This Practice Advisory was developed by the American College of Obstetricians and Gynecologists’ Immunization, Infectious Disease, and Public Health Preparedness Expert Work Group in collaboration with Laura E. Riley, MD; Richard Beigi, MD; Denise J. Jamieson, MD, MPH; Brenna L. Hughes, MD, MSc; Geeta Swamy, MD; Linda O’Neal Eckert, MD; Mark Turrentine, MD; and Sarah Carroll, MPH.
This Practice Advisory provides an overview of the currently available COVID-19 vaccines and guidance for their use in pregnant, recently pregnant, lactating, and nonpregnant individuals aged 12 years and older. For guidance and recommendations for the use of these vaccines in individuals aged 11 years or younger, please visit the website of the American Academy of Pediatrics. For additional information regarding severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and treatment, see ACOG’s Frequently Asked Questions.
This Practice Advisory has been updated to include the following:
At the time of this publication, three COVID-19 vaccines are currently approved under a BLA or authorized under an EUA by FDA:
For primary vaccination for all populations, an updated 2023-2024 COVID-19 vaccine should be administered.
COVID-19 vaccines are rapidly emerging and additional EUAs and BLA’s are likely to materialize. ACOG will strive to update this guidance as quickly as possible while maintaining accurate, evidence-based information.
The development and use of mRNA vaccines is relatively new. These vaccines consist of messenger RNA (mRNA) encapsulated by a lipid nanoparticle (LNP) for delivery into the host cells. These vaccines utilize the body’s own cells to generate the coronavirus spike protein (the relevant antigens), which, similar to all other vaccines, stimulates immune cells to create antibodies against COVID-19. The mRNA vaccines are not live virus vaccines, nor do they use an adjuvant to enhance vaccine efficacy. These vaccines do not enter the nucleus and do not alter human DNA in vaccine recipients. As a result, mRNA vaccines cannot cause any genetic changes (CDC, Zhang 2019, Schlake 2012). Based on the mechanism of action of these vaccines and the demonstrated safety and efficacy in Phase II and Phase III clinical trials, it is expected that the safety and efficacy profile of the vaccine for pregnant individuals would be similar to that observed in nonpregnant individuals. Further, a growing body of observational data so far have not identified any safety concerns for COVID-19 vaccination during pregnancy.
Protein subunit vaccines contain pieces (proteins) of the virus that causes COVID-19. These virus pieces are the spike protein. The Novavax COVID-19 Vaccine, Adjuvanted (Novavax COVID-19 vaccine), also contains another ingredient called an adjuvant that helps the immune system respond to that spike protein in the future. Once the immune system knows how to respond to the spike protein, the immune system will be able to respond quickly to the actual virus spike protein and protect against COVID-19. Protein subunit COVID-19 vaccines do not use any live virus nor can they cause infection with the virus that causes COVID-19 or other viruses. They do not affect or interact with our DNA. The protein pieces do not enter the nucleus of the cell where our DNA (genetic material) is located, so they cannot change or influence our genes (CDC).
Protein subunit vaccines have been used for more than 30 years. Other examples of protein subunit vaccines include the first licensed hepatitis B vaccine, some influenza vaccines, and acellular pertussis vaccines.
The Novavax COVID-19 vaccine uses an adjuvant known as Matrix M to boost the immune response against the virus that causes COVID-19. Adjuvants have been used in some vaccines for decades, and limited data on the use of aluminum-containing adjuvants in pregnancy are reassuring (Jamieson, 2012, Rasmussen 2021). Matrix M is a novel adjuvant in COVID-19 vaccines that has had limited study in pregnancy. It is made with saponins, which are naturally occurring in the bark of trees. Similar adjuvants have been used in other vaccines that have reassuring safety profiles in clinical trials. ACOG will continue to monitor data regarding the use of Matrix M adjuvant in COVID-19 vaccines.
All currently available COVID-19 vaccines have demonstrated high efficacy among their respective clinical trial endpoints. Additionally, a growing body of evidence suggests that fully vaccinated people are less likely to have asymptomatic infection or transmit SARS-CoV-2 to others. Finally, emerging data indicate that while individuals may still become infected with COVID-19, those who are up to date on their COVID-19 vaccines, including boosters, are less likely to experience severe illness and serious adverse outcomes as a result of SARS-CoV-2 infection (Barda 2021).
Based on results from clinical trials, the Pfizer-BioNTech COVID-19 vaccine was 95% effective at preventing laboratory-confirmed COVID-19 illness in people who received two doses who had no evidence of previous infection (CDC).
Based on results from clinical trials, the Moderna vaccine was 94.1% effective at preventing laboratory-confirmed COVID-19 illness in people who received two doses who had no evidence of being previously infected (CDC).
A prospective cohort study from two academic centers found that vaccinated pregnant and lactating women produced comparable immune responses to nonpregnant controls, and generated higher antibody titers than those observed following SARS-CoV-2 infection in pregnancy. Further, vaccine-generated antibodies were present in umbilical cord blood and breast milk after maternal vaccination (Gray 2021, Prabhu 2021, Juncker 2021).
Each of these vaccines appeared to have high efficacy in clinical trials among people of diverse age, sex, race, and ethnicity categories and among persons with underlying medical conditions. Further, during the rollout of COVID-19 vaccines, data continue to demonstrate high vaccine efficacy in preventing hospitalization and death (ACIP Slides).
On the basis of the results from clinical trials in the U.S., the Novavax COVID-19 vaccine has been shown to be approximately 90% effective overall and 100% effective at preventing severe COVID-19 illness after two doses (ACIP July 2022).
Expected side effects should be explained during counseling, including that they are a normal part of the body’s reaction to the vaccine and developing antibodies to protect against COVID-19 illness.
Most study participants for both the Pfizer-BioNTech and Moderna vaccines experienced mild side effects similar to influenza-like illness symptoms following vaccination (see Table 1 below). In the Pfizer-BioNTech study subgroup of persons aged 18–55 years, fever greater than 38 °C occurred in 3.7% after the first dose and 15.8% after the second dose (FDA 2020). In the Moderna vaccine trials, fever greater than 38°C was reported in 0.8% of vaccine recipients after the first dose, and 15.6% of vaccine recipients after the second dose (FDA 2020). Most of these symptoms resolved by day 3 after vaccination for both vaccines.
As with other available COVID-19 vaccines, most side effects following the Novavax COVID-19 vaccine were mild. Among study participants aged 18–64 years, less than 1% of individuals receiving a vaccine experienced fever greater than 38 °C following the first dose, and approximately 6% experienced fever following the second dose (FDA 2022). Among study participants aged 65 years or older, less than 0.5% of individuals receiving a vaccine experienced fever greater than 38 °C following the first dose, and 2% experienced fever following the second dose. Overall, the Novavax COVID-19 vaccine may result in fewer systemic side effects than mRNA vaccines (FDA 2022).
Patients should be counseled about more severe side effects and when to seek medical care. For more information and details on side effects, see Local Reactions, Systemic Reactions, Adverse Events, and Serious Adverse Events: Pfizer-BioNTech COVID-19 Vaccine from the CDC.
Allergic reactions including anaphylaxis have been reported to be rare following COVID-19 vaccination in nonpregnant individuals. Anaphylaxis has been observed in 5 cases per million doses administered for the Pfizer-BioNTech vaccine and 4.9 cases per million doses administered of the Moderna vaccine (ACIP August 2021). No cases of anaphylaxis were reported in Novavax COVID-19 vaccine clinical trials (ACIP July 2022).
If anaphylaxis is suspected in a pregnant individual after receiving a COVID-19 vaccination, anaphylaxis should be managed the same as in nonpregnant individuals (e.g., rapidly assess airway, breathing, circulation, and mental activity; call for emergency medical services; place the patient in a supine position, and administration of epinephrine) (CDC). Similar to nonpregnant individuals, anaphylaxis may recur after the individual begins to recover, and monitoring in a medical facility for at least several hours is advised, even after complete resolution of symptoms and signs.
For more information on the management of anaphylaxis after COVID-19 vaccination, see CDC’s website.
Since April 2021, cases of myocarditis (ranging from 1 per 100,000 to 2.13 per 100,000) and pericarditis (1.8 per 100,000) have been reported in the United States after mRNA COVID-19 vaccination (Pfizer-BioNTech and Moderna), particularly in adolescents and young adults (Diaz 2021, Witberg 2021). Additionally, cases of myocarditis and pericarditis have been identified in clinical trials following the receipt of the Novavax COVID-19 vaccine (7 per 100,000 in the vaccine group) (Novavax 2022). Reported cases have occurred predominantly in male adolescents and young adults aged 16 years and older. Onset was typically within several days after mRNA COVID-19 vaccination, and cases have occurred more often after the second dose than the first dose. Surveillance of these cases following mRNA COVID-19 vaccination are ongoing.
Clinicians should consider the diagnoses of myocarditis and pericarditis in adolescents or young adults with acute chest pain, shortness of breath, or palpitations. In this population, coronary events are less likely to be a source of these symptoms. In most cases, patients who presented for medical care have responded well to medications and rest and had prompt improvement of symptoms. Clinicians should report all cases of myocarditis and pericarditis post COVID-19 vaccination to VAERS.
For more information, see CDC and the American Heart Association.
To date there has been no association between mRNA vaccines and Guillain-Barre Syndrome (Abara 2023).
Despite ACOG's persistent advocacy for the inclusion of pregnant individuals in COVID-19 vaccine trials, none of the COVID-19 vaccines approved under EUA have been tested in pregnant individuals. However, studies in pregnant women have since been completed and post-market surveillance is ongoing.
Developmental and Reproductive Toxicity Data
Data from Developmental and Reproductive Toxicity (DART) studies for the Pfizer-BioNTech COVID-19 vaccine have been reported in Europe. According to the report presented to the European Medicines Agency, animal studies using the Pfizer/BioNTech COVID-19 vaccine do not indicate direct or indirect harmful effects with respect to pregnancy, embryo/fetal development, parturition, or postnatal development (EMA).
A combined developmental and perinatal/postnatal reproductive toxicity (DART) study of Moderna’s mRNA-1273 in rats was submitted to FDA on December 4, 2020. FDA review of this study concluded that mRNA1273 given prior to mating and during gestation periods at dose of 100 µg did not have any adverse effects on female reproduction, fetal/embryonal development, or postnatal developmental except for skeletal variations, which are common and typically resolve postnatally without intervention (FDA).
According to the Provider Fact Sheet for the Novavax COVID-19 vaccine, in a developmental toxicity study, 0.1 mL of a vaccine formulation containing the same quantity of SARS-CoV-2 rS protein (5 micrograms), one-fifth the quantity of adjuvant (10 micrograms), and inactive ingredients that comprise the formulation buffer (25 mM sodium phosphate, 300 mM sodium chloride, and 0.01% (w/v) polysorbate 80) contained in a single dose of the Novavax COVID-19 vaccine was administered to female rats by the intramuscular route on four occasions: 27 and 13 days prior to mating, and on gestational days 7 and 15. No vaccine-related adverse effects on female fertility, fetal development, or postnatal development were reported in the study (FDA Fact Sheet).
These DART studies provided the first safety data to help inform the use of the vaccine in pregnancy.
Among participants of Phase II/III COVID-19 vaccine clinical studies in nonpregnant adults, a few inadvertent pregnancies that have occurred are being followed to collect safety outcomes.
Post-Administration Pregnancy Surveillance Data
As of February 14, 2022, there have been over 201,000 pregnancies reported in CDC's v-safe post-vaccination health checker (CDC 2021). Based on limited self-reported information, no specific safety signals have been observed in pregnant people enrolled in v-safe; however longitudinal follow-up is needed.
Shortly following the rollout of COVID-19 vaccines CDC launched a v-safe pregnancy registry to collect additional data on COVID-19 vaccines during pregnancy. At the time the registry closed in May 2023 there were approximately 23,000 pregnant individuals enrolled. Data collected from the v-safe pregnancy registry did not indicate any safety concerns based on the reactogenicity profile and adverse events observed among pregnant individuals. Additionally, side effects were similar in pregnant and nonpregnant populations. Specific neonatal outcomes data published in The New England Journal of Medicine, along with pregnancy complication data from 275 completed pregnancies presented at the March 1, 2021 ACIP meeting are included in Table 1.
No differences have been seen when comparing pregnant individuals participating in the v-safe pregnancy registry with the background rates of adverse pregnancy outcomes. It appears that the spontaneous abortion rate following COVID-19 vaccination during pregnancy is consistent with the background rate; however the ideal denominator has not appeared in published literature (Shimabukuro 2021). Data reported by CDC indicate that the proportion of spontaneous abortions reported after COVID-19 vaccination is consistent with the known background rate of this outcome. However, a risk estimate has not yet been established (Shimabukuro 2021, Zauche 2021).
In addition to data reported from the v-safe pregnancy registry, multiple reports from the Vaccine Safety Datalink (VSD) continue to reinforce the safety of COVID-19 vaccination during pregnancy. A case-control study using data from the VSD found that 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 (Kharbanda 2021). In a subsequent retrospective cohort of >40,000 pregnant women in the VSD, COVID-19 vaccination during pregnancy was not associated with preterm birth or small-for-gestational age at birth overall, stratified by trimester of vaccination, or number of vaccine doses received during pregnancy, compared with unvaccinated pregnant women (Lipkind 2022).
In a research letter published in April 2022, investigators evaluated the association between COVID-19 vaccination during early pregnancy and risk of major fetal structural anomalies identified on ultrasonography. Of 2622 patients who received at least 1 dose of COVID-19 vaccine, 1149 (43.8%) were vaccinated within the teratogenic window. Results of this analysis found that vaccination within the teratogenic window was not associated with presence of a congenital anomaly identified on ultrasonography (Ruderman 2022).
Pregnancy was an exclusion criterion for the Novavax COVID-19 vaccine. However, 147 pregnancies were reported during the clinical trial. Of these pregnancies, 56 are ongoing and 41 resulted in a live birth. Additionally, 25 spontaneous abortions (17% of pregnancies, a rate consistent with the general population),13 voluntary terminations, and 1 ectopic pregnancy occurred. No stillbirths have been observed. These data do not indicate a potential risk to the pregnant person or fetus (ACIP July 2022).
A recent systematic review and meta-analysis that included 61 clinical and preclinical studies involving pregnant persons (n=17,719,495) found no safety concerns regarding the administration of COVID-19 vaccines to pregnant individuals (Ciapponi 2023).
Table 1. V-safe Pregnancy Registry Outcomes of Interest in mRNA COVID-19-Vaccinated Pregnant Individuals
Gestational diabetes
Preeclampsia or gestational hypertension