Study investigates COVID-19 vaccination in pregnancy

The coronavirus disease 2019 (COVID-19) pandemic caused over 519 million infections and over 6.2 million deaths over 2.5 years.

The development of vaccines with high efficacy against the ancestral variant failed to reduce the spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), due in part to the emergence of escape mutations in newer variants of the virus.

The vaccines do protect against severe and critical illness to a large extent, and their administration in pregnancy has been recommended by a number of professional bodies.

A recent paper, to be published in the American Journal of Obstetrics and Gynecology, discusses the risk of COVID-19-related complications in pregnancy and the role of vaccination in reducing this risk.

Introduction

Earlier studies have shown that pregnancy is a high-risk condition for COVID-19, but this has been contradicted by some other reports. The same confusion prevailed early on with respect to COVID-19 vaccination in pregnancy, especially as the pregnancy was a contraindication for inclusion in the vaccine clinical trials.

As a result, pregnancy was not a prioritized condition compared to non-pregnant women of the same age in the USA when vaccines began to be deployed in that country. The Centers for Disease Control and Prevention (CDC) displayed its customary caution in recommending that pregnant women were free to choose whether to take the vaccine or not, pending adequate safety data.

Healthcare workers were, however, prioritized for the vaccine, and as such, most were vaccinated even if pregnant. The situation was similar for pregnant women who also had comorbidities that put them at high risk for severe COVID-19. It was not until November 2021 that the World Health Organization (WHO) endorsed vaccination in pregnancy.

As the safety of the vaccine in pregnancy became more obvious, with safety data piling up alongside more reports of maternal and fetal harm due to the complications of COVID-19 in pregnancy, many professional bodies also took cognizance and shifted their stance to recommend vaccination in pregnancy. This includes the Royal College of Obstetricians and Gynaecologists (RCOG) and the American College of Obstetricians and Gynecologists (ACOG), the Society for Maternal-Fetal Medicine (SMFM), and the CDC.

The chief hindrance now is vaccine hesitancy among pregnant women, which has driven efforts to increase vaccine uptake in this group. These are especially necessary among those who do not acknowledge the risk of complications with the infection, and those who have not been educated with the proper knowledge about the vaccine’s safety. For this reason, the current report provides the latest information so as to enable proper counseling of those who would be benefited from vaccination, at all stages of pregnancy.

Risk from COVID-19 in pregnancy

The increased risk of maternal death or other adverse outcomes in COVID-19 was in part because of the complications of the disease, but also because of lower levels of care because of the pandemic.

Both pregnant women and controls were more likely to have severe COVID-19 in the presence of the same risk factors, such as a higher body mass index (BMI), lower socioeconomic status, other medical conditions, especially pre-existing diabetes, hypertension or chronic lung disease, and increasing age. Infection with this virus in the third trimester, when the lungs are under the greatest pressure because of the growing pregnancy, is another risk factor unique to this condition.

In addition to these host factors, the Delta variant of the virus was associated with the greatest severity of outcome among pregnant hosts, while the Omicron variant appeared to evade immunity induced by the earlier vaccines. These vaccines nonetheless conferred protection against severe disease, with 5% of Omicron cases in the unvaccinated going on to require supplemental oxygen vs no respiratory support in the vaccinated. 

Monitoring vaccine safety in pregnancy

Of the three types of vaccine now available against this virus, the mRNA vaccines have been most used in pregnancy and have the greatest safety and effectiveness data, making them the first choice in this category. Two doses of an mRNA vaccine are recommended 3-8 weeks apart, with a booster shot 5 or more months after completion of the primary series. For pregnant women with some degree of immunodeficiency or immunosuppression, three shots are recommended as the primary series.

Viral vector vaccines are not yet recommended in the UK or Canada for pregnant women, but the CDC permits their selective use. After the two-dose primary series, a heterologous mRNA booster dose is recommended.

Several randomized controlled trials are now ongoing on the COVID-19 vaccines in pregnancy, but their feasibility is an open question since pregnant women are already being encouraged to take the vaccine outside of trials. Such trials include those run by Pfizer-BioNTech, the Janssen vaccine Horizon 1 study, and the Preg-COV pragmatic trial.

The CDC is already monitoring a large cohort of vaccinated pregnant women via the CDC V-safe and V-safe COVID-19 vaccine pregnancy registry, most of whom have received an mRNA vaccine. The Public Health England Inadvertent Vaccination in Pregnancy (VIP) system, and the UK Medicines and Healthcare Products Regulatory Agency (MHRA) ‘Yellow Card’ monitoring system are monitoring vaccine safety in their countries.

The Vaccine Adverse Event Reporting System (VAERS) administered by the CDC is an important early repository of vaccine safety data; however, according to the researchers,

Healthcare providers should be aware that the data has been misappropriated by some groups on social media claiming vaccines are not safe for pregnant people.”

Both the CDC and the ACOG now express complete confidence that the vaccines are to be unreservedly recommended during pregnancy.

No safety concerns

Early findings have not shown any safety concerns from over 35,000 women being followed up by the CDC, over 80,000 in England and 10,000 in Scotland. Adverse reactions appear to be milder in pregnancy

Vaccine-associated myocarditis has not been observed in pregnant cohorts so far, and in the non-pregnant cohort its incidence is below 4 per million doses, 98% being in young males. Most such cases are mild and resolve spontaneously.

Vaccine-induced thrombosis and thrombocytopenia (VITT), alternatively called thrombosis with thrombocytopenia syndrome (TTS), has been reported at an incidence of 7 per one million doses of the viral vector vaccines from AstraZeneca or Janssen. It is most common in adults below 50 years, and a single case has been reported in pregnancy. This patient was not diagnosed correctly at the first visit and eventually died.

The findings of the study show that the use of an mRNA vaccine to confer immunity against COVID-19 is safe in pregnancy. Despite the very uncommon incidence of VITT, the adenovirus vector vaccines also appear to be safe, and are of great value in protecting pregnant women in developing countries against the complications of COVID-19 in pregnancy. The WHO has also classified several inactivated viral vaccines such as Sinopharm, Sinovac and Covaxin as permitted for pregnant women.

Moreover, there are no adverse perinatal outcomes in the babies of vaccinated mothers compared to those born to unvaccinated mothers. The risk of miscarriage, preterm delivery, low birth weight, or admission to the intensive care unit for either mother or child, was comparable in both cohorts. Neither was the risk of fetal anomaly, fetal death or pulmonary embolism increased after vaccination.

Earlier observational studies also confirmed the results of clinical trials of the vaccine in pregnant women, showing it to be highly effective in preventing severe disease following SARS-CoV-2 infection. Of course, long-term follow-up is not yet available but is being performed by the V-safe COVID-19 Vaccine Pregnancy Registry and the Preg-Cov-trial, for 3 and 12 months after birth, respectively.

No contraindications

No contraindication has ever been reported for any of the COVID-19 vaccines in lactation. Again, according to the researchers,

Those planning pregnancy should be reassured that there is no need to delay vaccination because they are trying to conceive or planning fertility treatment, nor is there any need to delay trying to conceive following vaccination.”

The first dose may be given at any time, but the second dose should be completed at least two weeks before the third trimester so as to allow for maximal immunity during this period of greatest risk.

Immunogenicity in pregnancy does not seem to be impaired in any way, and higher levels of maternal antibodies have been shown to cross the placenta following vaccination compared to natural infection.

Vaccine hesitancy is strongest in developed countries. The number of vaccinations needed to prevent one maternal death is 10-fold lower in low-and-middle-income countries, thus restoring the balance.

The strongest predictors of vaccine acceptance are confidence in vaccine safety and effectiveness, the level of worry about COVID-19, belief in the importance of vaccines to their own country, compliance with mask guidelines, trust in public health agencies and health science, as well as attitudes towards routine vaccination.”

Implications

While vaccination may carry a small potential risk, this is exceeded by the benefits to both mother and fetus. In view of their increased risk from COVID-19 complications, including pre-eclampsia, preterm birth, stillbirth and birth by Cesarean section, there is no reason to wait for more safety data when much evidence points to the effectiveness and safety of these vaccines during pregnancy.

Ensuring pregnant persons have unrestricted access to COVID-19 vaccination should be a priority in every country around the globe.”

Written by

Dr. Liji Thomas

Dr. Liji Thomas is an OB-GYN, who graduated from the Government Medical College, University of Calicut, Kerala, in 2001. Liji practiced as a full-time consultant in obstetrics/gynecology in a private hospital for a few years following her graduation. She has counseled hundreds of patients facing issues from pregnancy-related problems and infertility, and has been in charge of over 2,000 deliveries, striving always to achieve a normal delivery rather than operative.