Year: 2014
Type: dissertation
Study design: Observational Study
Abstract: Numerous medical conditions in pregnancy require pharmacotherapy. A conflict between optimal maternal treatment and risk of fetal teratogenicity arises if drug safety is not assured. Behavioural teratology, the science of central nervous system impairments due to a variety of prenatal exposures, is an inseparable part of reproductive drug safety studies and addresses the long-term neurodevelopment of exposed children. Research in behavioural teratology is sparse due to lack of funding priorities and methodological obstacles related to statistical power, cost/time effectiveness, and multiple confounders (with the genetics being the most difficult to control for). Implementing an appropriate study design is critical in overcoming these challenges. Depression is the most common psychiatric disorder in women, and up to 16% of pregnant women with depression require pharmacotherapy. Selective transmitter reuptake inhibitors (STRIs) are widely used to control depression in pregnancy. The objectives of this thesis were to define the long-term neurodevelopment of children exposed in utero to STRI antidepressants and to develop an advanced methodology for behavioural teratology in order to achieve the highest possible degree of evidence. Three studies were conducted using different designs. The first study measured the intelligence of three groups of children exposed in utero to either the serotonin-norepinephrine reuptake inhibitor drug venlafaxine, other STRIs (a disease control), or children of healthy women exposed to non-teratogenic agents. The second study included an additional group of children prenatally exposed to maternal depression, but not pharmacotherapy, in order to separate the effects of maternal depression from the effects of the antidepressant medications. The third study compared long-term neurodevelopmental outcomes of children prenatally exposed to STRIs to their unexposed siblings. It was found that untreated depression is associated with adverse pregnancy outcome and increased rates of postpartum depression. Children of depressed mothers may be at risk of future psychopathology. Factors other than prenatal STRIs strongly predict children's intellect and behaviour. The sibling design was able to better control for genetic and environmental factors, was more cost-effective, and able to achieve more valid results with a much smaller sample size. This novel design should be implemented in behavioural teratology drug safety studies.
Source: TSpace (University of Toronto)
Author: Irena Nulman
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W3152325778