Norman Beischer Medical Research Foundation research grants for Monash Women's and Children's Health research
Congratulations to the School of Clinical Sciences at Monash Health researchers on receiving the 2024 Norman Beischer Medical Research Foundation research grants.
A pilot feasibility randomised controlled trial investigating the effect of viral transmission mitigation measures on the incidence of preterm birth in highrisk pregnant women ($70,000)
Associate Professor Atul Malhotra and Professor Ben W. Mol
Preterm birth occurs when a baby is born before 37 weeks of pregnancy. It occurs in approximately 9% of Australian pregnancies, and is in quantity and severity the most important issue in obstetric care in Australia and worldwide. Prevention of preterm delivery is therefore a major perinatal research priority.
During the COVID-19 pandemic, it had been unexpectedly observed that there was an association between COVID-19 mitigation measures (community lockdowns in particular) and rates of preterm birth. At Monash Health, the largest maternity provider in Victoria, the team observed during stage 3 and stage 4 lockdowns (in 2020), with significant restriction of movement and human social contact, a 30% reduction in both spontaneous and medically indicated preterm birth, and a delay in delivery for those who still deliver preterm. Hypotheses on the mechanism include reduced rates of infection due to other viruses and pathogens, and reduced movement outside the home setting. In a more detailed analysis, we reported that this effect of mitigation measures during lockdown is strongest in women with previous preterm birth. The researchers have also found that the effect mainly occurs due to less spontaneous preterm labour in these women.
Our observations during the pandemic in combination with our team’s track record in the prevention and treatment of preterm birth provide a unique opportunity to further study this phenomenon. We now need to translate these observations into interventions that could potentially help women at risk of preterm birth. In this project, the team propose an innovative, randomised clinical trial in which they will evaluate whether an intervention in pregnancy mimicking COVID-19 infection transmission mitigation measures will reduce preterm birth rates in pregnant women with previous preterm birth.
The researchers have designed a trial for a pregnancy intervention based on COVID-19 mitigation measures. Described in detail in the proposal, it will contain advice for reduced activity, less social contacts, hand washing, and wearing a facemask when in public. In short, they will randomise 100 women with previous preterm birth (the highest risk group) for a 6-week intervention or care without restrictions as usual. Primary outcome will be delivery before 34 weeks.
This pilot feasibility project will evaluate whether this pregnancy intervention for women at high risk of preterm birth is feasible, and whether it has the potential to result in an improved preterm birth outcome for these women. Their very strong track record in research in preterm birth and in clinical trials provide, in combination with this unique finding of reduced preterm birth, and enormous opportunity in the battle to reduce preterm birth in Australia and globally.
Can biomarker and ultrasound grading detect fetal inflammation in pregnancy’s affected by chorioamnionitis (choriobug pilot)? ($66,567)
Dr Scott Stansfield, Dr Carmel Walsh, Associate Professor Kirsten Palmer, Associate Professor Samuel Forster, Professor Marcel Nold
Chorioamnionitis affects 1-4% of all pregnancies. It is a serious pregnancy condition in which the placenta and membranes surrounding the unborn baby become inflamed, usually as the result of bacterial infection. It is a major contributor to preterm birth; approximately one-third of births before 34 weeks are associated with chorioamnionitis (in Australia, this equates to over 2,700 babies a year). For these newborns, in addition to the significant sequelae of prematurity, there is the risk of significant complications including infection in the blood, pneumonia, severe lung disease, and inflammation of the brain and spinal cord. Chorioamnionitis is also a risk to the mother, as it may result in significant illness with fevers, tachycardia, and pain. If unrecognised or untreated, it may lead to sepsis – a potentially life-threatening condition.
The risk of chorioamnionitis is increased in pregnancies with predisposing complications, including preterm prelabour rupture of membranes, recurrent bleeding, and short cervix. Although these risk factors are well defined, there is currently no readily available test to confirm the diagnosis of chorioamnionitis. Instead, the diagnosis is clinically determined by assessment of a myriad of markers or waiting for overt chorioamnionitis to manifest. This carries great risk of sepsis for the mother and child. In addition to the challenge of accurately establishing a diagnosis, antibiotics (which are the mainstay of treatment), do not cross the placenta well or penetrate the fetal membranes, resulting in inadequate treatment and ongoing risk to the unborn baby.
Consequently, the diagnosis of chorioamnionitis always leads to expediting birth, to ensure the optimal antibiotic treatment for both mother and newborn. Studies of the placenta and membranes of preterm babies reveal the presence of chorioamnionitis even in the absence of clinical signs. This is known as subclinical chorioamnionitis. This is a significant concern for clinicians, as our research has shown that preterm babies born in the setting of subclinical chorioamnionitis demonstrate inflammatory changes that pre-dispose them to severe lung disease. Unfortunately, there is no current method to assess the degree of inflammation in the unborn baby, or to accurately detect subclinical chorioamnionitis. As a result, clinicians face the conundrum of either waiting until clinical signs of chorioamnionitis develop, despite knowing that undetected chorioamnionitis increases the risk to the newborn, versus early delivery, whereby preterm birth in the absence of these inflammatory processes also carries the risks of prematurity to the newborn resulting in unintended harm.
This project aims to identify biomarkers that enable the early identification and staging of chorioamnionitis to better inform timing of birth decisions. The researchers plan to use innovative minimally invasive techniques to assess pregnant women at high risk of chorioamnionitis, and correlate these with histopathology findings of the placenta and membranes, and with the clinical outcome for mothers and babies. The potential significance of this work is profound – accurate diagnosis of chorioamnionitis will allow clinicians to reduce the risk of severe infections for mothers and babies and prevent unintended harm of prematurity that arises when clinicians get the diagnosis wrong or due to subclinical chorioamnionitis.
Calming the immature gut - establishing the first biomarkers for necrotising enterocolitis ($69,950)
Professor Claudia Nold, Professor Marcel Nold, Dr Ina Rudloff, Dr Steven Cho, Dr Ramesh Nataraja, Dr Maurizio Pacilli
In Australia, up to 11% of babies are born prematurely and approximately 3,000 infants (1.6%) are born very preterm (prior to 32 weeks’ gestation). While medical advances have significantly improved their survival, sadly, these babies are at risk of diseases of prematurity such as necrotizing enterocolitis (NEC). NEC is a devastating disease in which parts of the baby’s gut become increasingly inflamed and porous, and ultimately die.
Early clinical symptoms of NEC are non-specific, making an early diagnosis difficult. Once NEC can be diagnosed with certainty, affected infants are often in an advanced disease state with disastrous damage to their gut that can lead to serious complications and death within hours. With a mortality rate of up to 65%, NEC is one of the most common causes of death in extremely premature infants between 15-60 days of life. Those who survive often face long-term consequences such as disability, epilepsy and poor growth. Currently, clinicians cannot predict which babies are at risk of developing NEC and unfortunately, once the disease is diagnosed there are no direct, safe and effective treatments available. Moreover, measures considered to lower a baby’s risk of developing the disease (such as breast- instead of formula-feeding) or that support healing of the gut (including bowel rest [i.e. intravenous administration of nutrition instead of oral feeding] and antibiotics to eradicate pathologic gut bacteria that might contribute to NEC) are largely ineffective once the disease is in an advanced stage.
Since 2012, the team has worked on advancing knowledge in this field, aiming to develop new diagnostic and therapeutic strategies. The researchers have started to collect and safely store blood samples from preterm babies at different time points (including days 1, 7, 14, 21 and 42 of life and day of discharge from hospital) and recorded their clinical data. While some of these babies developed normally without any diseases of prematurity, others were later diagnosed with NEC. For the study proposed here, samples from day 1 and day 7 of life (i.e. before any of the babies had NEC) will be subjected to cutting-edge tests that screen for the presence and abundance of blood protein markers at a scale never seen before (i.e. 7000 markers per sample) in the very low blood volumes (~0.5ml) available from preterm babies for research purposes. The comprehensive data generated by this test will be used to identify differences in the blood of babies that later developed NEC compared to those that did not, laying the foundation for the identification of the very first biomarkers for NEC, detectable in the babies’ blood before they get sick. Such biomarkers would be invaluable as in the future they could be used to easily screen all preterm babies by performing a simple blood test, informing clinicians whether or not babies are at risk of developing the disease. Simple changes in the care of those babies could potentially prevent the disease, ultimately making a real difference to the lives of our tiniest patients and their families in Australia and worldwide.