abreu A, Zampirolli Dias C, Vansan Ferreira R, Gonçalves Pereira R, Silva Julian G (2023) Adverse events of COVID-19 vaccines in pregnant and postpartum women in Brazil: A cross-sectional study. PLoS ONE 18(1): e0280284. https://doi.org/10.1371/journal.pone.0280284
Editor: Fernanda Penido Matozinhos, Universidade Federal de Minas Gerais, BRAZIL