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Neurodevelopment of Children Exposed in-Utero to Chemotherapy for Maternal Breast Cancer (Dr. I Nulman)
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Study seeks women between 4 and 12 weeks in their pregnancy with morning sickness (NVP)
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Motherisk Newsletters: Winter 2001, No. 13
Motherisk researchers have concluded that exposure during pregnancy to venlafaxine, a relatively new and increasingly popular antidepressant drug, does not increase the chances of major birth defects.
The Motherisk study, published in the October issue of The American Journal of Psychiatry, demonstrates that the use of venlafaxine does not increase the rates of major malformations above the expected baseline rate of one to three per cent.
This is the first study to evaluate the safety of this drug during pregnancy. The study was able to ascertain the outcomes of 150 pregnancies after exposure to venlafaxine from women in seven different geographical centres. All of the women used the drug in the first trimester with 34 using it throughout their pregnancies.
Two additional comparison groups of women were used in the study, with one group taking medications including fluoxetine, sertraline, fluvoxamine and paroxetine. The other group of women were exposed to nonteratogenic drugs including, loperamide, echinacea, sumatriptin and dextromethorphan. Factors such as age, smoking status and alcohol intake were taken into consideration. Most women were followed up between six to 12 months after delivering their babies.
Of the 150 pregnancies followed, there were 125 live births, 18 spontaneous abortions and 7 therapeutic abortions. Among the group using venlafaxine, two major malformations occurred. In the two comparison groups, there were three major malformations (among the group taking fluoxetine, sertraline, fluvoxamine or paroxetine) and one major malformation (among the group exposed to nonteratogenic drugs). The results suggest there is not an increased risk for major malformations above the baseline rate of one to three per cent.
"A substantial number of women of child bearing age suffer from depression and coupled with the fact that at least 50 per cent of pregnancies are unplanned, it is likely women may use venlafaxine in early pregnancy. We have found that some women may choose to abort a wanted pregnancy due to the lack of information on the safety of a particular drug. In another one of our studies, due to the lack of information, a number of women elected to abruptly discontinue needed antidepressants after pregnancy was diagnosed," said Adrienne Einarson, the study's lead author and the assistant director of the Motherisk program at The Hospital for Sick Children.
"Women who have been diagnosed with depression prior to becoming pregnant and are being successfully treated, should not feel they have to automatically stop their medications as soon as a pregnancy is confirmed. Failure to treat depression during pregnancy can have serious ramifications for both the mother and child. This evidence-based information can be helpful to women and their health professionals when making a decision whether or not to treat depression with this particular drug during pregnancy," Einarson added.
Funding for this research was provided by The Hospital for Sick Children Foundation and an educational grant from Wyeth-Ayerst.
|A. Einarson||P. Mastroiacovo|
|B. Fatoye||A. Addis|
|M. Sarkar||D. Matsui|
|S.V. Lavigne||L. Schuler|
|J. Brochu||T.R. Einarson|
|C. Chambers||G. Koren|
Motherisk researchers have recently completed a study in collaboration with the Department of Ophthalmology here at The Hospital for Sick Children, and Department of Medicine, University of Toronto. The study, entitled Ocular toxicity and antenatal eposure to chloroquine or hydroxychloroquine for rheumatic diseases, was published in the September 8th issue of Lancet.
The study looked at the fetal safety of maternal use of chloroquine and hydroxychloroquine. These medications are increasingly used to treat rheumatic diseases such as lupus. They are effective but are known to cause eye damage in patients receiving them. The drugs permeate the tissues of the eye and can cause degenerative changes that lead to loss of visual function.
There was concern that if a pregnant woman took them during pregnancy, the medication could affect the eyes of the unborn child. This study builds on previous research that indicates the medication does not cause birth defects.
The study completed by the Motherisk program followed 21 children between the ages of two-months and 10 years, who were exposed to the drugs in utero. Ophthalmologists led by Dr. J. Ray Buncic, Opthalmologist in Chief at the Hospital for Sick Children examined all the children in detail. No evidence of eye abnormality or visual malfunction, including acuity and colour vision, were found.
is the first study to suggest the eye safety of these effective
medications. The study was a typical collaboration between
pediatricians in the Motherisk program, ophthalmologists, and
rheumatologists who care for those women.
|G. Klinger||K.A. Spitzer|
|Y. Morad||G. Koren|
|C.A. Westall||S. Ito|
|C. Lakin||L. Schuler|
|J. Brochu||R.J. Buncic|
Researchers at The Hospital for Sick Children (HSC) and the University of Toronto have linked exposure to organic solvents during pregnancy to an increased risk of visual defects in exposed offspring. Organic solvents are chemicals found in paints, adhesives, lacquers and cleaning agents, and are used in industries such as dry cleaning, printing, and plastics manufacturing. This research was published in the September issue of the journal Teratology.
"We decided to look at the effects of prenatal exposure to organic solvents on child's vision because visual system impairment, including colour vision loss and reduced contrast sensitivity, is commonly associated with occupational exposure to organic solvents in adults," said Christine Till, the study's lead author and a University of Toronto graduate student. "We wanted to see if similar visual deficits would be found in children regularly exposed to organic solvents in the womb."
Till worked with a multidisciplinary team of researchers at The Hospital for Sick Children, including Dr. Carol Westall, an optometrist, electrophysiologist and vision scientist, Dr. Joanne Rovet, a neuropsychologist and senior scientist, and Dr. Gideon Koren, pediatrician, toxicologist and director of the Motherisk Program.
The study compared 32 children of women who were exposed occupationally to organic solvents during pregnancy between 1992 and 1996 with a matched control group. Participants were recruited from the Motherisk Program, a consultation service for pregnant or lactating women and their health care providers concerning the fetal risks associated with drug, chemical, infection, disease and radiation exposure during pregnancy.
Overall, the solvent-exposed children had poorer vision and problems with colour vision compared with the control group. The visual impairment may also be a marker of further central nervous system damage.
This research builds on an earlier Motherisk study that found an increased risk of major birth defects from occupational exposure to organic solvents during pregnancy, which was published in The Journal of the American Medical Association in 1999.
"We will now be looking at a larger, more comprehensive study to look at the risk of specific types of organic solvents and the levels of occupational exposure. This research may help delineate guidelines on safe levels of exposure for pregnant women," said Dr. Koren, director of Motherisk and a senior scientist in The Hospital for Sick Children Research Institute.
This research was supported by the Canadian Institutes of Health Research (CIHR), the Natural Sciences and Engineering Research Council of Canada (NSERC), The Hospital for Sick Children Foundation, and The Physicians Services Incorporated Foundation.
On September 7, 2001, the Brewers Association of Canada hosted an all-day Roundtable on fetal alcohol syndrome (FAS). Attended by industry and government representatives, as well as researchers, clinicians and community workers, the objective was to review current research and clinical activities, and identify interventions that offer the best hope of preventing FAS. Much of what was discussed will soon be available in a Summary of Proceedings.
Motherisk reported on research that ranged from molecular mechanisms, to population health and health economy, including current research on:
- The role of acetaldehyde in FAS.
- The use of meconium to identify heavy maternal drinking.
- Ecstasy use by young pregnant women.
- Use of marijuana for morning sickness by pregnant women.
- Refining a diagnostic list for FAS/FAE.
- The effects of labeling of alcohol beverages.
- The cost of FAS - Canadian perspective.
- The quality of life of children afflicted by FAS
Other research topics are now in their planning stage, including:
- The use of antioxidants to ameliorate fetal alcohol damage.
- The use of Ritalin for attention deficit disorder in children with FAS.
For more information on any of these research activities, or how to obtain a copy of the FAS Roundtable Summary of Proceeding, please call (416) 813-8084 or send an e-mail message.
The revised and expanded third edition of Maternal Fetal Toxicology, A Clinician's Guide, is now available. Edited by Gideon Koren, MD, this text book has been recognized as "...the most authoritative reference on the subject of human gestational toxicology in existence. It should be on the bookshelf of every health professional who may be faced with questions or decisions related to the potential problems of substance exposure during pregnancy." Pediatric Therapeutics & Toxicology
This reference presents a problem-based approach to the teratogenic risks of exposure to drugs, chemicals, viruses, and radiation during pregnancy-containing updated material on treatment programs and management approaches, as well as systematic reviews and meta-analyses of specific xenobiotics.
Summarizing recent large-scale prospective studies on the safety of drugs in pregnancy, initiated by the Motherisk Program in Toronto in collaboration with several American services, the Third Edition of Maternal-Fetal Toxicology provides:
- a guide for herbal products in pregnancy
- the latest analysis on alcohol consumption during pregnancy and
- the diagnosis of fetal alcohol syndrome
- timely information for the evaluation of fetal safety in chemical industries
- up-to-the-minute treatment for epilepsy and other chronic conditions in pregnancy
- current management of the neonatal abstinence syndrome
- modern uses of herbal medicine in pregnancy and during lactation, and more.