The Jennifer Brown Research Laboratory was established at the University of Edinburgh / MRC Centre for Reproductive Health by PiggyBankKids (now Theirworld) in 2004. The laboratory is home to a team of world class scientists and clinicians working with a unified focus and commitment to solving unanswered questions in perinatal medicine.
To improve the lives of women and children who suffer complications in pregnancy and the
Complications of pregnancy such as preterm birth, poor fetal growth, and certain maternal medical disorders are closely associated with abnormal brain development in the offspring. Disturbances to brain development can lead to significant long-term problems for survivors and their families, and prevent affected children from fulfilling their education and employment potentials.
Globally, fifteen million children are born at less than 37 weeks’ of gestation each year and this number is rising. Preterm birth is the single biggest cause of death and disability among newborn babies and it is a leading cause of neurodevelopmental impairment in childhood. Improved understanding of the disturbances to brain structure and function that accompany preterm birth, and other complications of pregnancy, is essential for the development of therapies designed to improve outcome. The goal of our translational research programme is to identify the triggers for preterm labour and treatments to prevent it, and to identify the mechanisms that lead to abnormal fetal or neonatal brain growth and poor outcome.
A major strength of our research projects is the unified focus on obstetric and neonatal problems. We study mouse models of preterm labour, brain injury and inflammation (Professor Girardi), and we use state-of-the-art magnetic resonance imaging (MRI) techniques to uncover the effects of perinatal adversity on brain development in fetal (Dr Denison) and neonatal life (Dr Boardman).
Who are we?
- Dr Ahmed Serag
- Dr Devasuda Anblagan
- Dr Emma Moore
- Dr Sarah Sparrow
- Dr Rozalia Pataky
- Mr Manuel Blesa Cabez
- Dr Vix Monnelly
PA: Karen Witherspoon
Professor Jürgen Schwarze (chair), Professor Philipa Saunders, Dr Rhona Hughes, Dr Julie-Clare Becher, Mr Geoff Carlson, Dr Ian Laing (emeritus), Professor Andrew Calder (emeritus).
- To develop advanced magnetic resonance imaging (MRI) as a tool for investigating causal pathways to fetal and neonatal brain injury that arise due to complications of pregnancy.
- To investigate the role of fetal and neonatal MRI for predicting impairment in childhood.
- To investigate the role of maternal and fetal inflammation in pregnancy on the developing brain.
- To provide an excellent platform for developing perinatal scientists and clinicians of the future.
Our current projects
1. Advanced MR imaging to investigate risk modulators for brain injury associated with
We have collected a large database of state-of-the-art MRI scans from preterm babies and babies born at full term. The image database is linked to detailed clinical and biological information. We are developing new methods to measure brain structure and are using these measures to investigate pathways to injury. Identifying the factors that lead to brain injury, or promote resilience, is essential for developing new treatment strategies.
2. Advanced MR imaging to predict neurodevelopmental impairment in childhood.
We are developing new ways of assessing cognitive function in infancy by measuring eye-gaze behaviour in response to visual stimuli. We are investigating whether preterm birth alters these early measures of cognition and whether MRI in the newborn predicts later cognition. If it does, then MRI could serve as a useful test for giving better and more detailed prognostic information to families, and as a clinically relevant early marker for studying new treatments.
3. In utero biomarkers of cognitive impairment in offspring of women with diabetes.
Diabetes is the most common medical disorder of pregnancy and the consequences of maternal diabetes for the offspring extend beyond pregnancy: under-performance at school age and learning problems are more common. It is unknown whether this is due to problems with brain development in the womb or to postnatal events. We are collecting very detailed fetal brain scans towards the end of pregnancy to see whether brain development in fetal life is altered in the offspring of diabetic women. The results of the study will help define the window period when therapeutic interventions should be targeted.
4. Complement to predict and prevent fetal brain injury.
The complement system forms part of the immune system. Prof Girardi has shown that altered function of complement is associated with preterm birth in mice, and she used sophisticated animal MR imaging techniques to show that the complement system also contributes fetal brain maldevelopment in the womb in some circumstances. The complement system can be modified using drugs, so these data provide an exciting new avenue of investigation of fetal neuroprotection. We are now investigating whether the same mechanism applies in humans.
5. Immune-mediated fetal brain development in maternal antiphospholipid syndrome and
Having established that preterm birth and specific maternal immune problems can led to fetal brain injury, we are now investigating which neural cell types are affected and how, and whether these processes can be attenuated with maternal drug treatment.
6. Magnetic resonance tractography of the developing human brain
We are developing new approaches for analysing MRI brain scans that will deepen understanding of how the brain is ‘wired’ in early life through a complex network of connections or tracts, and how networks are altered by preterm birth.
- Girardi G, Fraser J, Lennen R, Vontell R, Jansen M, Hutchison G. Imaging of activated complement using ultrasmall superparamagnetic iron oxide particles- conjugated vectors: an in vivo in utero non-invasive method to predict placental insufficiency, abnormal fetal brain development and behaviour disorders”. Mol. Psychiatry 2014 Sep 23. doi: 10.1038/mp.2014.110. [Epub ahead of print]
- Boardman JP, Walley A, Ball G, Takousis P, Krishnan ML, Hughes-Carre L, Aljabar P, Serag A, King C, Merchant N, Srinivasan L, Froguel P, Hajnal J, Rueckert D, Counsell S, Edwards AD. Common variants in genes associated with schizophrenia and lipid metabolism modulate brain injury after preterm birth. Pediatrics. 2014 Jun;133(6):e1655-63.
- Gonzalez JM, Pedroni SM, Girardi G. Statins prevent cervical remodeling, myometrial contractions and preterm labor through a mechanism that involves hemoxygenase-1 and complement inhibition. Mol Hum Reprod. 2014;20(6):579-89
- Shah DK, Wusthoff CJ, Clarke P, Wyatt JS, Ramaiah SM, Dias RJ, Becher J, Kapellou O, Boardman JP. Electrographic Seizures are an Independent Risk Factor for Brain Injury on MRI in Neonates undergoing Therapeutic Hypothermia for Encephalopathy. Arch Dis Child Fetal Neonatal Ed. 2014 May;99(3):F219-24.
- Lefkou E, Mamopoulos A, Fragakis N, Dagklis T, Vosnakis C, Nounopoulos E,Rousso D, Girardi G. Clinical Improvement and Successful Pregnancy in a Preeclamptic Patient With Antiphospholipid Syndrome Treated With Pravastatin. Hypertension. 2014 May;63(5):e118-9.
- Pedroni SM, Gonzalez JM, Wade J, Jansen MA, Serio A, Marshall I, Lennen RJ, Girardi G. Complement inhibition and statins prevent fetal brain cortical abnormalities in a mouse model of preterm birth. Biochim Biophys Acta. 2014;1842(1):107-15
- Girardi G. Can statins prevent pregnancy complications? J Reprod Immunol. 2014;101-102:161-7.
- Moore E and Boardman JP. Modifiable risk factors for preterm brain injury. Paediatrics and Child Health 24:9:401-406.
The Jennifer Brown Research Laboratory is hosted at the MRC/University of Edinburgh Centre Reproductive Health.
Imaging studies are carried out at the Clinical Research Imaging Centre (CRIC, University of Edinburgh) which houses a state-of-the art 3 Tesla Siemens MR imaging system that can accommodate pregnant women and neonates.
We collaborate with colleagues in the Centre for Clinical Brain Sciences (Dr Mark Bastin, Prof Joanna Wardlaw, Dr Sue-Fletcher-Watson), Child Life and Health (Prof Anne O’Hare), CRIC
(Dr Scott Semple, Dr Gillian Macnaught, Prof Neil Roberts), Centre for Cardiovascular Science
(Dr Mandy Drake) and NHS Lothian (Dr Graham Wilkinson).
NHS Lothian’s Simpson Centre for Reproductive Health (SCRH) delivers 7000 infants per annum and is the regional centre for women with high risk pregnancies. The Neonatal Intensive Care Unit at SCRH is the regional centre for tertiary level care of preterm infants. Research participants are recruited from this site.
Our current research programme is a platform for training basic and clinical scientists. We will offer four – year PhD studentships hosted by the MRC/CRH to aspiring basic and imaging scientists. This is a competitive and innovative programme that draws from an international pool of applicants and has proven to be successful since its inception in 2011. We will continue to build on the tradition of the Jennifer Brown Laboratory to support talented clinical academics in training.
Media attention in 2014
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