On Preliminary Findings of mRNA Covid-19 Vaccine Safety in Pregnant Persons – nejm.org

To the Editor

Shimabukuro et al. (June 17 issue)1 reported preliminary data on the safety of messenger RNA (mRNA) Covid-19 vaccines in pregnancy from the v-safe surveillance system and pregnancy registry. They reported that among 827 participants with a completed pregnancy, the pregnancy resulted in spontaneous abortion by week 20 in 104 (12.6%), and the authors indicated that this proportion was similar to that in the general population. This calculated metric is misleading and does not reflect the real risk of spontaneous abortion.

As stated in the article, among the 827 participants with a completed pregnancy, 700 received their first eligible vaccine dose in the third trimester. These participants should be excluded from the calculation because they had already passed week 20 when they received the vaccination. The risk of spontaneous abortion should be determined on the basis of the group of participants who received the vaccination before week 20 and were followed through week 20 or had an earlier pregnancy loss. Comparison with population-based rates of spontaneous abortion is complicated by the fact that women who are vaccinated at later times during early pregnancy have less time during which they are at risk for pregnancy loss; thus, a crude proportion is likely to underestimate the overall risk.2

Hong Sun, Ph.D.
Dedalus Healthcare, Antwerp, Belgium

No potential conflict of interest relevant to this letter was reported.

This letter was published on September 8, 2021, at NEJM.org.

  1. 1. Shimabukuro TT, Kim SY, Myers TR, et al. Preliminary findings of mRNA Covid-19 vaccine safety in pregnant persons. N Engl J Med 2021;384:22732282.

  2. 2. Sun H. Adjustment is required to calculate the risk of early pregnancy loss with COVID-19 infection or vaccination. Am J Obstet Gynecol 2021 August 3 (Epub ahead of print).

Response

The authors reply: Sun appropriately raises questions about the proportion of women reporting spontaneous abortion in our recent article. We agree that the denominator used in that proportion — 827 completed pregnancies — is not an appropriate denominator for the calculation of a risk estimate or rate.

The number of spontaneous abortions (104) reflects data reported by the participants as of March 30, 2021, during telephone follow-up. In this preliminary report, follow-up information was missing for the majority of pregnancies in which exposure to vaccination occurred in early pregnancy. Among the 1224 women who had been vaccinated before conception or in the first trimester, follow-up through 20 weeks of gestation had been completed for only 204 pregnancies that were known to be ongoing and for 1 pregnancy that resulted in stillbirth. Among the pregnancies that had not yet reached 20 weeks of gestation, there were 10 pregnancies with other outcomes before 20 weeks of gestation, including 8 ectopic pregnancies and 2 induced abortions. For the other 905 pregnancies, follow-up had not occurred to establish whether these pregnancies were ongoing past 20 weeks of gestation. We have amended Table 4 in our earlier publication and have clarified the text.

Subsequently, we completed telephone follow-up for the 905 pregnancies and enrolled additional persons in the v-safe pregnancy registry. To determine the cumulative risk of spontaneous abortion from 6 to less than 20 weeks of gestation, we used life-table methods to perform an updated analysis, now reported in the Journal, involving 2456 women who received at least one dose of an mRNA Covid-19 vaccine before conception or before 20 weeks of gestation.1 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.1

Dana M. Meaney-Delman, M.D.
Sascha R. Ellington, Ph.D.
Tom T. Shimabukuro, M.D.
Centers for Disease Control and Prevention, Atlanta, GA

This letter was published on September 8, 2021, at NEJM.org.

  1. 1. Zauche LH, Wallace B, Smoots AN, et al. Receipt of mRNA Covid-19 vaccines and risk of spontaneous abortion. N Engl J Med. DOI: 10.1056/NEJMc2113891.

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