By Dr Lalit Kant
Healthcare workers are at the top of the priority list of groups to receive the Covid-19 vaccine. Vaccines have started to be rolled out in some countries while others like India, are giving final touches to their plans. Vaccines that are or would be rolled out are being done after receiving emergency use authorization (EUA) from each country’s regulatory agency. According to the WHO about 70% of healthcare workers, who are the beating hearts of every healthcare system, are women. And a large proportion of them are in the reproductive age group. It is estimated that in US over 3 lakh health workers will be pregnant or breastfeeding as initial doses of vaccine(s) are being rolled out. In India, we have roughly 13 lakhs Anganwadi workers, 9 lakhs ASHAs, and 2 lakhs Auxiliary Nurse Midwives – all women; about 90% of over 30 lakh nurses are women. There are about 1 million MBBS doctors of which 13-15% may be women. A significant number are likely to be pregnant or breastfeeding when the vaccine(s) start to be distributed. Will they or won’t they get an emergency use authorized vaccine?
The fact is that vaccine(s) that have received EUA (like the Pfizer-BioNtech) or are in the pipeline (like the Moderna, AsraZaneca), have not been tested for safety and efficacy in pregnant and lactating women. The traditional sequential approach in a typical clinical trial is to conduct the efficacy trials in non-pregnant women. Vaccine trials do not enrol pregnant and/or breastfeeding mothers until the vaccine has been found to be safely tolerated in non-pregnant women. After a woman enrols in a vaccine trial and becomes pregnant subsequently, they are under intensive follow-up for pregnancy outcomes. Once a vaccine has been found to be effective and safe, a bridging study is usually performed enrolling pregnant women as volunteers. The major advantage of this approach is that pregnant women and the child they carry are protected from the potential risk of the candidate vaccine under trial. The down side is that it delays the vaccine being approved for pregnant women. And also, that a large number of frontline healthcare workers and first responders and essential services may remain unvaccinated. So, following this sequence, the pregnant and lactating women have been excluded from the Covid-19 vaccine trials. And there is no data on safety and efficacy among this group.
Let’s take a step back and see if SARS-CoV-2, the virus causing Covidv-19 disease, affects pregnant women differently than non-pregnant women.
Results of a surveillance being carried out by the US CDC provide information on over 23,400 pregnant women between 15 and 44 years with laboratory confirmed infection with SARS-CoV-2 virus. Even after taking into consideration age, ethnicity, and underlying health conditions, pregnant women were about three times higher risk of requiring admission in ICU (intensive care unit), or ventilator support or heart-lung by-pass machine compared to women who were not pregnant. Deaths were also more likely among pregnant women. The study did not include pregnant women who tested positive but had no symptoms. A report from Sweden shows that the risk of being admitted to ICU may be higher in laboratory confirmed pregnant women than non-pregnant women. In the UK information about outcome of over 400 pregnant women indicate that one in ten required intensive care. According to the WHO pregnant women or recently pregnant women who are older, overweight, and have pre-existing medical conditions such as obesity, hypertension and diabetes seem to have an increased risk of developing severe COVID-19.
Given that pregnant women are at a higher risk of developing severe Covid-19 disease as compared to non-pregnant women, how have regulatory agencies addressed this issue while giving EUA for Covid-19 vaccines?
The first COVID-19 vaccine to receive the EMU was Pfizer-BioNTech vaccine known as BNT162b2. Pfizer/BioNTech vaccine is an mRNA vaccine. The active ingredient is messenger RNA that carries instructions for making the virus’s spike protein. The mRNA is synthetic, not extracted from actual virus. It is delivered in a tiny sphere of inert fatty material called a lipid nanoparticle.
The UK government was the first to accord EUA to the Pfizer-BioNTech vaccine – an mRNA vaccine on 2nd December 2020, but has not recommended the vaccine for pregnant and those breastfeeding. Its Medicines and Healthcare products Regulatory Agency (MHRA) has advised that the Pfizer-BioNTech COVID-19 vaccine has not yet been assessed in pregnancy, until more information is available, those who are pregnant should not have this vaccine.
In the US, the FDA and the CDC have left the door open for the healthcare workers to decide for themselves. The FDA notes that while there have been no specific studies in these groups, there is no contraindication to receipt of the vaccine for pregnant or breastfeeding women. People who are pregnant and part of a group recommended to receive the COVID-19 vaccine, such as healthcare personnel, may choose to be vaccinated. They are advised to discuss potential benefits and risks of vaccination with their healthcare provider. In essence, the vaccine should not be withheld from pregnant individuals who meet the criteria for vaccination.
The Canadian Government has towed the line of its neighbour – the US. It says that though the safety and efficacy of Pfizer BioNTech vaccine in pregnant women has not yet been established, it encourages those who are pregnant and breastfeeding to talk to their doctors, if they are thinking of getting the shot. The vaccine has not been withheld.
It is learnt that Pfizer BioNtech has applied for emergency use authorization in India. Would the DCGI go the UK way or join the US and Canada group. Without the appropriate data, the regulatory agency in India is likely to lean towards the UK’s decision of not recommending the vaccine for healthcare workers who are pregnant or lactating.
It is not difficult to appreciate the dilemma of the regulators. They are dealing with a new virus and a vaccine developed using a new technology without much data specific to pregnancy and lactation. The Pfizer-BioNTech is not a live virus vaccine, and therefore there’s no reason to believe that it would put an expectant mother or her unborn child at risk, nor that it would cause any harm to breastfed babies. But evidence is needed.
Similar situation is likely to emerge when AstaZaneca and Serum Institute of India or Bharat Biotech submit their application for emergency use authorization. Pregnant healthcare personnel will continue to wait till safety and efficacy data emerges. We need far sighted and ethical actions, especially when it comes to such pandemic viral diseases as Covid-19, the precaution should be weighed vis-a-vis the benefits the vaccine would offer.
Generating evidence for Covid-19 in pregnancy and lactation should become a priority. Since the immune responses to vaccination in pregnant women cannot be assumed from that of non-pregnant women and because the assessment of safety of vaccination in pregnancy is unique, pregnant women should be included in appropriately designed vaccine trials. The vaccine developers/ manufacturers should ensure that at least some of the candidate vaccines prioritised for development should use platforms and adjuvants that have been found safe and effective in vaccines developed earlier for other infections.
At the global level the public health and medical establishments must move forward with the responsible and informed inclusion of pregnant women in the design, clinical trials, and implementation of vaccine programs both now and in the future. Their inclusion will ensure that pregnant and breastfeeding healthcare workers receive the same protection as the non-pregnant colleagues. They too should benefit from vaccines accorded emergency use authorization.
The write is dr Lalit Kant , MD ,Infectious Disease Epidemiologist, Independent Consultant