Project Update: Brain Development in Fetal Growth Restriction               

PhD students: Lisa Story & Mellisa Damodaram

Project Supervisors: Mr Sailesh Kumar & Professor Mary Rutherford

17th September 2009

Objectives

The objectives of this project are to asses potential changes that occur antenatally in pregnancies complicated by fetal growth restriction as these may have implications for long term development.  This is being performed using a number of modalities: fetal MRI, 2D and 3D ultrasound and laboratory assays measuring growth factors present in umbilical cord blood. The study is now in its third year, and to date, the results from this study have been presented at both International and National conferences, and manuscripts are being prepared for publication.

The longer term neurodevelopment outcome data from babies in this study will also be collected and analysed at a later date. This will ensure that we have a good understanding of the problems that these children may develop and hopefully give us insight into potential early interventions that may be of benefit.

Fetal Ultrasound & Laboratory assays

Ultrasound is being used to characterise changes in volume blood flow in both appropriately grown and growth restricted fetuses.  Clinically it is already known that there is increased blood flow to the brain in growth restricted fetuses, however how blood flow is redistributed in the rest of the fetus has previously not been characterised.  To date we have scanned over 130 women with uncomplicated pregnancies and 65 pregnancies complicated with growth restriction.  We have already found that many blood vessels within the fetus appear to be larger when standardised for the weight of the baby in growth restricted than in appropriately grown fetuses, this is in contrast to what was previously assumed. The collection of data from this aspect of the project is close to completion.

We hope to go on to assess factors that cause blood vessels to dilate/constrict by analysing samples of blood from the umbilical cord at delivery. Blood samples from the umbilical cord at the time of delivery for these women are being collected and stored, and will be analysed in the near future.

We are also planning to conduct a pilot study using 3D ultrasound to quantify the changes in vascularity that occur in different regions of the brain. This will help us to further understand the changes in brain blood flow that occur in growth restricted fetuses, and hopefully identify those fetuses at increased risk of long term developmental sequelae.

Fetal Magnetic Resonance Imaging

Magnetic Resonance Imaging is a non invasive tool that uses a magnet to acquire detailed images of the fetal brain. As there is no radiation involved, it is safe for use in pregnancy, and it is a very useful adjunct to ultrasound in the management of complicated pregnancies.
By performing scans of the whole uterus and fetus, we are able to obtain information on the changes that occur within the placenta in growth restricted fetuses, as well as the volumes of various organs within the fetus. Analysis of data from this aspect of the project is close to completion and manuscripts detailing these are being prepared for publication.

With the help of physicists and the computing department at Imperial College, we are optimising sequences that will allow us to re-construct 3D images of the fetal brain. Prior to 3D reconstruction, images are often distorted by the presence of fetal motion, and with the use of the reconstruction technique, we are able to perform analysis of volumes of various regions within the fetal brain. To date we have conducted 3D reconstructions of 38 growth restricted and 56 normal pregnancies. We have found that the cerebellum (a part of the brain that is important in coordination and motor learning) is proportionally smaller in growth restricted fetuses. Analysis of this data is ongoing and a manuscript will be prepared for publication once analysis is complete. 

Magnetic resonance spectroscopy (MRS) is a variation of magnetic resonance imaging but instead of forming a picture shows the levels of various chemicals within the fetal brain.  We have performed MRS on the fetal brain of 50 women with uncomplicated pregnancies and 25 women with pregnancies complicated with growth restriction.  So far we have found that levels of a substance called N-acetylaspartate (NAA), which is a marker of brain nerve growth, are lower in growth restricted fetuses than those which are appropriately grown.  The collection of data from this aspect of the project is still ongoing.

 

Project Publications:

  1. Vessel Diameter in Growth Restricted Fetuses. Story L, Damodaram M, Paramasivam G, Rutherford M, Kumar S. Arch Dis Child Fetal Neonatal Ed 2009;94 (3):Fa13  
  2. Three-dimensional MR reconstruction and evaluation of the cerebellum to whole brain ratio in intrauterine growth restriction. Damodaram M, Story L, Allsop J, McGuinness A, Kumar S, Rutherford M. Arch Dis Child Fetal Neonatal Ed 2009;94 (3):Fa16  
  3. Three-dimensional magnetic resonance imaging reconstruction and brain volumetry in intrauterine growth restriction. Damodaram M, Story L, Allsop J, McGuinness A, Kumar S, Rutherford M. Arch Dis Child Fetal Neonatal Ed 2009;94 (3):Fa19  
  4. M Damodaram, L Story, E Kulinskaya, S Kumar. Meta-regression analysis of adverse neonatal outcome in preterm growth restricted infants. Submitted for publication
  5. Proton Magnetic Resonance Spectroscopy and the Fetal Brain in Normally grown and Growth Restricted Fetuses. Story L, Damodaram M, Wylenzinska-Arridge M, Kumar S, Rutherford M. Arch Dis Child Fetal Neonatal Ed 2008;93(Suppl I):Fa 3
  6. Magnetic Resonance Imaging of the Placenta in Intrauterine Growth restriction.  Damodaram M, Story L, Paramasivam G, Kumar S, Rutherford M. Arch Dis Child Fetal Neonatal Ed 2008;93(Suppl I):Fa42
  7. S Kumar, L Story, M Damodaram, M Rutherford. Perinatal Brain Injury. Current Paediatric Reviews. 2008; 4(2): 71 - 79

Project Presentations:

  1. Vessel Diameter in Growth Restricted Fetuses. Story L, Damodaram M, Paramasivam G, Rutherford M, Kumar S. Presented to the British Maternal and Fetal Medicine Society, Liverpool, 2009, and to be presented to the International Federation of Obstetrics and Gynaecology, South Africa, 2009.
  2. Three-dimensional MR reconstruction and evaluation of the cerebellum to whole brain ratio in intrauterine growth restriction. Damodaram M, Story L, Allsop J, McGuinness A, Kumar S, Rutherford M. Presented to the British Maternal and Fetal Medicine Society, Liverpool, 2009, and to be presented to the International Federation of Obstetrics and Gynaecology, South Africa, 2009.
  3. Three-dimensional magnetic resonance imaging reconstruction and brain volumetry in intrauterine growth restriction. Damodaram M, Story L, Allsop J, McGuinness A, Kumar S, Rutherford M. Presented to the British Maternal and Fetal Medicine Society, Liverpool, 2009, and to be presented to the International Federation of Obstetrics and Gynaecology, South Africa, 2009.
  4. 2008- Proton Magnetic Resonance Spectroscopy and the Fetal Brain in Normally Grown and Growth Restricted Fetuses.  Presented to British Maternal and Fetal Medicine Society, Harrogate, 2008
  5. 2008- Cerebral Development and Intrauterine Growth Restriction: The Role of Magnetic Resonance Spectroscopy Presented at the Fetal MRI Congress, Vienna, 2008
  6. 2008- Magnetic Resonance Imaging of the Placenta in Intra-Uterine Growth Restriction. Presented at the Fetal MRI Congress, Vienna, 2008
  7. 2008- Magnetic Resonance Imaging of the Placenta in Intra-Uterine Growth Restriction. Presented to the British Maternal and Fetal Medicine Society, Harrogate, 2008