A study published in Nature Medicine looks at the protective effects of COVID-19 vaccination on pregnant women in Scotland.
Dr Edward Morris, President of the Royal College of Obstetricians and Gynaecologists, said:
“This paper shows the devastating consequences contracting COVID-19 in pregnancy can have for mothers and their babies and how crucial it is that pregnant women are vaccinated against the virus.
“While this study looks at the outcomes of births in Scotland, it reflects what we are seeing nationally – that contracting COVID-19 while pregnant can lead to an increased risk of having a stillbirth and the baby being born prematurely.
“The findings of this study are deeply concerning, with the extended perinatal death rate among babies born within 28 days of their mother developing COVID-19 standing at 23 per 1,000 births, while the rate for all babies born in Scotland, regardless of whether their mother had previously had COVID-19, was six per 1,000 births.
“All baby deaths occurred to women who were unvaccinated against COVID-19 at the time of infection.
“We want to reassure women that the vaccine and booster are safe in pregnancy and it is the best way of protecting you and your baby from COVID-19.”
Asma Khalil, Professor of Obstetrics and Maternal Fetal Medicine, St George’s, University of London, said:
“This study again highlights the urgent importance for all pregnant women to ensure that they are fully vaccinated, to protect their own health and that of their babies. This research demonstrates the relatively low uptake of COVID-19 vaccines in pregnant women, with only a third having had the vaccine compared to two thirds of their non-pregnant peers. The study also shows that the overwhelming majority of pregnant women and babies becoming unwell or dying as a result of COVID-19 were unvaccinated. For example, 98% of all pregnant women admitted to the Intensive Care Unit, and all baby deaths, were in unvaccinated women. The pandemic is far from over and with tens of thousands of COVID-19 cases still being reported in the UK every day, it is paramount that pregnant women continue to take up the offer of a vaccine.”
Dr Sarah Hillman, Clinical Lecturer in General Practice, Warwick Medical School, said:
“This national prospective cohort using whole population data from Scotland gives more evidence that vaccination uptake in pregnancy is lower than in the general population and that the morbidity and mortality caused by COVID 19, both for mothers and babies, is highest in those women that are not vaccinated. Increasing uptake of the COVID19 vaccination in pregnant women needs to be a priority. “
Dr Allyah Abbas-Hanif, Chair of the Policy and Communication Group at the Faculty of Pharmaceutical Medicine, and Honorary Senior Clinical Lecturer at Imperial College London, said:
“Women who develop covid-19 in late pregnancy are at increased risk of severe disease, critical care admission and death. This population level study now clearly demonstrates the impact of covid-19 also extends to their babies. Babies born to mums who develop covid-19 in the last trimester, had a four times higher death rate than the expected background rate. This distressing statistic needs to be urgently tackled. The team at Edinburgh, show us again, that pregnant women are bearing the brunt of vaccine hesitancy, with only 32.3% of women giving birth in October having had two doses of the vaccine. We have seen maternal deaths increasing with each progressive wave of the pandemic, a trend reversed in other high-risk groups by the protection afforded by vaccines. Soberingly, despite vaccine availability, intensive treatment protocols and heightened public awareness, covid-19 acquired during or up to 6 weeks after pregnancy led to the death of 17 women and 4 babies over the five months of May-October, in the UK. 15/17 women were unvaccinated (UKOSS data Dec 2021).
“Vaccine hesitancy has been difficult to combat, even with the widespread dissemination of positive safety and efficacy data from ~270,00 pregnant women and increasingly vocal messaging from doctors, academics and women’s advocates. With omicron looming (and covid-19 waves likely every winter), more needs to be done to turn this around. The H1N1 pandemic inspired targeted strategies to increase vaccination in pregnancy, and influenza vaccine coverage rose to 61% in 2020, comparable to the general adult population. We need to build confidence in vaccine safety versus the real risk of covid-19 in pregnancy. Taking the conversation to pregnant women in multiple forms, with consistent endorsement by all, will help this important public health issue U turn. The risks of covid-19 versus effectiveness and safety of vaccination need to be compassionately and consistently discussed on TV, via social media platforms and in person by leaders, advocates and practitioners.
“Deeper to this, is the need to urgently reevaluate the fifty-year-old status quo of excluding pregnant and breastfeeding women from clinical trials and drug development. There is now more medication use and disease in pregnancy than ever before, despite this, only one medicine designed for use in pregnancy has been licensed in four decades. Moving forwards, the covid-19 pandemic must catalyse improved research and health equity for pregnant women and their babies.”
Prof Kevin McConway, Emeritus Professor of Applied Statistics, The Open University, said:
“In statistical terms, this is a sensible study, and overall I do think it provides pretty strong evidence as to why pregnant women should be vaccinated against Covid-19. There is clear evidence that an infection with the virus that causes Covid-19 within a month of birth is associated with a substantial increase in the risk of some of the worst pregnancy outcomes (stillbirths or deaths of the baby within its first 28 days of life). The evidence of an association of an infection at any time during pregnancy with these sad outcomes isn’t so firm, statistically, but there is a certain amount of evidence. Also there’s no evidence from this study of an adverse effect of being vaccinated on the mother or the baby.
“That said, there are some issues to take into account when looking at these results. First, though the study looked at a large numbers of pregnancies (over 140,000), the accuracy of the estimates of the rates of bad outcomes depends more on the number of bad outcomes involved. Out of all the pregnancies studied, 620 of the mothers had an infection within 28 days of birth, and of those, just 14 ended in the sad event of a still birth or the death of the baby in its first 28 days of life. The researchers estimate from this that, in every 1,000 births to mothers with an infection within 28 days of birth, about 23 would end this way, but there’s quite a lot of statistical uncertainty attached to that estimate, and the data are consistent with the rate being somewhere between 13 and 39 of these deaths occurring in every 1,000 births to mothers infected towards the end of pregnancy. It’s more likely that the rate would be somewhere around the middle of this range than near the ends – but even if it were as low as 13 per 1,000 births, that’s still considerably higher than rate of these sad events in all pregnancies in Scotland during the pandemic, which was below 6 per 1,000 births. So the difference in the rate of these sad outcomes in women who became infected within 28 days of the birth, compared to the average for all pregnancies, is really substantial.
“Even in women who were infected in late pregnancy, I should mention that the great majority of pregnancies did not end with the death of the baby. But is it worth the increased risk of being infected by not being vaccinated, and the associated increased risk of a bad pregnancy outcome, given all the evidence that vaccination is not associated with substantial risks to the mother or the unborn baby?
“I should mention some of the limitations of the study, which are described in the research paper. This is an ongoing study. The researchers point out that full data on the outcomes of the pregnancies that occurred later in their data collection may be incomplete. But the data will eventually become available.
“More importantly, they point out that they did not make adjustments to allow for possible confounding factors. That is, there are very likely to be other differences between pregnant women who were vaccinated and those who were not, and between women who became infected during pregnancy and those who did not, apart from whether they were vaccinated or became infected. If some of those other differences are also associated with differences in pregnancy outcomes, then the cause of the observed differences in the rates of stillbirth and death in very early life could, in part at least, be the other differences rather than vaccination or infection. That’s true, and inescapable in an observational study like this. But, given the very much higher rate of bad outcomes in women infected towards the end of pregnancy, compared to the average rate, these other differences would have to have a very marked effect on rates to make the association with infection disappear, if adjustments could be made to allow for the other differences. The researchers say that they plan to look at the effect of such adjustments when they have enough data on pregnancy outcomes to estimate everything precisely enough. But in any case I don’t think that the possibility of these confounding factors changing the estimates should change the advice on the importance of vaccination for pregnant women, particularly given the lack of evidence of harmful effects of the vaccination itself on mother or baby.
“Though the researchers did look at some other possible associations of infection during pregnancy with bad outcomes, such as association with hospitalisation of the mother, the clearest evidence of association with bad outcomes was in the association between infection within 28 days of the birth and the rate of stillbirths and deaths in the baby’s first 28 days of life. An important question is how this association might depend on whether the mother was vaccinated. In fact none of the stillbirths and early baby deaths following infection at any time during pregnancy involved mothers who were vaccinated at the time of their Covid-19 infection. Because the number of stillbirths and early baby deaths found in the study was, thankfully, low – only 14 of these deaths occurred out of all the thousands of pregnancies – we can’t say that it’s absolutely impossible for a vaccinated mother ever to become infected in late pregnancy and then for her baby to die around the time of birth, but the results do indicate that that is very unlikely. But that the detailed estimates of the associations with late infection, in the research report, are about just that, the associations with late infection, and only indirectly about associations with vaccination.”
Dr Peter English, Retired Consultant in Communicable Disease Control, Former Editor of Vaccines in Practice, past Chair of the BMA Public Health Medicine Committee, said:
“This article is not “news” – it is further confirmation of what we have known for a long time. (I blogged about this previously here and here.)
“The study is, however, a good quality study, confirming – beyond any reasonable doubt – that, while pregnant women are no more at risk of catching Covid-19, they are at greater risk than other women of complications, including requiring intensive care or dying; and (even if they don’t require hospitalisation), they are more likely to lose their baby.
“This emphasises the point that pregnant women should be vaccinated; and that being pregnant is an extra reason to be vaccinated, not a contraindication.”
Prof Marian Knight, Professor of Maternal and Child Population Health, and Honorary Consultant in Public Health, Oxford Population Health (Nuffield Department of Population Health, University of Oxford), and NPEU (National Perinatal Epidemiology Unit), said:
“This extremely robust, national, Scottish study shows very clearly shows the strong protective effect of vaccination against covid-19 infection and its consequences. Restricting the cohort to the period when vaccines were available, 77% of covid-19 infections in pregnancy occurred in unvaccinated women, 91% of hospital admissions with covid in pregnancy occurred in unvaccinated women and 98% of intensive care unit admissions with covid-19 in pregnancy were in unvaccinated women. The researchers also highlight a more than four times higher rate of stillbirth or death within the first month of life among babies born within four weeks of their mother’s diagnosis of covid-19 in pregnancy compared with the rate amongst babies born to mothers with no infection. All the baby deaths that occurred were following infections in unvaccinated pregnant women, showing very clearly that vaccination protects both mother and baby.
“However, it also shows concerningly low vaccination rates amongst pregnant women, with only 42% of women who gave birth in October 2021 having received any vaccination. This compares to nearly 85% of women of reproductive age in the general population having received at least one dose of vaccine by the end of the same month. There is an urgent need to ensure that pregnant women can be enabled to receive vaccination wherever they receive care, including in antenatal clinics, in order to prevent further tragic losses of either mothers or their babies.”
Dr Victoria Male, Lecturer in Reproductive Immunology, Imperial College London, said:
“The study presents sobering findings about COVID infection in pregnancy, but reassuring ones about vaccination. Among 79,148 people giving birth in Scotland between 1 March 2020 and 31 October 2021, the chance that the baby would be stillborn or die shortly after birth was increased by roughly four-fold, and the chance of preterm birth by two-fold, in those who had been infected with COVID in the previous 28 days. On the other hand, vaccination was not associated with any increased risk of these outcomes. The findings emphasise the need to increase the uptake of vaccination in pregnancy.
“This study looks at everyone in Scotland who was pregnant on or after the 1st March 2020, with information about COVID infection, vaccination, hospital admission, and outcomes for their babies at birth. Because the study uses population data, it captures all infections and not just those that lead to hospitalisation. However, there may be some incomplete data, particularly within the last three months, because it takes a while to add new data to the database. One possible weakness is that the way the data is collected means the authors cannot distinguish between people going to hospital because of COVID, versus those who go to hospital for other reasons and happen to have COVID, although they have tried to account for this by looking at the background rates at which people go to hospital.
“The main finding of the study is that, for people giving birth within 28 days of a COVID diagnosis, the baby is about four times as likely to be stillborn, or die shortly after birth, as in the general population (22.6 versus 5.6 per thousand births). Babies are also about twice as likely to be born preterm (16.6 versus 8.0 per hundred births). However, there is no increased risk of stillbirth/death shortly after birth or preterm birth in people who are vaccinated in pregnancy.
“These figures for the increased risk of preterm birth and stillbirth following COVID infection in pregnancy are in line with those that have been reported elsewhere. Similarly, the finding that COVID vaccination is not associated with an increased risk of these outcomes is in line with the data we already have about the safety of COVID vaccination in pregnancy.”
Prof Andrew Shennan, Professor of Obstetrics, and Clinical Director South London CRN, Department of Women and Children’s Health, King’s College London, said:
“The benefit of Covid19 vaccination to improving outcomes for the baby has not been previously evaluated. This excellent paper confirms from whole population data in Scotland, pregnancy results in fewer women being vaccinated (32% vs 77%). However over 90% of admissions to hospital were in unvaccinated women. In 104 women admitted to
critical care, 102 were unvaccinated. Baby deaths occurred in around 2% of cases when background rate is about 0.5%, representing a 4 fold increase. This is consistent with data from the United States. The paper illustrates the importance of vaccination in pregnancy, which is known to be safe, and the impact covid has on mother and babies.”
Prof Penny Ward, Independent Pharmaceutical Physician, and Visiting Professor in Pharmaceutical Medicine at King’s College London, said:
“Data from Scotland published today confirm information from elsewhere demonstrating the significant benefits, for both mother and child, of vaccinating pregnant women against COVID-19. The vaccine protected mother from risk of critical illness and the baby from the risk of premature birth, stillbirth and neonatal death. In particular, critical care admissions, while, thankfully, occurring in small numbers of pregnancies, were none the less at least 10 fold more likely among unvaccinated women contracting covid infection than among vaccinated women. Neonatal death was 2-3 times more likely to be experienced by unvaccinated pregnant women than among vaccinated pregnant women. Based on these data, and other data demonstrating the safety of the vaccines at all stages in pregnancy now available, midwives, obstetricians and GPs should urge their pregnant mums to get the vaccine, and, if eligible, the booster for the benefit of themselves and their babies. There is nothing more distressing to families than to lose a young mother and/or her infant to a preventable disease. Let’s act now to stop this happening in the UK.”
‘SARS-CoV-2 infection and COVID-19 vaccination rates in pregnant women in Scotland’ by Sarah J. Stock et al. will be published in Nature Medicine at 16:00 UK time on Thursday 13 January 2022, which is also when the embargo will lift.
Dr Allyah Abbas-Hanif: “Co-chair of the ABPI Maternal Health Group.
No conflicts to disclose.”
Prof Kevin McConway: “I am a Trustee of the SMC and a member of its Advisory Committee. I am also a member of the Public Data Advisory Group, which provides expert advice to the Cabinet Office on aspects of public understanding of data during the pandemic. My quote above is in my capacity as an independent professional statistician.”
Dr Peter English: “Dr English is on the editorial board of Vaccines Today: an unpaid, voluntary, position. While he is also a member of the BMA’s Public Health Medicine Committee (and its chair until Oct 2020), this comment is made in a personal capacity. Dr English sometimes receives honoraria for acting as a consultant to various vaccine manufacturers, most recently to Seqirus.”
Prof Marian Knight: “I lead the national confidential enquiries into maternal deaths and a UK national study of hospitalisation with covid-19 in pregnancy.”
Prof Andrew Shennan: “No conflicts of interest.”
Prof Penny Ward: “I am semi-retired, but I am owner/Director of PWG Consulting (Biopharma) Ltd a consulting firm advising companies on drug and device development. Between December 2016 and July 2019 I served as Chief Medical Officer of Virion Biotherapeutics Ltd, a company developing antiviral treatments for respiratory viral diseases. Previous employee of Roche, makers of tocilizumab (anti IL6 antibody) and CMO of Novimmune, makers of empalumab (anti IFN gamma antibody).”
None others received.