Epigenetic Markers in Growth Restricted Human Pregnancies: a Case-controlled Study
Condition: Fetal Growth Retardation
MeSH terms: Fetal Growth Retardation
Study type: Observational

Summary: 
      This study is carried out to discover if a baby with restricted growth in the womb is subject
      to specific fetal programming which predisposes to the metabolic
      syndrome(diabetes,hypertension,heart disease) in adulthood.We have elected to first study
      this condition in Chinese population in Singapore with the eventual plan of studying all
      ethnic groups. This is important for understanding the molecular basis of adult-onset disease
      such as diabetes, identifying children at risk of developing this disease in future and
      targeting specific strategies for intervention and disease prevention.

      Intrauterine fetal programming is effected through epigenetic changes similar to those
      previously identified in animal studies. The epigenetic markers can be found in growth
      restricted Chinese pregnancies in the local population.
    

Detailed description: 
      Fetal growth restriction is associated with accelerated postnatal weight gain and increased
      obesity risk in later life.International epidemiological data suggest that the phenomenon of
      fetal programming links poor intrauterine growth to adult disease, primarily type II
      diabetes, obesity and metabolic syndrome, conditions increasingly common in Singapore.
      Suboptimal intrauterine environmental condition s are postulated to affect fetal development
      through effects on developmental plasticity through epigenetic processes. These effects
      manifest as poor glucose resistance, insulin resistance, obesity and cardiovascular disease
      in later life. There is increasing animal data to support this model.

      The aim of this study is to determine if epigenetic markers of the metabolic syndrome are
      present in selected Chinese pregnancies in Singapore.

      Hypothesis:

      Intrauterine fetal programming is effected through epigenetic changes similar to those
      previously identified in animal studies. The epigenetic markers can be found in growth
      restricted Chinese pregnancies in the local population.

      Methodology Umbilical cords and cord blood will be collected from twenty unequivocally
      growth-restricted Chinese pregnancies and twenty appropriately-grown Chinese pregnancies. DNA
      extracted from these tissues will be subjected to a custom-made DNA methylation array probing
      for specific changes in 262 candidate genes important to fetal endocrine and metabolic
      control.

      This will be done using either a methylation array or a Sequenorn 2 in the DNA extracts that
      have been identified through Epigen academic consortium of the Liggins Institute and UK
      collaborators.

      Anthropometric data will be collected from the infants at birth, and subsequently at
      3,6,12,18 and 24 months and we will seek differential measures of programming.

      Application The discovery of biomarkers indicating shifted developmental trajectories is the
      most important need in developmental programming research. Birth weight alone is not a valid
      measure. Biomarkers predictive of later obesity and the metabolic syndrome will be invaluable
      in formulating preventive strategies for these diseases.
    

Observational model: Case-Control
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Babies from Chinese women with single pregnancies