IUGR (intrauterine growth restriction) is a heterogeneous disorder. The common denominator for IUGR is impaired intrauterine fetal growth. Individuals with this condition are defined by birthweights less than 10th centile for gestational age and by other clinical characteristics. These include abnormal Doppler examinations of uterine and/or umbilical artery blood flow that reflect downstream increased vascular resistance. Based on the 337,856 births in Canada for 2005 (Statistics Canada, 2005), there are more than 30,000 infants with birthweights below the 10th centile born every year.
IUGR is often attributed to a broad and vaguely-defined condition called ‘placental insufficiency’ and may have very different maternal-fetal outcomes depending on the timing of onset. IUGR at term may only manifest itself as fetal distress requiring a caesarean section and leading to a favorable neonatal outcome. However, early-onset IUGR at 28 weeks may be so severe as to cause fetal death in utero. Early caesarean section may be performed to avoid fetal death, but may sometimes lead to major neurological handicaps following a period of intensive care.
Very little is known about the causes of IUGR. Familial and transgenerational effects have been described in IUGR but most cases seem to be sporadic. Our hypothesis is that IUGR is likely to be caused by epigenetic modifications, in particular DNA methylation, that affect the expression of important developmental and growth regulatory pathways.
We study DNA methylation patterns in IUGR placentas:
- At known imprinted loci using bisulfite pyrosequencing
- On the whole genome levels using methylated DNA immunoprecipitation (MeDip) and Agilent CpG island microarrays