COVID-19 vaccine does not raise miscarriage risk, show findings from a trio of new US studies
COVID-19 vaccine does not increase the risk of miscarriage in pregnant women, 3 studies show.
USA: According to results from three US studies, pregnant women who were administered at least one dose of the COVID-19 vaccine were not at higher risk of miscarriage than unvaccinated pregnant women.
COVID-19 vaccination during pregnancy and spontaneous abortion.
In a first study, published in the form of a research letter in JAMA, the researchers from the Vaccine Safety Datalink (VSD) surveillance network identified and assigned gestational ages of miscarriages and ongoing pregnancies from Dec 15, 2020, to Jun 28, 2021, using diagnostic and procedure codes and electronic health records.
The VSD is a collaboration between the Centers for Disease Control and Prevention (CDC) and nine health systems that represent about 3% of the US population.
Among 105,446 pregnancies, 13,160 miscarriages occurred, while 92,286 pregnancies were ongoing. Of all pregnant women, 7.8% had received at least one dose of the Pfizer/BioNTech mRNA vaccine, 6.0% received one or more doses of the Moderna mRNA vaccine, and 0.5% received the Johnson & Johnson one-dose adenovirus vaccine before 20 weeks gestation.
Based on the study, the researchers found the following:
- Among 105,446 pregnancies, 13,160 miscarriages occurred, while 92,286 pregnancies were ongoing.
- Of all pregnant women, 7.8% had received at least one dose of the Pfizer/BioNTech mRNA vaccine, 6.0% received one or more doses of the Moderna mRNA vaccine, and 0.5% received the Johnson & Johnson one-dose adenovirus vaccine before 20 weeks gestation.
- Eight percent of women with ongoing pregnancies had received a COVID-19 vaccine by 28 days, compared with 8.6% of women who experienced miscarriages.
- The proportion of women 35 to 49 years who miscarried was higher than the proportion with ongoing pregnancies in that age-group (38.7% vs 22.3%).
The researchers concluded, ", miscarriages were no more likely within 28 days of vaccination compared with ongoing pregnancies (adjusted odds ratio, 1.02), regardless of the type of vaccine and gestational age. "Despite limitations, these data can be used to inform vaccine recommendations and to counsel patients."
Accumulating evidence about the safety of mRNA Covid-19 vaccination in pregnancy
In a letter in the New England Journal of Medicine (NEJM), CDC scientists enrolled 2,456 women who were part of the agency's COVID-19 vaccine safety pregnancy registry.
The researchers found the following:
- Of all participants, 2,022 reported ongoing pregnancies at 20 weeks' gestation, 165 reported miscarriages (154 of whom miscarried before 14 weeks), 188 completed second-trimester follow-up before 20 weeks' gestation, 16 reported other pregnancy outcomes (eg, induced abortion, ectopic or molar pregnancies), and 65 were lost to follow-up.
- Most participants (77.3%) were at least 30 years old, 78.3% were White, and 88.8% were healthcare workers. A little over half the women (52.7%) had received the Pfizer COVID-19 vaccine.
- In the primary analysis, the cumulative risk of miscarriage from 6 to less than 20 weeks' gestation was 14.1%, while an analysis using direct maternal age standardization to the reference population showed a 12.8% risk. The risk of miscarriage rose with increasing maternal age.
- A sensitivity analysis that assumed that all 65 women with recent contact during their first trimester had a miscarriage, the cumulative risk of miscarriage from 6 to less than 20 weeks' gestation was 18.8%. The risk was slightly lower after age standardization, at 18.5%.
The researchers concluded, "our findings suggest that the risk of spontaneous abortion after mRNA Covid-19 vaccination either before conception or during pregnancy is consistent with the expected risk of spontaneous abortion; these findings add to the accumulating evidence about the safety of mRNA Covid-19 vaccination in pregnancy."
Estimated risks consistent with spontaneous abortion reported in the general population
In response to the letter in NEJM, a separate group of CDC researchers updated its analysis of 2,456 pregnant women who received one or two doses of an mRNA COVID-19 vaccine before conception or 20 weeks gestation.
Their preliminary findings, originally published on Jun 17, were based on telephone follow-up of the participants through Mar 30. The letter writer, Hong Sun, PhD, of Dedalus Healthcare in Antwerp, Belgium, had pointed out that the researchers had erroneously included 700 participants vaccinated with their first dose after 20 weeks gestation, arriving at a risk of miscarriage by week 20 of 12.6%. "This calculated metric is misleading and does not reflect the real risk of spontaneous abortion," Sun wrote.
The researchers agreed with Sun's assessment. Since the original analysis, the researchers had completed follow-up for the remaining pregnancies in those vaccinated before 20 weeks' gestation and enrolled more participants in the pregnancy registry.
The new risk estimate was only slightly higher. "The estimated risks (14.1% overall and 12.8% in age-standardized analyses) are consistent with the risks of spontaneous abortion reported in the general population," the authors wrote.
1) Kharbanda EO, Haapala J, DeSilva M, et al. Spontaneous Abortion Following COVID-19 Vaccination During Pregnancy. JAMA. Published online September 08, 2021. doi:10.1001/jama.2021.15494
2) (2021) On Preliminary Findings of mRNA Covid-19 Vaccine Safety in Pregnant Persons. N Engl J Med DOI: 10.1056/NEJMc2113516