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Maternal Perinatal Clinical Trials Unit

Discipline of Obstetrics and Gynaecology
The University of Adelaide
Women's and Children's Hospital
King William Road
North Adelaide South Australia 5006
Phone: 61 8 8161 7619
Fax: 61 8 8161 7652
Email: caroline.crowther@adelaide.edu.au

Specific trials in progress co-ordinated by the MPCTU are:

Trials in progress for which the MPCTU is a collaborating centre

ACTS: Australasian Collaborative Trial of Supplements with vitamin C and vitamin E for the prevention of pre-eclampsia – a randomised controlled trial

This trial has completed recruitment. Followup of the children until 18 months of age is continuing.

Hypertensive diseases of pregnancy are major contributors to maternal and perinatal death and morbidity. Oxidative stress has been implicated in the pathogenesis of pre-eclampsia and antioxidants have been suggested as preventative therapy for pre-eclampsia. There has been limited controlled evaluation of antioxidant therapy in pregnancy with only two randomised trials in women either with or at high risk of pre-eclampsia. There have been calls for large, well-designed randomised controlled trials in low risk women to determine the efficacy of antioxidant therapy in pregnancy. This study of antioxidants vitamin C and E given to nulliparous women from mid pregnancy determines the efficacy of supplementation in reducing the risk of adverse pregnancy outcome for women and their infants. Vitamin C and E supplementation was not found reduce the maternal and perinatal morbidity associated with pre-eclampsia.

Reference:

Rumbold AR, Crowther CA, Haslam RR, Dekker GA, Robinson JS for the ACTS Study Group. Vitamins C and E and the risks of preeclampsia and perinatal complications. New England Journal of Medicine 2006; 354: 1796-1806. (article as pdf)

Jeyabalan A, Caritis SN. Antioxidants and the prevention of preeclampsia--unresolved issues. N Engl J Med. 2006 Apr 27;354(17):1841-3. (Editorial as pdf)

Crowther C. A., Rumbold A. R., Robinson J., the ACTS Study Group. Vitamins C and E and the Prevention of Preeclampsia N Engl J Med 2006; 355:1065-1066. Correspondence (Letter as pdf)

ACHOIS: Carbohydrate Intolerance Study in Pregnancy

This trial has completed recruitment. Followup is continuing.

Reference:

Crowther CA, Hiller JE, Moss JR, McPhee AJ, Jeffries WS, Robinson JS for The ACHOIS Collaborative Group. Effect of treatment of mild gestational diabetes mellitus on pregnancy outcomes. The ACHOIS randomized controlled trial. New Eng J Med. 2005; 352: 2477-86. (article as pdf)

Michael F. Greene, and Caren G. Solomon. Gestational Diabetes Mellitus — Time to Treat (Editorial). New Eng J Med. 2005; 352: 2544-45. (Editorial as pdf)

Crowther C. A., Hiller J. E., Robinson J. S., the ACHOIS Trial Group. Treatment of Gestational Diabetes Mellitus. N Engl J Med 2005; 353:1629-1630. Correspondence (Letter as pdf)

ACTORDS: Australasian Collaborative Trial of Repeat doses of prenatal Steroids to women at risk of preterm birth to reduce neonatal morbidity

This trial has completed recruitment. Followup of the children to 2 years corrected age is continuing. There are plans for followup of the children at early school age.

Infants born preterm are at high risk of neonatal lung disease and its sequelae. Respiratory distress syndrome (RDS), as a consequence of immature lung development, is the principal cause of early mortality and contributes significantly to the high costs of neonatal intensive care. A single course of antenatal corticosteroids reduces the risk of RDS from 40% to 21% in babies born before 32 weeks gestation. Thus, even though prenatal corticosteroids remain the most effective known strategy for reducing the adverse consequences of preterm birth there is still significant neonatal morbidity despite postnatal intensive care and exogenous surfactant.

This trial aims to determine the efficacy or otherwise of repeat doses of prenatal corticosteroids to women who remain at risk of preterm birth more than 7 days after an initial corticosteroid course. If effective, repeat doses of prenatal corticosteroids would be a relatively simple and inexpensive way to improve the health of preterm infants, yield substantial cost savings for neonatal care and provide evidence to guide clinical practice.

References:

Crowther CA, Haslam RR, Hiller JE, Doyle LW, Robinson JS for the ACTORDS Study Group. Neonatal Respiratory Distress Syndrome after repeat exposure to antenatal corticosteroids. Lancet. 2006. (article as pdf)

Montan, Sven; Arulkumaran, Sabaratnam. Neonatal respiratory distress syndrome. (Comment)Lancet. 2006, Vol. 367 Issue 9526, p1878-1879. (Comment as pdf)

C.A. Crowther, R.R. Haslam, J.E. Hiller, L.W. Doyle, J.S. Robinson. Neonatal respiratory distress after antenatal corticosteroids. (Correspondence)(Letter to the editor) The Lancet Sept 23, 2006 v368 i9541 p1065 (Letter as pdf)

BAC - Birth After Caesarean: Planned vaginal birth or planned elective repeat caesarean for women at term with a single previous caesarean section.

This trial has completed recruitment and follow-up to 18 months is continuing .

In Australia in 2003, 28.5% of infants were born by caesarean section. As in most other developed countries the caesarean rate in Australia has continued to rise. Previous caesarean is the main reason (56.6%) for an elective caesarean and 13.9% of caesareans are in women who have had a previous caesarean. Specific clinical initiatives in several countries have focused on reducing the number of caesareans which includes increasing rates for vaginal birth after caesarean. However, recent reports of vaginal birth after caesarean have highlighted risks of increased morbidity including uterine rupture. VBAC rates are declining. There is renewed debate over the relative safety of vaginal birth after caesarean. Two policies of care are standard in current clinical practice within Australia: planned vaginal birth after caesarean (VBAC), and planned elective repeat caesarean. Current evidence from observational studies has limitations indicating a need for a study to assess the infant and maternal health outcomes in these two forms of care. This study will help provide better information about the safety of these two forms of care.

Borderline Gestational Diabetes Mellitus
Dietary and lifestyle advice for women with borderline gestational Diabetes Mellitus.

The trial is open for other centres to join the study.

With the publication of the ACHOIS trial it is now clear that treatment of pregnant women with mild gestational diabetes, formerly defined as impaired glucose tolerance, is beneficial for women and their infants (Crowther et al 2005). There remains, however, a lack of high quality evidence as to whether the benefits of similar treatment for women with borderline gestational glucose intolerance outweigh any harms. The recent report of a randomised trial in women who had a positive oral glucose challenge test and a subsequent normal oral glucose tolerance test and received treatment with dietary advice and blood glucose monitoring showed promising results, in that the risk of macrosomia was reduced (Bonomo et al 2005). However there are insufficient data from this or other studies about clinically important health outcomes such as other infant morbidity, maternal physical and psychological morbidity and costs to enable informed decision-making. The aims of this large, multicentre 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, (defined as a positive oral glucose challenge screening test followed by a normal oral glucose tolerance test), reduces neonatal complications without increasing maternal risks, and whether resources should be allocated for such treatment.

DAT: The influence of acupuncture stimulation on reducing period pain in young women: a randomised controlled trial

This trial has completed recruitment and followup to 12 months is continuing.

Period pain is frequently experienced by young women. This single blind trial examined whether acupuncture reduced period pain and improved their quality of life. Women were randomly allocated to an acupuncture treatment group or a control acupuncture group. The study intervention lasted three months with women receiving three weekly treatments prior to their period. Women received a postal questionnaire three and six months following their participation in the trial to assess longer term effectiveness from the treatment. The trial has completed recruitment.

Is periodontal disease a risk factor for preterm birth?

This study has completed recruitment.

Being born preterm (before 37 completed weeks of pregnancy) remains a major cause of babies dying and is associated with over 13% of all perinatal deaths. Babies born preterm who survive are at increased risk of developing breathing problems and other morbidities associated with immaturity. They also have a significant risk of longterm neurological disability. The prevention of preterm birth therefore remains an important health priority.

Periodontal disease is a chronic oral infection. Recent studies have provided some evidence that women with periodontal disease have an increased risk of preterm birth. There is promising, but limited evidence, that treating women with periodontal disease in other populations may reduce the risk of preterm birth.

Whether periodontal disease is a significant risk factor for preterm birth in the Australian population is unknown. This case control study will allow assessment of any association of periodontal disease with preterm birth, assess the incidence and severity of periodontal disease in the South Australian population, permit exploration of women’s knowledge, experiences and attitudes to dental health and their willingness to accept clinical practice recommendations.

Given the seriousness of preterm birth for the women and their infants, this is an important, priority research question.

MgSO4 Trial: What is the optimal rate of administration of Magnesium Sulphate for neuroprotection prior to preterm birth.

This trial is currently recruiting.

Magnesium sulphate immediately prior to very preterm birth may reduce the risk of cerebral palsy (Crowther et al 2004).
Intravenous administration leads to side effects sufficient to stop the medication in a significant number of women. This trial will examine different rates of giving the infusion to ensure the optimal dose is given to women but with minimal side effects.

Reference

Crowther CA, Hiller JE, Doyle LW, Haslam RR for the Australasian Collaborative Trial of Magnesium Sulphate (ACTOMgSO4) Collaborative Group. Effect of magnesium sulfate given for neuroprotection before preterm birth: a randomized controlled trial. JAMA 2003 Nov26; 290(20):2669-76. (article as pdf)

Obesity
Limiting weight gain in overweight and obese women during pregnancy to improve
health outcomes: a randomised trial.

The trial is open for other centres to join the study.

Obesity is a significant health issue for women during pregnancy and childbirth, with estimates suggesting that 35% of women aged between 25 and 35 years are overweight or obese. There are well documented risks associated with obesity during pregnancy and childbirth. Maternal complications include hypertensive conditions and pre-eclampsia, gestational diabetes, infection, thromboembolic events, need for induction of labour, caesarean section and perinatal death. Infants of mothers who are overweight or obese are more likely to be macrosomic, require admission to the neonatal intensive care unit, be born preterm, have a congenital anomaly, and to require treatment for jaundice or hypoglycaemia. While there is an extensive body of literature related to defining the problems and potential complications associated with obesity during pregnancy and childbirth, there is a lack of information available related to effective interventions that may be implemented to improve maternal, fetal and infant health outcomes. : The aims of this randomised controlled trial are to assess whether the implementation 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.

PROGRESS: PROgesterone after previous preterm birth for prevention of neonatal RESpiratory distress Syndrome

This trial is currently recruiting. The trial is open for other centres to join the study.

Neonatal respiratory disease, due to immature lung development, is a significant consequence of preterm birth and the major cause of early neonatal mortality and morbidity. The incidence of preterm birth (birth less than 37 weeks gestation) is approximately 7.0%, with 2.6% of all births occurring before 34 weeks gestation. The exact mechanism of the onset of labour in humans is complex. Progesterone is essential for maintaining pregnancy, having an important role in uterine relaxation. Although recent reports of progesterone supplementation for women at risk of preterm birth show promise, there is currently insufficient data to recommend the use of progesterone to prevent preterm birth. This trial will involve women who have a history of spontaneous preterm birth at less than 34 weeks in the preceding pregnancy and will compare vaginal progesterone pessaries with placebo pessaries.

PPROMT Trial: Preterm Prelabour Rupture Of Membranes near Term

This trial is currently recruiting.

The PPROMT Trial is a randomised controlled trial assessing two forms of management, early planned birth versus expectant management, in women with ruptured membranes between 34 weeks and 36 weeks 6 days of pregnancy.

Prelabour rupture of the membranes (rupture of the membranes prior to the start of labour) occurs in 20% of all births. When this occurs at term there is good evidence that early delivery soon after the membranes rupture is associated with less infection in the mother and increased satisfaction of the mother compared with expectant management (waiting for labour to begin). The best management of women with preterm prelabour rupture of membranes (PPROM), rupture of the membranes before 37 weeks, is not known.
Preterm prelabour rupture of membranes (PPROM) is a common clinical problem, occuring in approximately 2% of all pregnancies and is the cause of 40% of all preterm births. The PPROMT trial will provide guidance to clinicians about the management of PPROM near term. The trial will also establish whether early planned delivery is associated with fewer health costs.

Eligibility criteria for trial entry

Women eligible for randomisation will be those between 34 and 36 weeks 6 days gestation, with singleton pregnancies, with PPROM. Women who rupture their membranes prior to 34 weeks gestation will become eligible at 34 weeks should they remain undelivered at 34 weeks gestation. Rupture of the membranes will be determined clinically and/or confirmed by a positive amnicator swab performed at the time of speculum examination.

TWINS: Timing of Birth at Term- A randomised controlled trial.

This trial is currently recruiting. The trial is open for other centres to join the study.

Based on data that has looked back in time over a large number of twin pregnancies (called retrospective data), most women with a twin pregnancy give birth earlier (around 36 to 37 weeks gestation) than women with a singleton pregnancy. These studies suggest that there is an increase in the risk of stillbirth for twin pregnancies, from 37 weeks. While giving birth at 37 weeks may reduce the risk of stillbirth, any potential benefits for your babies’ in earlier birth need to be balanced against other risks (including that your babies’ may have some difficulty with their breathing and need to spend some time in the nursery). The Twins: Timing of Birth Trial is looking at whether elective delivery at 37 weeks pregnancy is better for mothers and their babies, than the current care women receive (called standard management). Standard management varies between hospitals and doctors, and may involve induction of labour (or caesarean section if this is appropriate) after 38 weeks, or waiting for labour to start spontaneously.

TWINS BIRTH STUDY

This trial is currently recruiting at The Women's and Children's Hospital, Adelaide.

This trial is co-ordinated by the University of Toronto Maternal, Infant and Reproductive Health Research Unit at The Centre for Research in Women's Health.