CHU Sainte-Justine Université de Montréal

Research projects

Use of SNRIs, bupropion, and mirtazapine during pregnancy and the risk of persistent pulmonary hypertension.

Antidepressants are among the most prevalent medications used during pregnancy (14%).  Among widely prescribed antidepressants, we find serotonin-norepinephrine reuptake inhibitors (SNRIs), bupropion, and mirtazapine. There are very few data available on the impact of the use of these medications during pregnancy. Recent studies have shown an association between the use of antidepressants during pregnancy and an increased risk of spontaneous abortion, major congenital malformations, preterm birth, low birth weight and slower cognitive development. Special attention was given to persistent pulmonary hypertension of the newborn (PPHN), a serious condition leading to disability and mortality.

The aims of this study are to quantify the association between 3 antidepressants (SNRIs, bupropion and mirtazapine) during pregnancy and the risk of: 1) PPHN, and 2) congenital heart defects. This study will be performed using two Canadian databases (Quebec pregnancy cohort and Saskatchewan database) and an American database (US Medicaid cohort).

Funding

Canadian Institutes of Health Research (CIHR)

HAART use during pregnancy and the risks of HIV transmission to the newborn, congenital malformations, and neonatal death.

The number of Canadians infected by HIV is increasing every year. At the same time, highly active antiretroviral therapy (HAART) is known to increase life expectancy. This means that we now observe an increasing number of HIV-positive women giving birth while on HAART. Available data shows that the mother-to-child transmission rate in developed countries has greatly diminished since HAART became available. The Canadian Pediatric AIDS Research Group (CPARG) showed that in the early 1990’s, 50 to 80 newborns each year were exposed to HIV during gestation. Over 2,851 newborns were exposed to HIV between 1984 and 2008, of whom 285 (18.3%) were infected.

The only available data on the safety of HAART during pregnancy comes from pharmacovigilance databases. These are partial data on adverse effects of HAART use during pregnancy. The aim of this study is to measure the impact of HAART initiation in the first trimester of pregnancy and the risk of mother-baby transmission and to compare these to second-trimester and third-trimester initiation in women infected with HIV. We will also be able to estimate the risk of congenital malformations and neonatal death in HAART users during the first trimester as compared to non-HAART users, after adjusting for HIV status. This study will be performed using two Canadian databases (the Quebec pregnancy cohort and Saskatchewan database) and an American database (US Medicaid cohort).

Founding

Canadian Institutes of Health Research (CIHR)

Obstetric follow-up standardized forms: Pilot study on the feasibility of computerizing medical records of pregnancy follow-up and delivery at CHU Sainte-Justine and the linkage of data with the Quebec Pregnancy Cohort.

Quebec is the second-largest province in Canada after Ontario with respect to number of births, with about 23% of all Canadian births. Nonetheless, Quebec has not established an electronic database of obstetric follow-up and delivery. However, in Quebec, standard forms (Feuilles 1,2,3+) are used for obstetric follow-up. Clinical data for this pilot project will be collected from the standard forms found in the women’s obstetric follow-up and delivery charts.

The aim of this project is to determine the possibility of matching perinatal clinical data collected from the charts of women who gave birth at CHU Ste-Justine between 2005-2008 with data from the  Quebec Pregnancy Cohort.

Funding

Researcher’s funds

Assisted reproductive technology (ART), including ovarian stimulation, and the risk of major congenital malformations – the AtRISK study.

Assisted reproductive technology (ART) encompasses all types of fertility treatments, including ovarian stimulation with or without intrauterine insemination (IUI) or assisted reproductive technologies (ART). The latter procedures include in vitro fertilization (IVF) and related procedures such as intracytoplasmic sperm injection (ICSI).

Infertility is a growing social and public health concern. Over 15% of women aged 15-44 have received services related to infertility. In North America and Europe, 1-3% of children are born following the use of ART. In Canada, 23,722 treatment cycles involving ART were reported by the Canadian Assisted Reproductive Technologies Registry in 2011, representing a marked increase of 29% since 2010.

Given the Quebec implementation of a publicly funded medically assisted reproduction program in 2010, we would expect a significant increase in the use of ART. However, there is not much data regarding the risk of major congenital malformations with the use of these technologies, and even less information on women using ovarian stimulation only. The increasing proportion of babies born through the use of ARt implies a need for closer monitoring.

The objective of this study was to quantify the risk of major cardiovascular, urogenital, musculoskeletal, and other congenital malformations associated with ART in the TWINPREG cohort.

Funding

This study was supported by the Drug Safety and Effectiveness Network (DSEN) and the Canadian Institutes of Health Research (CIHR).

Use of ovulation induction alone, intrauterine insemination, and assisted reproductive technologies and the risk of multiple births the TWINPREG study.

Following the implementation of a publicly funded medically assisted reproduction program in Quebec in 2010, it is expected that the number of treatment cycles will triple. One of the major medico-economic consequences of infertility treatments is the increase in multiple births. Multiple gestations are mainly attributable to multiple embryo transfer during in vitro fertilization. An elective single embryo transfer (eSET) strategy was implemented in several countries, and recently by the Quebec government, to decrease the rate of multiple gestation. Infertility treatments using ovarian stimulation alone or with artificial insemination do not require embryo transfer and are more frequently prescribed. However, little information is available on the incidence of multiple gestation associated with the use of ovarian stimulation alone.

The objective of this study is to estimate the risk of multiple birth associated with the use of each type of medically assisted reproduction technology (ovarian stimulation, intrauterine insemination and in vitro fertilization) in a cohort built from the linkage of medical, hospital, pharmaceutical, and birth databases in Quebec. We will also include maternal self-reported data on lifestyle factors and the use of medically assisted reproduction technologies. The linkage between administrative data and self-reported in formations obtained from the mother were used to create the  TWINPREG cohort.

Funding

This study was supported by le Ministère de la Santé et des Services sociaux du Québec (MSSS).

Antidepressant use during pregnancy and the risk of autism spectrum disorder.

Antidepressants are among the most frequently used medications during pregnancy. It is estimated that up to 14% of women use antidepressants during the gestation period. However, there is little evidence regarding the appropriate use of antidepressants during gestation and the long-term impact of prenatal antidepressants on children’s mental health, autism spectrum disorders (ASD) in particular. Health care professionals should consider the impact of the use of these drugs during pregnancy as well as the risk to the fetus of exposure to maternal depression.

The aims of this study were: 1) to assess the association between gestational exposure to antidepressants and the risk of ASD in children, after accounting for maternal depression; and 2) to quantify the effect of specific classes of antidepressants on the risk of ASD. This study was conducted using the  Quebec Pregnancy Cohort.

Founding

Fonds de la recherche en santé du Québec (FRSQ), Réseau québécois de recherche sur l'usage des médicaments (RQRUM), Réseau FRSQ pour le bien-être des enfants.

Use of antimalarial drugs during pregnancy and the risk of adverse pregnancy outcomes (low birth weight, preterm birth, miscarriage, congenital malformations).

Untreated malaria is a major health concern worldwide. The disease is responsible for 660,000 deaths in children less than 5 years old each year. Malaria during pregnancy causes the deaths of 10,000 women each year. Even though malaria affects 300 to 500 million people, or 7% of the entire healthy population, there is not much data in the literature on the use of antimalarial drugs and antibiotics with antimalarial activity during pregnancy and the risks to the mother and fetus.

The aims of this research project are to: 1) conduct a systematic review and meta-analysis on antimalarial use during pregnancy and the risk of low birth weight; 2) evaluate and quantify the association between the use of antimalarials and antibiotics with antimalarial activity during pregnancy and the risk of spontaneous abortion and congenital malformations; and 3) evaluate the association between antimalarials and antibiotics with antimalarial activity and the risk of depression and gestational hypertension in pregnant women. This research project uses data from the  Quebec Pregnancy Cohort .

Funding

Researcher’s fund

Antidepressant use during pregnancy: maternal health and child development.

Antidepressants are among the most prevalent medications used during pregnancy (14%). At this time, evidence-based data on the effects of continuing vs. discontinuing the use of antidepressants during pregnancy is lacking, both on the overall health of the mother and baby and on the cognitive and behavioural development of the child.

This study looks at the effects of discontinuing antidepressant use during pregnancy, on: 1) the health and behaviour of the mother during and after pregnancy; 2) the cognitive and behavioural development of the infant; and 3) the rates of preterm birth, major malformations, low birth weight, and admission to the neonatal intensive care unit. These different phases are studied using data from the North American field study on antidepressants. Ethics approval was obtained from the CHU Sainte-Justine, Sick Kids Hospital, and Children's Hospital of Western Ontario ethics committees.

Funding

Canadian Institutes of Health Research (CIHR), Fonds de la recherche en santé du Québec (FRSQ), and the Conseil du médicament du Québec.

Parental stress, attachment and development of the child.

Recent studies have shown that prenatal and perinatal stress can impact negatively on both mother and child. Mother-child attachment is very important for infant development. It has been demonstrated that a poor mother-child relationship is associated with health problems and poorer psychosocial and cognitive development of the child. Few studies have looked at the father, however, and none have focused on the impact of stress and attachment on cognitive and behavioural development of one-year-olds whose mother suffered from anxiety disorders and/or depression.

With this research project, we aim to evaluate the effects of parental stress during pregnancy and birth, and of maternal attachment, on the cognitive and behavioural development of one-year-old children. The various phases of this project are studied using data collected from  North American field study on antidepressants.

Funding

Canadian Institutes of Health Research (CIHR), Fonds de la recherche en santé du Québec (FRSQ), and Conseil du médicament du Québec.

Diabetes and pregnancy: Interventions, glycemic control, and risks to the fetus.

Given that type 2 diabetes is increasing and that 50% of pregnancies are unplanned, a growing number of pregnant women are exposed to hypoglycemic agents during the gestation period. However, because of concerns regarding the adequacy of glycemic control and the teratogenic potential of these agents, it is common practice to switch women with diabetes to insulin when pregnancy is diagnosed.

The aims of this study are to compare both glycemic control and the rate of birth defects associated with the use of either insulin or other hypoglycemic agents by pregnant women with type 2 diabetes. This study is conducted using the  Quebec Pregnancy Cohort.

Funding

Fonds de la recherche en santé du Québec (FRSQ), Réseau québécois de recherche sur l'usage des médicaments (RQRUM), Réseau FRSQ pour le bien-être des enfants.

Validation of the use of administrative databases in Quebec to measure drug exposure in pregnant women.

Approximately 60% of pregnant women use prescription drugs during pregnancy. However, pregnant women are excluded from most clinical trials for ethical concerns, so there is no data on the safety of drug exposure in pregnant women before the drug is on the market. Therefore, the collection and follow-up of observational data is the only ethical way to close the knowledge gap between the limited value of animal studies and human pregnancy exposure.

Large administrative databases are increasingly being used in perinatal pharmacoepidemiology and have many advantages but do not provide data on used medications; only data on filled prescriptions are available. Hence the debate on whether these databases provide valid measures of medication use during the gestational period. The completeness of registration and data that are collected prospectively are the main benefits of these databases. Several sources exist to measure maternal drug exposure such as medical records, patient interviews and also prescription fillings from pharmacy records, but there is no true gold standard, as each source is prone to information bias and may result in misclassification of exposure.

At present, few data exists on the concordance between maternal report of medication use and data on prescription fillings provided by administrative databases. The objective of this study was to determine the concordance between pharmacy records on prescriptions filled and maternal report of medication use during pregnancy.