A recent review in the journal Vaccines examines whether coronavirus disease 2019 (COVID-19) risks in pregnant women justify the rare but serious risks potentially linked to the administration of COVID-19 vaccines to pregnant individuals.
Study: Is the Immunization of Pregnant Women against COVID-19 Justified?. Image Credit: Marina Demidiuk/ Shutterstock
Background
Pregnant women have been immunized for decades against certain infections such as tetanus, yellow fever, pertussis, and influenza, to reduce their incidence and resulting sickness and death. However, the currently developed COVID-19 vaccines are not currently offered to pregnant women because they need to be evaluated for safety in both the mother and the fetus. Data is still accumulating to support the safety of COVID-19 vaccines.
However, new vaccines are not subjected to clinical trials in pregnant women, who are typically excluded from such groups. In the current pandemic, there was initial, limited evidence that COVID-19 might have a more severe presentation in pregnancy and might affect the fetus. This has not been considered while designing or executing clinical trials on most of the currently available COVID-19 vaccines.
Without such evidence, several expert bodies have advised that pregnant and lactating women be offered these vaccines. This has led to the belated inclusion of these groups in a few vaccine trials.
Factors arguing for immunization in pregnancy
During pregnancy, young women's typically low-risk COVID-19 profile is altered, putting them into a category at higher risk for COVID-19 complications. This is because changes in respiratory physiology increase the vulnerability of the pregnant woman to more severe disease following lung infections.
In general, COVID-19 in pregnancy is linked to a higher chance of hospitalization, admission to the intensive care unit (ICU), and treatment with invasive or non-invasive ventilation, as well as a higher mortality rate. Despite the low rate of severe COVID-19 in women of reproductive age overall, ICU admissions were required in approximately 10.5 per 1,000 vs. four in pregnant and non-pregnant women, respectively.
For invasive ventilation, the baseline risk of one was almost tripled in pregnancy, while the risk of death was 70% higher, at 1.5 per 1,000. Such findings were validated by a multicenter study (the Intercovid Multinational Cohort Study) on over 2,000 women in 18 countries, including approximately 750 in pregnancy.
In fact, this report showed a 22-times higher risk of death with COVID-19 in pregnancy, with a mortality of 1.6% - an order of magnitude higher than in earlier studies. ICU admissions were five times higher in pregnancy, and the duration of ICU stay was increased by almost four days.
Complications in pregnancy
The studies carried out in the earlier part of the pandemic did not suggest a higher risk of fetal death or miscarriage, probably because of significant heterogeneity between them. The women studied were at different terms of pregnancy, with variable risk factors and widely different levels of care.
The most common complications remain preterm delivery and stillbirth, followed by pre-eclampsia. One meta-analysis reported that the rates for these complications were increased by 82%, 200%, and 33%, respectively. Other researchers suggest the increase is much higher, with preterm births comprising up to 37% of births, and a five times higher stillbirth rate, in pregnancies with COVID-19 than the general population.
Pre-eclampsia risk was increased four times. Cesarean sections were also increased. Women with fever and breathlessness, indicating more severe disease, were more than twice as likely to have a complicated course.
Babies born to mothers with COVID-19 were 11 times more likely to require neonatal care facilities, 1.5 times the risk of jaundice, with 2.5 times the risk of dying.
Mechanisms of COVID-19 complications in pregnancy
The reasons for COVID-19 complications in pregnancy are still being investigated but are probably related to the effect of the illness on the heart and arterial system and the clotting cascade. These effects could lead to poor fetal perfusion and placental dysfunction, causing restricted fetal growth and development.
The pre-eclampsia during pregnancy in COVID-19 is subtly different from that seen in non-COVID-19 cases due to the absence of some markers, such as the placental changes typical of this condition.
While some studies have hinted that the virus causes placental inflammation, poor fetal perfusion, and lack of proper placental perfusion, these are mostly third-trimester studies. As a result, it is not clear whether the damage is caused by the virus or is due to the vascular injury that characterizes COVID-19 itself.
Direct infection of the placental cells by replicating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has not been shown. The levels of the angiotensin converting enzyme 2 (ACE2) receptor used for cell entry are low in placental cells, making it unlikely that the virus directly causes fetal complications. Further research is needed.
Vertical transmission is unlikely, from almost all the studies carried out so far. Breast milk is not considered a route of transmission either; neither is cesarean delivery safer than vaginal delivery in this respect.
Preventing COVID-19 in pregnancy
Available studies show that the current COVID-19 vaccines induce a strong immune response, both humoral and cellular, in pregnancy and lactation, comparable to that in other women. The response is more robust than that induced by natural infection.
Accordingly, babies born to women who have been vaccinated have breast milk antibody titers that are 15 times or higher than in uninfected mothers – even though the binding antibody titers in serum samples of these babies were half those in the mother's blood.
What is the conclusion?
The conclusion appears to be inescapable – pregnant women are at risk for severe illness with COVID-19, along with their unborn infants and newborn babies. Given available data, the messenger ribonucleic acid (mRNA) vaccines now in use are both safe and immunogenic in pregnancy.
Genetic risk factors for long-COVID uncovered in a large multi-ethnic study