Overview

My lab is studying fetal development under normal conditions, and with pregnancy complications impairing fetal health. Recent techniques to study fetal development in various animal species while the fetus lies undisturbed in its intrauterine environment, and the development of non-invasive methods to monitor the human fetus, such as ultrasound, has greatly increased understanding of fetal life. However, there is much to learn, particularly about fetus response to unfavourable conditions within the uterus, such as reduced supply of oxygen and other nutrients.

A second area of interest is the factors that determine the extent to which the fetus is exposed to drugs, particularly those administered during pregnancy to treat medical and obstetric complications such as pre-eclampsia, preterm labor, epilepsy, and clinical depression. These drugs can cause unwanted effects in the fetus, and the extent of this depends partly upon the drug concentration in the fetus. We are looking at factors that affect the drug disposition in the mother and fetus, and effects of drugs on fetal functions.

Research

Postnatal consequences of prenatal exposure to psychotropic medications
Maternal clinical depression is a significant complication of pregnancy and the postpartum period, and if untreated puts the mother and infant at risk. The most common treatment of depression is administration of selective serotonin reuptake inhibitors (SSRIs), such as Prozac and Paxil. While these drugs are very effective for the treatment of depression and various other psychiatric disorders, their effects on the serotonin systems in the brain could have impacts on brain function and development of the fetus and newborn, which are exposed to maternally administered SSRIs via the placenta and breast milk, respectively. Our previous research has demonstrated effects of these drugs on brain function in fetal sheep and on postnatal behaviour in infants. The current project involves longer-term follow-up of infants exposed to SSRIs in utero, to determine if the alterations in behaviour observed in the newborn period persist in older infants.

Mechanism of parturition
Preterm delivery is a major complication of human pregnancy, and is the cause of a large proportion of perinatal mortality and morbidity. Incomplete understanding of the mechanisms of both term and preterm labor hampers the development of effective treatments for this condition. Pregnant sheep have been commonly used to study mechanisms of labor onset and in this species the mechanism of labor onset was thought to have been well worked out. However, we have obtained recent evidence for an alternative mechanism that seems more similar to what appears to occur in the human. The aim of the project is to provide unequivocal evidence for this new mechanism of parturition in sheep.

Developmental pharmacokinetics of drugs in the brain
Many drugs administered during pregnancy and to newborn infants affect brain function. The blood-brain and blood-cerebrospinal barriers are important for regulating the interior milieu of the brain. While there is considerable information on the development of these barriers in terms of hydrophilic compounds, data on lipophilic compounds, including drugs, are much more limited. This project examines brain extracellular fluid and cerebrospinal fluid concentrations of drugs in relation to pre and postnatal development in sheep.