1. HRB Grant Holders Conference
Limerick
February 26-27, 2015

2. Consortium Background
All-Ireland multi-centre consortium focused on research into maternal and child health
Health Research Board (HRB) funded (€4.9 million)
Additional external funding (€2.8 million)
Friends of the Rotunda
National Children’s Research Centre
Children’s University Hospital Research Fund
Science Foundation Ireland
Wellcome Trust
Links seven maternity hospitals and associated academic centers across the island

3. Network Partners

4. Maternal Fetal Medicine Support Universal National Support
COOMBE
Bridgette Byrne
Sean Daly
Mairead Kennelly
Caoimhe Lynch
Aisling Martin
Carmen Regan
CORK
Richard Greene
John Higgins
Dan McKenna
Keelin O’Donoghue
Noirin Russell
NMH
Stephen Carroll
Mary Higgins
Shane Higgins
Rhona Mahony
Fionnuala McAuliffe
Peter McParland
ROTUNDA
Fionnuala Breathnach
Sharon Cooley
Jennifer Donnelly
Karen Flood
Fergal Malone
BELFAST
Carolyn Bailie
Samina Dornan
Aly Hunter
John Manderson
Stephen Ong
GALWAY
Geraldine Gaffney
John Morrison
LIMERICK
Amanda Cotter
John Slevin
WEXFORD
Liz Dunne

5. Additional Multidisciplinary Support
NEONATOLOGY
David Corcoran
Adrienne Foran
John Kelleher
Pamela O’Connor
Colm O’Donnell
David Sweet
CARDIOLOGY
Orla Franklin
Dermot Kenny
EPIDEMIOLOGY
Patrick Dicker
Richard Tremblay
INDUSTRY
Colin Paul
Gerald Seifriedsberger
PHARMACY
Brian Cleary
MIDWIFERY
Fiona Alderdice
Mary Brosnan
Emma Doolin
Phyl Gargan
Cecilia Mulcahy
Hilda O’Keeffe
Margaret Philbin
Ann Phillips
INTERNATIONAL
Zarko Alfirevic
Ted Barker
Mary D’Alton
Tim Lyons
Jane Norman
Michael Paidas
Andrew Shennan
Ian Young
MASTERS / CD’s
Sam Coulter Smith
Rhona Mahony
Sharon Sheehan
All clinical directors
RADIOGRAPHY
Fiona Cody
Edel Varden
RADIOLOGY
James Meaney
HSE
Michael Turner

6. Personnel Structure Chairman – Prof Fergal Malone
Programme Manager – Dr Liz Tully
Biostatistician – Dr Pat Dicker

7. Personnel Structure Chairman – Prof Fergal Malone
Programme Manager – Dr Liz Tully
Biostatistician – Dr Pat Dicker
PI – Prof F McAuliffe
RS- Cecelia Mulcahy
PI – Prof F Breathnach
RS- Fiona Cody
PI – Prof J Higgins
RS- Ann Phillips
PI – Dr G. Burke / Prof A Cotter
RS- K Irfah-Ismail
PI – Prof J Morrison
RS- Edel Varden
PI – Prof S Daly
RS- Emma Doolin
PI – Dr Aly Hunter/
Dr Samina Dornan
RS- Phyl Gargan

8. Scientific Advisory Board RCSI Research Institute
Management Structure
Steering Committee - comprised of Chairman, Site PIs , Programme Manager, Biostatistician, Sonographer & Patient representatives
Scientific Advisory Board
RCSI Research Institute
Health Research Board
Education & Training
Finance
Publication
Protocol
CLINICAL SITES
Rotunda Hospital
Coombe Women and Infants University Hospital
National Maternity Hospital
University College Hospital, Galway
Royal Jubilee Maternity Hospital, Belfast
Mid-Western Regional Maternity Hospital, Limerick
Cork University Maternity Hospital
Sub-Committees
SCM – RCSI Administrative Hub, support in activities such financial/grant award administration, technology transfer/IP protection, education and outreach activities in conjunction with the Programme Manager.
SAB - Mary D’Alton, Mark Kilby, Pran Pandya, Mike Clarke, Michael Turner, and Nadine Farah. - provides support and guidance on the scientific and clinical aspects of the consortium’s activities, including reviewing proposed studies and highlighting areas of clinical and scientific importance that should be addressed by the Consortium’s research studies.
Sub-committees - with responsibility for issues such as preparation and conduct of research studies, publications arising from the studies, finance, ethics and training, industrial relations, technology transfer and intellectual property.
Last official communication with SAB at Fetoscopy meeting in Carton House last year

9. Research Infrastructure
Unique, world-class research infrastructure comprising :
state-of-the-art imaging equipment
GE Voluson Ultrasound Equipment & Viewpoint Software
dedicated research and management personnel
Research Sonographers, Programme Manager, Biostatistician
central management and governance structure
Steering Committee, Scientific Advisory Board, RCSI Research Institute
access to associated support services
Pathology, Epidemiology, Range of specialist cross-disciplinary clinical expertise
Access to large patient populations (55,000+ births pa.):
uniquely positioned to carry-out ground-breaking
clinical research.

10. Network Aims
Perinatal Ireland was established with the mission of improving the standard of healthcare for women and children in Ireland.
Key goals and objectives
to establish a centre of excellence in perinatal medicine research, performing world-class clinical research
to build a national dedicated research capacity to conduct high-quality patient-oriented clinical research
to translate research findings into clinical practice for the benefit of women and children’s health
to develop collaborative, cross-disciplinary programmes to generate national research networks
to develop human capital through high-quality education and training programmes

11. Research to date ESPRiT – National Twin Study
Two year Programme to Jan 2010
Recruited over 1000 twin pregnancies
Multiple high profile publications
Multiple oral presentations at Society for Maternal Fetal Medicine Annual Clinical Meeting
Long term paediatric follow-up ongoing
Long term epigenetic studies ongoing
Published new national guidelines on the management of twin pregnancies

13. Research Studies
PORTO - investigation of multi-vessel Doppler in the management of growth restricted fetuses:
Two year programme to June 2012
Recruited over 1200 patients

14. PORTO 1:
The Optimal Definition of Intrauterine Growth Restriction Based on Perinatal Morbidity and Mortality J. Unterscheider on behalf of Perinatal Ireland Oral Presentations at SMFM, San Francisco, Feb 2013

15. PORTO 1:
Methods
1,200 consecutive singleton pregnancies 24 0/7 – 36 6/7 wks
EFW < 10th centile
Followed with twice weekly ultrasound / advanced Doppler:
Biometry / amniotic fluid
Uterine artery
Umbilical artery
Ductus venosus
Middle cerebral artery
Aortic isthmus
Myocardial performance index

16. PORTO 1: Methods Detailed obstetric and pediatric outcome
Neonatal US and MR Imaging
2 year Bayley’s assessments
Adverse outcome:
Perinatal mortality
NICU admission
IVH / PVL
HIE
NEC
BPD
Sepsis

17. PORTO 1: Methods Various definitions of significant IUGR:
EFW < 10th, < 5th, < 3rd centiles
AC < 10th, <5th, < 3rd centiles
All with or without oligohydramnios
All with or without abnormal umbilical artery Doppler (AEDF / PI >95%)

18. PORTO 1: Perinatal Mortality 1.4% (17)
Results
Perinatal Mortality % (17)
Composite Adverse Perinatal Outcome 6.2% (74)
NICU Admission % (372)

19. PORTO 1: Results Predictor EFW<3rd 828 53 (88.3%) 775 (73.3%) n
Adverse outcome (n=60)
Normal outcome (n=1058)
P-value
EFW<3rd
828
53 (88.3%)
775 (73.3%)
0.0095
EFW<5th
1049
57 (95.0%)
992 (93.8%)
0.6982
EFW<10th
1118
60 (100%)
1058 (100%)
N/A
AC<3rd
911
54 (90.0%)
857 (81.0%)
0.0809
AC<5th
1000
55 (91.7%)
945 (89.3%)
0.5649
AC<10th
1082
58 (96.7%)
1024 (96.8%)
0.9592
EFW<3rd + oligo
128
14 (23.3%)
114 (10.8%)
0.0030
EFW<5th + oligo
190
176 (16.6%)
0.1790
EFW<10th + oligo
232
16 (26.7%)
216 (20.4%)
0.2454
EFW<3rd + abnormal UA
251
42 (70.0%)
209 (19.8%)
<0.0001*
EFW<5th + abnormal UA
346
45 (75.0%)
301 (28.4%)
EFW<10th + abnormal UA
413
47 (78.3%)
366 (34.6%)

20. PORTO 1:
Conclusions:
EFW or AC < 10th or 5th centiles should no longer be used to define pregnancies at high risk adverse outcome
EFW < 3rd centile is reasonable cut-off to define high risk group
Abnormal UA Doppler is strongest predictor of adverse outcome whenever EFW < 10th centile
These data will allow more focussed use of obstetric resources whenever EFW < 10th centile

21. PORTO 2:
Sequential Doppler Changes in IUGR: Is There a Benefit of Advanced Multi-Vessel Doppler Assessment? J. Unterscheider on behalf of Perinatal Ireland Oral Presentation at SMFM, San Francisco, Feb 2013

22. PORTO 2: Results

23. PORTO 2: Results UA MCA DV AoI MPI GA at first abnormal Doppler 32 6/7UA
MCA DV
AoI
MPI
GA at first abnormal Doppler
32 6/7
32 5/7
32 4/7
30 6/7
33 1/7
Median time to delivery
23 d
21 d
17 d
29 d
GA at delivery
37 3/7
37 2/7
34 5/7
38 1/7
38 4/7

24. PORTO 2:
Conclusions:
Umbilical artery and MCA Doppler are most predictable in demonstrating progressive temporal changes for IUGR
Ductus venosus and cardiac indices demonstrated no added benefit in surveillance for IUGR
Surveillance for IUGR should be simplified and should rely primarily on finding of AEDF or REDF in umbilical artery
New HSE National Guideline published

26. Current Studies
GENESIS – Prospective observational study to assess the use of fetal head circumference (FHC), measured using ultrasound in the late third trimester, and other markers as predictive tools for labour dystocia and intrapartum caesarean section.
Recruitment target : (achieved Dec 2014)
Study duration : 36 months (outcomes ongoing)

27. Current Studies
GENESIS – Prospective observational study to assess the use of fetal head circumference (FHC), measured using ultrasound in the late third trimester, and other markers as predictive tools for labour dystocia and intrapartum caesarean section.
Recruitment target : (achieved Dec 2014)
Study duration : 36 months (outcomes ongoing)
AFFIRM – Fetal Movement study - Can promoting awareness of fetal movements and focussing interventions reduce fetal mortality - a stepped wedge cluster randomised trial?
Hospital education and intervention programme
Study duration : 24 months

28. Current Studies Pilot study target: 500 (250 recruited to date)
GENESIS – Prospective observational study to assess the use of fetal head circumference (FHC), measured using ultrasound in the late third trimester, and other markers as predictive tools for labour dystocia and intrapartum caesarean section.
Recruitment target : (achieved Dec 2014)
Study duration : 36 months (outcomes ongoing)
AFFIRM – Fetal Movement study - Can promoting awareness of fetal movements and focussing interventions reduce fetal mortality - a stepped wedge cluster randomised trial?
Hospital education and intervention programme
Study duration : 24 months
TEST – Randomised trial of aspirin therapy and early screening tests for pre-eclampsia and fetal growth restriction, during pregnancy in low-risk first-time mothers
Recruitment target : 5,700
Pilot study target: 500 (250 recruited to date)

29. Future Direction?

31. HRB Ireland Perinatal Clinical Trial Network: Mission
To improve health outcomes
for women and children,
both in Ireland and globally

32. HRB Ireland Perinatal Clinical Trial Network:
Bringing together two highly successful, existing, clinical research networks in the perinatal arena

33. Overwhelming need More than 1 in 10 babies are born preterm
Over 1 million children die each year due to complications of preterm birth
Many survivors face a lifetime of disability, including learning disabilities and visual and hearing problems
Born too soon, the global action report on preterm birth was published this year, This is the current situation today around the world then read headlines….

34. Economic need
Perinatal disease accounts for 10% of the global health burden1
R&D investment in perinatal health remains small and non-strategic
The number of registered pipeline drugs is only 1-5% that for other major disease areas
1. Fisk, N.M. and R. Atun, Market failure and the poverty of new drugs in maternal health. PLoS Med, (1): p. e22.
It is…as long as the message is (and I know it will be) that these are the implications of not investing in research in this area…but also AND I SUSPECT THIS MIGHT NOT BE IN THE MESSAGE…if Ireland now takes the opportunity to invest in this research thru Capture, and thus provides our industry partners with access to world-leading (please say it Louise) research leading to innovative technologies, and in turn leading to massive commercial opportunities in this vast market, a market that is untapped due to the unmet needs presented in the perinatal setting.

35. HRB Ireland Perinatal Clinical Trial Network: Vision
To establish a world-class centre of excellence in perinatal medicine research
To build an all-Ireland dedicated research capacity to conduct high-quality, patient-oriented clinical research
To translate research findings into clinical practice to improve the health of women and children
To develop collaborative, cross-disciplinary programmes to generate a self-sustaining national and international research infrastructure

36. HRB Ireland Perinatal Clinical Trial Network: International Collaborations

37. HRB Ireland Perinatal Clinical Trial Network: Expertise
General Practice
Epidemiology
Developmental Psychology
Pathology
Biochemistry
Cardiology
Haematology
Endocrinology
Neonatal Physiology
Masters &
Clinical Directors
Directors Nursing & Midwifery
Trials Methodology
Maternal Fetal Medicine
Neonatology
Not sure what this adds

38. HRB Ireland Perinatal Clinical Trial Network: Governance Structure
CLINICAL SITES
Rotunda Hospital
Coombe Women’s Hospital
National Maternity Hospital
University Hospital, Galway
Royal Maternity, Belfast
MW Regional Hospital, Limerick
Cork University Maternity Hospital
Executive Management Committee
External Scientific Advisory Board
Clinical Research Facilities
Health Research Board
Management Sub-Committees
Education & Training
Finance
Publication
Protocol
Industrial Liaison Business Development
Updated graphic

39. HRB Ireland Perinatal Clinical Trial Network: Portfolio of Trials - New
Implement two Definitive Intervention studies
Parrot DI
Strider DI
TEST
MINT
IRELAND
Pilot & Feasibility Work
Launch network programme of bespoke, clinical assessment of longer term paediatric outcomes
Paediatric Follow up
Core Outcome Set
Launch research programme in Clinical Trials Methodology