Researchers in this axis focus on embryonic and fetal developmental anomalies. Birth defects are the main cause of death in newborns and represent a major cause of pediatric morbidity. The intrauterine protective environment can be perturbed by pregnancy complications such as preeclampsia, diabetes or utero-placental failure, possibly leading to premature birth or intrauterine growth restriction (IUGR).
Prematurity can also cause newborn mortality or, more commonly, long term complications ranging from cerebral palsy to more subtle neurological impairments associated with cognitive deficiency. Lastly, intrauterine growth restriction predisposes to serious adult pathologies including hypertension, atherosclerosis and type 2 diabetes.
The CHU Sainte-Justine is among the most dynamic university hospital centers in Canada in the field of perinatology. Our researchers are interested in various aspects of fetomaternal health, such as the retinopathy of prematurity, cardiovascular pregnancy paradox, aortic isthmus and the effects of antidepressants on pregnancy.
Over the last few years, multidisciplinary teams have been responsible for many ambitious clinical research projects aimed not only at optimizing the performance of obstetrical departments, but also at creating policies and programs to improve the health of pregnant women and their newborns. A major initiative was set up in order to facilitate multicentric clinical trials. By using an integrated approach in epidemiological, clinical and biomedical research, the axis seeks to develop new high tech fields linked to its three main themes, while integrating knowledge transfer and technological valorization.
Placento-Fetal and Neonatal Circulatory Control and Oxygen Toxicity
Compared with adults, the fetus and newborn are differentiated by a placental transmission and delivery mode of oxygen to tissues, by oxygen use mechanisms and by the capacity to produce and eliminate toxic agents (free radicals).
Researchers are committed to explaining the mechanisms involved in oxidative processes as well as identifying the role of oxidation products (isoprostanes) on various physiological or pathological conditions observed during development and their impact on long-term complications for both the nervous and cardiovascular systems. Since peroxidation causes cytotoxic effects, the team is studying their hemodynamic repercussions on neural microvasculature with the help of high-frequency ultrasonography.
Along these lines, the biophysical impact of pressure modulations (mechanotransduction) on neural and vascular cellular biology is being examined. These activities will also involve the experimental study of epigenetic events in fetal and newborn vascular dysfunction programming as well as in humans (twin studies).
The team plans on continuing its fundamental and clinical research program on hemorrhage and cerebral ischemia mechanisms in the perinatal period. This program includes the identification of susceptibility causes in certain areas of the brain and important new mediators that signal a circulatory deficit or cytoxicity, along with the study of mechanisms that block nervous tissue revascularization. Similarly, researchers in this theme hope to apply new concepts aimed at understanding the genesis of ischemic retinopathy. They will continue evaluating the clinical potential of echocardiographic markers that signal neurological hypoxic dysfunction in the prenatal period.
Another research subject in this theme focuses on molecular development by rational design aimed at targets involved in perinatal pathologies. The group has already developed several innovative molecules (such as allosteric modulators), some of which have been licensed to pharmaceutical companies for clinical application.
Membres du thème
- Bigras, Jean-Luc
- Brochu, Michèle
- Chemtob, Sylvain
- Fouron, Jean-Claude
- Hardy, Pierre
- Infante-Rivard, Claire
- Leduc, Line
- Nuyt, Anne Monique
- Rey, Evelyne
- Sansregret, Andrée
- St-Louis, Jean
Congenital Birth Defects
This theme covers two research areas: developmental genetics and diagnostic and prenatal therapy. The first area seeks to encourage interaction between human genetics and animal models to optimize gene identification and study genes controlling the development of foetuses and children with birth defects.
Many genotyping projects involving patients with birth defects have been initiated with the aim of identifying genes responsible for heart defects, vesicoureteric reflux and congenital hypothyroidism. The prenatal cytogenetic team is attempting to measure the contribution of subtle chromosomal aberrations in the genesis of birth defects.
At the same time, fundamental research programs are being initiated to identify the underlying molecular mechanisms that control neuronal differentiation in mice and cardiac development in frogs. These projects will serve as a starting point for a developmental biology team that will support the work being done in human genetics research.
The second area pertains to prenatal diagnosis and therapy. In order to address numerous questions regarding the prognosis and treatment of fetal anomalies, a multidisciplinary team made up of sonographers, cardiologists, obstetricians, geneticists and surgeons was created. With the help of the other members of the prenatal diagnosis group, these researchers are working on identifying markers that will provide an accurate prognosis of birth defects and thereby optimize treatment.
Membres du thème
Prematurity and Neurodevelopment
Prematurity, IUGR and Environmental Contaminants: Their Developmental Impact
Researchers working in this theme study the mother’s health determinants during pregnancy. Research is done on inflammatory determinants of prematurity and the role of inflammations that occur away from the fetoplacental unit in this process in addition to identifying determinants of preeclampsia, including the role of peroxidation and antioxidant effectiveness.
The causes of intrauterine growth restriction (IUGR) may be maternal, placental or fetal. In collaboration with researchers from other axes, we are planning a fundamental and clinical program on the development of the major regulatory systems such as the prostanoid, angiotensin and andrenergic receptor sytems, both under normal conditions and in growth restriction models.
The role of steroids, growth factors and oxidants will also be studied. Furthermore, epigenic and hormonal determinants of adult vascular dysfunction (i.e. hypertension, normal vasomotoricity and arteriosclerosis) will be reviewed in clinical populations and tested on animal models. An investigation of new biochemical or electrophysiological factors predicting imminent delivery will also be initiated.
The sub-theme (Development of the Premature Newborn) looks at the impact of structural and functional changes, mostly cerebral, induced in the perinatal period. Studies conceived in multichannel cerebral electrophysiology and optical imaging will be paired with psychological evaluations in an effort to better understand the adaptive and maladaptive coping patterns of premature infants.
The theme also explores the effects of environmental contaminants on antenatal and postnatal human development. The research field aligns with national interests on key populations, such as that of the Canadian North, nosocomial exposure to potentially harmful products and short- and long-term studies of pharmacological agents regularly given to mothers and their newborns.
Membres du thème
- Boucher, Marc
- Chaillet, Nils
- Dumont, Alexandre
- Frasch, Martin
- Fraser, William
- Girard, Sylvie
- Gosselin, Julie
- Goulet, Céline
- Hatem-Asmar, Marie
- Lachance, Christian
- Lefebvre, Francine
- Lodygensky, Gregory A.
- Luo, Zhong Cheng
- Luu, Thuy Mai
- Payot, Antoine
- Roy, Marie-Sylvie
- Simard, Marie-Noelle
- Veilleux, Annie
- Wei, Shuqin