By Curtis Cook, MD, FACOG
A reviewer for the American Journal of Obstetrics & Gynecology (AJOG) and a recipient of several national teaching awards, Dr. Curtis Cook has spoken at several Symposia Medicus conferences over the last seven years. Here, Dr. Cook provides his evidence-based perspective on COVID-19 vaccination for pregnant patients.
The novel coronavirus known as SARS-CoV-2 is responsible for the worldwide pandemic known as COVID-19 after initial cases were reported out of Wuhan, China in December 2019. The first U.S. cases were reported in early 2020 and have, to date, been responsible for more than 500,000 U.S. deaths. Although social distancing, mask use, and good hand hygiene have slowed the spread of infection, our best hope to overcome this devastating disease is still to immunize our vulnerable population as well as a majority of our healthy population.
The CDC has recently elevated pregnant women to an at-risk population based upon data demonstrating an increased risk for hospitalization and severe morbidity and mortality in pregnant patients. A recent report from Washington state published in AJOG revealed that in a population of 240 pregnant patients with severe acute respiratory syndrome for COVID-19, 1 in 10 required hospitalization where 1 in 11 needed critical care and 1 in 80 died of their disease. This was a 3.5-fold higher hospitalization rate than matched, non-pregnant controls. The case fatality rate was 13.6-fold higher than non-pregnant controls. There was also a higher preterm delivery rate of 45.4% with severe or critical disease versus 5.2% in those with mild disease (1).
Thankfully, our scientific community was able to rapidly bring to market vaccines to combat the spread of this disease by building upon years of research into the plausibility of mRNA vaccines (Pfizer and Moderna) and the use of more traditional adenovector vaccine platforms (Johnson & Johnson). The difficulty lies in the exclusion of pregnant patients from these initial trials despite the requests from advocacy groups such as ACOG and SMFM. The WHO has recommended against the COVID-19 vaccine for pregnant patients unless they have increased exposure (e.g. healthcare worker or first responder) or underlying morbidities (e.g. asthma or diabetes). It is understandable that both patients and providers would have many questions about the safety of these vaccines in pregnancy.
Despite pregnant women being excluded from the trials, we do have some data from which to engage in shared decision making with our patients regarding vaccine safety in pregnancy. The risk from mRNA vaccines is believed to be low with the expected degradation of mRNA in the maternal circulation and the adenovector vaccines deliver the coronavirus spike protein gene to the host nucleus for transcription without being integrated into the host DNA. The Advisory Committee on Immunization Practices (ACIP) reports reassuring preclinical studies in animal models. In addition, more than 30,000 pregnant patients have reported to the CDC v-safe registry with no increased risk for birth defects, pregnancy complications, or fetal or neonatal deaths over background expected rates. Reports to the Vaccine Adverse Event Reporting System (VAERS) indicate miscarriage as the highest risk, but still not increased over background risks (2).
Recently, the NEJM released data on 35,691 pregnant patients that reported to v-safe and VAERS between December 14, 2020 and February 28, 2021. There was more injection-site discomfort reported in pregnant patients, but less headaches, myalgias, chills, and fever. Among the 3,958 that have enrolled in the v-safe pregnancy registry, 827 have completed their pregnancy with 86.1% resulting in a live birth and 13.9% reporting a pregnancy loss. The preterm birth rate was 9.4% and the small for gestation rate was 3.2% with no neonatal deaths reported. These numbers are similar to data in trials involving pregnant women obtained prior to the COVID-19 pandemic. Overall, the study reveals no initial concerning safety signals among pregnant patients who received mRNA COVID-19 vaccine (3).
There was a brief pause on the Johnson & Johnson adenovector vaccine over a concern for an induced rare clotting disorder. This pause was lifted on April 23, 2021 by the CDC and FDA on the advice of ACIP who found the risk to be 1.9 per one million people vaccinated. The risk for serious venous thromboembolism remains at least 10-fold higher with COVID-19 infection than with COVID-19 vaccination.
One of the additional benefits of vaccinating pregnant and lactating patients is the passive immunity acquired by their newborns. A recent study published in JAMA followed a cohort of 84 lactating and immunized patients who submitted more than 500 samples for antibody testing. IgG antibodies detected in breast milk reached a peak of 91.7% by week four and reached 97% by week six. No mother or infant experienced any serious adverse event during the study period (4).
Finally, it should also be noted that regulatory authorities required a completed developmental and reproductive toxicity (DART) study prior to approving the planned trials of COVID-19 vaccination in pregnant patients and no evidence of fertility concerns or reproductive toxicity found in animal subjects.
Both ACOG and SMFM recommend that COVID-19 vaccine not be withheld from pregnant and lactating women and encourage shared decision making between the patient and the provider. Hopefully this will provide you a solid foundation from which to have these challenging discussions as we await the data from planned phase 2/3 trials of COVID-19 vaccine in pregnant patients by Pfizer and BioNTech.
- AJOG | Coronavirus 2 in Washington
- SMFM | COVID-19 Vaccine Counseling
- NEJM | Covid-19 Vaccine in Pregnant Persons
- JAMA | SARS-CoV-2 Antibodies in Breast Milk
Dr. Cook is a Clinical Associate Professor at the University of Arizona, Phoenix and an Associate Clinical Professor for Creighton University School of Medicine. He lives in Chandler, Arizona.