Birth Defects Research Centre

Birth Defects Research Centre

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Birth defects as an international health challenge

Congenital malformations (i.e. birth defects) are important causes of infant morbidity and mortality in developed nations, for example affecting 1 in every 40 pregnancies in Europe (Dolk et al, 2010. Adv. Exp. Med. Biol. 686: 349-364). As perinatal and infant mortality have declined progressively, with improvements in prenatal, intra-partum and neonatal care, so congenital defects have come to represent an ever more significant proportion of the life-threatening conditions of infancy. While around 20% of individuals with birth defects die in utero, as stillbirths or as therapeutic abortions, the remainder survive beyond the first week of life. However, such infants have a 15-fold increased risk of death during the first year, with 9-10% dying during this period. Those who live beyond one year of age are often destined for a life-time of ill-health, with repeated medical and surgical interventions.

Of the 175,000 patient visits Great Ormond Street Hospital (GOSH) receives each year, 40% of these children are affected by a birth defect. This places ICH and GOSH in an ideal position both to derive research projects from the patients we see, and to translate research findings back into the clinical area. In terms of our scientific strengths, we are able to bring the following areas of expertise to bear on the issues of causation, pathogenesis, treatment and prevention of birth defects:

(i) Genetics.

The revolution in genomic technologies is enabling gene discovery for an ever-increasing number of inherited conditions including birth defects. While easiest to apply to single gene disorders, this technology should also begin to unravel the multifactorial aetiology of the commonest birth defects (e.g. congenital heart and neural tube defects). Through ICH/GOSH’s strength in clinical and molecular genetics, the hosting of UCL Genomics and the recent development of GOSgene, we are in a key position to lead in this area.

(ii) Developmental biology

Functional (post-genomic) studies of embryonic and fetal development, incorporating the role of genes, environmental factors and their interactions, are key to understanding how birth defects arise. Such studies have the potential to suggest key pathways for targeting in drug or other interventions. At ICH, there is a strong focus on animal models of congenital disease, encompassing a wide range of body systems and defect types. The Institute hosts the Developmental Anomalies Consortium within the MRC Mouse Network, enabling access to new knockout strains emerging from the International Mouse Phenotyping Consortium. The Human Developmental Biology Resource is co-directed from ICH providing unique access to human embryonic and fetal material for cellular/gene expression studies for congenital disease.

(iii) Novel therapeutic technologies

Gene and stem cell therapies hold great promise for many diseases, including birth defects. ICH/GOSH pioneered somatic gene therapy for immunodeficiency disease, and is now extending the clinical use of this technology to many other conditions. Stem cell therapies are also under intense research, with a major advance coming from the demonstration that functional rod photoreceptors can be replaced in the degenerating mouse retina. Tissue engineering is under development, as is research aimed at developing small molecular and nutritional supplements to prevent birth defects.

(iv) Population studies and clinical trials

ICH/GOSH has strength in epidemiology and biostatistics through its MRC Centre for Epidemiology of Childhood Disease, and is ideally placed to lead in the areas of population surveillance of birth defects and trials of novel preventive strategies. Hence, we can lead not only in applying the findings of our science to individual patients, but also in informing public health measures for primary prevention. The Somers Clinical Research Facility provides a dedicated centre clinical trials in children.

(v) Education and public engagement

ICH is actively engaged in university education with around 160 students studying for PhDs and 250 students enrolled on Masters’ courses each year. Additionally, the Institute teaches paediatrics to medical students at UCL Medical School and offers intercalated BSc courses International Health, and in Paediatrics & Child Health. A major goal is to establish a PhD programme within the BDRC, in order to train the next generation of scientists with a particular focus on this area of translational research. ICH is in regular contact with many patient groups and this will be taken forward systematically with the assistance of UCL’s Public Engagement Unit. We aim to explore the setting up of a regular dialogue with external stakeholders in order to involve patients/families/public in setting of birth defects research strategy, and to provide lay information via the BDRC web site on the latest research developments.