The authors present a new approach for evaluation and counseling of teratogenic risk, The Motherisk program in Toronto presently deals with 60 inquiries per day from the public and health professionals. Most calls are answered through the telephone, and 16-20 women per week are scheduled for our clinic following exposure to known or suspected teratogens, to new drugs with sparse information, to chronic drug therapy, or drugs of abuse. Also seen in clinic are women who want to be counseled or whose physicians want them to meet us due to high levels of anxiety. Since its inception in 1985 the Program has been very effective in preventing unnecessary terminations of otherwise wanted pregnancies. In addition to the clinical service we followup the outcome of these prospectively collected exposures, thus creating a large data base necessary to verify safety/risk of various agents. During the last 2 years Motherisk has completed singly, or in collaboration, large prospective studies on gestational exposure to lithium, antiepileptics, cocaine, and fluexitime. To study the reproductive risks of cocaine we compared first-trimester exposure to cocaine with two control groups. Infants exposed to cocaine did not have higher rates of any adverse perinatal outcome. Their cognitive function at 18 months of age was identical to the control infants. Meta analysis of all studies assessing gestational risks of cocaine reveals that the results of these studies were dependent on the type of comparison conducted. When babies exposed to cocaine were compared with middle class nonusers, the cocaine groups seemed to be more often different from their controls.(ABSTRACT TRUNCATED AT 250 WORDS)
Children exposed in utero to cocaine are at risk for long-term neurobehavioral damage not just because of the drug itself; but also because of clustering of other health determinants, including low socioeconomic status, low maternal education, and maternal addiction, to mention a few. One methodologic approach to separate the direct neurotoxic effects of cocaine from these synergistic insults is to follow up a cohort of children exposed in utero to cocaine and given up for adoption to middle-upper class families. The Toronto Adoption Study, supported by Health Canada, has proven the direct neurotoxic effects of cocaine on IQ and language. These effects are mild to moderate as compared to those measured in children exposed in utero to cocaine and reared by their natural mothers.
To determine the effect of first trimester cocaine use on pregnancy outcome we conducted a prospective cohort study of 30 women admitting to social cocaine use (SCU) during early pregnancy, 20 users of cannabis during the first trimester and 30 matched recreational drug-free control subjects. The groups were of similar age, marital status, and obstetric history and were predominantly white. They were of similar socioeconomic status (SES), however the spouses of the cocaine users were of significantly lower SES than those of both control groups (p less than 0.005). The number of years of education of the cocaine users and the fathers of the SCU-exposed fetuses was significantly lower than that of the recreational drug-free control subjects (p = 0.004), however, female IQ was similar among the three groups (109.1 +/- 12.4 cocaine; 109.1 +/- 25.2 cannabis; 114.1 +/- 11.7 drug-free). Alcohol and cigarette use was greater among the cocaine users than among subjects of the recreational drug-free control group (p less than 0.025). Cocaine and the associated lifestyle were not associated with any adverse obstetric or neonatal endpoint (pregnancy weight gain, incidence of delivery complications, gestational age, birth weight, Apgar scores, and rates of major and minor malformations). There were no differences between groups in attaining developmental milestones. Mental and motor scores on the Bayley Scales of Infant Development and Vineland Adaptive Behavior Scales were identical among the three groups, studied at a mean of 19.7 months of age. We conclude that outcome of pregnancy of social cocaine users and subsequent infant physical and cognitive development are within normal limits at 1.6 years of age.
There has been an increasing use of cocaine in North America among women of reproductive age. The potential effects of cocaine on the fetus have raised serious concerns about the health of large numbers of children exposed in utero to the drug. Using neonatal hair and urine tests for benzoylegconine (BE), we quantified the incidence of fetal exposure to cocaine among 600 babies born in 3 nurseries in Toronto from 1990-91. A total of 37 babies (6.25%) tested positive for cocaine exposure by either hair test, urine test, or both. The hair test detected 33 cases and failed to identify 4 babies who had low urine concentrations of BE. The urine test failed to identify 76% of the cases. In downtown Toronto, the overall rate of fetal exposure to cocaine was 12.5% (25/200), significantly higher than in the 2 suburban nurseries (3%; 12/400). Babies are born with hair which has grown during the last trimester of pregnancy; hence, our analysis identifies women who have used cocaine long after they became aware of pregnancy. Our figures translate to more than 5,000 babies annually in the greater Toronto area who are cared for postnatally by mothers regularly using cocaine. Because history and urine testing during delivery fail to identify the majority of these cases, most of these children are not likely to receive the appropriate medical and social services and follow-up.
To review the reports of fatal adverse drug reactions (ADRs) submitted to the Ontario Medical Association Adverse Drug Reactions Monitoring Program between 1990 and 1994; to identify drugs associated with fatal outcomes; and to assess the causative role of the drug in these events and the completeness of the data in these reports.
Drug(s) identified on each ADR report as being responsible for the reaction were considered. Agents were classified by the Anatomical Therapeutic and Chemical classification system. The causality of each ADR report was evaluated by using an algorithmic rating scale.
From the Ontario Medical Association database, 97 cases of ADRs that resulted in death were reviewed. One hundred fourteen medications were implicated as "suspect" drugs in the 97 deaths. The most commonly implicated drug classes were musculoskeletal agents, blood and blood-forming organ agents, and nervous system agents. Patients over 65 years of age comprised 60% of this series. After independent assessment as to causality, 13% of the cases were rated as probable, 86% were rated as possible and 1% were rated as doubtful. Seventy per cent of reports did not include information regarding medical history. Forty-two per cent of cases failed to provide adequate information to evaluate the feasibility of the time to onset of the ADR. The use of concomitant drugs was not reported in 12% of cases.
The drugs most frequently implicated in fatal ADRs were consistent with those reported in other studies. Algorithmic causality assessments were of limited value in these reports. The completeness of the reports and adequacy of the information were poor. The type of reporting forms and information provided were not homogenous. There is a need to improve quality of reporting and harmonize reporting forms between monitoring bodies. The feasibility of unique data collection forms and obligatory reporting for fatal ADRs should be considered.
OBJECTIVE: To compare the overall utilisation pattern of lipid-lowering drugs between 1990 and 1994 in Australia, Finland, Italy, Norway and Sweden as well as the pattern of use with respect to age and gender in Italy and Sweden. METHODS: Data were retrieved from regulatory authorities in each country for the 5-year period and analysed according to the ATC/DDD methodology (Anatomical Therapeutic Chemical classification/Defined Daily Doses). Utilisation was calculated as the DDDs for 1000 inhabitants per day for all drugs of the ATC category B04 (serum lipid-reducing agents). Data from Sweden and Italy were also compared with respect to gender and age. RESULTS: In 1994, Australia demonstrated the highest degree of utilisation (11.9 DDD) and the Nordic Countries the lowest (Sweden 5.6; Norway 4.9; Finland 4.0). In all countries except Italy, a steady increase was observed; in Italy, utilisation of these drugs reached a maximum in 1992 (11.5 DDD), but then underwent a reduction which was caused by restrictions in the reimbursement status in 1993 (10.4) and 1994 (6.7). Administration of statins increased in all countries, becoming the most used group of the B04 class. In 1988, the number of different drugs listed by each national health service ranged from 4 (Norway) to 16 (Italy); in 1994 it ranged from 6 (Norway) to 9 (Sweden). Analysis with respect to gender showed the opposite pattern in Sweden (males 4.6 and females 3.3 in 1992; 6.2 and 4.5, respectively, in 1994) than in Italy (males 10.8 and females 17.8 in 1992; 6.4 and 9.2, respectively, in 1994). Exposure was highest in people aged 60-69 years in both countries, followed by age group 50-59 in Sweden and 70-79 in Italy. CONCLUSIONS: Large variations in the utilisation of lipid-lowering drugs exist between countries, with Australia and Italy much higher than others. Of the drugs in the ATC category B04, the use of statins predominates in all countries, but to varying degrees. The large difference in the degree of drug utilisation with respect to age and gender between Italy and Sweden suggests major deviations from evidence-based medicine.