COVID-19 vaccine for pregnant women: The data so far
Vaccination with the BNT162b2 or mRNA-1273 mRNA vaccines against COVID-19 is safe and effective in pregnant women, suggests real-world evidence from the US CDC* surveillance data and Israel healthcare registry.
“Pregnant women were at greater risk than nonpregnant women for severe disease after COVID-19 infection ... yet they had been excluded from initial vaccine trials,” wrote Dr Laura Riley of New York–Presbyterian/Weill Cornell Medical Center and Weill Cornell Medicine, New York, New York, US, in a linked editorial. [N Engl J Med 2021;384:2342-2343]
“The dearth of safety information about pregnancy … [leaves] thousands of pregnant women grappling with decisions about vaccination,” she highlighted.
Navigating the black box
Based on data of more than 35,000 pregnant women in the US who had received mRNA-based COVID-19 vaccines, there was no significant difference in pregnancy complications between vaccinated and unvaccinated pregnant women. [N Engl J Med 2021;384:2273-2282]
“[The study] provides much-needed preliminary data on the safety of these vaccines in pregnancy on the basis of the v-safe surveillance system and pregnancy registry,” stated Riley. “[Otherwise,] pregnant women and their clinicians were left to weigh the documented risks of COVID-19 infection against the unknown safety risks of vaccination in deciding whether to receive the vaccine.”
V-safe, the US CDC smartphone-based surveillance system, held records of more than 55 million recipients of COVID-19 vaccines, which included 35,691 pregnant women (53.9 percent received the BNT162b2 vaccine and 46.1 percent had the mRNA-1273 vaccine).
Post-vaccination local and systemic reactions among these pregnant women occurred at similar rates as those in the larger group of nonpregnant women in the surveillance system — which as Riley explained, indicates “that the physiologic changes in pregnancy do not materially affect such reactions.”
The most commonly reported side effect was injection-site pain, which was more frequent among pregnant than nonpregnant women. On the other hand, the incidence of headache, myalgia, chills, and fever became substantially more frequent after the second dose compared with the first dose among pregnant women; but still lower than those reported in nonpregnant women.
Women identified as pregnant in the surveillance system could subsequently choose to enrol in the v-safe pregnancy registry, whereby participants would be contacted to answer in-depth questions via telephone calls. The first 3,958 participants in the registry were analysed in the study (43.3 percent were vaccinated in the second trimester, and 25.7 percent in the third trimester), of which 827 had completed their pregnancy.
Among those who had reached the end of pregnancy, 86.1 percent resulted in a live birth — which involved mostly women who had received the first vaccination dose in their third trimester.
Meanwhile, 104 women had spontaneous abortions (12.6 percent) and one resulted in stillbirth (0.1 percent). “These percentages are well within the range expected as an outcome for this age group of persons whose other underlying medical conditions are unknown,” Riley noted.
Among live-born infants, 9.4 percent were born preterm, 3.2 percent were considered small size for gestational age, and 2.2 percent had congenital anomalies — which, again, according to the researchers were consistent with expectation based on published literature.
There were no reports of neonatal deaths.
“These are reassuring data based on reports from pregnant women mostly vaccinated in the third trimester,” said Riley.
In addition, the rates of adverse pregnancy and neonatal outcomes mentioned above among vaccinated women with completed pregnancy were comparable to the incidence rates reported in pregnant populations before the COVID-19 pandemic.
“Although not directly comparable,” the authors noted, as such comparisons are likely limited by differences in clinical, demographic, and social characteristics between these populations, they pointed out that “such comparisons are helpful to provide a crude sense of whether there are any unexpected safety signals in these early data.”
Citing the registry data as “preliminary” and were from a small sample, the researchers said “the findings may change as additional pregnancy outcomes are reported and the sample size increases, which may facilitate detection of rare outcomes.”
Also, none of the live births captured in the v-safe pregnancy registry were from women who were vaccinated in early pregnancy so far, and follow-up is ongoing. Henceforth, the researchers said the risk of adverse outcomes such as congenital anomalies that might be associated with vaccine exposures earlier in pregnancy remains unknown.
“More longitudinal follow-up, including follow-up of large numbers of women vaccinated earlier in pregnancy, is necessary to inform maternal, pregnancy, and infant outcomes,” they said.
Efficacy data from mRNA vaccine
A separate real-world study in Israel showed that the BNT162b2 mRNA vaccine was 78 percent effective in preventing SARS-CoV-2 infection in pregnant women.
The retrospective cohort study followed 7,530 vaccinated pregnant women who were matched 1:1 to 7,530 unvaccinated pregnant women based on age, gestational age, parity, residential area, and influenza immunization status from a pregnancy registry in Israel. [JAMA 2021;doi:10.1001/jama.2021.11035]
During the follow-up period between days 28–70, 10 vaccinated women were infected compared with 46 on in the unvaccinated group (0.33 percent vs 1.64 percent; adjusted hazard ratio [HR], 0.22; 95 percent confidence interval [CI], 0.11–0.43) — corresponding to an estimated vaccine effectiveness of 78 percent.
“The benefit from the vaccine may be somewhat attenuated among this population compared with the general public [previously reported at >90 percent], because pregnant women were generally advised to take extra precautions during the pandemic and to maintain particular adherence to social distancing guidelines, regardless of vaccination status,” explained the researchers.
With increasing time from vaccination, the risk difference between the vaccinated and unvaccinated pregnant women also widened (absolute difference of cumulative incidence, 0.04, 0.77, 2.05 for 10, 28, and 70 days after the first dose), in favour of vaccination.
With regard to safety profile, there were no serious adverse events (AEs) reported. Vaccine-related AEs occurred in 68 women, with headache (0.1 percent) and general weakness (0.1 percent) being the most common, followed by nonspecified pain and stomachache (<0.1 percent for both).
Among the ~18 percent of women who reached the end of pregnancy, there were no differences between the two groups in terms of pregnancy or neonatal outcomes, including preeclampsia, intrauterine growth restriction, abortions, stillbirth, infant birthweight, maternal death, and pulmonary embolism.
“With the pandemic ongoing and pregnant women at high risk for serious illness if infected with COVID-19, vaccination is a critical prevention strategy,” endorsed Riley.
Experts have recommended that COVID-19 should be made accessible to pregnant women, according to guidance issued by CDC, ACIP, and ACOG**. Also, routine pregnancy testing is not required before receiving a COVID-19 vaccine.
Clinical trials are currently under way to specifically assess the effects of COVID-19 vaccines in pregnant persons and their infants.
*CDC: Centers for Disease Control and Prevention
**ACIP: Advisory Committee on Immunization Practices; ACOG: American College of Obstetricians and Gynecologists