3rd fact

There were 452 new cases of gynaecologic cancers in WA in 2010 and this is projected to rise to 517 new cases by 2015.

2008 Annual Report

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Women and Infants Research Foundation
Annual Report 2008
Affiliated with The University of Western Australia and King Edward Memorial Hospital
Carson House King Edward Memorial Hospital 374 Bagot Road Subiaco Western Australia 6008 Postal address PO Box 134 Subiaco Western Australia 6904 Telephone Facsimile Website Email (08) 9340 1437 (08) 9340 1642 www.wirf.com.au wirf@obsgyn.uwa.edu.au
Honorary Life Members: Mrs Janet Holmes à Court Mr John Rawlinson Emeritus Professor Con Michael Mr Rod Maslin
Contents
Research Reports
Our Mission and Primary Areas of Research ....................................................................... 02 Organisational Chart .................................................................................................................. 02 Honorary Board of Management ............................................................................................ 03 Chairperson’s Report .................................................................................................................. 04 Director’s Report.......................................................................................................................... 05 Governance Statement .............................................................................................................. 07 Grant Funding .............................................................................................................................. 08 The World Congress of the Society for the Developmental Origins of Health and Disease (DOHaD) ................................................................................................... 09 Research Units
Biostatistics and Research Design Unit ............................................................................................11 The Lotteries Commission / Women and Infants Research Foundation Perinatal Research Laboratories........................................................................................................ 12 Women and Infants Research Foundation / UWA School of Women’s and Infants’ Health Research Laboratories ............................................................................................ 13 Perron Rotary Express Milk Bank ...................................................................................................... 14 The Smile Study...................................................................................................................................... 16 Raine “Challenge Me Study” .............................................................................................................. 18 Prediction and Prevention of Pre-term Labour using Molecular Genetics ............................. 20 Placental Research................................................................................................................................ 23 Fetal Futures Program .......................................................................................................................... 24 Modeling Maternity Care Options for Women at Low Risk of Pregnancy Complications .. 25 Anaesthesia and Pain Relief ............................................................................................................... 26 Nutrition for the Newborn .................................................................................................................. 27 Impact of Caffeine and Maturation on Respiratory Control in Preterm Infants .................. 28 Mental Health during Pregnancy and the Postnatal Period ....................................................... 29 Neonatal Respiratory Medicine ......................................................................................................... 30 Breastfeeding Research ....................................................................................................................... 32 The Fetal and Childhood Origins of Polycystic Ovary Syndrome ............................................... 34 Mechanisms of Irregular Bleeding with Implanon Contraceptive Implants .......................... 35 Menopausal Symptoms following Breast Cancer ......................................................................... 36 Substance Use in Pregnancy............................................................................................................... 37 Teenage Pregnancy Intention, Contraceptive Use and Repeat Pregnancy ............................ 38 Family Vascular Risk Factors in the Prediction of Pre-eclampsia ............................................. 39 Evaluation of Preliminary Forensic Specimen Kits in Recent Sexual Assault ........................ 40
Publications .................................................................................................................................. 41 Major Supporters ........................................................................................................................ 46 Donors ............................................................................................................................................ 47 Volunteers .................................................................................................................................... 47 Research Support ........................................................................................................................ 48 Financial Statements ................................................................................................................. 51
Our Mission and Prime Areas of Research
Our Mission
To conduct, support and promote high quality research for the benefit of human health relating to the fields of reproductive health and diseases of women at all ages, and health and disease of early life and their influence on subsequent health and disease in later life.
Specific Objectives
• To conduct and support research reflecting the Foundation’s mission. • To inform and educate the scientific and wider community of the results and implications of such research. • To develop a sustainable funding and relationship management strategy to support the Foundation’s mission. • To strengthen the Foundation’s collaborative partnerships with the King Edward Memorial Hospital campus, the UWA School of Women’s and Infants’ Health and other research partners within the wider research community. • To foster research excellence from new and established investigators working towards the Foundation’s mission. • To enhance the research reputation and standing of the Foundation by raising its profile across the scientific and wider community.
Prime Areas of Research
• Prevention of brain damage. • Preventing and reducing the dangers of preterm birth. • The fetal origins of childhood and adult illness. • Improving pain relief in labour and after surgery. • Prevention of postnatal depression. • Promotion and evaluation of breastfeeding. • Women’s health problems in later life including menopause and cancer.
Organisational Chart
Honorary Board of Management
Director
Investment Committee
Scientific Grants Committee
Deputy Director
Finance
Marketing and Development Administration Assistant
Annual Research Grant Scheme
Biostatistics and Research Design Unit Volunteers Core Clinical Research Staff Women and Infants Research Foundation / The University of Western Australia Laboratories Clinical Fellow Programme Café and Gift Shop Baby Photography
Lotteries Commission Perinatal Research Laboratories (U.W.A. Campus)
Breastfeeding Centre
Maternal Fetal Medicine
Newborn Medicine
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Women and Infants Research Foundation Annual Report 2008
Honorary Board of Management
The Board of Management provides strategic direction to ensure the quality, efficiency and longevity of our research, and clinical and community activities. The Board meets six times a year. All Board members serve on a voluntary basis.
L to R: Alan Good, Jim Davies, Karen Simmer, Nicola Forrest, Peter Hartmann, Jann Rowley, Peter Hawkins, Anne Payne, John Newnham, Andrea Burns, Craig Pennell
Chairperson
Ms Anne Payne Solicitor
Ms Andrea Burns Journalist Mr Graeme Boardley Executive Director of Midwifery and Nursing King Edward Memorial Hospital Mr Jim Davies Managing Director Marketing Mrs Nicola Forrest Company Director Professor Peter Hartmann Professor of Biochemistry The University of Western Australia Chairman, Scientific Grants Committee Women and Infants Research Foundation Mr Peter Hawkins Company Director Mr Gerald Major Property Consultant
Gerald Major Graeme Boardley
Deputy Chairperson and Treasurer
Mr Alan Good Chartered Accountant
Director
Professor John Newnham Professor, Maternal Fetal Medicine King Edward Memorial Hospital Head, School of Women’s and Infants’ Health Deputy Dean, Faculty of Medicine, Dentistry and Health Sciences The University of Western Australia
Dr Craig Pennell Senior Lecturer, School of Women’s and Infants’ Health The University of Western Australia Certified Subspecialist in Maternal Fetal Medicine King Edward Memorial Hospital Ms Jann Rowley Artist Professor Karen Simmer Professor of Neonatal Medicine The University of Western Australia Medical Director, Neonatology Clinical Care Unit King Edward Memorial & Princess Margaret Hospitals
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Women and Infants Research Foundation Annual Report 2008
Chairperson's Report
It is with great pleasure that I welcome you to the 2007/8 Annual Report of the Women and Infants Research Foundation (WIRF). The continuing success of the Foundation is the result of hard work from many of our staff and volunteers.
WIRF was formed in 1976 with a vision to provide Western Australia with an organisation that could underpin the development of research in women’s health and reproduction. The original objectives have been more than achieved and our State now benefits from the success that has arisen from linking the community, the health care system and the University in this common goal. Many people contribute to this success, some as employees of the Foundation and partner organisations, and many as volunteers. The Board is pleased to report that the organisation remains in a sound financial position, despite the challenges posed by the current financial situation both locally and internationally. This sound position has resulted from wise investment strategies developed by our Investment Committee, chaired by Alan Good, who also serves as Deputy Chair of the Board. We are grateful to the other members of this Committee which includes Peter Hawkins and myself with support from Andrea Cole. During the year we appointed Graeme Boardley to the Board. Graeme has taken the position of Director of Midwifery and Nursing at King Edward Memorial Hospital and we welcome him to the Board. The continuing success of the Foundation is the result of hard work from many of our staff and volunteers. In particular, I would like to thank Paquita Sutherland, our Development and Marketing Manager; Andrea Cole our Accountant; Christine Spencer our Administration Assistant; and our chief sponsors including the Channel 7 Telethon Trust, the Lions Club of Floreat, the Lions District 201 W1, the Stan Perron Charitable Trust, Rotary and Andrew and Nicola Forrest. Our business success owes much to Annemarie Weekes, Manager of our Cafe and Gift Shop. Above all, I wish to thank our many volunteers whose hard work and enthusiasm is an inspiration to us all. Finally, I would like to express gratitude from the Board to our Honorary Director, Professor John Newnham; the Chair of our Scientific Grants Committee, Professor Peter Hartmann; and the Head of our Biostatistics and Research Design Unit, Dr Dorota Doherty. Together, we are achieving the goal outlined in our Constitution more than three decades ago of providing the people of Western Australia with a vibrant and productive scientific base to underpin high quality health care for women and infants. Anne Payne Honorary Chairperson
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Women and Infants Research Foundation Annual Report 2008
Director's Report
Welcome to the 32nd Annual Report of the Women and Infants Research Foundation. Our income from external competitive grant sources this year has increased 71% reflecting the rapid growth and success of the Foundation and its researchers.
The key to a successful health care system is for the clinical structure to be supported by a solid foundation of high quality research and education. That structure requires a vibrant base of scientists investigating clinical questions of direct relevance to the health needs of the local community, linked to an educational system that enables rapid and effective interchange between those who create knowledge and those who translate it into practice. It is here that the Women and Infants Research Foundation is so successful and plays such a vital role in Western Australia. The Foundation is the sole organisation in this State dedicated to research and education in the fields of women’s health and reproduction. At its heart is a fundamental policy of conducting and supporting clinically relevant research aimed at improving the health of our community and optimising the potential of our next generation. Success is ensured by close working relationships between clinicians, scientists and educationalists who work within this organisation.
Research activities
This year has witnessed ongoing expansion in the number and sophistication of research studies conducted through WIRF. Our income from external competitive grant sources this year has increased 71% reflecting the rapid growth and success of the Foundation and its researchers. Details are provided in the Research Support Section. We have also been active in supporting the research aspirations of new clinical services on the campus, with support provided for studies within the Sexual Assault Referral Centre and the Department of Psychological Medicine. Expansion into these fields has been based on strategic evaluation of the best ways to invest our resources to produce the greatest improvements in health in our community and elsewhere. Details of the various research programs and their investigators can be found in the following pages. I trust you will find them interesting and informative.
The Preterm Birth Genetic Initiative
During the year, members of the research team headed by Dr Craig Pennell, have become involved in the World Health Organisation (WHO) Preterm Birth Genome Project. This exciting global initiative funded by WHO, the March of Dimes (USA) and the Government of Mexico aims to unravel the genetic basis of preterm birth. Over the coming year, 2500 DNA samples from Canada, Mexico, Denmark, Korea and Australia will be analysed in Perth through WIRF and local partners. This expanding research project is a key component in the Foundation’s goal of preventing preterm birth and contributing to initiatives that have global implications and relevance.
Health Services Research
Research into the effectiveness of health care systems is now expanding and WIRF is making a substantial commitment to this very important field. Many of our new developments have been headed by our Biostatistics and Research Design Unit under the leadership of Dr Dorota Doherty. In essence, the research has been investigating the potential benefits and costs of various models of health care delivery in Perth, with a particular emphasis on options for birth. The studies are now expanding to include obstetric and midwifery services in rural and remote Western Australia. The Health Department of Western Australia is a key partner in these projects, ensuring the findings are available for translation into healthcare policy.
Women and Infants Research Foundation Annual Report 2008
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The Perron Rotary Express Human Milk Bank (PREM Bank)
The PREM Bank was developed in 2006 as a joint initiative involving WIRF, The Stan Perron Charitable Trust, Rotary Clubs of Belmont and Thornlie and Channel 7 Telethon Trust. The Bank provides donated human breast milk using processes that are as rigorous as those employed for blood donation. During the year, this service has expanded greatly and is making a substantial contribution to the health of many of the most vulnerable babies in the nursery. The success of the PREM Bank was acknowledged in 2007 by winning the Director General’s Choice Award.
Our Partners
WIRF benefits from a number of longstanding and cherished partnerships that together provide an ideal recipe for effective research support. We remain grateful to King Edward Memorial Hospital and the leadership of the North Metropolitan Region for the support that enables us to provide services on the campus; to The University of Western Australia for academic support that is provided primarily through the School of Women’s and Infants’ Health; and to the many national and international partners who are involved in collaborative research efforts. I would also like to acknowledge the substantial support we receive from our chief sponsors including the Channel 7 Telethon Trust, the Lions Club of Floreat, the Lions District 201 W1, The Stan Perron Charitable Trust, Rotary Clubs of Belmont and Thornlie, and Andrew and Nicola Forrest.
DOHaD 2007
WIRF was the official partner of the International Council of the Society for the Developmental Origins of Health and Disease (DOHaD) in hosting the 5th World Congress of the Society at the Perth Convention and Exhibition Centre Nov 6 – 10th, 2007. DOHaD is the new field in health that brings together the many disciplines that aim to improve life-long health by addressing diseases at their origins in early life. Research in this field addresses the epidemic of obesity, diabetes and related conditions, and is of particular importance for individuals and communities making the transition from traditional to Westernised lifestyles. The field includes almost all the major disciplines in medicine together with anthropology, sociology, economics and politics. The DOHaD 2007 Congress was a great success with more than 100 invited speakers and a total of more than 400 scientific presentations. Membership of the International Society expanded nearly four fold as a result of the Congress. As official and principal partner of the Society, WIRF provided invaluable support without which Perth would not have been able to attract and host this important international Congress. In so doing, WIRF has continued its commitment to one of its central objectives which is to “inform and educate the scientific and wider community of the results and implications of research”.
Our Businesses
The Foundation is committed to its policy of conducting businesses that provide services for patients, staff and visitors and that also provide profits to support research. The Cafe and Gift Shop continues to be highly successful and we are grateful to Annemarie Weekes for her leadership and enthusiasm as Manager. The success of this and other ventures is also the result of the dedication and commitment of our team of nearly 70 volunteers whose contributions are greatly appreciated. Their work is vital for our success and their presence on the campus provides an invaluable link between the hospital and the community. The Cafe and Gift Shop since its beginning has functioned with a policy of providing food of the highest possible quality. As the State Government has introduced its Healthy Options WA Food and Nutrition Policy during the year, our staff have further improved the quality of food and drinks to ensure that we promote nutrition at its highest standards. These initiatives are at the forefront of health promotion globally and are important contributors in our efforts to combat the epidemic of obesity and diabetes that are challenging our modern world. On behalf of the many researchers who work with the Foundation, I would like to extend my grateful appreciation to Paquita Sutherland our Marketing and Development Manager, Andrea Cole our Accountant, Claire Williams our Bookkeeper, Julie Rutgers and Dawn O’Brien who operate our Baby Photography Business, Chris Spencer our Administration Assistant, and the many volunteers who work in the central office.
Research Funding
WIRF aims to support early career researchers during the vulnerable years when clinical and laboratory scientists make the transition from student to independent investigator. The funding offered covers the spectrum from top-up support for PhD students, to Starter Grants to enable new researchers and teams to initiate their projects, and finally to Capacity Building Grants where researchers of high promise are provided with one-line grants over three years to assist them in attracting substantial support from external agencies. This program is proving to be highly effective and is assisting the development of a critical mass of talented and productive researchers on the campus. WIRF also aims to provide the infrastructure that enables its clinical and laboratory scientists to be successful. Support that is provided includes biostatistics and study design advice, laboratory equipment and the hosting of scientific events for researchers to present their findings and interact with colleagues. Partly as a result of the support offered to early career researchers, and partly as a result of success with recruitment, the number of externally funded research projects conducted through WIRF is expanding. Together, the research activities provided by these various individuals and teams are providing the fields of women’s health and reproduction in the State with a vibrant scientific base. This formula is ideal for underpinning high quality health care, with potential benefits for all Western Australians.
The Board
The WIRF Board provides the organisation with sound strategic policy and advice and the success of the Foundation is testimony to its effectiveness. Membership of the Board is diverse, providing us with a broad range of skills so vital for the organisation to thrive. I would like to extend my most sincere appreciation to Anne Payne, Chair of the Board, Alan Good, Deputy Chair of the Board, and each of the Board members for their support and wise counsel during the year. This Foundation is an organisation primarily of volunteers. Each of the Board members is a volunteer, the success of our businesses results from the commitment of our many volunteers, and we do not employ fundraisers. As a result, our overheads are kept at a minimum and all funds donated to the Foundation are allocated directly to support research. The success of the Foundation is a wonderful example of our community, Hospital and University working together to provide research and education that is improving health care for women and the next generation of Western Australians. Professor John Newnham Inaugural Director
Paquita Sutherland
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Christine Spencer
Andrea Cole
Claire Williams
Julie Rutgers
Dawn O'Brien
Women and Infants Research Foundation Annual Report 2008
Governance Statement
Board of Directors
The Board of Management provides strategic direction to Foundation management to ensure the quality, efficiency and longevity of our research, clinical and community activities. The Board meets six times each year, all Board Members serve on a voluntary basis.
Scientific Grants Committee
The Committee is chaired by Professor Peter Hartmann, Professor of Biochemistry and previously Dean of the Faculty of Science at The University of Western Australia. Members of this Committee are appointed by the Board on an honorary basis. Half of the members of the Committee are employed externally to the KEMH campus. The Committee meets to consider research applications for financial support and advises the Board on suitability for funding. The Committee also provides the Board with advice on scientific matters as required. Specifically they review applications for Starter Grants, Capacity Building Grants and PhD Scholarships.
Corporate and Research Ethics
All employees are expected to discharge their duties in good faith and act honestly in the best interest of the Foundation, striving at all times to enhance the reputation and performance of the Foundation. All scientific studies conducted by the Foundation are approved by the Ethics Committee of the Women and Children’s Health Service and / or the Human Research Ethics Committee and Animal Ethics Committee of The University of Western Australia.
Chairperson
Professor Peter Hartmann Professor of Biochemistry The University of Western Australia
Risk Management
All employees and volunteers of the Foundation undergo criminal screening and blood tests in compliance with the requirement of the Women and Children’s Health Service, irrespective of whether they have direct contact with WCHS children or not.
Committee
Professor John Newnham Professor, Maternal Fetal Medicine Director, Women and Infants Research Foundation Head, School of Women’s and Infants’ Health The University of Western Australia Professor Karen Simmer Professor of Neonatal Medicine The University of Western Australia Medical Director, Neonatology Clinical Care Unit King Edward Memorial and Princess Margaret Hospitals Professor Brendan Waddell Head, School of Anatomy and Human Biology The University of Western Australia Dr Daniela Ulgiati Research Fellow Biochemistry and Molecular Biology The University of Western Australia Dr Roberta Bencini School of Animal Biology The University of Western Australia
Financial Reporting
The Foundation’s financial year ended on 30th of June 2008. Our Chairperson and Treasurer jointly signed off on the Annual Financial Reporting process on behalf of the Board. A copy of the Foundation’s financial reports for year end 30th of June 2008 are available on www.wirf.com.au
Audit Governance
The Foundation engages Grant Thornton as an external audit team to independently review its financial reports and uphold the integrity of the reporting process.
Not for Profit Status
The Foundation operates as an incorporated not for profit organisation. The Australian Taxation Office has endorsed the Foundation as an Income Tax Exempt Charitable Entity and a Deductible Gift Recipient, this status ensures that anyone donating to the Foundation can claim the full tax benefit. The Foundation also holds a Charitable Collections Licence from the Department of Consumer and Employment Protection in Western Australia.
Women and Infants Research Foundation Annual Report 2008
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Grant Funding
Starter Grants funded by the Foundation 2007/2008
“The Relationship between suckling, swallowing and breathing in healthy term breastfeeding infants and those that are experiencing breastfeeding difficulty”
Dr D T Geddes, Dr L M Chadwick Amount funded: $15,000
Capacity Building Grants funded by the Foundation 2006-2008
In 2006 the Foundation established the Capacity Building Grant funding programme. The Capacity Building Grants are part of a wider strategy designed to nurture and develop promising researchers in line with the Foundation’s mission. The grants provide flexible support to allow investigators to develop their capacity to assist them in attaining a level of productivity and capability sufficient to attract nationally competitive grant funding. The Foundation funds a maximum of two Capacity Building Grants per year. Successful applications reviewed by the Scientific Grants Committee receive $105,000 in funding over three years. In 2006 a Capacity Building Grant was awarded to: Dr Jane Pillow
“A pilot study of supervised, home-based exercise for obese pregnant women”
Dr K J Guelfi, Dr T Power Amount funded: $15,000
“Evaluation of tidal volume and physiologic dead space in ventilated preterm infants”
Dr J J Pillow, Dr S M Schulzke Amount funded: $14,849
“Understanding ventilation of the preterm lung and implications for long term respiratory well being”
Brief Description The research involves the use of non-invasive respiratory tools to investigate the postnatal growth and development of the lung, and the consequences of preterm birth, antenatal exposures and events and acute/ chronic respiratory disease on longer term respiratory wellbeing. This research is aimed at optimising the ventilation strategies in NICU patients. Preterm infants with chronic lung disease have abnormal regional ventilation of the lung when compared to preterm infants without persisting respiratory disease.
“Does antenatal corticosteroid treatment alter pulmonary vascular development?”
Dr G R Polglase Amount funded: $14,714
“The influence of ventilation strategy and infection on diaphragm function”
Ms C J McLean, Dr J J Pillow Amount funded: $12,245.49
“Complexity of client presentation at the Sexual Assault Resource Centre”
Mrs D Nicholls, Ms T Towers, Ms J Stone, Ms L Nathan Amount funded: $14,960
“Pharmacological analysis of the partitioning of medetomidine and ketamine between maternal and fetal circulatory compartments in sheep”
Dr G C Musk, Dr S Petersen, Dr R Trengove Amount funded: $14,100
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Women and Infants Research Foundation Annual Report 2008
The World Congress of the Society for the Developmental Origins of Health and Disease (DOHaD)
The global increase in obesity and diabetes represents in numerical terms the largest epidemic ever experienced in humans.
In November 2007, WIRF was official partner of the International DOHaD Society in holding the 5th World Congress at the Perth Convention and Exhibition Centre, Western Australia. DOHaD is the relatively new field of health care that centres on the early life origins of many of the major chronic diseases in humans, including obesity and diabetes.
The field is of particular relevance to those individuals and communities making a rapid transition from traditional to Westernised lifestyles, such as indigenous Australians, South Asians and Pacific Islanders. The global increase in obesity and diabetes represents in numerical terms the largest epidemic ever experienced in humans. Tackling the problems at their origins presents the greatest opportunity for prevention. It is becoming increasingly clear that much of our behaviour and metabolism is programmed before birth, and the interactions between this programming and our early environment are crucial for our subsequent health. Research conducted in Western Australia through WIRF and other organisations is prominent in this field and underpinned our success in attracting this World Congress. The Congress was a major success. There were more than 100 invited speakers and in excess of 650 delegates, who came from all corners of the globe. Many initiatives arose from this meeting, including the establishment of formal research linkages between our own Raine Study and comparable projects underway in the UK and Brazil. This major international event could not have been held in Western Australia without the support of WIRF as the major local partner, both in terms of financial support and infrastructure. Support was also provided by The University of Western Australia and the Faculty of Medicine, Dentistry and Health Sciences; The Royal Australian and New Zealand College of Obstetricians and Gynaecologists; Kind Edward Memorial Hospital; the Health Department of Western Australia; the Raine Foundation; the Perinatal Society of Australia and New Zealand; the Australian Research Alliance for Children and Youth; Lotterywest; and the Welcome Trust (UK). We would like to express our most sincere gratitude to the staff in WIRF who worked so hard to make this Congress such a success. The next World Congress of the DOHaD Society will be held in Chile in November 2009. Professor John Newnham Congress Director Dr Craig Pennell Chair, Abstract Selection Committee
Women and Infants Research Foundation Annual Report 2008
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10 Women and Infants Research Foundation Annual Report 2008 10 Women and Infants Research Foundation Annual Report 2008
Research Units
Biostatistics and Research Design Unit
The role of the Biostatistics and Research Design Unit is to provide biostatistical collaboration, consultation and quantitative resources for research conducted at King Edward Memorial Hospital and affiliated institutions. Overview of Unit
The Unit members participate in a wide variety of activities including consultation on design and analysis for small pilot projects, development of study design for major projects, assistance and advice on database construction and management, and collaboration on large projects where outcomes measurement and statistical analysis considerations are nontrivial. Our involvement in research projects conducted on campus ranges from short-term consultations to ongoing long-term collaborations on studies supported by research funding. A short-term statistical consultation may require one or two sessions on designing experiments, formulating initial plans for data collection, or advice on statistical methodology for data analysis. Investigators are always encouraged to obtain statistical advice for their research at any stage of the project and these short-term consultations often develop into ongoing longer term collaborations. Most research studies supported by grants benefit from ongoing statistical collaboration, and in these studies we are involved from their conception to completion and dissemination of results in peer-reviewed scientific journals. During the study design we are involved in grant proposal writing that initially includes formulation of primary and secondary objectives, hypothesis formulation and testing, sample size estimation, planning for study monitoring and inclusion of interim analyses. Our involvement in the planning of experiments may also include the development of appropriate statistical approaches and computational algorithms to meet the needs that are project specific. At the design stage, we also consider the effects of potential major confounding variables because such confounders may affect study outcomes even when they are not directly related to the outcome of interest. We assist with the determination of sample sizes for the evaluation of the primary objectives and detection of clinically relevant alternative hypotheses. Design and conduct of randomised clinical trials requires the generation of patient randomisation algorithms that facilitate blinding of principal investigators whenever possible, and the development of plans for a method of analysis that may need to be performed on intention to treat basis. In ongoing large scale studies we often participate in various aspects of data management such as design of data collection forms, design and maintenance of databases and facilitation of data entry. We often monitor study progress and quality assurance by collating interim data summaries and we perform statistical analyses upon the study completion. We also contribute to the dissemination of study results by performing analyses of completed studies, preparing statistical reports and, when needed, writing of the statistical sections for research manuscripts. Apart from study design, conduct and analysis, we are also involved in the presentation of seminars on statistical methods in medical research and student supervision. We liaise with researchers and staff members on the campus to foster and facilitate future research interests. In the last 12 months we have also expanded our statistical activities to include health service research in obstetrics. Our main aim is to increase the level and effectiveness of the biostatistics use on campus and we look forward to meeting new challenges in women’s health and reproduction in the coming year. Dr Dorota Doherty Head
L to R : Angela Jacques, Dorota Doherty, Liz Nathan, James Humphreys
Women and Infants Research Foundation Annual Report 2008 11
Overview of Unit
Research Units
The Lotteries Commission / Women and Infants Research Foundation Perinatal Research Laboratories
Key Highlights
• The recruitment of a new Honours student, David Cruise - David is a science graduate from UWA who is supervised by Professor John Newnham and Dr Graeme Polglase. David’s Honours project will contribute significantly to a controversial area of research – Does the fetus feel pain? David’s thesis is entitled “Nociceptive Pathway Activation in the Pre-Term Fetal Sheep: Cerebrospinal Fluid and Plasma -Endorphin Concentrations”. • The recruitment of a new Research Assistant, Richard Dalton - Richard is a valuable asset to the group strengthening our molecular and morphometric abilities, and will be based at the Large Animal Facility. Richard will work alongside Dr Graeme Polglase and Associate Professor Jane Pillow. • Promotions for two members of our team – Dr Jane Pillow was promoted to Associate Professor while Dr Graeme Polglase was promoted to Research Fellow within The University of Western Australia. • Continued Grant success - A prestigious NIH Grant by our collaborator Dr Suhas Kallapur (Cincinnati), which incorporates significant contributions by our group was recently awarded. • Researchers within our team had National and local grant success, with grants awarded by the National Health and Medical Research Council, the National Heart Foundation of Australia, the Raine Medical Foundation, the New Investigator Researcher Infrastructure Support, the CASS Medical Foundation and The University of Western Australia.
The WIRF Perinatal Research Laboratories are housed on the main campus of The University of Western Australia and have been operational since the beginning of 1999. The Laboratories include a suite of offices for research staff and students, an operating theatre, several purpose-built laboratories and large animal holding facilities, together forming one of the best facilities of its type in the world. Much of the cost of construction of the Laboratories, and purchase of many of the state-of-the-art scientific instruments that are used by researchers working within this facility, was supported by grants from the Lotteries Commission and other agencies awarded to the Women and Infants Research Foundation. Staff and students based at the Laboratories are involved in research studies including investigations into: The developmental origins of health and disease; fetal responses to intrauterine inflammation and its effects on development of the fetal brain and lungs; studies of new ventilation techniques aimed at improving preterm infants’ chances of survival and wellbeing; interactions between ventilation and cardiovascular and pulmonary blood flows; and fundamental aspects of fetal development. Financial support for these projects has been awarded from several local, national and international competitive granting bodies, including the Women and Infants Research Foundation, The National Health and Medical Research Council (Australia), The National Heart Foundation of Australia, The Sylvia and Charles Viertel Charitable Foundation and The National Institutes of Health (USA). We also receive significant contributions from our commercial partners/collaborators including Fisher and Paykel Healthcare, Bunnell Inspired Infant Care Incorporated and Chiesi Pharmaceuticals. The budget for projects conducted within the Laboratories is sourced entirely from externally funded research grants. An ongoing commitment by WIRF to provide financial and infrastructural support for the running of the Laboratories ensures that research grants are dedicated to funding only experimental work. This year was the second year of our large collaborative sheep studies based at the Shenton Park Research Station, for which significant infrastructure and support has been provided by WIRF. The renovated sheep facilities purpose built for our requirements have enabled a high quality of research and exceptional working conditions for both humans and sheep, and ensured our continued ongoing sheep-based research. The facilities and support provided by WIRF have expanded the research capabilities of the Foundation and The University of Western Australia, and have contributed to the recruitment of research scientists and clinicians from Australia and overseas. Fruitful collaborations with researchers from Melbourne, Sydney, Adelaide, Brisbane, Canada, USA, Holland and Germany have been established as a result of the research capabilities of the Laboratories and the support provided by WIRF. Our research collaborations, excellent laboratory facilities, support from WIRF, and the dedication of researchers working within the Laboratories, will ensure that we continue our valuable contributions to improving the lives of people around the world. Dr Graeme Polglase Manager
Andrea Lee
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L to R: Jane Pillow, Carryn McLean, Ilias Nitsos, David Cruise, Richard Dalton, Graeme Polglase, Gabby Musk
Women and Infants Research Foundation Annual Report 2008
Overview of Unit
Research Units
Women and Infants Research Foundation / UWA School of Women’s and Infants’ Health Research Laboratories
The Women and Infants Health Research Laboratories (WIHRL) are jointly owned and managed by the Foundation and The University of Western Australia (UWA) School of Women’s and Infants’ Health. The bright, spacious and well equipped laboratories are located on the second floor in King Edward Memorial Hospital. Within the laboratories are separate suites for RNA, DNA, image analysis and tissue culture, plus a large general biomedical laboratory and freezer storage facilities. The purpose of the laboratories is to complement and enhance both clinical and basic research undertaken through the Foundation and the University, as well as to provide analytical facilities for research conducted in the Perinatal Laboratories on the UWA campus in Crawley. The laboratories currently support the research of two Professors, three Associate Professors, one Senior Lecturer, three Postdoctoral Fellows, four Research Assistants and two Research Midwives. The School also has six PhD, one Masters and three Honours students with laboratory-associated projects. A wide range of research projects is being undertaken in the laboratories, including: • Identifying links between periodontal disease, inflammation and preterm birth. • Studies aimed at identifying genes linked to increased risk of preterm birth. • Investigating how dietary supplementation with omega-3 fatty acids can protect the placenta from the effects of inflammation and oxidative stress. • Measuring urinary steroid hormone metabolite levels in young women at risk of developing polycystic ovarian disease. • Studying the effects of exposure to inflammation in the womb on the development of the fetal lung, diaphragm, heart and brain. • Investigating the role of the fetal environment in the womb in predisposing offspring to diseases such as diabetes, obesity and hypertension later in life. • Studying placental lipid transport and metabolism to elucidate its role in placental formation and function. This year saw the appointment of a new WIRF-funded Principal Research Fellow to head the laboratories - Associate Professor Jeff Keelan from Auckland, NZ. The laboratory also welcomed endocrinologist Dr Helen Atkinson, a PhD graduate of The University of Western Australia. Helen has returned to Perth from Bristol, UK, to work on reproductive disorders with Professor Martha Hickey and Associate Professor Roger Hart. Much of the Units research programme involves the extraction and culturing of placental cells and tissues to enable detailed studies of placental function and its regulation to be carried out. It was very fortunate and timely that, coincident with his arrival, funds were generously donated to the Foundation by the family of Dr Bertie Cohen to support its research endeavours. With these funds, augmented by a grant from The University of Western Australia and financial assistance from the School, the laboratory was furnished and equipped with a cell incubator, biological safety cabinet, inverted microscope, water baths, centrifuges, aspirators and a perfusion chamber. The “Dr Bertie Cohen Cell Biology & Tissue Culture Laboratory” was officially opened in November 2007 and now plays a central and indispensable role in the placental research programme. Some funds from the Bertie Cohen bequest remain in trust and will be used to assist with the annual costs of running the laboratory. WIRF, Dr Keelan and the rest of his team are indebted to Bertie and the Cohen family for their generosity and support of biomedical research at King Edward Memorial Hospital. Several years ago, the Lions Image Analysis Suite was established in the laboratory using funds generously donated by the Lions Club of Floreat District and Lions Clubs International (WA). This year, from funds raised through their Razzmatazz film festival, the Lions once again donated a considerable sum of money to the laboratory which was used to purchase an “ImageQuant” system to expand the lab’s image analysis capabilities. This technology will allow our scientists to view and quantitate images from gels and films with a high degree of sensitivity and accuracy. This state-of-the-art equipment had just been released by the manufacturer and was the first of its kind to be installed in Australia. Finally, as part of some operational changes instituted by the new Head of the laboratories, the laboratory’s electronic records and intranet presence/structure has been reorganized, plus a monthly journal club/seminar series has been introduced. Associate Professor Jeff Keelan Head
Key Highlights
• Arrival of a new Head of Laboratories, A/Professor Jeff Keelan, and research scientist, Dr Helen Atkinson. • Installation and inauguration of new cell and tissue culture facilities. • Acquisition of a new gel imaging/ documentation system. • Expansion of our Honours and PhD students. • Introduction of a WIHRL/School journal club & seminar programme.
L to R: Helen Atkinson, Karen Bosel, Blagica Penova-Veselinovic, Shaofu Li, Jeff Keelan
Women and Infants Research Foundation Annual Report 2008 13
Research Units
Perron Rotary Express Milk Bank
Overview of Unit
Key Highlights
• Tripled production capacity with the purchase of a 3 litre human milk pasteuriser which came online in October 2007 • Use of donor milk in the NICU’s at KEMH and PMH tripled in our second year of operation to almost 300 litres • The PREM Bank provided donor milk to over 130 hospitalised infants • The PREM Bank was awarded the inaugural Director Generals Choice Award in the 2007 Healthy WA Awards recognising the project from the pool of nominations that provided the greatest benefit to Western Australian patients • Shortlisted in the 2008 Premiers Awards for Excellence in Public Sector Management (Winner to be announced November 2008)
On 5th July 2006 the PREM Bank, Australia’s first donor human milk bank began dispensing Pasteurised Donor Human Milk (PDHM) to extremely preterm infants whose own mothers were unable to provide sufficient breastmilk for their needs. Easing these babies, born as much as 4 months early and weighing as little as 400g, on to oral feeds is one of the major challenges NICU doctors face. The immature gut is prone to complications such as necrotising enterocolitis (NEC or ‘gangrene of the gut’) which is 6-10 times more common in preterm infants fed artificial formula. Over 80% of babies with confirmed NEC require surgery, which may involve the removal of large sections of dead and dying bowel tissue. Of these newborns, half will not survive. Thus it is essential mothers provide their own breastmilk. Unfortunately, many mothers who give birth prematurely struggle to provide sufficient breastmilk for their babies and a safer alternative to preterm artificial formula is required. The PREM Bank has been established through collaboration between the Neonatal Intensive Care Units at King Edward Memorial and Princess Margaret Hospitals, The University of Western Australia and the Women and Infants Research Foundation and has been largely funded through donations by Belmont and Thornlie Rotary Clubs, The Stan Perron Charitable Trust and the Channel 7 Telethon Trust. In the first 2 years of operation almost 500 litres of donor milk have been dispensed to 194 hospitalised infants. Through the development and publication of Best Practice Guidelines for human milk banking and invited presentations at international conferences, the PREM Bank has already gained a significant reputation as a leader in the safe operation of donor human milk banks both in Australia and internationally. Dr Ben Hartmann Manager (Scientist-in-Charge)
L to R: Amanda Peacock, Ben Hartmann, Tracey Sedqwick
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Women and Infants Research Foundation Annual Report 2008
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Research Reports
The Smile Study
The Smile Study involved screening 3700 pregnant women at risk of periodontal disease, of whom 1082 were found to have gum disease.
The Smile Study is a randomised controlled trial designed to investigate the possibility that treating periodontal (gum) disease during pregnancy will reduce the rate of preterm birth. There has been increasing evidence from observational studies that women with gum disease are more likely to have complications of pregnancy, in particular preterm birth, pre-eclampsia (high blood pressure of pregnancy) and fetal growth restriction. None of these studies however has been able to provide proof of a definite link between gum disease and pregnancy problems.
Such proof can only come from a large study in which pregnant women with periodontal disease are treated, or not treated, and their outcomes compared. This study has now been performed in Perth. The Smile Study involved screening 3700 pregnant women at risk of periodontal disease, of whom 1082 were found to have clinically important disease. After full consent was obtained, these women were allocated at random to have full periodontal treatment during mid-pregnancy or when the pregnancy was completed. Comparing the pregnancy outcomes of these two groups will answer the question of whether treatment of periodontal disease can improve the outcome of pregnancy. The study was conducted through WIRF and The University of Western Australia in metropolitan Perth at King Edward Memorial Hospital, The Oral Health Centre of Western Australia (OHCWA), Osborne Park Hospital, Armadale Hospital, Rockingham Hospital and Swan Districts Hospital. The Smile Study is the largest randomised controlled trial in medicine to have been conducted in Western Australia. It has been conducted without difficulty and almost ontime and on-budget. The success of this large study reflects the enthusiastic support of our population in Perth for studies of this type and the competence of our staff. The last of the pregnant women in the Smile Study delivered her baby in June 2008. Analysis of the results is proceeding and will be available once published in early 2009.
John Newnham
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Dorota Doherty
Craig Pennell
Antonia Shand
Jonathan Swain
Ian A Newnham
Women and Infants Research Foundation Annual Report 2008
We thank the women and the staff who are making this project a success.
Chief Investigators
WIRF/UWA Professor John Newnham MD FRANZCOG Dr Dorota Doherty BSc (Hons) PhD Dr Craig Pennell MBBS (Hons) PhD FRANZCOG UWA School of Dentistry/Oral Health Centre of Western Australia Dr Ian Newnham MDSc FRACDS (Perio) Dr Jonathon Swain BDSc MDSc Professor John McGeachie BDSc PhD DSc Research Midwives Colleen Ball RN RM BN Desiree Cavill RN RM Delores Gasbarro RN RM BSc Nsg Hons Renate McLaurin RN RM BHlth Sc Cherry Young RN RM Melanie Mosey RN RM Sally Bakker RN RM Dental Hygienists Michelle Wright Assoc Degree Dental Hygiene Esther Jansen Assoc Degree Dental Hygiene Belinda Orrock Assoc Degree Dental Hygiene Dagmar Toman Assoc Degree Dental Hygiene Lyn Patrick Assoc Degree Dental Hygiene Rhona Brooksbank Assoc Degree Dental Hygiene Dental Assistant Lorraine Howard Major Sponsors National Health and Medical Research Council (NHMRC) of Australia Colgate-Palmolive Oral-B Channel 7 Telethon Trust
Colleen Ball
Desiree Cavill
Renate McLaurin
Delores Gasbarro
Cherry Young
Michelle Wright
Esther Jansen
Belinda Orrock
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Women and Infants Research Foundation Annual Report 2008
Research Reports
Raine “Challenge Me Study”
For the first time, this project has integrated Women and Infant Research Foundation Volunteers into our research program
Research Highlights
• The Raine “Challenge Me Study” will become the largest evaluation of stress induced hypothalamic-pituitary-adrenal axis function ever conducted in the world. • The environment of mother, infant and child are key contributors to diseases and conditions that represent some of today’s most important global public health issues. • This study provides a unique opportunity to investigate gene:environment interactions within the developing hypothalamic-pituitary-adrenal axis that impact on altered endocrine function, growth, behaviour and brain maturation throughout childhood and adolescence.
The Raine Study began in 1989 at King Edward Memorial Hospital with recruitment of a cohort of children to determine how events during pregnancy and childhood influence health in later life. Pregnant women were recruited at Carson House and our antenatal clinics between 1989 and 1992 into a randomised controlled trial evaluating the impact of serial ultrasound scans on pregnancy outcome. From this study, 2868 children, the Raine cohort, have been followed closely over the last 18 years by a collaborative team of researchers from The University of Western Australia (Schools of Women’s & Infants’ Health and Medicine & Pharmacology), the Women and Infant Research Foundation, the Telethon Institute for Child Health Research, the Western Australian Institute for Medical Research, Curtin University and the University of Notre Dame.
The Raine cohort is one of the largest and most successful prospective cohorts of pregnancy and childhood in the world with detailed longitudinal data on 2868 children and their families throughout pregnancy, childhood and adolescence. In 2008, eighteen years after the Raine Study began, the members of the cohort are back in Carson House for the “Challenge Me Study”. This project has been funded by the Canadian Institute of Health Research and is part of a larger project evaluating gene:environment interactions underlying the developmental origins of health and disease. The “Challenge Me Study” is a psychological challenge, similar to the TV show “Thank God You’re Here”. The exact nature of the challenge is only revealed to the member of the cohort once the challenge begins. This specific challenge utilised by the research team is considered the gold standard challenge of the hypothalamicpituitary-adrenal axis and the results of this study will allow a detailed evaluation of each individual’s response to psychological stress. The results of the study will be evaluated in a wider context relating to events during intrauterine growth, early life events and development during childhood and adolescence. For the first time, this project has integrated Women and Infant Research Foundation Volunteers into our research program. The utilisation of both men and women volunteers has greatly assisted in the conduct of this study and the research team is very thankful for their participation. The Challenge Me Study will take three years to complete and will become the largest evaluation of stress induced hypothalamic-pituitary-adrenal axis function ever conducted in the world.
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Women and Infants Research Foundation Annual Report 2008
Chief Investigators
Dr Craig Pennell MBBS(Hons) PhD FRANZCOG CMFM Senior Lecturer in Maternal Fetal Medicine Scientific Director, The Western Australian Pregnancy Cohort (Raine) Study The University of Western Australia Honorary Board Member, Women and Infants Research Foundation Dr Anke van Eekelen Research Fellow and Adjunct Senior Lecturer Telethon Institute for Child Health Research and Centre for Child Health Research at The University of Western Australia Professor John Newnham MD FRANZCOG CMFM DDU Professor of Maternal Fetal Medicine The University of Western Australia and Honorary Director, Women and Infants Research Foundation Professor Stephen Lye PhD Professor, Department of Obstetrics and Gynaecology University of Toronto Associate Director and Vice President Research Samuel Lunenfeld Research Institute, Mt Sinai Hospital, Toronto
Research Team
Karen Bosel BSc (Hon) Blagica Penova-Veselinovic MSc (Hon) Hilary Hii BSc (Hon) Catherine Coleman BSc (Hon) Krysia Zarzycki RN RM
Craig Pennell Anke van Eekelen
Karen Bosel, Krysia Zarzycki, Hilary Hii, Blagica Penova-Veselinovic
Women and Infants Research Foundation Annual Report 2008 19
Research Reports
Prediction and Prevention of Preterm Labour Using Molecular Genetics
Overview of Research
Research Highlights
• The utilisation of new technologies has provided us with the opportunity to develop a new non-invasive method of accurately and reliably diagnosing true preterm labour. • Distinct gene expression profiles in maternal white blood cells appear to predict delivery within 48 hours, delivery less than 34 weeks, and delivery less than 37 weeks gestation. • The results of this year’s work have culminated in filing North American and worldwide patents on the predictive “genetic signature” for true pre-term labour. • Through collaboration with the World Health Organization and the Preterm Birth International Collaborative, the research team is participating in a multinational genome-wide association study of pre-term birth resulting in more than one million dollars worth of genotyping being performed through the WIRF laboratories on samples from four continents.
The research program investigating the prediction and prevention of preterm labour utilising molecular genetics has three components: 1) the “true” preterm labour study; 2) identifying genetic markers of periodontal disease-associated pre-term birth; and 3) the preterm birth genome project lead by the World Health Organisation. The “true” preterm labour study is investigating the clinical condition of threatened pre-term labour. This condition, where women present to hospital with regular uterine contractions many weeks prior to their expected delivery, occurs in many women during pregnancy and accounts for one third of all antenatal hospital admissions for pregnant women. Fortunately most women who present with threatened pre-term labour do not progress to pre-term delivery; however, our ability to predict the 5% who will progress to delivery within 7-10 days is poor. Each year in Australia more than 120,000 women are admitted to hospital with threatened pre-term labour, yet only 6000 of these deliver within 7-10 days. Utilising molecular genetics techniques, our research team has identified specific “genetic signatures” that accurately predict delivery within 48 hours, prior to 34 weeks and prior to 37 weeks gestation. These signatures will allow the development of new noninvasive methods of accurately and reliably diagnosing true preterm labour which will provide the means to effectively triage patients and so reduce demands on limited health care resources, to limit the use of existing approaches to those patients whose preterm birth is imminent and, to define targeted patient groups to test new therapeutic approaches to prevent pre-term birth. There is a growing body of evidence suggesting an association between gum disease and pre-term birth; however, potential mechanisms for this association have yet to be established. Utilising the principle that our group discovered in the “true pre-term labour study”, we have been evaluating the effect of treatment of gum disease in pregnant women on patterns of gene activation in white blood cells. These studies will provide a genome wide evaluation of the potential mechanisms responsible for the association between gum disease and preterm birth. Further, they may offer novel targets for future treatment opportunities to prevent preterm birth. With the disclosure of the sequence of the entire human genome and the availability of high-throughput methods making genotyping of large numbers of samples faster and less expensive than ever, our ability to acquire genetic data has increased exponentially. Molecular genetic techniques have demonstrated that approximately one third of the risk of pre-term birth is genetic. During 2007 and 2008 a group of international investigators (including members of our research team) has formed the Preterm Birth Genome Project (PGP) Consortium. The PGP is lead by the World Health Organization through collaboration with the Preterm Birth International Collaborative (PREBIC). This consortium has assembled a team of international research leaders, 28000 DNA samples from women with preterm birth, and successfully obtained $1.5M to begin to unravel the genetic basis of preterm birth. Phase one and two of this project will occur within the Women and Infant Health Research Laboratories over the next twelve months and will involve 2600 DNA samples being genotyped for more than one million genetic variants in each patient. These samples will come from preterm birth studies from Perth, Denmark, Sweden, Mexico, Korea and Canada. This project has been funded by the World Health Organization, March of Dimes, Mexico’s government agency for science (CONACyT) and the Instituto Nacional de Perinatologia in Mexico. Through the establishment of a team of committed international researchers, we anticipate making major advances into the genetic basis of preterm birth.
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Women and Infants Research Foundation Annual Report 2008
The “true” preterm labour study is investigating the clinical condition of threatened pre-term labour.
Chief Investigators
Dr Craig Pennell MBBS (Hons) PhD FRANZCOG CMFM Senior Lecturer in Maternal Fetal Medicine The University of Western Australia and the Women and Infants Research Foundation Professor Stephen Lye PhD Professor, Department of Obstetrics & Gynaecology, University of Toronto Associate Director and Vice President Research, Samuel Lunenfeld Research Institute Mt. Sinai Hospital Toronto Professor Alan Bocking MD PhD Professor and Chairman, Department of Obstetrics & Gynaecology, University of Toronto Professor John Newnham MBBS MD FRANZCOG CMFM DDU Professor of Maternal Fetal Medicine The University of Western Australia and the Women and Infants Research Foundation
Researchers
Dr Jennifer Henderson PhD MPH Grad Dip (Adv Nursing) BSc RN RM Postdoctoral Research Fellow Karen Bosel BSc (Hons) Research Assistant Blagica Penova-Veselinovic BSc (Hons) Research Assistant
Major Sponsors
March of Dimes Birth Defects Foundation World Health Organization Mexico’s government agency for science (CONACyT) Instituto Nacional de Perinatologia in Mexico Raine Medical Research Foundation PSI Foundation in Ontario Canada Women and Infants Research Foundation
Craig Pennell
John Newnham
Stephen Lye
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Women and Infants Research Foundation Annual Report 2008
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Women and Infants Research Foundation Annual Report 2008
Research Reports
Placental Research
The Placental Research Group is headed by Associate Professor Jeff Keelan, a recent recruit to the School of Women’s and Infant’s Health, and is comprised of PhD students Ambika Singh and Irving Aye, and Honours students Shannon Cushing and Pui Mon Wong. The group has collaborative links with the Department of Anatomy and Human Biology, UWA, the School of Medicine and Pharmacology at Royal Perth Hospital, The Perinatal Research Centre at Melbourne’s Royal Women’s Hospital, and the Liggins Institute at the University of Auckland.
The Placental Research Group currently has three main areas of study: • The use of anti-inflammatory drugs to block placental inflammation, a leading cause or premature birth, in collaboration with Professor Murray Mitchell, Liggins Institute, University of Auckland. • Drug transporters in the placenta and their role in a) protecting the fetus from toxins and harmful chemicals, and b) modifying cellular lipids and survival during placental formation, in collaboration with Professor Arunasalam Dharmarajan, Department of Anatomy and Human Biology, UWA. • Dietary supplementation with omega-3 fatty acids in pregnancy to protect against common pregnancy disorders, in collaboration with Dr Trevor Mori, School of Medicine and Pharmacology, and Professor Brendan Waddell, School of Anatomy and Human Biology, UWA. The Placental Research Group members are the main users of the new Dr Bertie Cohen Cell Biology & Tissue Culture Laboratory. Each week they collect normal term placentas from Caesarean section deliveries, and extract and grow cells from the placenta and attached membranes for their studies. Although the tissue culture facilities became operational late in 2007, progress was unexpectedly delayed due to problems with a key reagent used to isolate placental cells (a problem which also affected other labs in Australia and New Zealand). This was finally resolved mid 2008 after much time and effort. Despite these delays, progress has been made in all projects. To date, the group’s major findings include: • Identifying the presence of novel recognition molecules responsible for triggering inflammation within the placental and fetal membranes. • Defining how changes in cellular sphingolipid synthesis and metabolism are necessary for successful placental cell differentiation. • Identifying changes in gene expression in the fetal membranes in response to bacteria and anti-inflammatory drugs. • Localising cholesterol transporters to specific placental cell types, suggesting a role for transporters in delivery of cholesterol to the fetus. • Identifying periodontal bacteria as highly potent stimulators of inflammation in the fetal membranes. • Showing that exposure of placental tissues to fish oil-derived fatty acids can modify placental inflammation and oxidative stress. Grants from The University of Western Australia ($21,000) and the Ada Bartholomew Trust ($30,000) to investigate aspects of the omega-3 fatty acid project have been awarded to Dr Keelan and his collaborators. Other major grant applications are pending.
The Placental Research Group members are the main users of the new Dr Bertie Cohen Cell Biology & Tissue Culture Laboratory.
Chief Investigators
WIRF/UWA School of Women’s and Infants’ Health Associate Professor Jeffrey Keelan BSc. (Hons.) MSc. PhD MRSNZ UWA School of Anatomy and Human Biology Professor Arunasalam Dharmarajan BSc. MSc. MMedSci. PhD Professor Brendan Waddell BSc. (Hons.) PhD UWA School of Medicine and Pharmacology (Royal Perth Hospital Unit) Dr Trevor Mori BSc. (Hons.) PhD Liggins Institute, University of Auckland, New Zealand Professor Murray Mitchell DPhil. DSc. FAIC C.Chem FRSC FRSNZ
L to R: Ambika Singh, Pui Mon Wong, Irving Aye, Jeff Keelan, Shannon Cushing
Women and Infants Research Foundation Annual Report 2008 23
Research Reports
Fetal Futures Program
In 2007 the Fetal Futures program was established, with the principal aim being to assess the long term outcomes in children who had recognised problems in fetal life.
With advances in scientific knowledge many serious conditions impacting upon the fetus prior to birth are now identified. Prenatal ultrasound has been the cornerstone of fetal welfare management both in terms of diagnostic capabilities and access to the fetus for therapeutic interventions. It is now uncommon for fetuses to be delivered with serious conditions that are not detected prior to birth. The detection of serious structural abnormalities in the fetus has several advantages. Firstly, it may alter the place of birth to facilitate early interventions by paediatric staff to optimise the outcome for the baby. Secondly, it provides the opportunity for parental counselling in regards to the long and short term outcomes that may occur. Thirdly, in some circumstances there may be interventions available for the fetus itself that can improve outcome (fetal blood transfusion and placental laser ablation being two successful interventions). As short term outcomes for babies have improved with the prenatal recognition of problems and neonatal treatment strategies, it has become evident that the long term impact of these conditions and our medical interventions need review. Thus, we have established the Fetal Futures Program, an ambitious research innovation to assess the impact of fetal problems on the growth and development of children. Our first project has been to assess the cardiac function of children who received blood transfusions as a fetus to investigate the impact of anaemia and hypoxia upon the developing fetal heart. The cardiac function of children and adolescents who received intrauterine transfusions for severe fetal anaemia secondary to red cell isoimmunization between 1992 and 2002 at King Edward Memorial Hospital is being performed, and this project is nearing completion with data analysis about to commence. Our second project is the assessment of the long term outcomes of children born with gastroschisis, a congenital defect in the anterior abdominal wall. Medical investigators in Western Australia have had an interest in this condition for several years and the Fetal Futures Program provides us with the opportunity to further develop this research area. This project is currently in the design phase and should start assessing our adolescent population in early 2009. The Fetal Futures Program new research initiative is a collaborative venture between the Womens and Infants Research Foundation and the Channel 7 Telethon Trust. We are extremely grateful and appreciative to Telethon for providing us with the financial support to conduct these projects and facilitate research into the impact of fetal diseases upon childhood development.
Investigators
Associate Professor Jan Dickinson MD FRANZCOG Professor John Newnham MD FRANZCOG Dr Luigi D’Orsogna MBBS FRACP Joan Sharpe M Cardiac Ultrasound, AMS Teresa Warner RN RM DMU (Obstetric & Gynaecology) Associate Professor Ronnie Hagan FRANCP Dr Corrado Minutillo FRANCP Dr Madhur Ravikumara Dr Emma Harris
Major Sponsors
Channel 7 Telethon Trust Women and Infants Research Foundation
Joan Sharpe
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Teresa Warner
John Newnham
Jan Dickinson
Luigi D'Orsogna
Women and Infants Research Foundation Annual Report 2008
Research Reports
Modeling Maternity Care Options for Women at Low Risk of Pregnancy Complications
Women in Western Australia receive their pregnancy care in a hospital to the extent that less than 1% of births occur in other settings. Maternity care in Western Australia is undergoing reform with an aim to expand the currently available models of care. The introduction of new alternatives requires detailed evaluation of maternal and neonatal outcomes to provide women and health professionals with information about the risks associated with any proposed changes in maternity care delivery.
Our project aim is to provide information about the pregnancy outcomes expected if the models of maternity care under consideration were introduced into practice. We only considered models of maternity care for women at a low risk of pregnancy complications because these women should be able to receive their antenatal care in out-of-hospital settings and should be able to choose their home or a birth centre for the birth of their baby instead of hospital based care. We considered twelve different models of maternity care involving midwives, GP’s, GP obstetricians and traditional public obstetric led care, as well as planned home births, births at a family birth centre and in a hospital. Evaluation of each model of care included rates of antenatal, intrapartum and postpartum transfers between models of care along with clinical outcomes and associated costs. Evaluation of models of maternity care utilised computer simulations of pregnancy outcomes. Using the Western Australian pregnancy data 2,500,000 hypothetical pregnancies were generated. Antenatal complications and pregnancy outcomes were simulated according to maternal characteristics such as parity, age, weight and smoking during pregnancy. Pregnancy complications such as gestational diabetes or gestational hypertension were simulated to occur at any time from 20 pregnancy weeks until the baby’s birth. These occurring complications often required a change of care provider: For example, if a woman receiving midwifery care developed gestational diabetes she was transferred into obstetric care in a hospital setting for the remainder of her pregnancy and birth of her baby. Similarly, women who were simulated to begin labour at home or in a birth centre, were modelled to require transfers into a hospital if labour was prolonged or the baby was in distress during or after birth. Our simulated data closely resemble the pregnancy outcomes observed in WA women at low risk of pregnancy complications. This allowed us to estimate transfer rates between the newly proposed models of care during pregnancy and transfers during labour and birth. This project complements the WA Health reform process by providing an evaluation of the health outcomes and economic implications of the proposed models of maternity care. It was the first large project in the area of health services research conducted at the Women and Infants Research Foundation, and we hope to expand our health services research activities in obstetrics over the next few years. We are grateful to the Health Department of Western Australia for providing us with a State Health Research Advisory Council grant.
Research Objectives
• Evaluation of antenatal care models for care provided by midwives, community GP’s or hospital based obstetricians. • Evaluation of birth outcomes for care provided in three settings of labour and birth: At home, at a birth centre or in a hospital. • Estimation of pregnancy complications and transfers between models of care due to these complications. • Estimation of complications during labour and birth and transfers from a home or a family birth centre to a hospital due to complications. • Estimation of costs for each proposed model of pregnancy care.
Investigators
Dr Dorota Doherty BSc (Hons) PhD Dr Janet Hornbuckle MB ChB MRCOG FRANZCOG Maureen Hutchinson RN RM Professor John Newnham MD FRANZCOG Gerard Montague BEc Grad Dip Bus Fin Dr Jennifer Henderson RN RM Grad Dip (Adv Nursing) MPH PhD Jeffrey Cannon BSc BBus Student
Major Sponsor
State Health Research Advisory Council, WA Department of Health
Dorota Doherty
Janet Hornbuckle Maureen Hutchinson
John Newnham
Jennifer Henderson
Jeffrey Cannon
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Women and Infants Research Foundation Annual Report 2008
Overview of Unit
Research Reports
Anaesthesia and Pain Relief
The Department of Anaesthesia and Pain Medicine is actively involved in a number of lines of investigation in both applied science and clinical management. These activities focus on anaesthesia and pain relief for the pregnant woman, with special interests in the application of spinal and epidural drugs, novel technologies, nasal delivery of strong pain killers, wrist bands for prevention of nausea during labour and the effects of drugs used at the time of surgery on patient physiology and recovery. The Department Research Fellows in the past 12 months have been Drs Melanie Thew and Neil Muchatuta. They are supervised by Professor Michael Paech, who was awarded the Australian and New Zealand College of Anaesthetists Lennard Travers Professor in 2008. The research efforts are coordinated by two outstanding part-time research midwives, Desiree Cavill and Tracy Bingham, who have shown long-standing support. Members of the department are increasing their involvement in study design and conduct, especially Dr Nolan McDonnell. We have research collaborations with colleagues in Anaesthesiology overseas and interstate; with the Pharmacology Unit and other units within the School of Medicine and Pharmacology; and with The University of Western Australia's School of Women’s and Infants’ Health. Dr Dorota Doherty and Liz Nathan from the Foundation’s Biostatistics and Research Design Unit provide essential and exceptional support in planning and analysing our studies.
Research Highlights
• Publication of the results of a large Australasian multi-centre observational study on general anaesthesia for caesarean section and a clinical trial on a new approach to pain control after caesarean section. • Publication in the Lancet of the results of a large multinational research study involving more than 100 countries and 9,500 perioperative patients. • Presentations at research congresses in Perth, Sydney, Indonesia, Japan and South Africa. • Continued research into novel methods of drug delivery and the transfer of drugs into breast milk. • New research into inflammatory markers of injury to the central nervous system and the effects of drugs on immune function.
Chief Investigators
Professor Michael Paech FANZCA DM Dr Nolan McDonnell FANZCA Dr Melanie Thew FRCA Dr Neil Muchatuta FRCA Dr Katherine Shelley FANZCA Dr Roger Browning FANZCA Dr Lloyd Green FANZCA Dr Shane Merriman FANZCA Dr Stuart Allen FANZCA
Researchers/Investigators
Desiree Cavill RM Tracy Bingham RM Dr Timothy Pavy FANZCA Dr Joel Butler FANZCA
Major Sponsors
The National Health and Medical Research Council The Australian and New Zealand College of Anaesthetists Pfizer Pharmaceuticals
L to R: Neil Muchatuta, Desiree Cavill, Tracy Bingham, Michael Paech
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Research Reports
Nutrition for the Newborn
The goal of providing nutritional support for preterm infants is to promote growth at intrauterine rates. Unfortunately, due to gut immaturity and feeding intolerance, many preterm infants develop a nutrition deficit in the early days and weeks of life making this goal difficult to achieve - intravenous feeding is an important source of nutrients during this time. Our research has shown that more aggressive nutrition support can safely be provided and is necessary for ensuring the early nutrition needs of preterm infants are met. We have implemented a new intravenous feeding regime that provides important nutrients from day one of life.
Recommended protein and energy intakes for preterm infants are much higher than for term infants so although human milk is the feed of choice, it must be fortified with extra protein and energy to provide recommended intakes. Current practice across neonatal units is to fortify human milk assuming a standard milk composition and to estimate nutrition intakes. Our laboratory analysis of the composition of pooled human milk feeds has enabled us to more accurately estimate the protein and energy intakes of our preterm infants and has provided evidence to suggest total protein intake and the ratio of protein to energy in human milk feeds are key determinants in promoting weight gain. Measuring the composition and rate of this weight gain is important in assessing the adequacy of nutrition and its impact on later health outcomes. The PEA POD Body Composition System, donated by The Stan Perron Charitable Trust, has given us the opportunity to easily and safely measure the body composition of our preterm infants and to begin to assess these important outcomes. Preliminary results, based on current fortification and feeding practices, suggest preterm infants at the corrected age of term are fatter than term-born infants at the same age and that female preterm infants are fatter and weigh less than their male counterparts. Ethics approval has been granted to conduct an intervention trial early next year – ‘The PEA-NUT Trial. This trial will compare the growth and body composition of infants whose milk is individually fortified according to measured milk composition with those who are fed according to our current fortification practice. The PEA-NUT Trial should further advance our knowledge of how best to optimise the fortification of human milk to promote appropriate and adequate growth of our preterm infants. We thank all of our Supporters and acknowledge the contribution of NCCU medical and nursing staff and the mothers and infants who have participated in this research.
Chief Investigators
Gemma McLeod MSc APD A/Professor Jill Sherriff PhD Adv-APD Professor Peter E Hartmann PhD Professor Karen Simmer PhD FRACP Liz Nathan BSc, Biostatistician
Major Supporters
The University of Western Australia Australian Rotary Health Research Fund Rotary Club of Thornlie The Stan Perron Charitable Trust
Gemma McLeod
Jill Sherriff
Peter Hartmann
Karen Simmer
Liz Nathan
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Women and Infants Research Foundation Annual Report 2008
Research Reports
Impact of Caffeine and Maturation on Respiratory Control in Preterm Infants
Overview of Research
Preterm infants frequently have immature breathing patterns that occasionally necessitate support by applying positive air pressure to the airways (‘CPAP’) or assisted ventilation. Caffeine is routinely given to preterm infants to improve breathing patterns and to minimize the need for these interventions. This study aims to examine the early maturation of breathing control in preterm infants and to quantify the impact that caffeine has on the respiratory control system using new complex mathematical techniques that analyse fluctuation patterns present during normal breathing. We have recently obtained ethical approval for this study and are in the process of recruiting our first infants. We are fortunate to have state-of-the-art lung function equipment (kindly provided by Associate Professor Jane Pillow) available to measure respiratory traces from sleeping infants in the special care nursery during normal breathing. We have employed a research nurse to assist with measurements, data entry and laboratory management. In collaborative studies, we have previously measured breathing patterns in preterm infants at 36 weeks post-menstrual or corrected age. In this study we hope to measure even younger infants at 34 w corrected age in order to learn more about lung function during the very early period of development. Such measurements in themselves are technically challenging and have been limited to only several centres worldwide. We hope that the results of this study will help us learn more about how the complex memory system that is responsible for breathing control matures in preterm infants during the first months of life, and how this system is affected by caffeine treatment. This study may lead to further investigations that may help us to answer questions such as: When should we cease caffeine in preterm infants? Which preterm infants are at more risk of abnormal breathing patterns after stopping caffeine and should continue the medication for longer? Should some babies go home on caffeine? All these questions currently remain unanswered.
Research Aims
• To examine the early maturation of respiratory control in preterm infants. • To examine the impact of caffeine on respiratory control function in preterm infants.
Investigators
Dr David Baldwin FRACP BMedSc PhD (Chief Investigator) Ann McDonald RN Dr Sven Schulzke MD Professor Jane Pillow FRACP BMedSc PhD Professor Karen Simmer FRACP PhD
Sponsor
Channel 7 Telethon Trust
David Baldwin
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Sven Schulzke
Jane Pillow
Karen Simmer
Women and Infants Research Foundation Annual Report 2008
Research Reports
Mental Health during Pregnancy and the Postnatal Period
Overview of Research
Major Depressive Disorders and Anxiety Disorders increase during pregnancy and the postnatal period. Some women can be managed with counselling, psychological therapies and/or lifestyle changes. A significant number need the addition of an antidepressant. This research was aimed at assessing the degree of transfer of these antidepressants across the placenta and measuring whether or not there was any withdrawal or discontinuation syndrome in the neonate. Placental transfer was measured by taking blood from the mother in labour and taking a sample from the cord soon after birth. Both active patients and control patients agreed to assessment of their babies in the postnatal period using a very detailed assessment of behaviour and autonomic responses in neonates. Two of the authors were specially trained in the process of doing these assessments and conducted all of the assessment on both active and control neonates. The research confirmed that significant transfer of antidepressants occur across the placenta during pregnancy. Some differences in responses in some of the fields tested were found in the neonates whose mothers had taken antidepressants. However, clinically these differences were not of great concern. This research goes a long way in terms of our understanding of the transfer of antidepressant across the placenta and should reassure most mothers that the neonatal consequences while potentially present should not detract them from effective management of their mood disorder during pregnancy.
Research Highlights
• Assessment of transfer of new antidepressants across the placenta. • Detailed assessments of neonates to assess whether or not they experienced any discontinuation syndromes.
Chief Investigators
Dr Jonathan Rampono MBChB MFGP FRANZCP Professor Karen Simmer PhD FRCPCH Emeritus Professor Kenneth Illett BPharm PhD
Major Sponsors
Women and Infants Research Foundation The University of Western Australia
Researchers/Investigators
Lawrence Hackett LRCS AAIMLS Dr Dorota Doherty BSc (Hons) PhD Robin Elliot RN Yen Chooi Heen Kok MsNsg Arlette Coenen BSc Tiffany Forman RN RM CNC
Women and Infants Research Foundation Annual Report 2008
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Research Reports
Neonatal Respiratory Medicine
From 2004-2006 we actively measured the growth and development of lungs in healthy newborn babies as well as those born prematurely with and without lung disease.
Overview of Research Research Highlights
• Completed one year follow-up of infants who had lung function measurements in the newborn period. • Commencement of bedside assessment of deadspace volume in ventilated newborn infants. • Commencement of a study assessing the effect of caffeine on breathing patterns in premature infants at different gestations. • Publication of a study assessing measurements of lung volume and ventilation inhomogeneity using nasal versus face mask. • Curosurf Innovative Research Awarded to Dr Schulzke for his follow-up study on lung function in premature infants. • PhD awarded to Dr David Baldwin for studies assessing control of breathing in newborn infants. The neonatal respiratory research group aims to understand the growth and development of the lung and the systems controlling breathing after preterm birth. We also aim to learn more about the factors that cause lung injury in the neonatal period and to investigate new technologies with the purpose of minimizing lung injury and finding ways to optimize the long term respiratory health and well-being of premature babies. From 2004-2006 we actively measured the growth and development of lungs in healthy newborn babies as well as those born prematurely with and without lung disease. This work is under consideration for publication. Dr Sven Schulzke undertook a one year follow-up lung function study in these infants at one year of age in collaboration with the Department of Respiratory Medicine at PMH. This study has now been completed, and results are being analysed and prepared for publication. Dr Schulzke was awarded the Curosurf Innovative Research Award. In January 2008, Dr David Baldwin was awarded a PhD for his thesis on control of breathing in newborn infants, a study undertaken in collaboration with the Institute of Child Health and the University Children’s Hospital in Berne, Switzerland. Dr Baldwin has just commenced his study assessing the effect of caffeine (a routine medication given to preterm infants to assist their breathing) and gestation (maturity at birth) on the breathing patterns of preterm infants prior to discharge home from hospital.
Chief Investigators
Dr Jane Pillow FRACP PhD (Distinction) Dr David Baldwin MBBS BMedSc Dr Sven Schulzke MD
Major Sponsors
Women and Infants Research Foundation Raine Foundation, UWA Fisher & Paykel Healthcare Channel 7 Telethon Trust
Researchers
Dr Rolland Neumann Neonatal Senior Registrar Ann McDonald RN
Jane Pillow
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David Baldwin
Sven Schulzke
Women and Infants Research Foundation Annual Report 2008
Women and Infants Research Foundation Annual Report 2008
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Research Reports
Breastfeeding Research
Overview of Research
Research Highlights
• Development of further collaborations within the hospital setting. • The expansion of understanding of the factors that affect milk expression • Advanced knowledge in the area of infant feeding has led to the reporting of the first results on ultrasound imaging of infants with tongue-tie. • Identified novel strategies to improve the quality of donor breastmilk for pre-term infants
The International reputation of the Human Lactation Research Group led by Professor Peter Hartmann has been further enhanced by the International Society for Research into Human Milk and Lactation recognizing the work of Medela Postdoctoral Research Fellow Donna Geddes. She received the Early Career Research Award at their Conference that was hosted by The University of Western Australia at the University Club in Perth this year. 2008 has been an exciting year with both the continuation and establishment of new collaborations in the clinical setting that will ultimately provide the foundations for the very best nutrition for infants in this State. Successful culmination of a project investigating the feeding dynamics of infants with tongue-tie (short frenulum) resulted in publication of the findings in the international publication Pediatrics. Researchers from both KEMH and UWA were the first to use ultrasound imaging to assess infant tongue movement during breastfeeding in a project headed by Professor Karen Simmer. The group is continuing this research with mothers and infants experiencing breastfeeding difficulties. PhD student Holly McClellan has found that two-thirds of infants exert very high vacuums during feeding thus causing their mothers much pain and discomfort. Furthermore she has found the use of nipple shields normalize these vacuums allowing mothers to continue feeding. The expression of breast milk for both the pre-term and term infant is a major focus for the group. PhD student Danielle Prime has found that both breasts eject milk simultaneously eradicating the need to separate individually controlled pumps for expressing mothers. This year collaboration with industry has produced a state-ofthe-art experimental breast pump that will be commissioned in October 2008 at the Breastfeeding Centre of WA and will allow much more sophisticated research in this area in the future. The highest quality of expressed breastmilk is of the utmost importance for preterm infants. Collaboration between PhD student Charles Czank, Professor Hartmann, Professor Simmer and Dr Ben Hartmann (Manager of Perron Rotary Express Milk Bank) has identified conditions of pasteurization of breastmilk that effectively eliminate viruses and bacteria from milk while allowing retention of immune components that are so critical in protecting the preterm infant. A new exciting collaboration has begun this year with the Anaesthetic Department to determine if the initiation of lactation and suckling behaviour is affected by the administration of pethidine. In addition levels of pethidine will be measured in breastmilk. Professor Micheal Paech, Dr Yasir Al-Tamimi and Professor Hartmann were successful in acquiring a WIRF Starter Grant to realize this project. We look forward to continuing our research collaborations with KEMH into 2009 as we strive to improve both breastfeeding and nutrition for all infants.
Peter Hartmann
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Donna Geddes
Naomi Trengrove
Jacqueline Kent
Ching Tat Lai
Jane Deacon
Catherine Garbin
Women and Infants Research Foundation Annual Report 2008
Chief Investigator
Professor Peter Hartmann BRurSc (Hons) PhD
Research Students
Holly McClellan BSc (Hon) Charles Czank BSc (Hon) Danielle Prime BSc (Hon) Gemma McLeod MSc APD Ibrahim Abdul MSc Sadaf Khan BSc Vanessa Sakalidis BSc (Public Health)
Associate Investigators
Dr Donna Geddes PhD Dr Naomi Trengove PhD Dr Jacqueline Kent PhD Dr Ching Tat Lai PhD Dr Lynda Chadwick MBBS FRAP (Paed) Dr Jane Deacon MBBS Dr Marnie Rowan MBBS Catherine Garbin IBCLC Ylenia Casadio BSc(Hon) Tracey Williams BSc Lukas Christensen HF (Med Eng; Switzerland)
Assistant
Ruth Abbott
Major Sponsors
Women and Infants Research Foundation Medela AG
Tracey Williams
Lukas Christensen
Holly McClellan
Charles Czank
Danielle Prime Gemma McLeod
Ruth Abbott
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Women and Infants Research Foundation Annual Report 2008
Research Reports
The Fetal and Childhood Origins of Polycystic Ovary Syndrome
Overview of Research
Research and Highlights
• The study is completed with 250 girls having undergone timed ultrasound scans of their ovaries and blood plasma hormonal assessment. Approximately 10% have been diagnosed with PCOS. • First research group to study the intrauterine and early childhood precursors of PCOS. • Analysis may establish whether PCOS arises in association with raised intrauterine androgen exposure. • Will publish the prevalence of dysmenorrhoea (painful periods), menorrhagia (heavy periods) and premenstrual syndrome in this group of adolescents. • In a subset of 349 girls we have demonstrated for the first time that both birth weight and weight gain in childhood predict age at menarche. • Lower birth weight ratio combined with higher body mass index (BMI) at eight years of age, predicted earlier age at menarche and this relationship existed across normal birth weight and BMI ranges.
The Polycystic Ovary Syndrome (PCOS) affects up to 10% of women of reproductive age, which translates into around 350,000 women in Australia. It is the most common hormonal disorder in women. The syndrome has far-reaching adverse implications for general and reproductive health, including menstrual disorder, obesity, infertility, miscarriage, pregnancy complications, increased risk of diabetes and possibly heart disease. PCOS commonly causes cosmetic problems such as excess body hair and acne. The underlying causes of PCOS are not known but are thought to arise during intrauterine (fetal) life and to be modified by aspects of childhood health, particularly overweight and obesity. Using a large and unique cohort of adolescents aged 14-16 from the Raine Study we are investigating the intrauterine and early childhood causes of PCOS.
Investigators
Professor Martha Hickey BA (Hons) MSc MBChB MRCOG MD FRANZCOG A/Professor Roger Hart MRCOG FRANZCOG CREI Dr Deb Sloboda BSc (Hons) MSc PhD Dr Dorota Doherty BSc (Hons) PhD
Major Sponsors
National Health and Medical Research Council The University of Western Australia Department of Health of Western Australia
Researchers/Investigators
Professor Steve Franks FRCP PhD RS
Research Staff
Lee Ann Mahoney RN RM Project Manager Sarah Simpson RN Helen Box RN RM Cherry Young RN RM
Martha Hickey
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Roger Hart
Deb Sloboda
Dorota Doherty
Lee Ann Mahoney
Sarah Simpson
Helen Box
Cherry Young
Women and Infants Research Foundation Annual Report 2008
Overview of Research
Research Reports
Mechanisms of Irregular Bleeding with Implanon Contraceptive Implants
Abnormal uterine bleeding (AUB) limits the use of long-term progestin-only contraceptives (LTPOCs): LTPOCs are safe, effective, and recommended when estrogencontaining contraceptives are contraindicated by hypertension, coronary and cerebral vascular disease, venous thrombotic disorders, lactation, hepatic adenomas, cholelithiasis, breast and endometrial carcinoma and other estrogen-responsive pathologies. The most popular LTPOC is Implanon, a subdermal implantable contraceptive. Implanon is a single rod containing etonogestrel, a 3rd generation progestin that is effective for three years. Approximately, 600,000 women now use Implanon world-wide with the numbers rapidly increasing. Australia has had one of the most enthusiastic uptakes of Implanon of any country in the world. Implanon has gained wide spread popularity because it provides prolonged, highly effective contraception which greatly improves compliance and contraceptive efficacy. Like all LTPOCs, Implanon is highly effective with very low pregnancy rates but its use is limited by irregular and prolonged AUB. The association between the high rate of discontinuation of LTPOC use and AUB reflects the perception that a normal menstrual pattern is an indicator of both reproductive health and the absence of pregnancy.
Preliminary Data
This project is ongoing. To date 12 women have been enrolled.
Research Highlights
• To understanding the mechanism of irregular bleeding with long-acting progestin only contraceptives. • To establish whether Implanon, the only available implantable system, impairs endometrial perfusion. • Develop new treatment approaches for irregular bleeding.
Chief Investigators
Professor Martha Hickey BA (Hons) MSc MBChB MRCOG MD FRANZCOG Professor Charles Lockwood MD PhD Chair of OBGYN Yale University CT USA
Research Staff
Dr Sweta Agarwal MD Dr Manju Ambekar FRANZCOG Dr Helen Atkinson BSc (Hons) PhD Sarah Simpson RN Lee Ann Mahoney RN RM Project Manager
Major Sponsors
National Institute of Health (USA) Department of Health of Western Australia
Martha Hickey
Sarah Simpson
Lee Ann Mahoney
Helen Atkinson
Women and Infants Research Foundation Annual Report 2008 35
Overview of Research
Research Reports
Menopausal Symptoms following Breast Cancer
Breast cancer affects one in eleven women in Australia and is the commonest cause of death in women of middle years. Survival from breast cancer is improving and menopausal symptoms are now one of the most common and debilitating side effects of breast cancer treatments with longlasting effects on quality of life, body image, sexuality, sexual function and self esteem. Menopausal symptoms can be so severe that a significant percentage of women stop their breast cancer treatments because of them. Hormone replacement therapy (HRT) is the most effective treatment for menopausal symptoms. However, it has recently been demonstrated that HRT may increase the risk of breast cancer recurrence. As survival for breast cancer continues to improve, the number of women suffering from menopausal symptoms is likely to increase. The importance of safe and effective treatments for severe menopausal symptoms after breast cancer has become paramount. At King Edward Memorial Hospital in Western Australia we have established the world’s first menopause clinic dedicated to women with a history of cancer (MSAC: “menopausal symptoms after cancer”). So far, we have seen over 600 women, the majority of whom have a history of breast cancer and others with gynaecological and haematological cancers. We have also seen around 150 women considering surgical menopause to reduce their risk of developing ovarian, breast or uterine cancer.
Research Highlights
• Development and evaluation of a Menopause Information booklet for young breast cancer patients. The National Breast and Ovarian Cancer Centre has taken this publication which will be printed and available Australia wide and also web-based for international use. • We have established a database to compare menopausal symptoms and quality of life in women with and with out a cancer diagnosis and currently have over 250 women recruited with a cancer diagnosis. • The development and publishing of evidence based guidelines for the management of menopausal symptoms after cancer. • We have presented this model of care at both medical and nursing national and international meetings.
Chief Investigators
Professor Martha Hickey BA (Hons) MSc MB ChB MRCOG FRANZCOG MD Professor Christobel Saunders MBBS FRACS FRCS
Major Sponsors
National Breast Cancer Foundation Department of Health of Western Australia National Health and Medical Research Council, Australia The University of Western Australia
Researchers/Investigators
Jane Gregson Bch Nsg RN Chris Laird RN RM Anne Breadcell BBus
Martha Hickey
36 Women and Infants Research Foundation Annual Report 2008
Research Reports
Substance Use in Pregnancy
Buprenorphine, marketed as Subutex or Suboxone, is increasingly being used to treat people dependent on opioid drugs. Buprenorphine is a category C drug and is not recommended for use in pregnancy or breastfeeding, however a growing number of women are choosing to use the drug (either prescribed or obtained illegally).
We established the Pilot Study of the Western Australian Register of buprenorphine treatment in pregnancy and the early postnatal period. Thirteen women participated in the study. No significant obstetric or neonatal adverse effects were observed. Buprenorphine appears to be a viable alternative to methadone for treatment of pregnant opioid dependent women. Further research is needed to confirm this and we will seek permission to extend the study as the proportion of women on buprenorphine attending the Womens’ Antenatal Drug and Alcohol Service (WANDAS) clinic is now equal to that on methadone (12% of the clinic population). There are few data on the placental transfer of buprenorphine. A study by Nanovskaya et al using isolated perfused human placental lobules showed that there was sequestration of buprenorphine by the placental tissue, with low transfer to the fetal side of the circuit and less than 5% metabolism to norbuprenorphine. In a study of placental transfer of buprenorphine at birth we have demonstrated low levels of the drug regardless of dose. After administration, buprenorphine is metabolised to its primary pharmacologically active metabolite norbuprenorphine13 by hepatic cytochrome P450 3A4. However, the placenta lacks significant amounts of CYP3A4, and the minor amount of metabolism that occurs in this tissue is attributable to the enzyme aromatase. Buprenorphine has been ascribed a Lactation Risk Category of L3. That is, there are no controlled studies on breast-feeding and there is a possibility of untoward effects on breastfed infants. The elimination half-life of buprenorphine is 24-37 hours; however it is retained on the opioid receptor site for long periods and may produce effects longer than the elimination half life would suggest.The benefits of breastfeeding are well documented. Breastfeeding is recognised as the best nutrition for the infant. As with most opiates breastmilk levels of buprenorphine are probably low. We have been funded by WIRF to conduct a study on the transmission of buprenorphine in breastmilk of lactating mothers which will shortly commence at King Edward Memorial Hospital. The investigation is designed to obtain quantitative information on milk concentrations of buprenorphine to enable appropriate information to be provided to the mothers. This will allow them to make informed decisions about breastfeeding, something that has potential to have considerable influence on their infant’s wellbeing.
Research Highlights
• Establishment of the Buprenorphine Registry. • Estimation of placental transfer of buprenorphine at birth.
Investigators
Professor Anne Bartu PhD FRCNA Dr Dale Hamilton FRANZCOG Emeritus Professor Ken Ilett BPharm PhD Dr Dorota Doherty BSc (Hons) PhD Sean O’Halloran Msc Renata McLaurin RN RM BHlth Sc
Anne Bartu
Dale Hamilton
Dorota Doherty
Renate McLaurin
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Women and Infants Research Foundation Annual Report 2008
Research Reports
Teenage Pregnancy Intention, Contraceptive Use and Repeat Pregnancy
Research Highlights
• The two year follow-up has been completed. • Analysis of the baseline questionnaire, postnatal, six week, three month, nine month and one year questionnaires has been completed. In addition an audit of the medical records of the study participants has also been completed. • Median age at recruitment was 17 years, with 13 the youngest. • At baseline the majority n=134 (75%) of teenagers reported that they did not intend to become pregnant, however n=131 (73%) reported not using contraception or using contraception inconsistently at the time they conceived. • By the end of the two year follow up a total of n=83 (55%) of the teenagers had elected to use Implanon for contraception. • By the end of the two year follow up contraceptive use had fallen and n=65 (42%) teenagers had experienced a repeat pregnancy. Of these pregnancies n=28 (18%) were in the first year and n= 37 (24 %) in the second.
Whilst the birth rate among Australian teenagers (15-19 years) has fallen in recent decades, Australia continues to have a teenage birth rate several times higher than other comparable countries and OECD nations. Teenage mothers and their children are at greater risk of poor physical, emotional, educational and social outcomes than the general population.
Teenage mothers have a particularly high rate of repeat pregnancy and effective contraceptive use is an important goal in delaying repeat pregnancy in young teenage mothers. However, the reliable use of the oral contraceptive pill can be problematic for some teenagers. This study aims to determine whether Etonogestrel implantable contraceptive (Implanon), is acceptable to this group of teenagers and can reduce repeat unwanted pregnancy. 179 (70%) of the booked teenage pregnancies attending the King Edward Memorial Hospital Adolescent Clinic were recruited and followed up every three months, over a two year period. Of n=179 recruited, only n=152 were followed up as n=27 only gave consent to complete the baseline questionnaire and have their clinical records audited. Questionnaires were used to gather data in relation to demographic details, psychosocial risk factors for teenage pregnancy, contraceptive use, barriers to contraceptive use and a validated measure of unplanned pregnancy. Where possible, items that had been found to be valid and reliable in a teenage population were used.
Investigators
Dr Rachel Skinner FRACP MBBS PhD Professor Martha Hickey BA (Hons) MSc MB ShB MRCOG FRANZCOG MD Dr Dorota Doherty BSc (Hons) PhD Lucy Lewis RN RM BSc Health Sciences MN (PhD Candidate)
Rachel Skinner
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Martha Hickey
Dorota Doherty
Lucy Lewis
Women and Infants Research Foundation Annual Report 2008
Overview of Research
Research Reports
Family Vascular Risk Factors in the Prediction of Pre-eclampsia
Pre-eclampsia is a serious complication of pregnancy, causing increased perinatal and maternal morbidity and mortality. It afflicts 5-6% of pregnancies in WA and is responsible for approximately 15-20% of preterm births. The incidence of the condition is higher in first time pregnancies (approximately 10%). As there is no prior pregnancy history in nulliparous women to inform the risks of developing pre-eclampsia, we believe it is important that this group be looked at in detail. Pre-eclampsia is characterized by hypertension, endothelial damage, activation of inflammatory pathways and activation of coagulation pathways. These disturbances are associated with impaired placental perfusion and often poor fetal growth with an increased risk of stillbirth, abruption of the placenta and maternal complications related to severe hypertension and widespread vascular damage. The cause of pre-eclampsia is unknown. It is likely that there is no single cause and that the disorder may result from a variety of predisposing states. Major contributors are hypertension, renal disease, autoimmune disorders, thrombophilic states and multiple pregnancy. During routine antenatal appointments we are asking 1000 first-time mothers and their partners, a series of questions about their family health history. After delivery we are collecting pregnancy and birth outcomes. A database will be used to assess any relationships found. This study will interrogate the hypothesis that the risk of pre-eclampsia and associated pregnancy complications relate to family history of cardiovascular disease in the pregnant woman and her partner. We believe the medical history of the father of the baby may additionally inform the prediction of the incidence of pre-eclampsia in the mother. In collaboration with groups of international researchers, we are also looking at ways to better predict the progression of pre-eclampsia during individual pregnancies; to improve management of the condition and ultimately to improve outcomes for mothers and their babies.
This study will interrogate the hypothesis that the risk of pre-eclampsia and associated pregnancy complications relate to family history of cardiovascular disease in the pregnant woman and her partner.
Investigators
Clinical Associate Professor Barry NJ Walters FRACP Claire Parker BSc (Masters by Research Candidate) Dr Dorota Doherty BSc (Hons) PhD Dr Natalie Oud MBBS
Major Sponsor
Pfizer Australia
Dorota Doherty
Barry NJ Walters
Claire Parker
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Women and Infants Research Foundation Annual Report 2008
Research Reports
Evaluation of Preliminary Forensic Specimen Kits in Recent Sexual Assault
This project aims to assess the usefulness of the PFSK and the effectiveness of specific SARC training about their use.
Overview of Research
It is vital that after a recent sexual assault, a person has access to not only a medical assessment but also a forensic assessment if they wish. Forensic evidence deteriorates rapidly and if not collected early, may be lost completely. However an immediate forensic examination is not always possible to provide due to conflicting medical and psychosocial requirements or a lack of forensically trained medical staff in regional areas. Preliminary forensic specimen kits can be used to collect early forensic evidence specimens in order to prevent the loss of evidence which may occur when there is a delay in conducting a complete medical and forensic examination. The use of Preliminary Forensic Specimen Kits (PFSK) prevents the loss of potential evidence while allowing the person who has been recently sexually assaulted to wash their mouth, pass urine or open their bowels if they need to, prior to a full medical and forensic examination. The W.A. Police and Health workers in Emergency Departments in both metropolitan and regional areas have access to PFSK. This project aims to assess the usefulness of the PFSK and the effectiveness of specific SARC training about their use. As part of the project SARC Doctors have provided the police officers of the Sex Assault Squad (SAS) and Major Incident Group (MIG) with practical training to allow them to guide a person to self-collect early oral, vulval, peri-anal and urine specimens when indicated, in a nonintrusive manner, prior to a full medical examination being conducted. It is hypothesized that early collection of forensic evidence by the consistent and accurate use of PFSK will lead to greater recovery of forensically significant material, greater identification of alleged perpetrators of sexual assault, and improved patient care and outcomes. DNA analysis of the preliminary specimens and comparisons with forensic specimens obtained at the subsequent full medical forensic examination will bring a scientific evidence-base to current practices. It is envisaged that the use of the PFSK will improve the comfort of the person who has been recently sexually assaulted while also preventing the loss of forensic evidence. This study is being carried out in collaboration with the WA Police and PathWest Forensic Biology.
Chief Investigators
Dr Maureen Phillips MBBS Grad Dip Clinical Forensic Medicine Dr Debbie Smith MBBS Dr Catherine Nixon MBBS DRANZCOG FRACGP Grad Cert Clinical Forensic Medicine Liz Nathan BSc
Associate Investigators
Laurance Webb Senior Forensic Scientist and Team LeaderMajor Crime, Forensic Biology, PathWest Detective Senior Sergeant John Hindriksen, Sex Assault Squad, WA Police
Support Staff
Rae Cummins
Major Sponsors
Women and Infants Research Foundatio
Debbie Smith
Maureen Phillips
Rae Cummins
John Hindriksen Laurance Web
40 Women and Infants Research Foundation Annual Report 2008
Publications
Geddes DT, Langton DB, Gollow I, Jacobs LA, Hartmann PE, Simmer K. Frenulotomy for breastfeeding infants with ankyloglossia: effect on milk removal and sucking mechanism as imaged by ultrasound. Pediatrics, 2008; 122(1):e188-94. Geddes DT, Kent JC, Mitoulas LR, Hartmann PE. Tongue movement and intra-oral vacuum in breastfeeding infants. Early Human Development, 2008; 84:471–477. Geddes DT, McCellan HL. Breastfeeding – from Breast to Baby New Perspectives. Nova, 2008 (in press). Gera PK, Kikiros CS, Charles A. Chronic diarrhoea: a presentation of immature neuroblastoma. Australian and New Zealand Journal of Surgeons, 2008; 78(3):218-9. Hart RJ, Hickey M, Maouris P, Buckett W, Garry R. Excisional surgery versus ablative surgery for ovarian endometriomata. The Cochrane Database Systematic Reviews, 2008 (April 16); (2):CD004992. Henderson JJ, Hartmann PE, Moss TJM, Doherty DA, Newnham JP. Disrupted Secretory Activation of the Mammary Gland after Antenatal Glucocorticoid Treatment in Sheep. Reproduction, 2008 (in press). Henderson JJ, Hartmann PE, Newnham JP, Simmer K. Effect of preterm birth and antenatal corticosteroid treatment on lactogenesis II in women. Pediatrics, 2008; 121;e92-e100. Henderson JJ. Disrupted Lactogenesis II After Antenatal Glucocorticoid Treatment in Sheep. Reproduction, 2008 in press). Hickey M, Doherty DA, Fraser IS, Sloboda DM, Salamonsen, LA. Why does menopausal hormone therapy (HT) lead to irregular uterine bleeding? Changes to endometrial blood vessels. Human Reproduction, 2008; 23(4):912-8. Hickey M, Saunders CS, Partridge A, Santoro N, Stearns V, Hadine H. Practical clinical guidelines for assessing and managing menopausal symptoms after breast cancer. Annals of Oncology, 2008 Jun 16 (in press). Hickey M, Salamonsen LA. Endometrial structural and inflammatory changes due to exogenous progestogens.Trends in Endocrinology & Metabolism, 2008; 19(5):167-174. Hillman NH, Moss TJ, Nitsos I, Kramer BW, Bachurski CJ, Ikegami M, Jobe AH, Kallapur SG. Toll-like receptors and agonist responses in the developing fetal sheep lung. Pediatric Research, 2008; 63(4):388-93. Ilett KF, Paech MJ, Page-Sharp M, Sy SK, Kristensen JH, Goy R, Chua S, Christmas T, and Scott KL. Use of a sparse sampling study design to assess transfer of tramadol and its O-desmethyl metabolite into transitional breast milk. British Journal of Clinical Pharmacology, 2008; 65:661-6. Kent JC, Mitoulas LR, Cregan MD, Geddes DT, Larrson M, Doherty DA, Hartmann PE. Importance of vacuum for breastmilk expression. Breastfeeding Medicine, 2008; 3(1):11-19. Laurvick CL, Milne E, BlairE, de Klerk N, Charles AK, Bower, C. Fetal growth and the risk of childhood non-CNS solid tumours in Western Australia.British Journal of Cancer, 2008; 99:179-81. Leslie K, Myles P, Chan M, Peyton P, Paech M, Forbes A. Risk factors for severe post-operative nausea and vomiting in a randomised trial of nitrous oxide-based versus nitrous oxide-free anaesthesia. British Journal of Anaesthesia, 2008 doi:10.1093/bja/aen230. MacDonald SJ, Henderson JJ, Faulkner S, Evans S F, Hagan R. Effect of an extended midwifery postnatal support program on the duration of breastfeeding: A randomised controlled trial. Midwifery, 2008 (in press). Magann EF, Doherty DA, Briery CM, Niederhauser A, Chauhan SP, Morrison JC, Obstetric characteristics for a prolonged third stage of labor and risk for postpartum hemorrhage, Gynecologic Obstetric Investigation, 2008; 65(3):201-205. Makepeace AE, Bremner AP, O’Leary P, Leedman PJ, Feddema P, Michelangeli V, Walsh JP. Significant inverse relationship between free T4 concentration and body mass index in euthyroid subjects: differences between smokers and non-smokers. Clinical Endocrinology, 2008 (in press). McClellan HL, Geddes DT, Kent, JC, Garbin CP, Mitoulas LR, Hartmann PE. Infants of mothers with persistent nipple pain exert strong sucking vacuums. Acta Paediatrica, 2008 (in press). McDonnell NJ, Paech MJ, Clavisi OM, Scott KL and the ANZCA Trials Group. Difficult and failed intubation in obstetric anaesthesia: An observational study of airway management and complications associated with general anaesthesia for caesarean section. International Journal of Obstetric Anesthesia, 2008; doi:10.1016/j.ijoa.2008.01.017. Menninger I, Hart R. Hysteroscopic sterilisation. In Fallopian Tubes (Eds) Djahanbakhch, Saridogan and Allahbadia Anshan Publishing House, Tunbridge Wells, UK. 2008. Metcalfe SA, Bittles AH, O’Leary P, Emery J. Australia: Public Health Genomics. Public Health Genomics, 2008 (in press). Mitchell MD, Sato TA, Wang A, Keelan JA, Ponnampalam AP, Glass M. Cannabinoids stimulate prostaglandin production by human gestational tissues through a tissue and CB1 receptor specific mechanism, American Journal Physiology Endocrinology & Metabolism, 2008; 294(2):E352-6. Molster C, Charles T, Samanek A, O’Leary P. Australian study on community knowledge of human genetics and health. Public Health Genomics, 2008 (in press).
Publications in peer review scientific journals
1 January – 30 June 2008
Audette MC, Connor KL, Braun T, Li S, Moss TJ, Sloboda DM, Newnham JP, Challis JRG. Maternal glucocorticoid administration in early pregnancy and the relationship between 11 HSD2 mRNA in ovine placenta and fetal weight across gestation Reproductive Sciences, 2008; 15(2):753. Biggio J, Christiaens I, Katz M, Menon R, Merialdi M, Morken NH, Pennell C, Williams SM. A call for an international consortium on the genetics of preterm birth.American Journal of Obstetrics & Gynecology, 2008; 199(2):95-7. Blank, V, Hirsch, E, Challis, JRG, Romero, R, Lye, SJ. Cytokine signaling, inflammation, innate immunity and preterm labour - a workshop report. Placenta, 2008; 29, Suppl A:S102-104. Brameld K, Dickinson J, Bower C, Goldblatt J, Murch A, Hewitt B, Stock R, O’Leary P. Association of first-trimester maternal serum PAPP-A, free-beta subunit human chorionic gonadotropin concentration, nuchal translucency and the combined risk measurement for Down’s Syndrome with adverse pregnancy outcomes. Australian & New Zealand Journal of Obstetrics & Gynaecology, 2008 (in press). Braun T, Li S, Mathhews SG, Sloboda DM, Moss TJM, Newnham JP, Challis JRG. Maternal glucocorticoid injections in early pregnancy altered pituitary-adrenal axis in sheep. Reproductive Science, 2008; 15 (2):385. Burrage D, Green LR, Moss TJ, Sloboda DM, Nitsos I, Newnham JP, Hanson MA. The carotid bodies influence growth responses to moderate maternal undernutrition in lategestation fetal sheep. British Journal of Obstetrics and Gynaecology, 2008; 115(2):261-8. Chauhan SP, Magan EF, Doherty DA, Ennen CS, Neiderhauser A, Morrison JC. Prediction of small for gestational age newborns using ultrasound estimated and actual amniotic fluid volume: published data revisited, Australian & New Zealand Journal of Obstetrics & Gynaecology, 2008; 48(2):160-164. Cheah FC, Jobe AH, Moss TJ, Newnham JP, Kallapur SG. Oxidative stress in fetal lambs exposed to intra-amniotic endotoxin in a chorioamnionitis model. Pediatric Research, 2008; 63(3):274-9. Cocciolone R, Brameld K, O’Leary P, Haan E, Muller P, Shand K. Combining first and second trimester markers for Down syndrome screening – think twice. Australian & New Zealand Journal of Obstetrics & Gynaecology, 2008 (in press). Daniels L, Gibson RA, Simmer K, Van Dael P, Makrides M. Selenium status of term infants fed selenium-supplemented formula in a randomized doseresponse trial, American Journal of Clinical Nutrition, 2008; 88(1):70-6. Doherty DA, Magann EF, Chauhan S, O’Boyle A, Busch J, Morrison J. Factors affecting caesarean operative time and the effect of operative time on pregnancy outcomes, Australian and New Zealand Journal of Obstetrics and Gynecology, 2008; 48(3):286-291. Dunstan JA, Simmer K, Dixon G, Prescott SL. Cognitive assessment of children at age 2(1/2) years after maternal fish oil supplementation in pregnancy: a randomised controlled trial. Archives of Disease in Childhood Fetal Neonatal Edition, 2008; 93(1):F45-50. Fetherston C. Recurrent Blocked Duct/s in a Mother with Immunoglobulin A Deficiency: A case Study. Breastfeeding Medicine, 2008 (in press). Garefalakis M, Hickey M. Role of androgens, progestins and tibolone in the treatment of menopausal symptoms: a review of the clinical evidence.Clinical Interventions in Aging, 2008; 3(1):1-8. Garefalakis M, Johnson N, Hickey M. Gynaecological Morbidity. Chapter in Encylopaedia of Public Health. World Health Organisation Publications, 2008 (in press). Gatford KL, Owens JA, Li S, Moss TJM, Newnham JP, Challis JRG, Sloboda DM. Repeated betamethasone treatment of pregnant sheep programs persistent reductions in circulating IGF-I and IGF-binding proteins in progeny. American Journal of Physiology Endocrinology & Metabolism, 2008; 295(1):170-178.
Women and Infants Research Foundation Annual Report 2008
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Publications Continued
Moss TJ, Knox CL, Kallapur SG, Nitsos I, Theodoropoulos C, Newnham JP, Ikegami M, Jobe AH. Experimental amniotic fluid infection in sheep: effects of Ureaplasma parvum serovars 3 and 6 on preterm or term fetal sheep. American Journal of Obstetrics & Gynecology, 2008; 198(1):122.e1-8. Myles PS, Chan MTV, Leslie K, Peyton P, Paech M, and Forbes A. Effect of nitrous oxide on plasma homocysteine and folate in patients undergoing major surgery. British Journal of Anaesthesia, 2008; 100:780-6. Napolitano PG, Wakefiled CL, Elliott DE, Doherty DA, Magann EF. Umbilical cord plasma homocysteine concentrations at delivery in pregnancies complicated by preeclamsia, Australian and New Zealand Journal of Obstetrics and Gynecology, 2008; 48(3):261-265. Paech MJ, Ilett KF, Hackett LP, and Page -Sharp M. Disposition and clinical outcome after intraperitoneal meperidine and ropivacaine administration during laparoscopic surgery. Anesthesia and Analgesia, 2008; 106:278-86 Paech MJ, Scott KL, Clavisi OM, Chua S, McDonnell N and the Australian and New Zealand College of Anaesthetists Trials Group. A prospective survey of awareness and recall associated with general anaesthesia for caesarean section. International Journal of Obstetric Anesthesia, 2008; doi:10.1016/j/ijoa.2008.01.016. Pedrana G, Sloboda DM, Pérez W, Newnham JP, Bielli A, Martin GB. Effects of Pre-natal Glucocorticoids on Testicular Development in Sheep. Anatomia Histolosia Embryologia, 2008 May 2. POISE Study Group. Effects of extended-release metoprolol succinate in patients undergoing non-cardiac surgery (POISE trial): a randomized controlled trial. The Lancet, 2008; 371:1839-47. Polglase GR, Hillman NH, Ball MK, Kramer BW, Kallapur SG, Jobe AH, Pillow JJ. Lung and Systemic Inflammation in Preterm Lambs on CPAP or Conventional Ventilation, Pediatric Research, 2008 (in press). Polglase GR, Moss TJ, Nitsos I, Allison BJ, Pillow JJ, Hooper SB. Differential effect of recruitment manoeuvres on pulmonary blood flow and oxygenation during HFOV in preterm lambs. Journal of Applied Physiology, 2008; 105(2):603-10. Resnick SM, Hall GL, Simmer KN, Stick SM, Sharp MJ. The hypoxia challenge test does not accurately predict hypoxia in flight in ex-preterm neonates. Chest, 2008; 133(5):1161-6. Salafia CM, Zhang J, Charles AK, Bresnahan M, Shrout P, Sun W, Maas EM. Placental characteristics and birthweight. Paediatric Perinatal Epidemiology, 2008; 22(3):229-39. Sharp J, Bartu A. The threat of loss: the central problem experienced by illicit drug using mothers. Journal of Paediatrics and Child Health, 2008; 44:sup.1 A80. Shelley K, and Paech MJ. The clinical applications of intranasal opioids. Current Drug Delivery, 2008; 5:55-8. Simmer K, Patole SK, Rao SC. Longchain polyunsaturated fatty acid supplementation in infants born at term. The Cochrane Database Systematic Reviews, 2008 Jan 23; (1):CD000376. Review. Simmer K, Schulzke SM, Patole S. Longchain polyunsaturated fatty acid supplementation in preterm infants. The Cochrane Database of Systematic Reviews, 2008 Jan 23;(1):CD000375. Review. Sloboda DM, Moss TJM, Li S, Matthews SG, Challis JRG, Newnham JP. Expression of glucocorticoid receptor, mineralocorticoid receptor, and 11b-hydroxysteroid dehydrogenase 1 and 2 in the fetal and postnatal ovine hippocampus: ontogeny and effects of prenatal glucocorticoid exposure. Journal of Endocrinology, 2008; 197: 213-220. Srinivasjois RM, Kohan R, Keil AD, Smith NM. Congenital Mycoplasma pneumoniae Pneumonia in a Neonate. Pediatric Infectious Disease Journal, 2008; 27(5):474-475. Sweet DG, Huggett MT, Warner JA, Moss TJ, Kloosterboer N, Halliday HL, Newnham JP, Kallapur SG, Jobe AH, Kramer BW. Maternal betamethasone and chorioamnionitis induce different collagenases during lung maturation in fetal sheep. Neonatology, 2008; 94(2):79-86. Thew ME, and Paech MJ. Management of post-dural puncture headache in the obstetric patient. Current Opinion in Anesthesiology, 2008; 21:288-92. Vani S, Critchley HOD, Fraser IS, Hickey M. Endometrial expression of steroid receptors in postmenopausal hormone replacement therapy users: relationship to bleeding patterns. Journal of Family Planning Reproductive Health Care, 2008; 34(1):27-34. Vujanic G, Charles A. Renal tumours of childhood update. Pathology, 2008; 40(2): 217-27. Wang LP, and Paech MJ. Neuroanaesthesia for the pregnant woman. Anesthesia and Analgesia, 2008; 107;193-200.
2007
Abou-Setta AM, D’Angelo A, Hart RJ and Sallam H. Post embryo transfer interventions for in vitro fertilization / intracytoplasmic sperm injection patients (Protocol), The Cochrane Database of Systematic Review, CD006567: 2007. Adkins RM, Fain JN, Krushkal J, Klauser CK, Magann EF and Morrison JC. Association Between Paternally Inherited Haplotypes Upstream of the Insulin Gene and Umbilical Cord IGF-II Levels, Pediatric Research, 2007; 62:4:451-455. Adkins RM, Klauser CK, Magann EF, Krushkal J, Boyd TK, Fain JN and Morrison JC. Site - 2548 of the leptin gene is associated with gender-specific trends in newborn size and cord leptin levels, International Journal of Pediatric Obesity, 2007; 2:3:130-137. Barrilleaux PS, Magann EF, Chauhan SP, York BM, Philibert L and Lewis DF. Amniotic Fluid Index as a Predictor of Adverse Perinatal Outcome in the HELLP Syndrome, The Journal of Reproductive Medicine, 2007; 52:4:293-298. Beydon N, Davis SD, Lombardi E, Allen JL, Arets HGM, Aurora P, Bisgaard H, Davis GM, Ducharme FM, Eigen H, Gappa M, Gaultier C, Gustafsson PM, Hall GL, Hantos Z, Healy MJR, Jones MH, Klug B, Lodrup CKC, McKenzie SA, Marchal F, Mayer OH, Merkus PJFM, Morris MG, Oostveen E, Pillow JJ, Seddon PC, Silverman M, Sly P, Stocks J, Tepper RS, Vilozni D and Wilson NM. An Official American Thoracic Society/European Respiratory Society Statement: Pulmonary Function Testing in Preschool Children, American Journal of Respiratory and Critical Care Medicine, 2007; 175:1304-1345. Braun T, Li S, Moss TJ, Newnham JP, Challis JRG, Gluckman PD and Sloboda DM. Maternal betamethasone administration reduces binucleate cell number and placental lactogen in sheep, Journal of Endocrinology, 2007; 194:2:337-347. Briery CM, Rose CH, Hudson WT, Lutgendorf MA, Magann EF, Chauhan SP and Morrison JC. Planned vs emergent cesarean hysterectomy, American Journal of Obstetrics & Gynecology, 2007; 197:154.e1-154.e5. Chauhan SP, Taylor M, Shields D, Parker D, Scardo JA and Magann EF. Intrauterine Growth Restriction and Oligohydramnios among High-Risk Patients, American Journal of Perinatology, 2007; 24:4:215-221. Chauhan SP, Cole J, Laye MR, Choi K, Sanderson M, Moore RC, Magann EF, King HL and Morrison JC. Shoulder Dystocia with and without Brachial Plexus Injury: Experience from Three Centers, American Journal of Perinatology, 2007; 24:6:365-371. Chauhan SP, Christian B, Gherman RB, Magann EF, Kaluser CK and Morrison JC. Shoulder dystocia without versus with brachial plexus injury: A case-control study. The Journal of Maternal-Fetal and Neonatal Medicine, 2007; 20:4: 313-317. Cregan MD, Fan YP, Appelbee A, Brown ML, Klopcic B, Koppen J, Mitoulas LR, Piper KME, Chong YS, Hartmann PE. Identification of nestin positive putative mammary stem cells in human breastmilk. Cell and Tissue Research, 2007; 329:129 – 136. Crossley KJ, Morley CJ, Allison BJ, Polglase GR, Dargaville PA, Harding R and Hooper SB. Blood Gases and Pulmonary Blood Flow During Resuscitation of Very Preterm Lambs Treated With Antenatal Betamethasone and/or Curosurf: Effect of Positive End-Expiratory Pressure, Pediatric Research, 2007; 62:1:37-42. Czank C, Henderson JJ, Kent JC, Lai CT and Hartmann PE. Hormonal Control of the Lactation Cycle, Hale & Hartmann’s Textbook of Human Lactation, ed Hale, T.W. and Hartmann, P., United States, Hale Publishing, L.P. 2007; pp 89-111. Czank C, Mitoulas LR, Hartmann PE. Human Milk Composition – Fat. In “Hale and Hartmanns’ Textbook of Human Lactation” Ed. Hale, T.W. and Hartmann, P.E. (Hale Publishing, L.P.: Amarillo) 2007; pp 63–81. Czank C, Mitoulas LR, Hartmann PE. Human Milk Composition – Carbohydrates. In “Hale and Hartmanns’ Textbook of Human Lactation” Ed. Hale, T.W. and Hartmann, P.E. (Hale Publishing, L.P.: Amarillo) 2007; pp 83–87. Czank C, Mitoulas LR, Hartmann PE. Human Milk Composition – Nitrogen and Energy Content. In “Hale and Hartmanns’ Textbook of Human Lactation” Ed. Hale, T.W. and Hartmann, P.E. (Hale Publishing, L.P.: Amarillo) 2007; pp 89–102. Czank C, Henderson JJ, Kent JC, Lai CT, Hartmann PE. Hormonal Control of the Lactation Cycle. In “Hale and Hartmanns’ Textbook of Human Lactation” Ed. Hale, T.W. and Hartmann, P.E. (Hale Publishing, L.P.: Amarillo) 2007; pp103–125. Deshpande G, Rao S and Patole S. Probiotics for prevention of necrotising enterocolitis in preterm neonates with very low birthweight: a systematic review of randomised controlled trials, The Lancet, 2007; 369:1614-1620. Dickinson JE. Amnioreduction therapy for twin-twin transfusion syndrome, Twin-Twin Transfusion Syndrome, ed Quintero, R.A., United Kingdom, Informa UK Ltd, 2007; pp 91-97. Dickinson JE. Neurological outcomes after therapeutic interventions for twin-twin transfusion syndrome, TwinTwin Transfusion Syndrome, ed Quintero, R.A., United Kingdom, Informa UK Ltd, 2007; pp 173-181. Dickinson JE, Prime DK and Charles AK. The role of autopsy following pregnancy termination for fetal abnormality, Australian and New Zealand Journal of Obstetrics and Gynecology, 2007; 47: 445-449. Dong X, Sweet J, Challis JR, Brown T, Lye SJ. Transcriptional Activity of Androgen Receptor is Modulated by RNA Splicing Factors, PSF and p54nrb. Molecular Cell Biology, 2007; 27(13):4863-75.
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Women and Infants Research Foundation Annual Report 2008
Dunstan JA, Mitoulas LR, Dixon G, Doherty DA, Hartmann PE, Simmer KN and Prescott SL. The Effects of Fish Oil Supplementation in Pregnancy on Breast Milk Fatty Acid Composition Over the Course of Lactation: A Randomized Controlled Trial, Pediatric Research: International Journal of Human Developmental Biology, 2007: 62:6:689-694. French N. Consensus statement on perinatal care, Journal of Paediatrics and Child Health, 2007; 43:492-493. Garefalakis M and Hickey M. Present understanding of abnormal uterine bleeding mechanisms, Gynaecology Forum, 2007; 12:2:6-8. Garefalakis M, Hickey M. The improvement of gynaecological conditions with hormonal contraception, Gynaecology Forum, 2007; 12:1:25-30. Geddes DT. Inside the Lactating Breast – the latest on breast anatomy. Journal of Midwifery and Womens Health, 2007; 52:556-563. Geddes DT, Mizuno K. The anatomy of the human lactating breast. Perinatal Care, 2007 May (in press). Geddes DT. The anatomy of the lactating breast: Latest research and clinical implications. Infant, 2007; 3(2):59-63. Geddes DT. The anatomy of the lactating breast. In “Hale and Hartmanns’ Textbook of Human Lactation” Ed. Hale, T.W. and Hartmann, P.E. (Hale Publishing, L.P.: Amarillo) 2007. Gellhaus A, Schmidt M, Dunk C, Lye SJ and Winterhager E. The circulating proangiogenic factors CYR61 (CCN1) and NOV (CCN3) are significantly decreased in placentae and sera of preeclamptic patients. Reproductive Sciences, 2007; 14(8):46-52. Gill AW, Colvin J. Use of naloxone during neonatal resuscitation in Australia: Compliance with published guidelines, Journal of Paediatrics and Child Health, 2007; 43:795-798. Gilles MT, Dickinson JE, Cain A, Turner KA, McGuckin R, Loh R, Prescott SL and French MA. Perinatal HIV transmission and pregnancy outcomes in indigenous women in Western Australia, Australian and New Zealand Journal of Obstetrics and Gynecology, 2007; 47:362-367. Glujovsky D, Pesce R, Fiszbajn G, Sueldo C, Hart RJ and Ciapponi A. Endometrial preparation for women undergoing embryo transfer with frozen embryos or embryos derived from donor oocytes (Protocol), The Cochrane Database of Systematic Reviews, CD006359: 2007. Hart RJ. Polycystic ovarian syndrome - prognosis and treatment outcomes, Current Opinion in Obstetrics & Gynecology, 2007; 19:6:529-535. Hart RJ and Karthigasu K. The benefits of virtual reality simulator training for laparoscopic surgery, Current Opinion in Obstetrics & Gynecology, 2007; 19:4:297-302. Hart RJ, Karthigasu K and Garry R. Virtual reality simulation training can improve technical skills during laparoscopic salpingectomy for ectopic pregnancy, British Journal of Obstetrics & Gynaecology, 2007; 144:5: 656. Hartmann PE. The lactating breast: an overview from down under – MACY - GYORGY Award 2006. Breastfeeding Medicine, 2007; 2:2-9. Hartmann BT, Pang WW, Keil AD, Hartmann PE and Simmer K. Best practice guidelines for the operation of a donor human milk bank in an Australian NICU, Early Human Development, 2007; 83:10:667-673. Hartmann PE. Mammary Gland: Past, Present and Future. In “Hale and Hartmanns’ Textbook of Human Lactation” Ed. Hale, T.W. and Hartmann, P.E. (Hale Publishing, L.P.: Amarillo) 2007 pp17–30. Henderson JJ, Hornbuckle J and Doherty DA. Models of Maternity Care: A Review of the Evidence 2007; 01:1-115, Australia. Henderson JJ, Hartmann PE, Newnham JP, Simmer K. Effect of preterm birth and antenatal corticosteroid treatment on lactogenesis II in women. Pediatrics, 2007; 121; e92–e100. Hickey M. Bleeding with menopausal hormone therapy: physiological or pathological? Menopause International, 2007; 13:4:188-190. Hickey M, Saunders CM and Stuckey BGA. Non-hormonal treatments for menopausal symptoms, Maturitas, 2007; 57:1:85-89. Hickey M, Higham J and Fraser IS. Progestogens versus oestrogens and progestogens for irregular uterine bleeding associated with anovulation (Review), The Cochrane Database of Systematic Reviews, CD001895: 2007. Hillman NH, Moss TJ, Kallapur SG, Bachurski C, Pillow JJ, Polglase GR, Nitsos I, Kramer BW and Jobe A. Brief, Large Tidal Volume Ventilation Initiates Lung Injury and a Systemic Response in Fetal Sheep, American Journal of Respiratory and Critical Care Medicine, 2007; 176:575-581. Hornbuckle J and Robson S. The role of maternal and fetal Doppler in pre-eclampsia, Pre-eclampsia Etiology and Clinical Practice, ed Lyall, F. and Belfort, M., United Kingdom, Cambridge University Press 2007 pp 489-505.
Huang RC, Burke V, Newnham JP, Stanley FJ, Kendall GE, Landau L, Oddy WH, Blake KV, Palmer LJ and Beilin LJ. Perinatal and childhood origins of cardiovascular disease, International Journal of Obesity 2007; 31:2:236-244. Ilett KF, Hackett LP, Kristensen JH and Kohan R. Transfer of dexamphetamine into breast milk during treatment for attention deficit hyperactivity disorder, British Journal of Clinical Pharmacology, 2007; 63:3:371-375. Jacobs LA, Dickinson JE, Hart PD, Doherty DA and Faulkner SJ. Normal Nipple Position in Term Infants Measured on Breastfeeding Ultrasound, Journal of Human Lactation, 2007; 23:52-59. Jobe AH, Moss TJ, Nitsos I, Ikegami M, Kallapur SG and Newnham JP. Betamethasone for lung maturation: testing dose and formulation in fetal sheep, Americal Journal of Obstetrics & Gynecology, 2007; 197:5:523.e1-523.e6. Kallapur SG, Jobe A, Ball MK, Nitsos I, Moss TJ, Hillman NH, Newnham JP and Kramer BW. Pulmonary and Systemic Endotoxin Tolerance in Preterm Fetal Sheep Exposed to Chorioamnionitis, The Journal of Immunology, 2007; 179:12: 8491-8499. Karthigasu K and Hart RJ. Response to Dr Valle re: Failed tubal occlusion with Essure pbc, Australian and New Zealand Journal of Obstetrics and Gynaecology, 2007; 47:349. Kent JC, Geddes DT and Hartmann PE. The anatomy and physiology of breastfeeding. In “Child Nutrition Research Trends” Nova, 2007. Klauser CK, Briery CM, Magann EF, Martin RW, Chauhan SP and Morrison JC. Tocolytic Preference for Treatment of Preterm Labor, Mississippi State Medical Association Journal, 2007; 48:2:35-38. Knight BS, Pennell CE, Shah R and Lye SJ. Strain Differences in the Impact of Dietary Restriction on Fetal Growth and Pregnancy in Mice, Reproductive Sciences, 2007; 14:81-90. Knight BS, Pennell CE, Adamson SL and Lye SJ. The impact of murine strain and sex on postnatal development after maternal dietary restriction during pregnancy, The Journal of Physiology, 2007; 581. Kramer BW, Joshi SN, Moss TJ, Newnham JP, Sindelar R, Jobe A and Kallapur SG. Endotoxin-induced maturation of monocytes in preterm fetal sheep lung, American Journal of Physiology: Lung Cellular and Molecular Physioloogy, 2007; 293:2:L345-L353. Kristensen, J.H., Ilett, K.F., Rampono, J., Kohan, R. and Hackett, L.P. Transfer of the antidepressant mirtazapine into breast milk, British Journal of Clinical Pharmacology, 2007; 63:3:322-327. Ledowski T, Bromilow J, Wu J, Paech M.J.Storm H, and Schug SA. The assessment of postoperative pain by monitoring of skin conductance: results of a prospective study. Anaesthesia, 2007; 62:989-93. Ledowski T, Pruess J, Ford A, Paech MJ, McTernan C, Kapila R, and Schug SA. New parameters of skin conductance compared with bispectral index monitoring to assess emergence from total intravenous anaesthesia. British Journal of Anaesthesia, 2007; 99:547-51. Leslie K, Skrzypek H, Paech MJ, Kurowski I, and Whybrow T. Dreaming during anesthesia and anesthetic depth in elective surgery patients: a prospective cohort study. Anesthesiology, 2007; 106:33-42. Ludlow J, Whybrow T, Paech MJ, and Orr B. Drug abuse and dependency during pregnancy: anaesthetic issues. Anaesthesia and Intensive Care, 2007; 35:881-93. Lynch A, Goodman C, Choy PL, Dawson B, Newnham JP, McDonald S and Blanksby B. Maternal Physiological Responses to Swimming Training During the Second Trimester of Pregnancy, Research in Sports Medicine, 2007; 15:1:33-45. Magann EF, Chauhan SP, Doherty DA, Lutgendorf MA, Magann MI and Morrison JC. A review of Idiopathic Hydramnios and Pregnancy Outcomes, Obstetrical and Gynecological Survey, 2007; 62:12:795-802. Magann EF, Doherty DA, Turner K, Lanneau Jr GS, Morrison JC and Newnham JP. Second trimester placental location as a predictor of an adverse pregnancy outcome, Journal of Perinatology, 2007; 27:1:9-14. Magann EF, Chauhan SP, Doherty DA, Magann MI and Morrison JC. The Evidence for Abandoning the Amniotic Fluid Index in Favor of the Single Deepest Pocket, American Journal of Perinatology, 2007; 24:9:549-555. McDonnell NJ and Paech MJ. The management of a super morbidly obese parturient delivering twins by caesarean section. Anaesthesia and Intensive Care, 2007; 35:979-83. McDonnell N, Paech MJ, and Kwei P. A disposable device for patient-controlled intravenous analgesia: evaluation by patients, nursing and medical staff. Acute Pain, 2007; 9:71-5. McGurgan PM and O’Donovan P. Second-generation endometrial ablation - an overview, Best Practice & Research Clinical Obstetrics and Gynaecology, 2007; 21:6: 931-945. McLeod GT and Sherriff J. Preventing postnatal growth failure - The significance of feeding when the preterm infant is clinically stable, Early Human Development, 2007; 83:659-665. Measey M, Charles A, d’Espaignet ET, Harrison C, de Klerk N and Douglass C. Aetiology of stillbirth: unexplored is not unexplained, Australian and New Zealand Journal of Public Health, 2007; 31:5:444-449.
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Meloncelli PJ, Williams TM, Hartmann PE and Stick RV. The synthesis of 2-, 3-, 4- and 6-O-a-D-glucopyranosyl-D-galactopyranose, and their evaluation as nutritional supplements for pre-term infants. Carbohydrate Research, 2007; 342:1793–1804. Mitchell MD, Helliwell RJA, Fraser M and Keelan JA. Lipocalin-type prostaglandin D2 synthase: Placental and fetal aspects, Prostaglandin D2 Synthase-A multitude of biological functions, ed Ragolia, L., India, Research Signpost, 2007 pp 79-97. Molster C, Bower C and O’Leary P. Australian Survey on Community Knowledge and Attitudes Regarding the Fortification of Food with Folic Acid, Birth Defects Research (Part A): Clinical and Molecular Teratology, 2007; 79:664-670. Molster C, Bower C and O’Leary P. Community attitudes to the collection and use of identifiable data for health research - is it an invasion of privacy? Australian and New Zealand Journal of Public Health, 2007; 31:4:313-317. Myles PS, Leslie K, Chan MTV, Forbes A, Paech M, Peyton P, Silbert B , Pascoe E and the ENIGMA Trial Group. Avoidance of nitrous oxide for patients undergoing major surgery. A randomized controlled trial. Anesthesiology, 2007; 107:221-31. Newnham JP and Moss TJ. Antenatal corticosteriod treatment, Preterm Birth Mechanisms, Mediators, Prediction, Prevention and Interventions, ed Petraglia, F. Strauss, J.F. Gabbe, S.G. Weiss, G., United Kingdom, Informa Healthcare, 2007 pp 181-191. Newnham JP. Antenatal steriods: iconic advance or ticking bomb? The Yearbook of Obstetrics and Gynaecology, ed Tim Hillard, United Kingdom, Royal College of Obstetricians and Gynaecologists 2007 pp 288-297. Newnham JP. Improving outcomes in pregnancy, British Medical Journal, 2007; 334:807-808. Newnham JP. The developmental origins of health and disease (DOHaD) - why it is so important to those who work in fetal medicine, Ultrasound in Obstetrics & Gynecology, 2007; 29:2:121-123. O’Leary CM, de Klerk N, Keogh J, Pennell C, de Groot J, York L, Mulroy S and Stanley FJ. Trends in mode of delivery during 1984-2003: can they be explained by pregnancy and delivery complications? British Journal of Obstetrics & Gynaecology 2007; 114:855-864. Obermair A, Fuller A, Lopez-Varela E, van Gorp T, Vergote I, Eaton L, Fowler J, Quinn M, Hammond IG, Marsden D, Proietto A, Carter J, Davy M, Tripcony L and Abu-Rustum N. A new prognostic model for FIGO stage 1 epithelial ovarian cancer, Gynecologic Oncology, 2007; 104:607-611. Orlikowski CEP, Dickinson JE, Paech MJ, McDonald SJ and Nathan E. Authors’ reply (2007), Australian and New Zealand Journal of Obstetrics and Gynecology, 2007 ;47:155. Paech MJ, Goy R, Chua S, Scott K, Christmas T and Doherty DA A Randomized, Placebo-Controlled Trial of Preoperative Oral Pregabalin for Postoperative Pain Relief After Minor Gynecological Surgery, Anesthesia and Analgesia, 2007; 105:5:1449-1453. Paech MJ, Rucklidge MWM, Lain J, Dodd PH, Bennett E and Doherty DA. Ondansetron and Dexamethasone Dose Combinations for Prophylaxis Against Postoperative Nausea and Vomiting, Anesthesia and Analgesia, 2007; 104:808-814. Paech M and Whybrow T. The prevention and treatment of post dural puncture headache. ASEAN Journal of Anaesthesiology, 2007; 8:86-95. Pang WW, Hartmann PE. Initiation of Human Lactation: Secretory Differentiation and Secretory Activation. Journal of Mammary Gland Biology and Neoplasia, 2007; 12: 211–22. Patole S. Prevention and treatment of necrotising enterocolitis in preterm neonates, Early Human Development, 2007; 83:635-642. Patole SK, Kumaran V, Travadi JN, Brooks JM and Doherty DA. Does patent ductus arteriosus affect feed tolerance in preterm neonates? Archives of Disease in Childhood, Fetal and Neonatal Edition, 2007; 92:1:F53-F55. Pennell CE, Muglia LJ, Relton C. Genetic epidemiological studies of preterm birth: studies of disease or of “rescue by birth”? American Journal of Obstetrics & Gynecology. (2007) Pennell CE, Jacobsson B, Williams SM, Buus RM, Muglia LJ, Dolan SM, Morken N, Ozcelik H, Lye SJ and Relton C. Genetic epidemiologic studies of preterm birth: guidelines for research, American Journal of Obstetrics & Gynecology, 2007; 196:107-118. Pillow JJ, Hillman N, Moss TJ, Polglase GR, Bold G, Beaumont C, Ikegami M and Jobe A. Bubble Continuous Positive Airway Pressure Enhances Lung Volume and Gas Exchange in Preterm Lambs, American Journal of Respiratory and Critical Care Medicine, 2007; 176:63-69. Polglase GR, Nitsos I, Jobe AH, Newnham JP and Moss TJ. Maternal and Intra-amniotic Corticosteriod Effects on Lung Morphometry in Preterm Lambs, Pediatric Research, 2007; 62:1:32-36. Prime D, Geddes DT and Hartmann PE. Oxytocin: Milk Ejection and Maternal-Infant Well-being. In “Hale and Hartmanns’ Textbook of Human Lactation” Ed. Hale, T.W. and Hartmann, P.E. (Hale Publishing, L.P.: Amarillo) 2007 pp 155–168. Rac VE, Scott CA, Small C, Adamson SL, Rurak D, Challis JR and Lye SJ. Dose dependent effects of meloxicam administration on cyclooxygenase-1 and cyclooxygenase-2 protein expression in intrauterine tissues and fetal tissues of a sheep model of preterm labour. Reproductive Sciences, 2007; 14(8):750-764. Rampono J, Kristensen JH, Ilett KF, Hackett LP and Kohan R. Quetiapine and Breast Feeding, The Annals of Pharmacotherapy, 2007; 41:711-714. Salafia CM, Zhang, J, Miller RK, Charles AK and Shrout P Sun W. Placental Growth Patterns Affect Birth Weight for Given Placental Weight, Birth Defects Research (Part A), 2007; 79:281-288. Schultz CC, Wood JY, Magann EF, Campbell LA, Chauhan SP and Morrison JC. Prediction of a caesaren delivery by labour and delivery nurses, Australian and New Zealand Journal of Obstetrics and Gynaecology, 2007; 47:402-405. Schulzke S, Rao S and Patole SK. A systematic review of cooling for neuroprotection in neonates with hypoxic ischemic encephalopathy - are we there yet? BMC Pediatrics, 2007; 7. Schulzke S, Deshpande GC and Patole SK. Neurodevelopmental Outcomes of Very Low-Birth-Weight Infants with Necrotizing Enterocolitis, A Systematic Review of Observational Studies, Archives of Pediatrics and Adolescent Medicine, 2007; 161: 583-590. Schulzke S, Trachsel D and Patole SK. Physical activity programs for promoting bone mineralization and growth in preterm infants (Review), The Cochrane Database of Systematic Reviews, CD005387:2 (2007). Shynlova O, Tsui P, Dorogin A, Langille BL and Lye SJ. The expression of transforming growth factor beta in pregnant rat myometrium is hormone and stretch dependent. Reproduction 2007; 1 34(3):503-511. Shynlova O, Williams SJ, Draper H, White BG, MacPhee DJ and Lye SJ. Uterine Stretch Regulates Temporal and Spatial Expression of Fibronectin Protein and Its Alpha 5 Integrin Receptor in Myometrium of Unilaterally Pregnant Rats. Biology of Reproduction, 2007; 77(5):880-888. Simmer KN. Aggressive nutrition for preterm infants - Benefits and risks, Early Human Development, 2007; 83:631-634. Simmer KN. Editorial - Nutrition of the preterm infant. Best Practice Guidelines on nutrition of preterm infants, Early Human Development, 2007; 83:629. Sloboda DM, Hart RJ, Doherty DA, Pennell CE and Hickey M. Age at Menarche: Influences of Prenatal and Postnatal Growth, The Journal of Clinical Endocrinology & Metabolism, 2007; 92:1:46-50. Sloboda DM, Moss TJ, Li S, Doherty D, Nitsos I, Challis JRG and Newnham JP. Prenatal betamethasone exposure results in pituitary-adrenal hyporesponsiveness in adult sheep, American Journal of Physiology: Endocrinology and Metabolism, 2007; 292:1:E61-E70. Strunk T, Gardiner K, Simmer KN, Atlas D and Keil AD. Rhodococcus equi Meningitis After Ventriculoperitoneal Shunt Insertion in a Preterm Infant, The Pediatric Infectious Disease Journal, 2007; 26:11:1076-1077. Strunk T, Simmer KN, Kikiros C and Patole S. Late-onset right-sided diaphragmatic hernia in neonates - case report and review of the literature, European Journal of Pediatrics, 2007; 166:521-526. Strunk T, Richmond P, Simmer KN, Currie A, Levy O and Burgner D. Neonatal immune responses to coagulase- negative staphylococci, Current Opinion in Infectious Diseases, 2007; 20:4:370-375. Travadi J, Patole S, Thonell S and Simmer KN. Survey of the current practices for neonatal gastrointestinal contrast studies in Australia, Australiasian Radiology, 2007; 51:5:437-439. Upadhyaya M, Orford JE, Smith N, Barker A and Gollow I. Incorporation of Integra in tissue defects: a pilot study in the rat model, Pediatric Surgery International, 2007; 23:669-673. Walters BNJ. Personal carbon trading: a potential “stealth intervention” for obesity reduction? Medical Journal of Australia, 2007; 187:668. Walters BNJ. Pregnancy and Medicine: Sine qua non or non sequitur? Australian and New Zealand Journal of Obstetrics and Gynaecology, 2007; 47:91-94. Wang LP, McLoughlin P, Paech MJ, Kurowski I and Brandon EL. Low and moderate remifentanil infusion rates do not alter target controlled infusion propofol concentrations necessary to maintain anesthesia as assessed by bispectral index monitoring. Anesthesia and Analgesia, 2007; 104:325-31. White L, Dharmarajan A and Charles A. Caspase-14: a new player in cytotrophoblast differentiation, Reproductive BioMedicine Online, 2007; 14:3:300-307. Zheng-Fischhöfer Q, Kibschull M, Schnichels M, Kretz M, Petrasch-Parwez E, Strotmann J, Reucher H, Lynn BD, Nagy JI, Lye SJ, Winterhager E and Willecke K. Characterization of Connexin31.1 deficient mice reveals impaired placental development. Developmental Biology, 2007; 312(1):258-271.
44 Women and Infants Research Foundation Annual Report 2008
Women and Infants Research Foundation Annual Report 2008
45
Major Supporters
Our Heartfelt Thanks
The Foundation is proud to acknowledge and thank our major supporters who provide vital support to our research programs.
Channel 7 Telethon Trust
The Channel 7 Telethon Trust has been supporting the Women and Infants Research Foundation since 2003. In 2007 Telethon sponsored an exciting new program known as The Fetal Future Program. This program involves the finding and evaluation of children of various ages who have previously undergone complex treatment before birth. Typically, women receive treatment for their unborn child, give birth (usually at KEMH), and then return to their community with no formal follow-up to ascertain the ongoing consequences of the fetal disease and its treatment. Government databases with computer linkages do not contain the outcomes necessary for such a follow-up program. With the support of Telethon we are able for the first time to develop the first stage in a follow-up program. We plan to follow-up children who have received prenatal treatment within the context of a specific hypothesis. Telethon also funds the Caffeine Project. Preterm infants frequently have immature breathing patterns that occasionally necessitate support by applying positive air pressure to the airways (‘CPAP’) or assisted ventilation. Caffeine is routinely given to preterm infants to improve breathing patterns and to minimize the need for these interventions. This study aims to examine the early maturation of breathing control in preterm infants and to quantify the impact that caffeine has on the respiratory control system using new complex mathematical techniques that analyse fluctuation patterns present during normal breathing.
Andrew and Nicola Forrest
The Forrest family is descended from a distinguished list of prominent Western Australians acclaimed for pioneering the early development of this State. This pioneering tradition lives on through Andrew and Nicola Forrest in the context of the modern mining industry. It has been their wish to support advancement through research in fetal medicine which represents a pioneering edge of contemporary science, with a promise to improve lives of people through interventions at early times in life.
Lions
Lions have been fundamental in their support of the Women and Infants Research Foundation / UWA Laboratories since 2000. The donations received from Lions have enabled the Foundation to establish a world class molecular biology research laboratory based at King Edward Memorial Hospital. Support from Lions has also allowed the Foundation to purchase laboratory equipment which has enabled us to apply for National and International grants which then amplifies every dollar received from Lions many fold. Lions has also funded the establishment of an Image Analysis Suite; this facility is primarily devoted to the microscopic analysis of tissue sections.
The Stan Perron Charitable Trust
The Stan Perron Charitable Trust in conjunction with Rotary has provided funds to the Women and Infants Research Foundation for the establishment of the first modern human milk bank in Australia. The funds donated have enabled the purchase of specialised equipment needed for the safe processing of human milk. The human milk bank, now named the Perron Rotary Express Milk Bank (PREM Bank), aims to optimise the nourishment of Western Australian preterm and ill infants who require more breast milk than their mothers can provide.
Grant Thornton
We gratefully acknowledge the pro bono provision of financial auditing and accounting services provided by Grant Thornton for the 2007/2008 Financial year.
46 Women and Infants Research Foundation Annual Report 2008
Thank You to Donors
Thank You
We are very grateful to all of the individuals, companies and organisations who have helped to provide a strong financial base for the Foundation’s research, some of whom are listed below: 303 Advertising Pty Ltd Allgrove, Catherine Anti, Carolyn Balfour, Yatiha Barker, Lynda Bower, Caroline Brown, Paul Burnaby, Valerie Carrington-Jones, Ann Channel 7 Telethon Trust Christie, Meredith Cimetta, Barbara Collins, Robyn Farrington, Kim Fiu, Yusze Forrest, Nicola Forrest Family Investment Pty Ltd French, Noel Guscott, John and Donna Hammer, Amy Harrington, Sophie Harris, Faamama Hartleys Charity Committee Hart, Jen Hastings, Reahanan Ho, Karen Hoye, Mr & Mrs Hutchinson, Maureen Isherwood, Karen Kaitse, Kelley Karczub, Anne Leonard, Timothy Lions Club of Floreat Lions District 201 W1 Martelli, Mr & Mrs Maslin, Jack Mid-Life & Menopause Support Group Moore, Ian & Katherine Murdoch, Marjorie Newnham, John NIC Christmas Fund Paech, Michael Parker, Amy Parker, K & D Passmore, RI & KF Payne, Anne Pennell, Craig Rowley, Jann Schofield, Lynette Stocks, Rowena Sutherland, Katherine The Royal Australian & New Zealand College of Obstetricians & Gynaecologists The Stan Perron Charitable Trust Titelius, Melissa Tran, Hue Hoa Tyco Healthcare Van Eer, Maria West Australian Business Ladies’ Golf Assoc (Inc) Williams, Raelene
For further information about donating to the Foundation, including the Foundation in your bequest or other gifting opportunities please contact us on; telephone: (08) 9340 1437 email: cspencer@obsgyn.uwa.edu.au website: www.wirf.com.au
Thank You to Volunteers
The Foundation values the generosity and skills of our volunteers. Much of our research is made possible through the funds raised by our volunteers. Volunteers in our Café and Gift Shop ensure that we remain highly profitable. Our office and marketing volunteers assist in the Development team offices. A big thank you goes to all the volunteers who joined us in the following years: 1999 Jill Berecry Raie Bradshaw Janice Braekevelt Kate Campbell Margaret Cooper Maria Crawford Gay Cruikshank Norma Garbin Diane Hoffman Jill Hunt Annette Lazberger Gaile Martyn Delphine Moore Betty Redmond Jan Schofield Marie Smith Isobel Sprivulis Julie Wilson Osra Wisbey 2000 Beverley Boyd Ruth Cohen Win Froude Maria Gapper Beryl Lawler Leah McVeigh 2001 Maggie Cooper Suzanne Draper Nina Leahy Kay Lodge Yvonne Neurauter Helen Roatch Helen Robertson 2002 Sylvia Webster 2003 Gillian Ball Elizabeth Hyde Pam Imms Rema Starina Joy Tillett 2004 Ann Carrington-Jones Corinne Kilbee Patricia McInnes 2005 Fay Bannister Loretta Connery Pam Sulc 2006 Flora Amiel Meredith Cziesche Beattie Ramel 2007 Sonje Bernardini June Fox Elaine Horton Elizabeth Luzar Frances Lyons Robin Simon Tina Relf 2008 Carol Darby Zoe Hewitt-Dutton Mary Li Anne Marney Julie Nolan Hafidah Visser
Women and Infants Research Foundation Annual Report 2008
47
Research Support
External Research Grants Affiliated with the Women and Infants Research Foundation
The Women & Infants Research Foundation provides the infrastructure and funding to allow our researchers to successfully compete for external grants from organisations such as the National Health & Medical Research Council. Following is a list of competitive grants supported during the current financial year: National Health & Medical Research Council (NHMRC) (AUSTRALIA) Prevention of Preterm Birth By Treatment of Periodontal Disease During Pregnancy. Investigators: J Newnham, J McGeachie, D Doherty (2005-2008 $894,750). The Fetal and Early Childhood Origins of PCOS: A Prospective Cohort Study. Investigators: M Hickey, R Hart, S Franks, D Sloboda, D Doherty, M Davies (2006-2008 $487,550). Intrauterine Ureaplasma Infection During Pregnancy: Fetal Effects and Characteristics of Ureaplasma Pathogenicity. Investigators: J Newnham, C L Knox, I Nitsos, A H Jobe, T J M Moss (2007-2009 $507,750). Does Variable Ventilation Offer Physiological and Biological Benefits for the Preterm Lung. Principal Investigator: J Pillow (2007-2009 $307,686). Clinical Career Development Award. T Moss (2004-2008 $520,000). Clinical Career Development Award. M Hickey (2006-2010 $305,375). Peter Doherty Fellowship: Influence of Intra-Luminal Pressure on Pulmonary Haemodynamics in Fetal Sheep. G Polglase (2007-2010 $274,000). National Institute for Health (USA) Control of Menstrual Bleeding Disturbances in Women. Principal Investigators: I Fraser, L Salamonsen, J Findlay, M Hickey. (2003-2007 $287,409). Consortium Grant - New Mediators of Clinical Lung Maturation. Investigators: A Jobe, M Ikegami, J Newnham. (2005-2008 USD$470,159). Neonatal Resuscitation and Preterm Lung Injury. Principal Investigators: A Jobe, M Ikegami, J Pillow. (2005-2009 USD$283,829). Postnatal Consequences of Fetal Inflammation. Principal Investigators: A.Jobe, J. Pillow, G Polglase, B. Kramer (2006-2008 USD$140,400). The University Of Western Australia Es Gordon Bequest – Seeding Research Grant. Investigator: J Keelan (2007 $20,000). Raine Medical Research Foundation The Effects of Antenatal Inflammation on Cardiopulmonary Haemodynamics in Preterm Lambs. Investigators: G Polglase, M Kluckow, S Hooper (2008-2009 $129,408). National Heart Foundation of Australia The Effects of Antenatal Inflammation on Cardiopulmonary Haemodynamics in Preterm Neonatal Lambs. Investigators: G Polglase, M Kluckow, S Hooper, J Pillow. (2008-2009 $122,886). Canadian Institutes of Health Research (CIHR) Gene-Environment Interactions Underlying the Developmental Origins of Health & Disease. Investigators: S Lye, C Pennell. (2006-2010). Control of Parturition. Investigators: J Challis, J Newnham. (2005-2009). Mount Sinai Hospital, Toronto, Canada March of Dimes - The Diagnosis of Pre-Term Labour. Investigators: S Lye, C Pennell, A Bocking, A Oldenhoff. (2005-2008 $316,956).
48 Women and Infants Research Foundation Annual Report 2008
$173,252 $165,696 $254,368 $159,642 $47,947 $68,801 $108,137
$53,309 $132,393 Pending $96,110
$20,000
$63,574
$45,972
$143,528 $68,273
$ 31,694
Sylvia & Charles Viertel Charitable Foundation Senior Medical Research Fellowship – Understanding the Relevance of Biological Complexity and Fractal Structures for Ventilation of the Preterm Lung. Principal Investigator: J Pillow (2007 – 2011 $975,000). Yale University Progestins and Irregular Bleeding. Investigator: M Hickey (2007 – 2009 USD$365,945). Cincinatti Children’s Hospital New Mediators of Clinical Lung Maturation. Investigators: A Jobe, M Ikegami, J Newnham. Department of Health - WA Evaluation of Pregnancy Outcomes and Cost-Effectiveness of Models of Antenatal Care and Preferred Setting for Labour and Birth Care in Women at Low Risk Of Pregnancy Complications. Investigators: D Doherty, J Hornbuckle, M Hutchinson, R Brinsmead, J Newnham (2008 $82,338). New Independent Research Infrastucture Support Award G Polglase (2008 $10,000). Nurses Memorial Charitable Trust Feeding and Sleeping Outcomes of Nicu Graduates and Healthy Term Infants. Investigator: S Zuiderduyn (2007 $18,500).
$195,454
$117,392
$48,000
$82,338 $10,000
$18,500
Commercial Research Support Organon (Australia) Pty Ltd – Evaluating the contraceptive efficacy, cycle control, safety and acceptability of a monophasic $40,270 Combined Oral Contraceptive. Investigator: M Hickey (2006 – 2008). Bayer Schering Pharma AG – Study of Oral Estradiol Valerate / Dienogest tablets for the treatment of dysfunctional $125,688 uterine bleeding. Investigator: M Hickey (2006 – 2008). Pfizer Australia Pty Ltd – Evaluating the efficacy and safety of PD0299685 for the treatment of moderate to severe vasomotor $32,406 symptoms associated with menopause. Investigator: M Hickey (2006 – 2007.) Glaxo Smith Kline Australia – Treatment of VMS study In post-menopausal women. $67,985 Investigator: M Hickey (2007 – 2008). Schering-Plough – Neonatal Resuscitation and Preterm Lung Injury. $62,411 Investigators: A Jobe, J Pillow, S Kallapur, B Kramer. Fisher & Paykel Healthcare Ltd – New Mediators of Clinical Lung Maturation. $49,980 Investigators: A Jobe, M Ikegami, J Newnham. Pfizer Australia – Family Vascular Risk Factors in the Prediction of Pre-eclampsia. $50,000 Chief Investigator: B Walters. Direct Research Expenditure by the Women and Infants Research Foundation The Foundation Provides Financial Support For Researchers By Direct Funding Through The Research Starter Grant Program, As Well As Infrastructure Support For The External Research Grants Outlined Above. As Detailed In The Foundation’s Financial Statements, The Total $1,052,453 “Monetary” Value Of This Support For The Current Financial Year Was: $3,585,573 Total Research Support for 2007/2008
Women and Infants Research Foundation Annual Report 2008 49
50
Women and Infants Research Foundation Annual Report 2008
Financial Statements
Women & Infants Research Foundation Inc.
Income Statement for the Year Ended 30 June 2008
2008 $ 2,603,557 -100,196 -116,057 -936,396 -249,626 -986,781 -6,522 207,979 207,979 636,928 2007 $ 2,939,317 -90,565 -52,334 -996,067 -250,115 -908,686 -4,622 636,928 -
Revenue Depreciation expenses Research grants approved Other research expenses Administration expenses Trading Activities - Cost of Goods Sold & other expenses Finance Costs Profit before income tax Income tax expense Profit from ordinary activities for the year
A full copy of the Foundation’s audited general purpose financial report for the year ended 30 June 2008 is available at www.wirf.com.au
Women and Infants Research Foundation Annual Report 2008
51
Financial Statements Continued
Women & Infants Research Foundation Inc.
Balance Sheet as at 30 June 2008
2008 $ Current Assets Cash And Cash Equivalents Trade And Other Receivables Inventories Other Current Assets Total Current Assets Non-Current Assets Financial Assets Property, Plant And Equipment Total Non-Current Assets Total Assets Current Liabilities Trade and other payables Short term provisions Total Current Liabilities Non-Current Liabilities Long Term Provisions Total Non-Current Liabilities Total Liabilities Net Assets Equity Retained Earnings Reserves Total Equity 1,576,160 184,626 22,756 42,432 1,825,974 4,772,021 493,015 5,265,036 7,091,010 1,552,786 80,031 1,632,817 21,904 21,904 1,654,721 5,436,289 5,307,162 129,127 5,436,289 2007 $ 869,841 597,898 19,788 43,177 1,530,704 5,344,449 454,819 5,799,268 7,329,972 1,029,291 67,381 1,096,672 18,373 18,373 1,115,045 6,214,927 5,120,200 1,094,727 6,214,927
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Women and Infants Research Foundation Annual Report 2008
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