After the emergency clearance for the messenger RNA (mRNA) vaccines BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) was granted, people at highest risk for Coronavirus Disease 2019 (Covid-19) – related diseases and Deaths prioritized vaccination.1 These included pregnant women who were excluded from initial vaccine trials. Pregnant women and their doctors had to weigh the documented risks of Covid-19 infection against the unknown safety risks of vaccination when deciding whether to receive the vaccine.
Prior to the introduction of the vaccine, several cohort studies documented that pregnant women were at higher risk of developing serious illnesses after a Covid-19 infection than non-pregnant women, resulting in ICU admission, mechanical ventilation and death.2.3 Pregnant women with comorbidities like diabetes, high blood pressure, and obesity are at even greater risk.4th Studies have also shown an increased risk of pregnancy complications – including premature birth, caesarean section, and preeclampsia – associated with Covid-19 infection during pregnancy.5 As a result, clinicians relied on Moderna developmental and reproductive animal data that showed no safety concerns, and there was no biologically plausible reason that mRNA technology could be harmful in pregnancy. Pregnant women were advised to consider the available data and, in the absence of safety data for humans, to make personal decisions about vaccination.
In this edition of the diary, Shimabukuro et al.6th provide much-needed preliminary data on the safety of these vaccines in pregnancy based on the v-safe surveillance system and pregnancy registry. V-safe, a new smartphone-based monitoring system from the Centers for Disease Control and Prevention available to all Covid-19 vaccine recipients, sends text messages to assess general health and pregnancy status for a period of 12 months after vaccination . People who identify themselves as pregnant can register in the v-safe pregnancy register, which the participants will contact by phone to answer any questions they may have.
The report by Shimabukuro et al. contains safety results for 35,691 v-safe participants aged 16 to 54 who were identified as pregnant and the first 3,958 participants who enrolled in the v-safe pregnancy registry. In both cohorts, 54% of participants received the Pfizer BioNTech vaccine and 46% received the Moderna vaccine. Age distribution, race and ethnic status, and the timing of the first dose were similar for each vaccine. Of the v-safe participants, 86.5% had a known pregnancy at the time of vaccination and 13.5% reported a positive pregnancy test after vaccination. Among the participants in the v-safe pregnancy registry, 28.6% received a vaccine in the first trimester, 43.3% in the second trimester, and 25.7% in the third trimester.
Of 827 registry participants who reported a completed pregnancy, the pregnancy led to spontaneous abortion in 104 (12.6%) and stillbirth in 1 (0.1%); these percentages are well within the range expected as a result for this age group of people whose other underlying diseases are not known. A total of 712 pregnancies (86.1%) resulted in a live birth, mostly in participants who received their first dose of vaccine in the third trimester. In the live-born infants, the incidences of premature birth (9.4%), small size for gestational age (3.2%), and congenital abnormalities (2.2%) were also expected based on the published literature. There were no newborn deaths. This is reassuring data based on reports from pregnant women who were vaccinated primarily in the third trimester.
In addition, the rates of local and systemic reactions after vaccination in v-safe participants identified as pregnant were similar to those in a larger group of non-pregnant women, suggesting that the physiological changes in pregnancy did not significantly affect such reactions . The most common side effect was pain at the injection site, with tiredness, headache and myalgia being significantly more common after the second dose. Fever has been reported in a small number of people after the first dose and in approximately one-third of recipients after the second dose.
Because the number of completed pregnancies was relatively low and live births typically occurred after vaccination in the third trimester, Shimabukuro et al. recognize the limitations of their ability to draw conclusions about congenital abnormalities and other potentially rare neonatal outcomes. Despite these limitations, this report contains important information that was not previously available.
As the pandemic continues and pregnant women are at high risk of serious illness if they contract Covid-19, vaccination is an important prevention strategy. The lack of safety information about pregnancies, which existed at a time when thousands of pregnant women were struggling with vaccination decisions, underscores the importance of recent efforts to include pregnant women in studies, including ongoing vaccine studies; A study is currently ongoing to investigate the effect of the BNT162b2 vaccine in pregnant women and their infants (ClinicalTrials.gov number, NCT04754594).
It is noteworthy that by April 26, 2021, more than 100,000 pregnant women reported having received a Covid-19 vaccination and yet only a small fraction (4.7%) had registered in the v-safe pregnancy register.7th This situation underscores the urgent need not only to include pregnant women in clinical trials, but also to invest in public health surveillance systems for pregnancies, in which many more women are involved. To prepare for the next pandemic and improve health outcomes for pregnant women in general, it is high time to invest in maternal health monitoring and research.