Biomedical subjects
Publications and source records attributed to Irena Nulman.
Significant numbers of therapeutic abortions are performed for radiation-exposed pregnant women because of concerns about the teratogenic risk. However, available data suggest that current diagnostic radiation procedures are not teratogenic.
QUESTION: Increasing numbers of pregnant patients are treated with valproic acid, not just for epilepsy, but also for psychiatric conditions. Are there teratogenic risks other than the risk of spina bifida? ANSWER: It has now become evident that valproic acid might cause more than just neural tube defects (NTDs). In a systematic review of all cohort studies intended to answer this question, higher rates of major malformations (and not just NTDs) were found in most studies. The calculated relative risk was 2.59 when compared with other antiepileptic drugs and was 3.77 when compared with risk in the general population. There is compelling evidence that the risk is dose dependent. The risks appear to begin increasing at doses of 600 mg/d and to become more prominent at doses above 1000 mg/d.
Despite an accumulating body of evidence demonstrating that the visual system is an important target for organic solvent toxicity in adults, little attention has been paid to the visual functioning of children with prenatal exposure to organic solvents. The present study aimed to: (1) determine prospectively whether prenatal solvent exposure increases the risk of visual deficits in infants and (2) assess the relationship between estimates of exposure level and integrity of visual responses. A sample of 21 infants born to women who were occupationally exposed to solvents during pregnancy was compared with 27 non-exposed age-matched control infants. All mothers were recruited from Motherisk, an antenatal counseling service in Toronto, Canada. Contrast sensitivity and grating acuity were assessed using a sweep visual evoked potential (VEP) technique whereas chromatic- and achromatic mechanisms were assessed using a transient VEP technique. Exposure level was estimated from questionnaire data obtained during pregnancy. Testers were masked to exposure status. Results showed a significant reduction in contrast sensitivity in the low and intermediate spatial frequency range in solvent-exposed infants compared to controls (p<0.001). With respect to grating acuity, there was a significant effect of exposure level, with children in the high exposed having reduced grating acuity compared with children in the low exposed group (p<0.025) and controls (p=0.02). Regarding color vision, 26.3% of infants in the exposed group versus 0% of the controls produced abnormal VEP responses to the red-green onset stimulus (p<0.01), but not to either blue-yellow or achromatic stimuli. No differences were found with respect to latency or amplitude of chromatic and achromatic response. These findings suggest that prenatal solvent exposure is associated with selective visual deficits, including reduced contrast sensitivity and abnormal red-green vision. Increasing levels of exposure may lead to further visual deficits affecting grating acuity. These findings support the need for a re-evaluation of current occupational exposure standards for pregnant women.
BACKGROUND: It is widely quoted that women with epilepsy have a higher than baseline risk for giving birth to a child with malformations, independent of the effects of antiepileptic drugs. OBJECTIVE: To determine, based on available evidence, if epilepsy per se represents a teratogenic risk. To systematically review all studies investigating the occurrence of major malformation rates among children of treated or untreated women with epilepsy and non-exposed controls who do not have epilepsy. METHODS: A meta-analysis, using a random effects model, was conducted of all cohort and case-control studies reporting malformation rates in children of women with epilepsy exposed or unexposed to antiepileptic drugs compared with that of children of nonepileptic women. Medline (1966-2001), EMBASE, the Cochrane database as well as REPROTOX (an information system on environmental hazards to human reproduction and development) databases were accessed. RESULTS: We found ten studies reporting results of untreated epilepsy (n = 400) and their non-epileptic healthy controls (n = 2492). Nine out of ten studies also reported results on 1443 patients exposed to antiepileptic drugs and their 2526 unexposed healthy controls. The risk for congenital malformations in the offspring of women with untreated epilepsy was not higher than among nonepileptic controls (odds ratio [OR] = 1.92; 95% CI 0.92-4.00). There was evidence of publication bias, thus with bias removed the OR was 0.99 (95% CI 0.49-2.01). In contrast, the offspring of epileptic women who received antiepileptic drugs had higher incidences of malformation than controls (OR 3.26; 95% CI 2.15-4.93). CONCLUSION: Our study does not support the commonly held view that epilepsy per se represents a teratogenic risk. Our study suggests that this view is the result of a publication bias, with several small (< 100 participants) positive studies leading to a premature conclusion.
Explore the source record for details and available documents.
BACKGROUND: We assessed the effects and safety of aspirin treatment during pregnancy on fetal and neonatal outcomes. METHODS: We searched MEDLINE (1966-2001), EMBASE (1980-2000), TOXLINE (1994-2000), EB M Cochrane Database of Systematic Reviews (1991-2000), Reproductive Toxicology (2001), teratology texts, and bibliographies of all the included studies. We looked for published randomized controlled studies reporting aspirin treatment to improve outcomes of moderate- and high-risk pregnancies. The key words used to search for articles about exposure to aspirin were salicylic acid, pregnancy, and pregnancy complications; key words used to search for outcome were neonatal diseases and abnormalities. Based on our search strategy, 1904 citations were identified; their titles and abstracts were reviewed by one reviewer. Of these citations, 182 papers were selected for detailed review. Two reviewers independently determined whether a study should be included in the final analysis. In cases of disagreement, the decision was based on the assessment of a third reviewer. RESULTS: Data were extracted independently by each reviewer. We calculated the pooled relative risk (RR) or weighted mean difference and 95% confidence intervals (CI), assuming a random-effect model. Thirty-eight studies met the inclusion criteria. The risk for miscarriage did not differ between women treated with aspirin andplacebo (seven studies; RR, 0.92; 95% CI, 0.71-119). Women who took aspirin had a significantly lower risk of preterm delivery than did those treated with placebo (22 studies; RR, 0.92; 95% CI, 0.86-0.98). There was no significant difference in perinatal mortality (20 studies; RR, 0.92; 95% CI, 0.81-1.05) and in the rate of small-for-gestational-age infants (12 studies; RR, 0.96; 95% CI, 0.87-1.07) among offspring of mothers treated with aspirin and those of mothers treated with a placebo. CONCLUSION: For women with moderate- and high-risk pregnancies, aspirin treatment seemed to have a small but significant effect on reducing the rate of preterm deliveries, but did not reduce the rate of perinatal death.
BACKGROUND: Alcohol is the most widely used drug in the world that is a human teratogen whose use among women of childbearing age has been steadily increasing. It is also probable that Fetal Alcohol Syndrome is under diagnosed by physicians. The objectives of this study were twofold: 1) to evaluate the experience, knowledge and confidence of family physicians with respect to the diagnosis of FAS and 2) to evaluate physicians awareness of maternal drinking patterns. METHODS AND PARTICIPANTS: A multiple choice anonymous questionnaire was sent to a randomly selected group of family physicians in the Metropolitan Toronto area. RESULTS: There was a 73% (75/103) total response rate; Overall, 6/75 (8%) of family physicians reported that they had actually diagnosed a child with FAS. 17.9% had suspicions but did not make a diagnosis and 12.7% reported making a referral to confirm the diagnosis. Physician rated confidence in the ability to diagnosis FAS was low, with 49% feeling they had very little confidence. 75% reported counselling pregnant women and 60.8% reported counselling childbearing women in general on the use of alcohol. When asked what screening test they used to detect the use of alcohol, 75% described frequency/quantity. Not a single respondent identified using the current accepted screening method for alcohol use (TWEAK) which is recommended by The Centre for Addiction and Mental Health. CONCLUSIONS: Family physicians do not feel confident about diagnosing FAS. None of the physicians were aware of the current screening methods to accurately gage alcohol use in pregnant and childbearing women.
OBJECTIVE: The purpose of this study was to determine, on the basis of published reports, whether aspirin use during the first trimester of pregnancy is associated with an increased risk of congenital malformations. STUDY DESIGN: We reviewed the literature for published studies that reported exposure to aspirin during the first trimester of pregnancy and congenital malformations. Two reviewers independently determined whether a study should be included in the final analysis and extracted the data. We calculated the pooled odds ratio and 95% CI. RESULTS: Twenty-two studies met the inclusion criteria. In the eight studies that reported an overall risk, the risk of congenital malformations in offspring of women who were exposed to aspirin was not significantly higher than that in control subjects (odds ratio, 1.33; 95% CI, 0.94-1.89). However, a significantly increased risk of gastroschisis (odds ratio, 2.37; 95% CI, 1.44-3.88) was found. CONCLUSION: We found no evidence of an overall increase in the risk of congenital malformations that could be associated with aspirin. Aspirin exposure during the first trimester may be associated with an increased risk of gastroschisis.
OBJECTIVE: Previous work suggested that first-trimester exposure to tricyclic antidepressants or fluoxetine does not affect adversely child IQ and language development. However, many women need antidepressants throughout pregnancy to avoid morbidity and suicide attempts. Little is known about the fetal safety of tricyclic antidepressants and fluoxetine when taken throughout pregnancy. The goal of this study was to assess the effects of tricyclic antidepressants and fluoxetine used throughout gestation on child IQ, language, and behavior. METHOD: In a prospective study, mother-child pairs exposed throughout gestation to tricyclic antidepressants (N=46) or fluoxetine (N=40) and an unexposed, not depressed comparison group (N=36) were blindly assessed. The three groups were compared in terms of the children's IQ, language, behavior, and temperament between ages 15 and 71 months. The authors adjusted for independent variables such as duration and severity of maternal depression, duration of pharmacological treatment, number of depression episodes after delivery, maternal IQ, socioeconomic status, cigarette smoking, and alcohol use. RESULTS: Neither tricyclic antidepressants nor fluoxetine adversely affected the child's global IQ, language development, or behavior. IQ was significantly and negatively associated with duration of depression, whereas language was negatively associated with number of depression episodes after delivery. CONCLUSIONS: Exposure to tricyclic antidepressants or fluoxetine throughout gestation does not appear to adversely affect cognition, language development, or the temperament of preschool and early-school children. In contrast, mothers' depression is associated with less cognitive and language achievement by their children. When needed, adequate antidepressant therapy should be instituted and maintained during pregnancy and postpartum.