Pregnant women excluded from coronavirus drug trials in precautionary move that 'compounds the problem'
Pregnant women have been excluded from around three-quarters of the coronavirus trials seeking to find an effective treatment for the infection and its complications, research suggests.
Early in the outbreak, the UK’s chief medical adviser Professor Chris Whitty warned “infections and pregnancy are not a good combination in general”.
With the research into the risk being inconclusive, the NHS considers pregnant women to be clinically vulnerable.
The health service does not recommend, however, pregnant women have the coronavirus vaccine, with limited doses being prioritised for the most at-risk individuals.
While there is no evidence Britain’s only approved jab – developed by Pfizer and the German biotechnology company BioNTech – is dangerous during pregnancy, data showing it to be safe are equally lacking.
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Writing in The Lancet Global Health, scientists from the World Health Organization (WHO) argue there is a “public health obligation” to include pregnant women in coronavirus clinical trials, with them having fewer “medical options” if they develop complications.
Other experts largely agreed, with one arguing excluding pregnant women from these trials “compounds the problem”.
‘Exclusion of pregnant women cannot be justified’
“Without explicit and proactive efforts to recruit and retain pregnant women in therapeutic trials for COVID-19 [the disease caused by the coronavirus], expectant mothers will suffer from having fewer medical options available to them, because we are not including them in clinical trials,” said study author Dr Melanie Taylor.
“There is a very real possibility treatment could become approved for treatment of COVID-19 without evidence-based guidance for use in pregnant women.”
While evidence is limited, pregnant women with the coronavirus appear to be at greater risk of requiring intensive care and ventilation.
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“The systematic exclusion of pregnant women cannot be justified on the basis of safety as many of the medications being evaluated are either not harmful in pregnancy, or their risks are minimal,” said co-author Dr Loulou Kobeissi.
“We are concerned the resulting evidence gaps and delays will limit our understanding of the effects of treatment, dosing and side effects in this important population, which can be vastly different from other groups due to the physiological changes that come with pregnancy.”
This echoes similar calls from other medical societies, like the American Academy of Obstetrics and Gynecologists, and the Society of Fetal Medicine in India.
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‘Public health obligation’ to include pregnant women
The WHO scientists analysed the exclusion criteria of studies listed in 10 international clinical trial registries.
Of the 155 trials registered in April, 124 (80%) excluded pregnant women.
By July, 538 of the 722 trials (74%) did not allow expecting mothers to take part.
Six key drugs were evaluated in 176 trials, of which 130 (73%) excluded pregnant women, despite these same medications being known to be safe while expecting.
Out of the 35 trials evaluating the effectiveness of high-doses vitamins like A and D, 27 (77%) left out expecting mothers.
This is despite safety data showing these vitamins have a minimal risk on birth outcomes, or none at all.
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Explanations were not always given as to why pregnant women were excluded from these trials.
The WHO scientists believe it is likely due to “perceived risks around use in expectant mothers and medication exposure to foetuses or neonates [newborns]”.
This is despite the Council of International Organizations of Medical Sciences issuing international ethical guidelines in 2016, stating expecting mothers should not be considered vulnerable in clinical research.
It also gave detailed guidance on how to safely include pregnant and breastfeeding women in trials.
The WHO team believes pregnant women should be given the right to make their own informed decision when it comes to taking part in studies.
“With the emergence of the COVID-19 crisis and future epidemics to come, we have a public health obligation to promote inclusion of pregnant women’s interests in research and reduce their vulnerability,” said Dr Kobeissi.
“Pregnant women should be provided with clear messaging in lay language on the potential benefits and risks of exposure to candidate medications for treatment through their participation in clinical research, and should have facilitated access to obtain the needed health information, so they can make an informed decision as soon as they perceive the need to.”
Are pregnant women more at risk of coronavirus complications?
The Royal College of Obstetricians and Gynaecologists has stressed “there is no evidence pregnant women are more likely to get seriously ill from coronavirus but pregnant women have been included in the list of people at moderate risk (clinically vulnerable) as a precaution”.
Concerns were raised early in the outbreak that an infected mother could pass the coronavirus to her unborn baby.
After looking at all the research available up to April, scientists from Midwestern University in Arizona stated there was “no conclusive evidence” to back this up.
With some babies testing positive for the infection, it has been suggested they likely caught it “after being brought into the world rather than in the womb”.
This could be in the delivery room, via the birth canal or even from a mother’s fingers, experts have speculated.
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Speaking of the WHO’s research, Professor Neena Modi from Imperial College London said: “The issue is important because pharmacokinetics, pharmacodynamics, safety profiles and toxicity differ between pregnant and non-pregnant women.”
Dr Luke Allen from the University of Oxford added: “Whilst it is easy to understand why drug companies, trial leaders and ethics committees might be nervous about including pregnant women in studies, the truth is leaving them out actually compounds the problem, as we will not know whether emerging COVID treatment options are effective for this special group.
“The situation is especially damnable when trials are testing medicines and vitamins that are already known to be safe.”
Dr Catriona Waitt from the University of Liverpool argued, however, it is vital to be “cautious”.
“I think we need to take a cautious approach particularly with novel compounds and where the actual risk versus benefit for that pregnant woman and infant might be less clear,” she said.
“For example, during the Ebola outbreak, pregnant women would almost all die without treatment and all newborns died.
“However, pregnancy is not a massive risk factor in COVID-19, the issue is more to do with ventilation being more challenging in late pregnancy, should it be required.
“Therefore, for Ebola, it made sense to take greater risks earlier; whereas for COVID-19 it is preferable to wait until more is known about the general risk profile of a novel drug or therapeutic before giving it to pregnant women.
“However, if a drug is known to be safe in pregnancy there is really no reason at all to use pregnancy to exclude women from research.”
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