COVID-19 Vaccines Do Not Significantly Influence Pregnancy Outcomes, Preliminary Study Shows

Investigators are still very limited in understanding the safety surrounding regulated messenger RNA (mRNA) COVID-19 vaccines in pregnant recipients, according to preliminary findings from an ongoing vaccine pregnancy safety registry.

In new data published to The New England Journal of Medicine and compiled by the CDC v-safe COVID-19 Pregnancy Registry Team, US-regulated COVID-19 vaccines BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) were not associated with any apparent pregnancy nor neonatal outcomes in a recipient’s third trimester of pregnancy.

However, the outcomes require more longitudinal follow-up assessment of pregnant vaccine recipients, as well as a greater rate of observed vaccinated women at different stages of pregnancy and afterward.

Led by Tom T. Shimabukuro, MD, of the Immunization Safety Office at the Centers for Disease Control and Prevention (CDC), investigators observed data from a trio of vaccine safety registries from December 14, 2020 – February 28, 2021:

• The “v-safe after vaccination health checker” surveillance system
• The v-safe pregnancy registry
• The Vaccine Adverse Event Reporting System (VAERS)

The timing of their real-world assessment aligned with the initial rollout of the 2 mRNA COVID-19 vaccines, after their Emergency Use Authorization (EUA) indications from the US Food and Drug Administration (FDA) in December 2020.

As Shumabukuro and colleagues noted, the CDC, Advisory Committee on Immunization Practices (ACIP), American College of Obstetricians and Gynecologists, and the American Academy of Pediatrics have each contributed to guidelines stating COVID-19 vaccines should not be withheld from pregnant persons. However, the novel qualities of mRNA vaccine production—including lipid nanoparticles and a unique manufacturing process—requiring real-world safety monitoring in the particular population of pregnant persons.

“Furthermore, establishing their safety profiles is critical to inform recommendations on maternal vaccination against COVID-19,” they wrote.

Assessed vaccine outcomes included participant-reported local and systemic reactogenicity from either vaccine on the day after administration. The trial’s population included all pregnant persons 16-54 years old, whose reported events were compared to nonpregnant women of the same age group.

Completed pregnancy outcomes—including live-born infant, spontaneous abortion, induced abortion, or stillbirth—were assessed in each participant. Neonatal outcomes including preterm birth, congenital anomalies, small size per gestational age, and neonatal death were also assessed.

v-safe Surveillance Outcomes

Investigators identified 35,691 participants who were pregnant between the age of 16-54 years old. Pregnant persons were more likely to report injection-site pain than non-pregnant comparators, though fewer instances of headache, myalgia, chills, and fever.

v-safe Pregnancy Registry Outcomes

Nearly 4000 (n = 3958) participants were enrolled in the registry. Among them, 827 had a completed pregnancy. Investigators observed 115 (13.9%) pregnancy losses and 712 (86.1%) live births. A majority of live-birth outcomes occurred among persons vaccinated during their third trimester of pregnancy.

Preterm births were prevalent among 9.4% of registry participants, and small size for gestational age was prevalent among 3.2%. Shimabukoro and colleagues observed no reported neonatal deaths.

Though the comparison is not directly equitable, investigators did observe similar proportion of adverse pregnancy and neonatal outcomes among COVID-19 vaccinated persons to the rate of such incidences occurring in pregnant persons prior to the pandemic.

VAERS Outcomes

Among the 221 pregnancy-related adverse events reported to the FDA vaccine surveillance system, the most frequently reported event was spontaneous abortion (n = 46).

“This is similar to what was observed during the influenza A (H1N1) pandemic in 2009 after the introduction of the 2009 H1N1 inactivated influenza vaccine, where miscarriage was the most common adverse event reported by pregnant persons who received that vaccine,” investigators wrote.

Next Steps

Shimabukoro and colleagues concluded that their preliminary analysis suggest persons—who are being vaccinated in varying trimesters of pregnancy—have thus far reported pregnancy and neonatal outcomes at a frequency similar to those not vaccinated for COVID-19 or observed prior to the pandemic.

However, the findings are notably limited by a litany of factors, including the patient-reported element of surveillance across these nationwide registries, the lacking follow-up of pregnant persons from the surveillance system to the registry, and the passive characteristics of the surveillance metrics.

That said, the broad outcomes should be enough to inform clinical decision-making on pregnant person vaccination against the pandemic virus.

“Continued monitoring is needed to further assess maternal, pregnancy, neonatal, and childhood outcomes associated with maternal COVID-19 vaccination, including in earlier stages of pregnancy and during the preconception period,” investigators concluded.