Overview

The early treatment of fetal diseases in-utero may lead to improved outcomes for these babies. Integral to any early treatment program is the ability to evaluate the structure and physiology of the fetus in utero, both in normal and abnormal situations, as well as the animal models where therapies/theories can be tested prior to application in humans. My research interest attempts to meld all three areas towards the common goal of improved fetal therapy. Therefore, my research involves two main areas: prenatal ultrasound/imaging with regards to fetal diagnosis, disease and normal physiology; and the use of the fetal sheep model to investigate novel therapeutic approaches.

Research

Flow-mediated vasodilation
The endothelium is an organ involved in a variety of functions: it regulates vascular tone, permeability, coagulation, inflammation and smooth muscle proliferation in order to maintain normal tissue perfusion and a quiescent vascular wall. The predominant effect at rest is thought to be maintenance of low arterial tone by the production of mediators that regulate peripheral resistance. The best-studied mediator of endothelial function is nitric oxide (NO). NO synthesis and release is stimulated by a number of circulating factors that act through specific membrane receptors and also by increased blood flow, which causes an increase in shear stress on the endothelial cell. NO diffuses into the adjacent smooth muscle cells where it increases cGMP, resulting in lowered intracellular calcium and muscular relaxation. The biological half-life of NO is about 15 seconds, allowing rapid changes in smooth muscle tone. It is thought that endothelial function is increased in pregnancy, explaining why pregnancy is associated with lower blood pressure despite a larger blood volume and cardiac output and reduced sensitivity to circulating pressors. A number of techniques have been used to assess the ability of the endothelium to regulate the lumen of blood vessels. Flow-mediated dilatation (FMD) measures endothelium­-mediated vasodilation in conduit arteries using high-resolution ultrasound of the brachial artery. This study is to examine the changes in flow-mediated vasodilation between diabetic and euglycemic pregnant women

In-utero drug administration in the fetal sheep model
The goal of in-utero fetal therapy is to improve child health by early recognition and treatment of diseases. Many conditions affecting babies prior to birth are easily diagnosed, and many are amenable to in-utero treatment. For example, some babies develop abnormally fast heart rates (super-ventricular tachycardia) while still in the mother's womb; if left untreated this will likely result in fetal death. Although the main route to administering medicine to the fetus is through the maternal blood stream (uterus/placenta), this route is sometimes unavailable or ineffective in achieving adequate drug levels if the fetus is quite ill. Also, transplacental administration of medication to the fetus exposes the mother to medication toxicity, as high drug levels in the mother are often needed to achieve therapeutic levels in a fetus. This project will explore alternative avenues for delivering medicine to babies prior to birth. We propose to compare three different methods of in-utero drug delivery of Digoxin in the fetal lamb model.

The prenatal detection of congenital heart disease
Congenital heart disease (CHD) is one of the most common birth defects. Prenatal detection allows parents to be informed about their child's condition and to arrange for delivery in a tertiary care centre with full cardiac services. There is growing evidence that outcomes in children with CHD are improved with prenatal detection and planned delivery in a specialized centre. Second trimester prenatal ultrasound has been the primary screening tool in detecting CHD. Unfortunately, the standard views imaged this way only detect 20-50% of CHD. This pilot project will answer questions about the efficacy of second trimester scanning to detect CHD and whether modification of this scan by adding several ultrasound markers of CHD will enhance the detection rate.

Grants

CIHR Operating Grant - Project: "The Canadian STRIDER Trial: sildenafil for dismal prognosis IUGR" (2014-2019)

Research Group Members

Mohamed Elgendi
Larry Li
Chirag Kariya
Daria Hutchinson