Is COVID-19 booster vaccination in early pregnancy associated with an increased risk of spontaneous abortion?
A recent study published in JAMA Network Open determined the relationship between coronavirus disease 2019 (COVID-19) booster vaccination in early pregnancy and spontaneous abortion.
Study: COVID-19 Booster Vaccination in Early Pregnancy and Surveillance for Spontaneous Abortion. Image Credit: MarinaDemidiuk/Shutterstock.com
COVID-19 in healthy young adults is often mild or asymptomatic; however, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections during pregnancy have been linked to increased morbidity and poorer pregnancy outcomes.
Vaccinations can reportedly lower the risks of severe COVID-19 during pregnancy and confer immune protection against complications among newborns.
However, abidance to SARS-CoV-2 vaccine booster guidelines among pregnant women is lower than expected. Barriers to booster vaccinations include uncertainties concerning the effectiveness, safety, and durability of COVID-19 vaccine boosters, especially in pregnant individuals.
Moreover, the increase in immunity post-booster vaccination compared to pre-booster levels among pregnant individuals is not well characterized.
About the study
In the present observational, population-based case-control, SARS-CoV-2 surveillance study, researchers investigated whether COVID-19 vaccine boosters administered before 20 gestational weeks can increase miscarriage risks.
The study, conducted between 1 November 2021 and 12 June 2022, included women aged between 16 and 49 who were six to 19 weeks pregnant and registered with Vaccine Safety Datalink (VSD) healthcare systems.
The team assessed women with miscarriages (cases) and those with ongoing pregnancies (controls) over successive surveillance periods based on calendar times and pregnancy outcome dates.
The primary study exposure was the administration of the third (booster dose) messenger ribonucleic acid (mRNA) SARS-CoV-2 vaccine (Moderna’s mRNA-1273 or Pfizer-BioNTech’s BNT162b2) dose within four weeks before miscarriage or the index date (the middle point of the surveillance period among control individuals).
Secondary study exposures included booster mRNA vaccinations during 42 days of exposure and the administration of any SARS-CoV-2 vaccine booster during 28 days and 42 days of exposure. The team identified cases and controls by applying validated algorithms to patients’ electronic medical records.
The adjusted odds ratio (AOR) values were derived using generalized estimating equations (GEE), adjusting for covariates such as maternal age, gestational age, visits to healthcare facilities during pregnancy, site, ethnicity, and race.
Surveillance was performed between November 2021 and mid-June 2022, with the final data extraction on 3 August 2022. For the primary analysis, assessing a 28.0-day vaccine exposure window, eight surveillance periods of 28 days each were included.
Likewise, for the secondary analyses, assessing a 42-day exposure and including Janssen’s Ad26.COV.2.S vaccination, five surveillance periods of 42 days each were included. The VSD systems included Kaiser Permanente (KP) of Colorado, Washington, the Northwest, North California, and South California; Marshfield Clinic; Health Partners; and Denver Health.
Pregnant women were identified using the Current Procedural Terminology (CPT) and the International Classification of Diseases, tenth revision, clinical modification (ICD-10-CM) codes, and weekly updated clinical data.
The team excluded gestational trophoblastic diseases, pregnancies resulting in therapeutic abortion, ectopic pregnancies, pregnancies resulting from assisted reproduction, and pregnancies with an unknown gestational age from the analysis.
A total of 112,718.0 unique pregnancies were identified, and the mean age of the participants was 31 years. Pregnant women were non-Hispanic Asians (15%), non-Hispanic Blacks (7.50%), Hispanics (36%), non-Hispanic Whites (31%), or belonged to other ethnicities (11%).
Across eight 4.0-week periods of surveillance, out of 270,853 control individuals, 4.0% (n=11,095) had received their booster dose in the 4.0-week window period; out of 14,226 case individuals, 4.0% (n=553) received their booster dose within four weeks of the miscarriage.
Among unique pregnancies, 13% (n=14,226) resulted in miscarriages. The receipt of the booster vaccination was not related to miscarriage in the 4.0-week window period (AOR 0.9). Secondary analyses, including 42 days of exposure (AOR 1.0) and any SARS-CoV-2 vaccine booster in the 4.0 weeks (AOR 0.9) or the 42-day period (AOR 1.0), yielded similar results.
The findings indicated that the chances of receiving a SARS-CoV-2 mRNA vaccine booster during 28 days or 42 days of exposure before miscarriage were not elevated compared to ongoing pregnancies, irrespective of the booster vaccine manufacturer.
The findings of an AOR of 0.9 for the association between booster vaccination and miscarriage were concordant with those of studies previously conducted by the authors following the first and second mRNA vaccine doses (AOR 1.0).
Overall, the study findings showed that COVID-19 vaccine booster administration during the initial pregnancy period was not related to miscarriage, underpinning COVID-19 booster vaccine safety for pregnant women.
However, further research must include prospective studies, active participant recruitment, and bivalent COVID-19 vaccines, adjusting for potential confounders such as maternal level of education, body mass index, and previous history of miscarriage and SARS-CoV-2 infections.