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Preliminary Findings of mRNA Covid-19 Vaccine Safety in Pregnant Persons

Our take —

The study evaluated adverse events among pregnant people, primarily health care workers, who received an mRNA COVID-19 vaccine in the US from December 2020 to February 2021. Using v-safe, the CDC active surveillance system, they found that the most commonly reported reactions were injection site pain, fatigue, and headaches; they did not identify significant differences in vaccine reactions by pregnancy status. In the v-safe pregnancy registry, the proportions of stillbirth, preterm birth, and other adverse birth outcomes were within expected ranges for US samples from prior studies, though the v-safe sample was not representative of pregnant populations in the US and these numbers cannot be compared without accounting for other risk factors. Likewise, VAERS included few reports of adverse events associated with COVID-19 vaccines among pregnant women. Longer follow-up will be required to assess the potential for congenital anomalies and other outcomes potentially associated with vaccination during the first trimester. Despite the limitations of the early surveillance data, these preliminary results suggest that mRNA vaccines are well-tolerated and safe among pregnant people.

Study design

Prospective Cohort

Study population and setting

This study investigated the safety of the messenger RNA (mRNA) COVID-19 vaccines among pregnant individuals, using US post-vaccination surveillance data from those receiving a first or second dose from December 14, 2020 through February 28, 2021. The first study sample was drawn from the CDC v-safe COVID-19 vaccine surveillance system, a new smartphone-based text message and online survey application. Participation in v-safe was voluntary; individuals could register to participate after getting a COVID-19 vaccine. A subset of pregnant v-safe participants was contacted by phone for recruitment into the v-safe pregnancy registry if they were 18 years or older and received the vaccine during pregnancy or periconception (defined as 30 days before the last menstrual period until 14 days after). Registry participants completed a telephone survey on sociodemographic, medical and obstetric history, pregnancy complications, and birth outcomes. Medical records were also obtained for obstetric and pediatric care; infants were followed until age 3 months. Finally, data from the Vaccine Adverse Event Reporting System (VAERS), a longstanding passive surveillance system, was used to describe the number and types of adverse events reported following an mRNA COVID-19 vaccine where pregnancy status was also noted. Descriptive statistics were reported for pregnant persons in each of the three study samples, overall and stratified by vaccine and/or age group.

Summary of Main Findings

In total, 35,691 v-safe participants (61% aged 25-34 years; 76% non-Hispanic white) reported vaccination with either Pfizer-BioNTech or Moderna mRNA vaccines during pregnancy or the periconception period, of whom 16,982 and 12,273 reported a reaction one day following their first and second dose, respectively. The most common reaction was pain around the injection site (after dose 2, 91.9%), followed by fatigue (after dose 2, 71.5%), headache (after dose 2, 55.4%), and body aches (after dose 2, 54.1%). The relative frequency of these reactions was similar among non-pregnant female v-safe participants aged 18-54 years. The v-safe pregnancy registry (65% aged 25-34 years; 94% health care workers) included individuals who were vaccinated in all trimesters of pregnancy (25.7% third trimester, 43.3% second trimester, 28.6% first trimester, and 2.3% periconception). Pregnancy-related outcomes were assessed among the 827 individuals whose pregnancy ended in a live birth or pregnancy loss by the time of analysis. Spontaneous abortion occurred in 104 (12.6%), primarily during the first trimester (96 of 104, 92%). There was one stillbirth. There were 712 pregnancies that ended in the live birth of 724 neonates, including multiples; most received dose 1 in their third trimester.  Preterm birth occurred among 60 of 636 neonates born to those vaccinated before 37 weeks gestation (9.4%) and major congenital anomalies were reported among 16 of 724 neonates (2.2%). No neonatal deaths were reported. In the VAERS, there were 221 reports of adverse events after the COVID-19 vaccine among pregnant people, of which 66 (29.9%) involved pregnancy or neonatal outcomes. The most frequently reported pregnancy-related adverse event was spontaneous abortion (46 of 221, 20.1% of adverse events reported) and there were three reports of stillbirth. No congenital anomalies were reported in VAERS.

Study Strengths

The study triangulated data from several sources, including the new v-safe active surveillance system, the associated v-safe pregnancy registry, and the VAERS to rapidly disseminate early data on adverse events among pregnant persons. The v-safe pregnancy registry followed individuals prospectively to assess pregnancy and perinatal outcomes, and confirmed outcomes through medical records. Data was available from both the Pfizer-BioNTech and Moderna vaccines, giving insight into both mRNA vaccines and enabling comparisons of adverse events between the two.

Limitations

Due to the short study period, most pregnancies were ongoing at the time of analysis; therefore, the data on pregnancy-related and neonatal outcomes was limited to a smaller sample primarily vaccinated in the third trimester. Assessment of congenital anomalies will require longer follow-up to observe outcomes among those vaccinated during the first trimester of pregnancy during organ development. Since the study collected data during a timeframe when vaccine availability was limited to prioritized groups, the source populations were not representative of the pregnant population in the US and the v-safe sample was further self-selected to those who proactively registered online. There is an overrepresentation of non-Hispanic white respondents and health care workers among the v-safe samples, and the observed frequency of negative pregnancy and neonatal outcomes among those in the registry may not be generalizable to populations with more risk factors for these outcomes. The study lacked a comparison group of pregnant women with similar risk profiles who did not receive the vaccine, and the authors acknowledged that the external estimates from prior studies are not directly comparable. Finally, the adverse events reported through VAERS are difficult to interpret given the selectivity of reporting.

Value added

This is the largest study with real-world data examining adverse events among pregnant people who received an mRNA vaccine, filling an important knowledge gap for this population, which was excluded from the initial vaccine trials.

This review was posted on: 20 June 2021