13th February 2021, Dr Chee L Khoo
As often occurs with new medications and vaccines, pregnant individuals were excluded from the clinical trials for these vaccines. As the vaccine roll out begins, women who are pregnant or planning to become pregnant will want to discuss the safety of the vaccines with their GP. We better be up to date with the relevant issues so that we can have a meaningful discussion with our patient.
Which Covid-19 vaccines?
We explored the Covid-19 vaccine candidates back in November 2020 here. Australians will be getting either the Pfizer or AstraZeneca/Oxford (AZO) vaccines. The Pfizer vaccine is an mRNA vaccine while the AZO vaccine uses modified chimpanzee adenovirus ChAdOx1 as a vector to deliver the double-strand (ds) DNA coding for the Covid-19 spike protein . The mRNA and ds DNA code for the spike protein which generates neutralising antibodies. These mRNA codes do not contain live virus and in theory, should be safe for administration during pregnancy.
Nearly all vaccines are allowed during pregnancy if the benefits are expected to outweigh potential risks with the exception of live-attenuated vaccines (such as the measles-mumps-rubella vaccine), which are contraindicated because of theoretical risks of the virus crossing the placenta and infecting the foetus.
Data on the safety of the Covid-19 vaccines administered to pregnant women is limited. None of the clinical trials included pregnant women. We do have pending data on pregnancy outcomes of the small number of pregnant individuals inadvertently exposed during the clinical trials but the data is not yet available because pregnancies are ongoing.
The Conversation
Pregnant women considering COVID-19 vaccination will benefit from a discussion with their GP to weigh up the benefits and potential risks of vaccination. Before we do that, we need to discuss the effect of a Covid-19 infection on the pregnancy. Only after that can we weigh up the pros and cons of vaccine vs the pros and cons if the woman is unfortunate enough to catch Covid-19 infecttion.
Does pregnancy increase the susceptibility to Covid-19?
As expected, there is no data on whether pregnancy increases a woman’s susceptibility to covid-19 infection. There are too many variables which affects a woman’s susceptibility to the infection – age, population density, co-morbidities, exposure, social distancing and mask wearing.
Do pregnant women get more severe Covid-19 infections?
Although data were initially unclear as to whether pregnant women are at increased risk of severe complications from COVID-19, a large study from the Centers for Disease Control and Prevention (CDC) provided data suggesting an increased risk. In 450, 000 symptomatic women of reproductive age who were pregnant, admission to an intensive care unit, invasive ventilation, extracorporeal membrane oxygenation, and death were all more likely compared with nonpregnant women of reproductive age (1).
In an analysis from the UK, the rate of stillbirths was 2 to 3 times higher among pregnant women during vs before the pandemic, with rates of 9.3 vs 2.4/1000 births, respectively, although whether the increase is related to COVID-19 infection or other pandemic-related factors is unknown (2).
Does the virus cross the placenta?
Intrauterine transmission of Covid-19 was recently described by Zheng H. et al (4). 6 mothers had mild confirmed Covid-19 infection. All had caesarean deliveries in their third trimester in negative pressure isolation rooms. All mothers wore masks, and all medical staff wore protective suits and double masks. The infants were isolated from their mothers immediately after delivery. This was to ensure that the newborns were not infected by droplets or aerosol during the neonatal period.
Covid-19 was not detected in the serum or throat swab by RT-PCR in any of their newborns. However, virus-specific antibodies were detected in neonatal blood sera samples. The IgG concentrations were elevated in 5 infants. IgG is passively transferred across the placenta from mother to fetus beginning at the end of the second trimester and reaches high levels at the time of birth. However, IgM, which was detected in 2 infants, is not usually transferred from mother to fetus because of its larger macromolecular structure. Inflammatory cytokine IL-6 was significantly increased in all infants. None of the infants presented any symptoms as of March 8, 2020.
Other cases of potential perinatal transmission have been previously reported but presented several unaddressed issues. Some failed to detect Covid-19 in neonates or only reported the presence of specific antibodies (5-6).
Others found the virus in the newborn samples but the transmission route was not clear as placenta, amniotic fluid and maternal or newborn blood were not systematically tested in every mother-infant pair. Transmission via breast milk appears to be unlikely; among 64 samples from 18 mothers, one sample tested positive for Covid-19 RNA, but no replication-competent virus was detected (7).
What about breast feeding?
Data regarding mother-to-infant transmission in the postnatal period have been reassuring when appropriate precautions are taken. In a study of 116 Covid-19–positive mothers who breastfed their newborns, all newborns tested negative for Covid-19 and were asymptomatic. In this study, the infants roomed in with their mothers in a closed Isolette and mothers used a surgical mask and careful hand and breast hygiene before breastfeeding and other interactions with the infant (8).
Data on the effects of COVID-19 vaccines on the breastfed infant are also unavailable. However, the CDC, American College of Obstetricians and Gynaecologists (ACOG) and Society for Maternal-Fetal Medicine (SMFM) are all reassuring about initiating or continuing breastfeeding in a recently vaccinated individual, given the benefits of breastfeeding to the infant and what is known about the safety of other vaccines given during lactation.
The Discussions
Some of the issues to discuss with the pregnant woman are risks of vaccine reactogenicity (eg, fever), timing of vaccination by trimester, evidence for safety of other vaccines who also do not have trial safety data for pregnant women, potential for mitigation of Covid-19 exposure risk (eg, working from home), risk of COVID-19 to the foetus or newborn, and the individual’s risk of complications due to pregnancy, her age, and underlying conditions. Studies to examine the effects of COVID-19 vaccines during pregnancy are in progress. Perhaps, vaccinating the pregnant mother might help to protect the offspring during the immediate neonatal period against Covid-19 infection.
For persons planning pregnancy, there is no evidence nor theoretical concerns regarding effects of COVID-19 vaccines on fertility. It is not necessary to delay pregnancy after COVID-19 vaccination.
References:
- Zambrano LD, Ellington S, Strid P, et al. Update: characteristics of symptomatic women of reproductive age with laboratory-confirmed SARS-CoV-2 infection by pregnancy status—United States, January 22-October 3, 2020. MMWR Morb Mortal Wkly Rep. 2020;69(44):1641-1647
- Khalil A, von Dadelszen P, Draycott T, et al. Change in the incidence of stillbirth and preterm delivery during the COVID-19 pandemic. JAMA. 2020;324(7):705-706. doi:10.1001/jama.2020.12746
- Vivanti, A.J., Vauloup-Fellous, C., Prevot, S. et al. Transplacental transmission of SARS-CoV-2 infection. Nat Commun 11, 3572 (2020). https://doi.org/10.1038/s41467-020-17436-6
- Zeng, H. et al. Antibodies in infants born to mothers with COVID-19 pneumonia. JAMA 323, 1848–1849 (2020)
- Dong, L. et al. Possible vertical transmission of SARS-CoV-2 from an infected mother to her newborn. JAMA 323, 1846–1848 (2020)
- Zeng, L. et al. Neonatal early-onset infection with SARS-CoV-2 in 33 neonates born to mothers with COVID-19 in Wuhan, China. JAMA Pediatr. https://doi.org/10.1001/jamapediatrics.2020.0878 (2020)
- Perlman, J. M. et al. Part 7: neonatal resuscitation: 2015 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations (Reprint). Pediatrics 136, S120–S166 (2015)
- Singh, Y. et al. International evidence-based guidelines on point of care ultrasound (POCUS) for critically ill neonates and children issued by the POCUS Working Group of the European Society of Paediatric and Neonatal Intensive Care (ESPNIC). Crit. Care 24, 65 (2020).