To the editors:
Pregnant women with coronavirus disease 2019 (Covid-19) are at increased risk of adverse effects, and vaccination against Covid-19 is recommended during pregnancy.1.2 However, safety data on Covid-19 vaccination during pregnancy remains limited.3.4
We performed a case-control study using data from Norwegian registries on first trimester pregnancies, Covid-19 vaccination, background characteristics and underlying health conditions (Supplementary Methods and Tables S1 to S3 in the Supplementary Annex, available with the full text of this letter at NEJM.org). We identified all women registered between February 15 and August 15, 2021, who had miscarried before 14 weeks gestation (case patients) and those with first-line confirmation of ongoing pregnancy in the first trimester (controls). Although vaccination during the first trimester is not recommended in Norway, except in women with underlying risk conditions, women who did not know they were pregnant can still be vaccinated in the first trimester. We estimate odds ratios with 95% confidence intervals for Covid-19 vaccination within 5 weeks and 3 weeks before miscarriage or ongoing pregnancy, adjusted for woman’s age, country of birth, marital status, education level, family income, number of children, employment in healthcare, underlying risk conditions for Covid-19, previous test positive for severe acute respiratory syndrome coronavirus 2 and calendar month.
Of the 13,956 women with ongoing pregnancy (of whom 5.5% were vaccinated) and 4,521 women with miscarriages (of whom 5.1% were vaccinated), the median number of days between vaccination and miscarriage or confirmation of ongoing pregnancy was 19 (Fig. S2). In women who had miscarried, the adjusted odds ratios for Covid-19 vaccination were 0.91 (95% confidence interval.) [CI], 0.75 to 1.10) for vaccination in the previous 3 weeks and 0.81 (95% CI, 0.69 to 0.95) for vaccination in the previous 5 weeks (table 1). The results were similar in an analysis that included all available vaccine types (Table S5), in an analysis stratified by the number of doses (one or two) received (Table S6), and in sensitivity analyzes limited to healthcare personnel (for whom vaccination is routinely was recommended except in the first trimester) or women with a follow-up of at least 8 weeks after confirmed pregnancy (to exclude later pregnancy loss) (Table S7).
A limitation of our report is that the registry has no gestational age information at the time of early pregnancy registration, and therefore we were unable to match patients and controls based on gestational age. However, most recognized miscarriages are known to occur between gestational weeks 6 and 10,5 a period comparable to the gestational age at which women in Norway consult a doctor to confirm pregnancy (Fig. S1). Also, only about 40% of women in Norway have a primary care appointment to confirm pregnancy, but the characteristics of these women appear to be similar to those of women who do not have a registered pregnancy confirmation (Table S4). We cannot comment on associations between vaccination and miscarriage that were not recognized clinically. Although adjustment for possible confounders had minimal effect on our results, the registry does not contain information on lifestyle and other factors that could confound our findings (see Supplementary Appendix).
Our study found no evidence of an increased risk of early pregnancy loss following Covid-19 vaccination and complements the findings of other reports supporting Covid-19 vaccination during pregnancy.3.4
Maria C. Magnus, Ph.D.
Håkon K. Gjessing, Ph.D.
Helena N. Eide, MD
Norwegian Institute of Public Health, Oslo, Norway
Allen J. Wilcox, MD, Ph.D.
National Institute of Environmental Health Sciences, Durham, NC
Deshayne B. Fell, Ph.D.
School of Epidemiology and Public Health, University of Ottawa, Ottawa, ON, Canada
Siri E. Huberg, MD, Ph.D.
Norwegian Institute of Public Health, Oslo, Norway
Partly supported by the
Disclosure forms provided by the authors are available with the full text of this letter at NEJM.org.
This letter was published on NEJM.org on October 20, 2021.
1. Center for Disease Control and Prevention. COVID-19 vaccines during pregnancy or breastfeeding. August 11, 2021 (https://www.cdc.gov/coronavirus/2019-ncov/vaccines/recommendations/pregnancy.html).
2. National Health Service. Pregnancy, breastfeeding, fertility and coronavirus (COVID-19) vaccination. September 2, 2021 (https://www.nhs.uk/conditions/coronavirus-covid-19/coronavirus-vaccination/pregnancy-breastfeeding-fertility-and-coronavirus-covid-19-vaccination/).
3. Zauche LH, Wallace B, Smoots AN, et al. Reception of mRNA Covid-19 vaccines and risk of spontaneous abortion. N Engl J Med 2021;385:1533–1535.
4. Khabanda EO, Haapala J, DeSilva M, et al. Spontaneous abortion after COVID-19 vaccination during pregnancy. JAMA 2021 September 8 (E-publication before printing).
5. Mukherjee S, Velez Edwards DRO, Baird DD, Savitz DA, Hartmann KE. Risk of miscarriage in black and white women in a US prospective cohort study. Ben J Epidemiol 2013;177:1271–1278.
|Vaccination status||5 week exposure window||3 week exposure window|
|Ongoing Pregnancies||miscarriages||Unadjusted odds ratio (95% CI)||Adjusted odds ratio (95% CI)*||Ongoing Pregnancies||miscarriages||Unadjusted odds ratio (95% CI)||Adjusted odds ratio (95% CI)*|
|Among all women|
|vaccinated||772||231||0.92 (0.79-1.07)||0.81 (0.69-0.95)||449||146||1.00 (0.83-1.21)||0.91 (0.75-1.10)|
|Among healthcare staff|
|vaccinated||261||75||0.92 (0.70-1.20)||0.93 (0.70-1.22)||147||43||0.94 (0.66-1.33)||0.92 (0.64-1.32)|