Investigating the Impacts of Viral Infections Including SARS-COV-2 in Pregnancy
“Better data is urgently needed to understand the risks to mothers and babies from COVID-19 and other RNA viral infections, as well as which interventions may benefit pregnant women.”
Written by Clare Whitehead MBChB BSc, (Hons) PhD FRANZCOG CMFM, Royal Women’s Hospital and Dept of Obstetrics & Gynaecology, University of Melbourne and Doug Brooks PhD, Clinical and Health Sciences, University of South Australia, Adelaide
12th April 2021
High quality data about the impact of COVID-19 in pregnancy is still lacking.
Despite the immunological changes that occur during pregnancy, to date there is no evidence that pregnant women are more susceptible to becoming infected with SARS-COV-2 compared to women who are not pregnant.
However, emerging data suggests that pregnant women, especially those in the third trimester are more at risk of severe disease. In hospitalised pregnant women in the UK, 1 in 10 required admission to ICU. In the USA, pregnant women were 50% more likely to require ICU admission, and 70% more likely to require mechanical ventilation. In the UK, the case fatality rate was nearly 1%, whereas in Brazil the maternal case fatality rate is as high as 6%. Older mothers (> 35 years) and those with comorbidities including obesity, hypertension and diabetes are at highest risk of adverse outcomes.
The effect of SARS-COV2 on the developing fetus and placenta is unknown. Rates of maternal to child transmission appear low (4-5%), and the majority of neonatal infections likely occurr after birth. A recent case study demonstrated transplacental infection in late pregnancy, with sequelae in the neonate. However, the mother was viremic, which is rare with SARS-COV2.
There are also no reports of congenital anomalies in pregnancies infected early in gestation, but babies are only now being born, so the true impact is awaited. However, it is possible that SARS-COV2 may have adverse effects on placental development leading to abnormal fetal growth later in pregnancy. We are exploring the effect on placentation and vascular development of the placenta in affected pregnancies, as well as investigating transmission of both the virus and protective antibodies to the fetus and neonate.
We are studying maternal both innate and acquired immune responses in pregnant women to SARS-COV-2 to try and identify those who may be more susceptible to severe disease. We recently published in an animal model that another RNA virus has dramatic effects on immune response and pathological sequalae in viral infection during pregnancy.
In this study, we demonstrate that influenza A virus (IAV) causes maternal and foetal pathology via innate and adaptive vascular inflammation. IAV infection during pregnancy causes severe maternal and perinatal complications despite a lack of vertical transmission of IAV across the placenta. IAV infection during pregnancy drives a significant systemic vascular alteration in pregnant dams, which likely suppresses critical blood flow to the placenta and foetus. Effects on the vasculature were not evident in non-pregnant mice. Maternal IAV infection also elicited hypoxia in the placenta and foetal brain, exacerbating systemic inflammation in the form of cell free foetal DNA and soluble Flt1, as well as placental growth retardation and intrauterine growth restriction.
This study in mice provides a fundamental mechanistic insight and a new paradigm into how an immune response to respiratory viruses, such as IAV, is likely to specifically drive maternal and foetal pathologies during pregnancy. We demonstrated that IAV infection in pregnancy describes a pathogenic pathway that is used by RNA viruses and is exacerbated in pregnancy. This pathway can potentially be used as targets for therapeutic intervention. With relevance to the SARS-Cov-2 virus, the pathway will likely be the same and this has major implications for short and long term maternal and foetal health.
Given the vulnerability of pregnant women to adverse outcomes, it is disappointing that they have been largely excluded from clinical trials of potential therapeutics and vaccines. Many proposed treatments have existing safety profiles in pregnancy, yet systematic exclusion by trial sponsors mean a lack of both safety and efficacy data for these treatments in this population. We are encouraged by inclusion of pregnant women in the UK based RECOVERY trial, and also that the adaptive Australasian ASCOT trial is now being supported by the sponsors to also include pregnant women. Ongoing advocacy is essential to ensure pregnant women and their offspring are not disadvantaged by exclusion from evidence-based care.
Better data is urgently needed to understand the risks to mothers and babies from COVID-19 and other RNA viral infections, as well as which interventions may benefit pregnant women.
Whilst the CHOPAN Registry was rapidly developed to evaluate outcomes for pregnant women in Australia with COVID-19, Australia has no long-term, funded surveillance system for emerging pathogenes in prengnant women. This gap must be addressed to ensure future threats from viral infections to pregnant women and their offspring can be met in a timely manner as well as which interventions may benefit pregnant women.
Student Essay Writing Competition
A big congratulations to Madina Sarwari, who’s essay was just one of many great entries to an essay writing competition run by the Graduate Diploma of Reproductive Sciences (GRS) course, Monash University, and RHA.
First offered through Monash University 32 years ago, the Graduate Diploma of Reproductive Sciences fosters students’ interest in human fertility/ infertility, agricultural production, and wildlife conservation and the environment. Each year we proudly produce between 30-40 graduates that enter all facets of the reproductive science community here in Australia, and further abroad for our international alumni.
This year was a tough one for our students. The world in which they enrolled in this degree will not look the same as the one they will graduate into. Moving a largely practical course online to accommodate for the lockdown restrictions placed on Victorians has been a challenge to educators and students alike. However, it has also forced us to work in new and innovative ways. From starting crowdsourcing campaigns that fight for social justice in women’s health, to creating podcasts and video abstracts, the graduating year of 2020 knows how to be adaptive, resilient and savvy when faced with challenging circumstances.
To promote student motivation alongside our crowdsourcing campaign with Marie Stopes, which aims to generate funding that will allow women who have had an abortion to access long-acting reversible contraceptives for free, we teamed up with RHA to create an essay competition.
(By Dr Kiri Beilby, Senior lecturer and GRS course coordinator)
Madina’s essay addresses the question:
If we know that contraceptives are physiologically 99.7% effective, why do 51% of pregnancies remain unplanned in Australia?
Essay competition winner, Ms Madina Sarwari
“National surveys have reported that 51% of pregnancies are unintentionally conceived each year, with part of this statistic reflecting women who were taking at least one form of contraception at the time of the unplanned pregnancy. This statistic is reflected in both Australian and American studies (1, 2). Improving accessibility and education of contraception, for both women of reproductive age and healthcare providers, is essential in preventing unplanned pregnancy”.
It's Time for More Reproductive Research In Australia
by RHA Founder and Convenor, Prof Jock Findlay
15th May 2020
Australia has experienced an unprecedented number of devastating events in recent times, including drought and animal feed restrictions, floods and massive bushfires. The bushfires alone have burnt out over 18 million hectares in all the States and the Australian Capital Territory. The ecosystems subjected to these onslaughts have suffered greatly, with immense losses of wildlife and of genetically superior breeding stock on affected farms and stations. One billion wildlife animals are estimated to have died and, as a result, 16 mammalian species are now listed as Critically Endangered, Endangered or Vulnerable. Whether these events impact on human fertility is not known. Now is the time to apply our knowledge and expertise in the reproductive sciences to these situations.
Applying the Reproductive Sciences
Many endangered species can be bred in captivity, using assisted reproductive technologies, developed originally for humans and many by Australians, such as freezing sperm, in vitro fertilization (IVF) and embryo transfer. For some species, this will require further research before it can be applied in the field. For others, it is available now. Examples are the recent use of IVF and embryo transfer to produce cheetah cubs in the USA1 and Corroboree frogs in Australia2.
Livestock producers who have spent years (if not generations) establishing genetically superior stock have had to reduce their herds and flocks to a bare minimum because of floods and droughts. As conditions improve, they need to re-establish the genetically superior stock as quickly as possible. This can be done by harnessing reproductive technologies and, at the same time, reducing the generation intervals to a minimum.
New Research in Reproductive Health
Stress and environmental factors influence human fertility. We know that environmental factors, not only during pregnancy but also as early as the time of formation of eggs and spermatozoa, can influence pregnancy and the health of the child during its life course. Australian reproductive scientists and clinicians have been at the forefront in providing much of this information (e.g. 3). Smoking during pregnancy is known to affect the outcome of pregnancy and the health of the child4. What effect does bushfire smoke have on human eggs, spermatozoa, and pregnancy and child and adult health? It is well known from global studies that maternal exposure to fine particulate matter is associated with pregnancy disorders that affects maternal and child health both in the short-term as well as life-long effects5. It is reasonable to speculate that exposure to bushfire smoke could increase the risk of pregnancy complications.
Reproductive researchers in Australia have the knowledge and expertise to investigate these questions.
Resolving Competing Interests
Drugs used by humans can have detrimental effects on wildlife fertility. Oral contraceptives that contain steroids, particularly estrogenic-like compounds, are in widespread use. The by-products, excreted mainly in the urine, enter the sewerage systems and can ultimately end up in our waterways. The presence of these estrogenic by-products in the environment are of concern because they can affect the behaviour and fertility of aquatic animals, such as fish. Other human drugs, such as fluoxetine (marketed as Prozac), have also been found to disturb reproduction in wildlife6,7.
These examples of pollution of the waterways by human excretory products underlines a tension between medicinal human use and safety and fertility of aquatic fish and animals. Understanding the dosage effects and minimising the concentrations in waterways is another example where the knowledge and expertise of reproductive scientists in Australia can be critical.
Steroidal compounds are used to stimulate growth in ruminants, particularly in cattle8. Growth stimulants are banned by the EU, so beef exports to that region must be certified free of growth stimulants. This may not always be relevant to other local or overseas markets. Ruminants excrete steroidal growth stimulants in both their faeces and urine that ultimately contaminates the vegetation and waterways used by humans and aquatic wildlife9-11. This situation has created a tension between livestock producers and wildlife exponents that needs resolution by proper research in reproductive biology.
The COVID19 Pandemic
To date, there are no peer-reviewed reports that infection with the SARS-CoV-2 virus causes disruption of the reproductive systems of humans or animals. Some animal species (minks, tigers, cats and dogs) may be susceptible to infection with SARS-CoV-2. It is well known that other viral infections can cause infertility in men and women, including mumps and chlamydia. Now is the time to set up investigations to monitor species infected with SARS-CoV-2 for fertility and fecundity, and any long-term health consequences of infection that can be related back to effects on the reproductive systems. Given their expertise and experience with these type of studies, Australian reproductive scientists are well-placed to provide evidence-based information to underpin policies.
A New Research Field in Reproductive Toxicology
The examples cited above emphasise the dearth of reproductive toxicologists in Australia, compared with the USA and Europe. In the USA for example, there has been a large body of research on the fertility effects of pesticides on alligators (e.g. 12) and bisphenol acetate (BPA), used in plastics, on laboratory animals (e.g. 13). We need to encourage and financially support reproductive toxicology as a field of research in Australia so that we can apply toxicological knowledge to our unique ecosystems and agricultural practices. In addition to research on the influence of substances like steroids and fluoxetine on fertility, there is the added source of environmental contaminants in waste dumps and on ovals, golf courses, and bowling greens that have contaminated soils that should be investigated for their effects on fertility.
Reproductive science in Australia
Australia has a very strong contingent of scientists and clinicians working in the reproductive sciences who are capable of providing the information that we need to maximise the health and future of our people, our livestock and our wildlife.
Jock Findlay, RHA Founder and Convenor
1 Seaworld 2020, “All About Cheetahs”
RHA member Dr Kiri Beilby selected for the Science Technology Australia (STA) STEM Ambassador program
18th March 2020
Dr Kiri Beilby and Ms Nicola Rivers representing RHA at Science Meets Parliament last year
Reproductive biologist and RHA member Dr Kiri Beilby from Monash University’s Department of Obstetrics and Gynaecology has been selected for the Science & Technology Australia (STA) STEM Ambassador Program.
Science Technology Australia (STA) has a long history connecting Parliamentarians with leaders in science and technology to enable federal politicians to gain a deep understanding of the impact of science, technology, engineering and mathematics (STEM) in Australia. Via her Ambassador role, Dr Beilby will work with Labour MP Clare O’Neil in the Victorian Hotham electorate to bridge the gap between science and government.
Dr Beilby is an excellent advocate for the benefits of medical and reproductive research and is a member of the executive board of directors of the Australian Society of Medical Research (ASMR).
RHA were thrilled to have Dr Beilby represent our organisation at Science Meets Parliament in Canberra last November. Dr Beilby was able to inform Parliamentarians of the benefits of Australian reproductive research and how RHA can support their need for evidence-based information.
Meeting a politician? A science advocate's top tips
10th December 2019
· Know your politician before you meet them. Read their maiden speech as a minimum and you will learn a lot about their motivations and what’s important to them.
· Always ask them what you can do for them. Stand in their shoes; hundreds of people tell them what they want from the government. But how can you help them achieve their legacy?
· Never embarrass a politician. You can’t influence someone that won’t talk to you. Praise them for what they have done and advocate for ways to improve policy. Always be respectful no matter what their political persuasion.
· Never go to a meeting with a politician empty handed. Leave them a one-page summary (dot points are ideal) of your key messages (substantiated with evidence where possible).
· Leave the meeting with something to do; a great opportunity to re-engage with them. They may ask you for further information. If they do, always follow through.
· Ask for a photo and share positively on social media. Works for them and for you.
For more information, see here
RHA can also help you by providing material and advice
Public consultation on mitochondrial donation for the prevention of mitochondrial disease
20th November 2019
Mitochondrial DNA disease is a rare, heritable condition that can cause serious health problems and premature death. Mitochondrial donation, used during assisted reproduction, can avoid the transmission of mitochondrial disease from parents to their children. However mitochondrial donation is not permitted in Australia.
The Australian Government has asked NHMRC to consult with the Australian community regarding the potential to introduce mitochondrial donation into clinical practice. The NHMRC is facilitating public consultation from the community to consider the social and ethical issues associated with mitochondrial donation. The public consultation is open until the 29th of November 2019.
RHA’s Founder elected a Fellow of the Australian Academy of Health and Medical Sciences
11th October 2019
Professor Jock Findlay AO has been elected a Fellow of the Australian Academy of Health and Medical Sciences (AAHMS), acknowledging his significant achievements in reproductive health research and his contributions to the field of female reproduction.
Research in reproductive health has led to major advances in the development of assisted reproduction technologies such as IVF, where Australian researchers have led the way in reproductive medicine therapies used around the world. Prof Findlay has been a leader in reproductive biology in Australia and overseas since the 1970s and is internationally recognised for his contributions to our understanding of ovarian physiology. His research continues to investigate the regulation of the ovarian reserve of eggs, and chemoresistance and metastasis of ovarian cancer.
Prof Findlay has long been a passionate advocate for research in reproduction and in 2018 he founded Reproductive Health Australia to highlight the broad impact of Australian reproduction research on human health, wildlife and the environment and agricultural productivity.
Australian researchers part of a global effort to improve the diagnosis and treatment Polycystic Ovarian Syndrome
16th August 2019
Polycystic Ovarian Syndrome (PCOS) is a complex condition in women, involving ovarian changes and altered hormones that can produce a wide variety of symptoms such as abnormal menstrual cycles, reduced fertility, acne, weight gain, excessive hair growth and sleep and mood disturbances. The condition affects 12-18% of reproductive age, yet more than two thirds of women remain undiagnosed.
Diagnosis of PCOS is delayed by an average of two years and the care is often inconsistent due to the multifaceted nature of the condition. Women report a high level of dissatisfaction with the quality of information provided and the importance of prevention, risk reduction for associated chronic disease and mental health is commonly not communicated.
To increase the quality of care for PCOS patients, the first evidence-based international guideline on PCOS was recently published and a summary of the recommendations was later co-published in 3 high quality journals.
The Australian Centre for Research Excellence in PCOS (CREPCOS) led the development of the guideline in partnership with the American Society for Reproductive Medicine (ASRM) and European Society of Human Reproduction and Embryology (ESHRE). The consultation also involved 63 international multidisciplinary experts and consumer members representing 37 international societies and consumer groups across 71 countries, resulting in 166 recommendations and practice points.
The PCOS Guideline provides clinicians with clear advice on best practice based on the best available evidence, expert multidisciplinary input and consumer preferences. Research recommendations have been generated and a comprehensive multifaceted dissemination and translation program supports the guideline with an integrated evaluation program.
View the PCOS guideline here
Find details of the first online course for medical practitioners here
Find resources for women with PCOS here
Reproductive Health Australia publishes review in the international journal Reproduction
17th July 2019
The review “Reproductive science and the future of the planet” showcases how reproductive science can be used to advance human health, livestock production and environmental management.
The review also highlights how Reproductive Health Australia plans to advocate for, and publicise, the health, economic and social benefits of reproductive health research.
You can find the published version of the manuscript here.
Helping the laws of nature
29th May 2019
Interview with Dr Melissa Parrott, reproductive biologist at Zoos Victoria and RHA member
“I hope my research contributes to having the best conservation programs possible, because every species is precious, important and worth saving.”
Dr Marissa Parrott is a reproductive biologist at Zoos Victoria. She has a deep love for animals, especially Victoria’s beautiful indigenous species. She works in an evolving and exciting area of research – ‘female mate choice’ – using animals’ natural behaviours to improve breeding success, which is significant for zoos and captive breeding institutions. Marissa’s work over her career has focussed on devising simple tests using scents from genetically suitable males to provide a choice of mates for females. Marissa monitors the female’s behaviour and timing to determine her choice. This work has more than doubled the breeding success, and reduced the time to pregnancy in species such as the Stripe-faced Dunnart and Mainland Eastern Barred Bandicoot, which is extinct in the wild and the focus of a long-term recovery program.
“One of my favourite moments was finding new critically endangered Mountain Pygmy-possum joeys following our mate-choice research at Healesville Sanctuary.”
Marissa’s work has a practical application for zoos and captive breeding institutions where, traditionally, animals are paired based on pedigree and relatedness to manage the genetics of the population. Choosing suitable males to manage the population genetics, and then providing a female with a choice of those males, may increase breeding success, decrease the time taken to become pregnant, reduce aggression between pairs, and improve the quality, success and survival of young. Females often choose males that are most genetically suitable for themselves, which leads to healthy and fit young.
Marissa’s vision is big. She plans to build on this research to advance local and international breeding programs by freezing scents and then offering them to females. Frozen scents could determine which male would be most successful and accepted by a female, and could be transported across the globe. This would save a large amount of stress, time and cost when moving animals for breeding, and avoiding compatibility issues.
Marissa says, ”there is much to do as each species is different, some females choose mates based on genetic relatedness, while others may choose based on familiarity, age, social dominance, secondary sexual characteristics, displays or other criteria. The more we can find out about a species’ natural behaviours, the better our breeding and reintroduction programs will be”.
“My work at Zoos Victoria is fighting extinction for our most critically endangered species. We have a commitment that no Victorian terrestrial vertebrate species will go extinct on our watch”.