Karen Graham

BIAS AGAINST THE NULL HYPOTHESIS: THE REPRODUCTIVE HAZARDS OF COCAINE

To examine whether studies showing no adverse effects of cocaine in pregnancy have a different likelihood of being accepted for presentation by a large scientific meeting, all abstracts submitted to the Society of Pediatric Research between 1980 and 1989 were analysed. There were 58 abstracts on fetal outcome after gestational exposure to cocaine. Of the 9 negative abstracts (showing no adverse effect) only 1 (11%) was accepted, whereas 28 of the 49 positive abstracts were accepted (57%). This difference was significant. Negative studies tended to verify cocaine use more often and to have more cocaine and control cases. Of the 8 rejected negative studies and the 21 rejected positive studies, significantly more negative studies verified cocaine use, and predominantly reported cocaine use rather than use of other drugs. This bias against the null hypothesis may lead to distorted estimation of the teratogenic risk of cocaine and thus cause women to terminate their pregnancy unjustifiably.

Hair Analysis of Cocaine: Differentiation Between Systemic Exposure and External Contamination

Cocaine has been shown to accumulate in hair of admitted users. Before using this test to verify cocaine use, however, it is crucial to differentiate between systemic exposure and external contamination from being in contact with crack smoke. In the present studies, the authors document that pyrolysis of crack results in hair accumulation of cocaine, but not its benzoylecgonine metabolite, whereas after admitted cocaine use both species are detectable in hair. External contamination with crack smoke is washable, whereas systemic exposure is not. The authors suggest these two criteria to distinguish systemic exposure from external contamination.

Accumulation of cocaine in maternal and fetal hair; The dose response curve

Cocaine and its major metabolites are incorporated into hair during the growth of the shaft and stay there for the whole life of the hair. Cocaine crosses the placenta and its metabolites for example Benzoylecgonine (BZ), have been found in neonatal urine, meconium and hair. In order to utilize hair measurements of cocaine as a biological marker of systemic exposure, we conducted both animal and human investigations on the dose response characteristics of this phenomenon. Our data suggest that both maternal and fetal accumulation of cocaine and its metabolite follow a linear pattern within the clinically used doses. Similarly, a good correlation was observed in animals between maternal dose and fetal hair accumulation.

Evaluation and Counseling of Teratogenic Risk: The Motherisk Approach

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 he counseled or whose physicians want them to meet us due to high levels of anxiety. Since its inception in 1935 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 16 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 he more often different from their controls. Conversely, when cocaine‐exposed infants were compared with babies of women exposed to other drugs of abuse but not cocaine, most of these differences cancelled out, suggesting that clustering of other risk factors may cause some of these adverse effects.

Potential Misclassification of a Case of SIDS: Maternal and Neonatal Hair Analysis for Cocaine and Heroin

Verification of illicit drug use by the mother during pregnancy is crucial when an attempt is made to correlate such exposure with fetal outcome. However, maternal report has been shown to be very inaccurate, and urine and blood testing for illicit drugs are positive only during the few days after their use [1]. Meconium testing is a very sensitive tool to detect in utero exposure to drugs; however, it has to be performed during the first days of life [2]. We have recently reported the sensitivity and specificity of hair analysis for intrauterine cocaine exposure; accumulation of cocaine in the hair is maintained for the life of neonatal hair [3].We describe a case in which analysis of maternal and neonatal hair yielded important information about drug history, which was not elicited from the mother.

Determination of gestational cocaine exposure by hair

Exercise prescription in pregnancy: Weight-bearing versus nonweight-bearing exercise Artal R.; Masaki DI; Khodiguian N; Romem Y; Rutherford Department of Obstetrics and Gynecology, University of Southern Carlfornia School of Medicine, Women’s Hospital, 1240 NMission Road, Los Angeles, CA 90033, USA AM J OBSTET GYNECOL 1989,161/6 1(1464-1469) Bicycle ergometry (non-weight-bearing exercise) and treadmill (weight-bearing exercise) were compared to assess physiologic responses to similar work loads. A total of 22 subjects at 29.3 f 1.6 (+ SEM) weeks’ gestation who performed nonweight-bearing exercise were compared with 15 similarly fit subjects at 26.1 k 2.3 weeks’ gestation who performed weightbearing exercise at three submaximal levels. Measurements by indirect calorimetry indicate preferential carbohydrate use during non-weight-bearing exercise at submaximal levels.