Spontaneous Abortion Following COVID-19 Vaccination During Pregnancy

Abstract

This study presents findings from case-control surveillance of COVID-19 vaccination during pregnancy and spontaneous abortion.

COVID-19 infection during pregnancy can be associated with severe maternal morbidity.¹ In the United States, 1 COVID-19 vaccine has been approved and 2 have been authorized for use for pregnant women. To date, data on maternal COVID-19 vaccine safety come primarily from passive surveillance, and studies lack an unvaccinated comparison group.^2,3 Spontaneous abortion has been identified as a priority outcome in studies of maternal vaccine safety,⁴ and concerns regarding risks of spontaneous abortion may be a barrier to vaccination during pregnancy. We present findings from case-control surveillance of COVID-19 vaccination during pregnancy and spontaneous abortion.

Methods

The Vaccine Safety Datalink is a collaboration between the Centers for Disease Control and Prevention and 9 health systems, representing approximately 3% of the US population.⁵ We applied a validated pregnancy algorithm, which incorporates diagnostic and procedure codes and electronic health record (EHR) data, to identify and assign gestational ages for spontaneous abortions and ongoing pregnancies.⁶ Data from 8 health systems (Kaiser Permanente: Washington, Northwest, Northern California, Southern California, and Colorado; Denver Health; HealthPartners; and Marshfield Clinic, Wisconsin) over seven 4-week surveillance periods from December 15, 2020, through June 28, 2021, were included. Ongoing pregnancies between 6 and 19 weeks’ gestation were identified on the last day of each 4-week surveillance period (index date) and contributed data to 1 or more surveillance periods. Spontaneous abortions were assigned to a 4-week surveillance period based on their outcome date; these spontaneous abortions could have been included in the ongoing pregnancy categories during prior periods (eFigure in the Supplement). Vaccination data came from EHRs, medical and pharmacy claims, and regional or state immunization information systems.

We analyzed the odds of receiving a COVID-19 vaccine in the 28 days prior to spontaneous abortion compared with the odds of receiving a COVID-19 vaccine in the 28 days prior to index dates for ongoing pregnancies. Both spontaneous abortions and ongoing pregnancies were assigned to gestational age groups (6-8, 9-13, and 14-19 weeks), surveillance periods, site, maternal age groups (16-24, 25-34, and 35-49 years), number of antenatal visits (≤1 or ≥2), and race and ethnicity. Generalized estimating equations with binomial distribution and logit link were used to account for repeated ongoing pregnancies across surveillance periods. Analyses by manufacturer and gestational age group were also conducted. Analysis was performed using SAS/STAT software version 9.4 (SAS Institute Inc).

This surveillance was approved by the institutional review boards of all participating sites with a waiver of informed consent.

Results

Of 105 446 unique pregnancies, 13 160 spontaneous abortions and 92 286 ongoing pregnancies were identified. Overall, 7.8% of women received 1 or more BNT162b2 (Pfizer-BioNTech) vaccines; 6.0% received 1 or more mRNA-1273 (Moderna) vaccines; and 0.5% received an Ad26.COV.2.S (Janssen) vaccine during pregnancy and before 20 weeks’ gestation. The proportion of women aged 35 through 49 years with spontaneous abortions was higher (38.7%) than with ongoing pregnancies (22.3%). A COVID-19 vaccine was received within 28 days prior to an index date among 8.0% of ongoing pregnancy periods vs 8.6% of spontaneous abortions (Table 1). Spontaneous abortions did not have an increased odds of exposure to a COVID-19 vaccination in the prior 28 days compared with ongoing pregnancies (adjusted odds ratio, 1.02; 95% CI, 0.96-1.08). Results were consistent for mRNA-1273 and BNT162b2 and by gestational age group (Table 2).

Table 1. Receipt of COVID-19 Vaccine in Prior 28-Day Window, by Baseline Characteristics and Surveillance Period, December 15, 2020, Through June 28, 2021.

	Ongoing pregnancy periodsa		Spontaneous abortions
	No.	COVID-19 vaccine, No. (%)	No.	COVID-19 vaccine, No. (%)
All	250 944	20 139 (8.0)	13 160	1128 (8.6)
Maternal age group, y
16-24	37 210	1325 (3.6)	1433	69 (4.8)
25-34	156 166	12 451 (8.0)	6640	493 (7.4)
35-49	57 568	6363 (11.1)	5087	566 (11.1)
Race and ethnicityb
Asian	35 938	4433 (12.3)	2028	262 (12.9)
Black, non-Hispanic	18 790	715 (3.8)	1079	48 (4.4)
Hispanic	86 108	5207 (6.0)	4346	322 (7.4)
White, non-Hispanic	81 834	7571 (9.3)	4272	373 (8.7)
Unknown/other	28 274	2213 (7.8)	1435	123 (8.6)
Gestational age group, wk
6-8	57 355	5196 (9.1)	5238	482 (9.2)
9-13	88 982	6067 (6.8)	6652	528 (7.9)
14-19	104 607	8876 (8.5)	1270	118 (9.3)
Antenatal visits
≥1	89 913	6850 (7.6)	3203	244 (7.6)
≥2	161 031	13 289 (8.3)	9957	884 (8.9)
Surveillance periods
December 15, 2020–January 11, 2021	36 964	711 (1.9)	1767	21 (1.2)
January 12–February 8, 2021	36 981	1696 (4.6)	2097	68 (3.2)
February 9–March 8, 2021	37 030	2322 (6.3)	1871	97 (5.2)
March 9–April 5, 2021	37 144	4934 (13.3)	1903	204 (10.7)
April 6–May 3, 2021	36 191	5654 (15.6)	1864	330 (17.7)
May 4–May 31, 2021	34 545	3485 (10.1)	1811	272 (15.0)
June 1–June 28, 2021	32 089	1337 (4.2)	1847	136 (7.4)

^aFour-week surveillance periods included December 15, 2020, through January 11, 2021; January 12 through February 8, 2021; February 9 through March 8, 2021; March 9 through April 5, 2021; April 6 through May 3, 2021; May 4 through May 31, 2021; and June 1 through 28, 2021. Unique ongoing pregnancies may be counted in more than one 4-week surveillance period and were identified at the last date of the 4-week period.

^bRace and ethnicity came from electronic health data, based on self-report. Race and ethnicity are included because both COVID-19 vaccine uptake and rates of spontaneous abortion vary by race and ethnicity.

Table 2. Adjusted Odds Ratios for Receipt of COVID-19 Vaccine Within 28 Days Prior to a Spontaneous Abortion, December 15, 2020, Through June 28, 2021, Across 8 Vaccine Safety Datalink Sites and Among 264 104 Pregnancy Periods^a.

	Adjusted odds ratio (95% CI)b
Full population	1.02 (0.96-1.08)
By gestational age, wk
6-8	0.94 (0.86-1.03)
9-13	1.07 (0.99-1.17)
14-19	1.08 (0.89-1.29)
By vaccine typec
mRNA-1273 (Moderna)	1.03 (0.94-1.11)
BNT162b2 (Pfizer-BioNTech)	1.03 (0.95-1.11)

^aSee Table 1 footnote a for 4-week pregnancy periods. Unique ongoing pregnancies may be counted in more than 1 surveillance period.

^bGeneralized estimating equation models included gestational age group, surveillance period, maternal age group, number of antenatal visits, site, and race and ethnicity factors and accounted for repeated ongoing pregnancies across surveillance periods.

^cThe Ad26.COV.2.S vaccine is not included due to the small number of exposures.

Discussion

Among women with spontaneous abortions, the odds of COVID-19 vaccine exposure were not increased in the prior 28 days compared with women with ongoing pregnancies. Strengths of this surveillance include the availability of a multisite diverse population with robust data capture. Several limitations should be noted. First, gestational age of spontaneous abortions and ongoing pregnancies were not chart confirmed; pregnancy dating may be inaccurate early in pregnancy. Second, although vaccination status was identified using multiple data sources, the COVID-19 vaccine rollout has been complex and some vaccines may have been missed, potentially biasing findings to the null. Third, data on important confounders, such as prior pregnancy history, were not available. Fourth, it was not possible to assess risks specific to the Ad26.COV.2.S vaccine given the small number of exposures. Despite limitations, these data can be used to inform vaccine recommendations and to counsel patients.

Section Editors: Jody W. Zylke, MD, Deputy Editor; Kristin Walter, MD, Associate Editor.

Supplement 1.

eFigure. Examples of spontaneous abortion cases and ongoing pregnancy controls categorized across 4-week surveillance periods