How safe are COVID-19 vaccines in pregnancy, and why is it important to include pregnant women in clinical trials?

Recent news stories have reported that one in six patients requiring life-saving care for COVID-19 in England are unvaccinated pregnant women.

Pregnant women have received inconsistent advice from medical authorities and many have been wary of receiving COVID-19 vaccinations. Dr Allyah Abbas-Hanif and Professor Neena Modi , from Imperial College London’s School of Public Health, recently wrote an editorial in the BMJ calling for pregnant women to be included in medicines and vaccine development from the outset to avoid such public health issues.

In the Q&A below, Emily Head speaks to the researchers to understand more about why there is relatively low uptake of the COVID-19 vaccine in pregnant women, the safety of the COVID-19 vaccine in pregnancy, and why it’s important to include pregnant women in clinical trials.

How much lower is COVID-19 vaccine uptake in pregnant women, and why?

AAH: There aren’t comparable rates available, but looking at the numbers we can see that since April 2021, 81,000 pregnant women have received one dose and about 65,000 have received two. When compared with the general population’s uptake of 41 million first doses and 37 million second doses, this is worryingly low.

For most pregnant women, especially if they are vaccinated, COVID-19 will be a mild illness, but it can lead to severe complications for both mum and baby. Over the summer (July to September 2021), 13 pregnant women died of COVID-19 in the UK, 11 of whom were unvaccinated. Sadly, we’ve seen maternal deaths increase with every wave of the pandemic and we are keen to help protect these women.

How has this happened?

AAH: Many women, understandably, have questions about vaccines given during pregnancy, as they want to ensure there are no side effects for their baby. However, for COVID-19 vaccines, these worries have really been compounded by false information that vaccines affect fertility, suspicions surrounding the vaccines’ swift rollout, and inconsistent guidance from authorities on whether or not pregnant women should be vaccinated.

"There is a default position to exclude pregnant women from clinical trials before medicines are approved, which meant the information doctors needed to guide advice in pregnancy was lacking when COVID-19 vaccines were first approved." Dr Allyah Abbas-Hanif Imperial's School of Public Health

There is a default position to exclude pregnant women from clinical trials before medicines are approved, which meant the information doctors needed to guide advice in pregnancy was lacking when COVID-19 vaccines were first approved. It also meant that doctors and medical authorities were not armed with the facts to dispel misinformation, allowing false claims and conspiracy theories to take root and fill the information void. We are now, unfortunately, seeing the devastating effects of this.

NM: The lack of evidence on the use of COVID-19 vaccines in pregnancy also shifted responsibility for decision-making from medicines developers and medical regulators to women and their healthcare advisors, who then had to make a decision without evidence. Extraordinarily, breastfeeding women were also advised not to receive COVID-19 vaccines even though their biology is completely different from that of a pregnant woman. It additionally meant that a woman who was breastfeeding had to choose between stopping breastfeeding (despite the health benefits for her and her baby) and getting the vaccine, which is an unacceptable choice to have to make.

If pregnant and breastfeeding women had been included in clinical trials from the outset they would never have been put in this invidious and unfair position.

How can we be sure COVID-19 vaccines are safe for pregnant women and their babies?

"COVID-19 vaccines protect mums from the severe risks of infection, and there is no data to show increased risk of miscarriage, preterm birth or birth defects.” Dr Abbas-Hanif

AAH: Although clinical trial data in pregnant and breastfeeding women were limited in the first few months following approvals, there is now a huge amount of positive data. There are eight clinical studies that include nearly 80,000 pregnant women, plus real-world data from 220,000 pregnant women vaccinated in the UK and US. Data continues to accumulate and all of these studies show the benefits outweigh any risks. COVID-19 vaccines protect mums from the severe risks of infection, and there is no data to show increased risk of miscarriage, preterm birth or birth defects in the babies of women who received COVID-19 vaccines. In fact, the data show protective antibodies actually pass to the baby in the womb and through breastfeeding.

NM: Vaccination during pregnancy is routine for many diseases, but ‘live’ vaccines are not used in pregnant women. COVID-19 vaccines are not live, and the methods to make them have been used for other vaccines already in use in pregnancy.  This is another reason why it would have been reasonable to include pregnant women in the initial COVID-19 vaccine trials.

Why are pregnant and post-partum women typically not included in clinical trials?

AAH: In response to the thalidomide and diethylstilboestrol tragedies fifty years ago, the usual position when developing medicines has been to exclude pregnant women from clinical trials. However, this has led to 98% of all medicines we routinely use having insufficient or no safety data to guide treatment of pregnant or breastfeeding women, which puts them and their unborn babies at risk from unknown side effects.

"If pregnant women had been included in trials from the beginning, advice about getting vaccinated could have been clear from the outset." Professor Neena Modi Imperial's School of Public Health

Sometimes there are good biological reasons to exclude women who are pregnant or might become pregnant from clinical trials, such as if data suggests a chance of effects on the unborn baby. However, if there is no reason that there might be such adverse effects, then these groups should be offered the opportunity to participate in clinical trials.

Well-intentioned but ultimately paternalistic decisions to always exclude pregnant women from trials have left them vulnerable and this needs to be reversed. Women are capable of making informed decisions about whether or not to participate in a trial. Women need to be able to benefit from research, and not be excluded. They also need to be able to participate safely.

NM: We now know pregnant women are at greater risk of severe outcomes from COVID-19 than non-pregnant women. So, if they had been included in trials from the beginning, advice about getting vaccinated could have been clear from the outset. Instead, authorities around the world have issued inconsistent advice, and continue to do so. It’s no wonder in our interconnected world that women do not know whom to believe, and bad actors with completely misleading and false views have been able to flourish.

How can we safely include pregnant women in trials?

NM: Our new editorial in the BMJ argues that inclusion should become the default unless there is good scientific justification (such as the likelihood of harming the unborn baby) to exclude them. This will enable women to be informed on the basis of evidence – not supposition or fear, help counter vaccine hesitancy and misinformation, and improve confidence in new treatments. Women should be consulted about their views on trial participation. Medicines regulators have a responsibility to ensure that the interests of all segments of society are represented in medicines and vaccines development.

"Inclusion should become the default unless there is good scientific justification to exclude pregnant and breastfeeding women." Professor Modi

AAH: Developing new treatments is a rigorous process, with lots of steps . The first priority of medicines development is to understand how the treatment works inside biological systems, so investigators look at animal data and use pharmacokinetic modelling techniques. A lot of work has to be performed to ensure medicines are as safe as possible before they are tested in volunteers. Medicines developers need to work closely with regulators and pregnancy experts to ensure they thoughtfully consider pregnant women at these early stages. If the benefits outweigh the risks, there is no reason to automatically exclude pregnant women in the later stages of clinical trials.

Going beyond that, medicines developers also need to actively diversify who they include in clinical trials to ensure data are available to support patients from all stages of life and all ethnicities.

COVID-19 has forever changed how medicines are developed - for the better. Academics, industry partners, the NHS and regulators are all working together to ensure the findings of critical research are accelerated, but pregnant women and their babies must also be able to benefit from these achievements.

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' Covid-19 treatments and vaccines must be evaluated in pregnancy ' by Allyah Abbas-Hanif, Neena Modi, Stephen Kevin Smith, and Azeem Majeed, published 14 October 2021 in the BMJ