Clincial Studies and Trials
Research Leaders: Professor Caroline Crowther, Professor Jodie Dodd, Ms Philippa Middleton, Dr Rosalie Grivell, Professor Alastair MacLennan, Dr Bill Hague, E/Professor Jeffrey Robinson, A/Professor Ross Haslam, Dr Andrew McPhee, Dr Chad Andersen
The Clinical Studies and Trials Division conducts, promotes and supports high quality randomised trials and studies, to answer research questions of major importance in maternal and perinatal health, across the spectrum from preconception, through pregnancy and childbirth, infancy and later life, of relevance to women and babies worldwide.
ARCTURUS: Australasian Randomised Collaborative Trials Uniquely aRe Us
Three new research initiatives within the Division are focused around the priority themes of care for women with a high-risk pregnancy to improve health outcomes and care around preterm birth.
A*STEROID: Australian Antenatal Study To Evaluate the Role of Intramuscular Dexamethasone versus Betamethasone prior to preterm birth to increase survival free of childhood neurosensory disability.
Both dexamethasone or betamethasone, given to women at risk of preterm birth, substantially improve neonatal and child health. There are conflicting reports as to whether dexamethasone is better than betamethasone. The aims of this randomised trial are to compare the benefits and harms associated with these treatments. This multicentre randomised trial commenced recruiting in 2009, with 13
hospitals participating within Australia by December 2009.
MCA Doppler Study: Fetal middle cerebral artery Doppler velocimetry to determine the timing of second and subsequent fetal blood transfusions in the treatment of fetal anaemia secondary to red cell alloimmunisation - a randomised controlled trial.
Red cell alloimmunisation is estimated to affect 0.1% to 0.6% of all live births. Treatment of the resultant fetal anaemia with intrauterine fetal blood transfusion has been associated with survival rates in excess of 90%. However, intrauterine fetal blood sampling and transfusion is an invasive procedure, with recognised serious complications, which may result in the need for early birth and, rarely, mortality. This multicentre trial aims to assess in the fetus where one intrauterine transfusion has been performed for anaemia due to red cell alloimmunisation whether fetal middle cerebral artery (MCA) peak systolic velocity (PSV) can be safely used to determine the timing of second and subsequent fetal blood transfusions without increasing the risk of adverse fetal and neonatal health outcomes.
DIAMIND Study: Postpartum reminders to test for Type 2 diabetes in women who have experienced gestational diabetes mellitus.
Women who have had gestational diabetes mellitus may go on to develop Type 2 diabetes. Having blood glucose tests after child-birth is important in preventing or delaying Type 2 diabetes through early identification and management. However what is not known is the best time to do the testing, or the best way of sending reminders to women who require a test. The DIAMIND study is a randomised controlled trial designed to help answer these questions, using mobile phone technology.
Six ongoing major trials/studies coordinated by ARCH
The Division's six ongoing major research studies are evaluating care during pregnancy and childbirth, care around preterm birth and care for women with a multiple pregnancy.
LIMIT: Limiting weight gain in overweight and obese pregnant women to improve pregnancy outcomes: a randomised trial. Obesity is a significant health issue for women during pregnancy and childbirth, with estimates suggesting that over 35% of Australian women aged between 25 and 35 years are overweight or obese. There are well-documented risks associated with obesity. The aims of this randomised controlled trial are to assess whether the distribution of a package of dietary and lifestyle advice to overweight and obese women during pregnancy to limit weight gain is effective in improving maternal, fetal and infant health outcomes.
IDEAL: Investigation of dietary advice and lifestyle for women with borderline gestational diabetes. Current clinical practice involves the treatment of women with mild gestational diabetes. It is currently unclear whether the benefits of similar treatment for women with more borderline gestational glucose intolerance outweigh any harm. The aims of this randomised clinical trial are to assess whether treatment of dietary and lifestyle advice, given to pregnant women who have borderline glucose intolerance on screening for gestational diabetes, reduces neonatal complications without increasing maternal risks.
PROGRESS : Progesterone after previous preterm birth for the prevention of neonatal respiratory distress syndrome. Respiratory distress syndrome associated with preterm birth is the major cause of early neonatal mortality and morbidity. Amongst survivors, there is considerable risk of chronic lung disease and long-term neurological disability. Progesterone is involved in maintaining uterine quiescence, and its withdrawal leads to the onset of labour. Although recent reports of progesterone supplementation for women at risk of preterm birth show promise, there is currently insufficient data on clinically important outcomes to enable informed decision-making. This large, international randomised trial is evaluating whether antenatal vaginal progesterone for women who have had a previous preterm birth is effective in reducing the risk of subsequent preterm birth and its associated risk of adverse infant health outcomes.
TWINS: Timing of birth at term; a randomised trial. This multicentre randomised trial is evaluating the optimal time of birth for women with an uncomplicated twin pregnancy at 37 weeks gestation.
PPROMT: Preterm prelabour rupture of membranes close to term. This large, multinational randomised trial is coordinated from the University of Sydney, and is evaluating the optimal time of birth for women with preterm prelabour ruptured membranes between 34 and 37 weeks gestation.
CLOSURE: Skin and subcutaneous fascia closure at caesarean section. This randomised controlled trial is assessing the effects of different methods of skin and subcutaneous fascia closure on maternal wound complication rates. It compares absorbable versus non-absorbable subcuticular suture material for skin closure and closure of subcutaneous fascia versus non-closure.
STARS: Studies, Trials and Assessments after Research Studies
Cerebral Palsy Research Group
The South Australian Cerebral Palsy Research Group continues to lead international research into the causes of cerebral palsy. It has NHMRC funding for its project "Genomic and environmental triggers for cerebral palsy" and has recently been awarded a research grant by the Cerebral Palsy Institute and Foundation of New South Wales.
In the current project, DNA from over 4,000 cases and controls around Australia have been collected using cheek swabs. Large amounts of epidemiological data are being collected from the same pregnancies. New studies are beginning, looking at possible major chromosomal structural changes in cerebral palsy children.
The Cerebral Palsy Research Group has published several novel papers in high impact journals and has presented its research at national and international scientific meetings.
The Group has found significant associations between mutations in genes that control the fetal response to infection and inflammation, and exposure to viruses, particularly of the herpes virus group. These viruses are also associated with increased risk of pregnancy hypertension and preterm birth. These outcomes are more likely when the fetus is genetically susceptible to infection.
The research group has found common gene mutations (polymorphisms) in babies with cerebral palsy and other mutations that may lead to preterm birth. Very preterm birth may result in brain haemorrhage, secondarily causing cerebral palsy. There appears to be an interaction between environmental risk factors for cerebral palsy, for example, prematurity, infection, chronic growth restriction etc. and cytokine polymorphisms. The latter may increase susceptibility to infection, either by down regulating the normal fetal inflammatory response, making the developing fetal neurons vulnerable to destructive viruses, or by up regulating an excessive cytokine response that can damage the developing brain.
Major Follow-up Studies Underway
The ongoing follow-up of children born following antenatal interventions is essential to understand the longer-term implications of pregnancy care on infant and childhood development. Four key multicentre trials, all funded by NHMRC project grants, are underway:
ACTORDS 6-8 year follow-up: the followup of children to early school age to assess the effect of repeat antenatal corticosteroids on childhood growth and development.
ACTOMgSO4: the follow-up of children to early school age to assess the effect of antenatal magnesium sulphate on childhood development.
MiG TOFU: the follow-up of children at early school age to assess the effect of metformin on childhood development.
LIMIT: the follow-up of children at six and 18 months to assess the effect of dietary and lifestyle advice to overweight and obese women during pregnancy to limit weight gain on childhood development.
