The GRIT longterm follow up study on cognitive and motor function language and behaviour at 6-9 years

Lead Research Organisation: University of Nottingham
Department Name: School of Medicine

Abstract

Doctors often deliver babies early if they are failing to thrive in the womb with the aim that the baby will do better delivered into a special intensive care unit. However, there are risks from premature delivery and choosing the right time is an inexact science. It has only been evaluated properly once, by the MRC s Growth Restriction Intervention Trial, which included 548 women delivering 589 babies. That trial showed that as far as mortality was concerned obstetricians were delivering babies at about the right time i.e. - stillbirths from leaving the baby too long were almost exactly counter balanced by neonatal deaths from prematurity. However, we still do not know which course of action is best for the development of the baby s brain, both the prevention of cerebral palsy and also for intellectual development. The babies from the trial are currently being evaluated at 2 years of age but some of the older ones are already nearing the age of 6. The present study is to evaluate all the babies again between the ages of 6 and 9 and look in detail at their physical and educational attainments to see if either obstetric policy is beneficial at this late stage.

Technical Summary

Babies with growth restriction have an increased risk of impaired long-term neurodevelopment, and babies delivered prematurely an increased risk of motor impairment. Timed delivery is widely used as a treatment option in pre-term growth restricted pregnancies but has only been evaluated in one study, our own MRC and EU funded Growth Restriction Intervention Trial in which 548 women and 589 babies were randomly allocated to immediate or delayed delivery. That showed no difference in short-term perinatal mortality. Stillbirths in the delay group balanced additional perinatal deaths in the deliver now group. Two year Griffiths developmental assessment is currently underway. The present application is to evaluate the 235 surviving UK children at the ages of 6-9 years to test the effect of varying the timing of delivery on more subtle motor defects, and later developmental, speech educational and behavioural outcomes. The primary hypothesis is that early delivery in cases of fetal compromise improves overall general performance IQ. The aim is firstly to help guide obstetricians delivery timing decisions. Secondly, this unique cohort of patients will provide experimental data on how the intrauterine environment affects long-term human brain development. The study is likely to lead to a large number of future testable hypotheses.

Publications

10 25 50

publication icon
Boers KE (2007) Disproportionate Intrauterine Growth Intervention Trial At Term: DIGITAT. in BMC pregnancy and childbirth

publication icon
Churchill D (2013) Interventionist versus expectant care for severe pre-eclampsia between 24 and 34 weeks' gestation. in The Cochrane database of systematic reviews

publication icon
Ganzevoort W (2017) How to monitor pregnancies complicated by fetal growth restriction and delivery before 32 weeks: post-hoc analysis of TRUFFLE study. in Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology

publication icon
Ganzevoort W (2020) Comparative analysis of 2-year outcomes in GRIT and TRUFFLE trials. in Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology

publication icon
Hornbuckle J (1997) Netpoints: Patient randomisation on the web in BRITISH MEDICAL JOURNAL

publication icon
Hornbuckle J (2000) Bayesian interpretation of trials: the example of intrapartum electronic fetal heart rate monitoring in BRITISH JOURNAL OF OBSTETRICS AND GYNAECOLOGY

publication icon
Lees C (2013) Perinatal morbidity and mortality in early-onset fetal growth restriction: cohort outcomes of the trial of randomized umbilical and fetal flow in Europe (TRUFFLE). in Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology

publication icon
Lees C (2005) The TRUFFLE study--a collaborative publicly funded project from concept to reality: how to negotiate an ethical, administrative and funding obstacle course in the European Union. in Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology

 
Guideline Title The Investigation and Management of the Small-for-Gestational-Age Fetus
Description The Investigation and Management of the Small-for-Gestational-Age Fetus
Geographic Reach Multiple continents/international 
Policy Influence Type Citation in clinical guidelines
Impact Encourages deferral of delivery
URL https://www.rcog.org.uk/globalassets/documents/guidelines/gtg_31.pdf
 
Guideline Title Management of growth restriction
Description Timing of delivery
Geographic Reach Multiple continents/international 
Policy Influence Type Citation in clinical guidelines
Impact Has influenced practitioners to delay delivery
URL https://www.rcog.org.uk/globalassets/documents/guidelines/gtg_31.pdf
 
Description Research for patient benefit
Amount £240,000 (GBP)
Funding ID PB-PG-0610-22275 
Organisation National Institute for Health Research 
Sector Public
Country United Kingdom
Start 01/2012 
End 01/2016
 
Description research for patient benefit
Amount £240,000 (GBP)
Funding ID PB-PG-0610-22275 
Organisation National Institute for Health Research 
Department Research for Patient Benefit
Sector Public
Country United Kingdom
Start 01/2008 
End 03/2011
 
Description DIGITAT 
Organisation Leiden University Medical Center
Country Netherlands 
Sector Academic/University 
PI Contribution Helped with trial design
Collaborator Contribution We have developed and completed the DIGITAT trial
Impact 17623077
 
Description TRUFFLE 
Organisation Addenbrooke's Hospital
Country United Kingdom 
Sector Hospitals 
PI Contribution I assisted with design, and chaired the data monitoring committee
Collaborator Contribution trial has been completed
Impact 1568567
 
Description TRUFFLE-2 study 
Organisation Queen Charlotte's and Chelsea Hospital
Country United Kingdom 
Sector Hospitals 
PI Contribution I am co-applicant. I helped design the trial and write two grant applications. Nottingham will be a recruiting centre.
Collaborator Contribution A randomised trial comparing delivery based on cerebral doppler redistribution or on reduced Fetal heart rate short term variability in growth resticted fetuses between 32 and 36 weeks
Impact Two unsuccesfful grant applications. One to NIHR and one to SANDS. chief investigator Christoph lees
Start Year 2015