Michel Tournaire

Venous thromboembolism during pregnancy: a retrospective study of enoxaparin safety in 624 pregnancies

Objective To assess the maternal, fetal and neonatal safety of enoxaparin in pregnant women who require antithrombotic therapy.

Cancer Risk in Women Exposed to Diethylstilbestrol in Utero.

OBJECTIVE To evaluate the overall cancer risk, primarily breast cancer, for women exposed to diethylstilbestrol (DES) in utero in France. METHODS A cohort of 3 436 prenatally DES exposed women and a comparable cohort of 3256 unexposed women were recruited retrospectively from voluntary responses to questionnaires, and cases were ascertained by medical history at the time of recruitment. RESULTS One hundred ninety-five cancers were observed in exposed women (136 breast cancers, and 59 in other sites) and 141 cancers in unexposed women (90 breast cancers, and 51 others). A significant increase of breast cancers was found in exposed women, with a multivariate incidence rate ratio of 2.10 (95% CI 1.60-2.76) when compared with unexposed women. When exposed women were compared with the general population in France, the standardized incidence ratio was 2.33 (95% CI 1.93-2.72). CONCLUSION Our results suggest a significant increase of breast cancer in prenatally DES exposed women when compared with unexposed women and with the general population. For other cancers, except clear cell carcinoma of the cervix or vagina, there was a global non-significant increase.

The use of the antiprogestin RU486 (Mifepristone): As an abortifacient in early pregnancy — clinical and pathological findings; predictive factors for efficacy☆

RU486, a potent antiprogesterone steroid was administered to 124 women requesting therapeutic abortion. All were less than 49 days from their last menstrual period. Ten of these subjects (Group I) received high doses of RU486 in a decremental dose regimen (400, 300, 200 and 100 mg/day) over 4 successive days and 14 received 50 mg/day for 7 days (Group II). A further 50 subjects (Group III) received 100 mg/day for seven days and the remaining 50 subjects (Group IV) received 450 mg in a single dose. In the first three groups, half the daily dose was given in the morning and the remainder in the evening. Blood was collected before, and on Days 4 and 7 and then once a week after commencing therapy until disappearance of circulating beta HCG. In addition to beta HCG, estradiol-17 beta (E2), progesterone (P), cortisol, and various metabolic and hematological parameters were measured. Plasma RU486 concentrations were also assayed in Group II, III and IV subjects on Day 7 of therapy and in some cases on Days 14 and 21. Ultrasonography was performed in all cases on Day 1 and on Day 14. All the patients bled within five days following RU486 administration, for 1 to 21 days. A complete abortion occurred in 60% in Group I, 50% in Group II, 86% in Group III, and 80% in Group IV. The difference between the last two groups and the first two was significant at p less than 0.01. The non-responders were submitted to a uterine vacuum aspiration. A stepwise discriminant analysis was performed and indicated that the best predictors of the outcome of therapy were beta HCG values and the gestational sac diameter. With these criteria, the prediction was accurate in 86.4% of the cases. The best results were obtained in the cases where the ultrasonic measurement of gestational sac was under 10 mm in diameter and the initial beta HCG values under 15,000 mIU/ml. Among the observed side effects were moderate pelvic cramps (20.9%), nausea (27%), fainting (4.8%); 61.3% of the women complained of fatigue. Heavy bleeding occurred in 15.3% of the women but only one of them required blood transfusion. In the patients with complete abortion, beta HCG values decreased to below 500 mIU/ml by Day 14 (but in 11 cases values fell below 2,000 mIU/ml only by Day 21). Plasma estradiol and progesterone also fell. Cortisol levels increased during therapy especially in subjects of Group I, but returned to basal values after termination of treatment.(ABSTRACT TRUNCATED AT 400 WORDS)

Diethylstilbestrol exposure: evaluation of the doses received in France

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The daughters of diethylstilbestrol: Lessons from an error

Diethylstilbestrol (DES) has been used extensively to prevent pregnancy disorders in Europe but at different levels depending upon the countries. Lessons from the DES story can be learned for research, information for physicians, communication, administration and industry. However, this paper will focus on the incidence of this story in our practice. We will propose guidelines for different conditions: clear cell adenocarcinoma, adenosis, cervical dysplasia, infertility and pregnancy.

Evaluation of the fetal state by automatic analysis of the heart rate

1.1 Subjective classifications Many authors [l, 2, 4, 16] have tried to classify FHR patterns into different categories in attempts, to help in the detect on of early Symptoms of fetal distress. All known classifications have the same flaw: they are subjective and could be interpreted differently. On the other hand, the appearence of fetal heart rate (FHR) patterns also depends on the Strip chart speed and the scale. Moreover the prognostic significance of these classifications appears to be a relatively weak one and fetal distress has been reported in cases of Dip I or early decelaration. The physiopathologic meaning of these various types of classification is also questionable. The Information derived from such fetal heart rate recordings is qualitative and is difficult to correlate with quantitative clinical and biological findings.

Evaluation of the fetal state by automatic analysis of the heart rate. 2. Deceleration areas and umbilical artery blood pH

Fetal heart rate (FHR) deceleration areas were studied to obtain by objective measurement of the FHR, their prognostic value of the new-born state. 1. There is a reasonably good correlation between FHR deceleration areas and UApH (Tab. II). Such a correlation was found by SHELLEY and TIPTON [6] for the whole deceleration area, and by TOURNAIRE et al. [10] for areas divided in a slightly different way. The correlation coefficients between FHR deceleration areas and Apgar score at 1 minute are within a close range of those of the FHR deceleration area and UApH (Tab. I and II). 2. According to the time relationship between deceleration areas and uterine contractions the best correlation coefficient was obtained surprisingly for total, followed by residual and then simultaneous areas. These results agree with those of SHELLEY and TIPTON [6] suggesting that in practice a simple measurement of the whole deceleration area, regardless of the uterine contractions is a sufficient method in evaluating FHR patterns. 3. The special purpose computer built by the BAUDELOCQUE research group can be used on-line, thus in clinical practice. It was not the case for the manual method [4] or the method using a large programmed computer [10]. 4 The evaluation of deceleration areas appears to have several advantages: 1. It provides objective measurements. 2. The unit used is independant of factors such as display speed or scale of the strip-chart. 3. The data is reduced: A few numbers replace the long descriptions of the usual clinical classifications.

Evaluation of the fetal state by automatic analysis of the heart rate: decelereation area and fetal pH

Abstract The authors monitored FHR and UC of 53 high risk patients during labor. pH measurements were made at the beginning of the monitored period and at full dilatation. Total, residual and simultaneous decelereation areas were automatically measured during the whole time of labor. The authors evaluated each type of area in 3 ways: (1) from the beginning to the end of the tracing (area 1); (2) by computation of the mean value per hour of deceleration areas (area 2); (3) during the last 30 min of labor (area 3). Each parameter of area was correlated with the difference between the two values of pH and with the value of antenatal pH. The best correlations were found between areas measured during the whole time of labor and antenatal pH. For each type of area a limit value was determined between normal and abnormal antenatal pH. When none of the limits was exceeded antenatal pH was >7.25 in 35 out of 38 cases. If one of the 3 limits was exceeded antenatal pH was

Venous thromboembolism during pregnancy: A retrospective study of enoxaparin safety in 624 pregnancies

Venous thromboembolism is much more frequent in pregnant women than in nonpregnant women of similar age, and it remains a major cause of maternal morbidity and mortality. Low-molecular-weight heparins such as enoxaparin are more bioavailable and have longer half-lives than unfractionated heparin, and they produce more predictable responses. For these reasons they have become the standard for preventing and treating venous thromboembolism in nonpregnant individuals. There also is a convenience factor, because these heparins may be self-administered at home for long periods. The risks of thrombocytopenia and osteoporosis may be less than with unfractionated heparin. This retrospective study enrolled 604 enoxaparin-treated women with 624 pregnancies, seen at 55 perinatal centers in France in the years 1988-1997. The agent was used prophylactically in 92% of cases and to treat acute venous thromboembolism in 8%. Previous thromboembolism was recorded in 30% of women, and known thrombophilia, in 15%. Treatment began in the first, second, and third trimesters in 8%, 25%, and 67% of women, respectively. Nearly one third of deliveries were within 24 hours of the last injection. A mean daily dose of 97 mg (1 mg/kg twice daily) was delivered for a mean time of 84 ½ days. There were eight documented venous thrombolic episodes (1.3%), five before delivery and three afterward. None of these women were known to be thrombophilic when entering the study. Adverse events were recorded in 38% of women. Eleven of 72 hemorrhages were viewed as serious; five of these women had placental abruption, and three, placenta previa. None of 32 bleeds occurring at delivery were considered to be serious. The incidence of maternal thrombocytopenia was 1.6%; neither of the two serious cases seemed related to enoxaparin. No other adverse events could be related to enoxaparin. The rate of preterm gestation was 28% and of stillbirth, 1.1%. No stillbirth was ascribed to enoxaparin administration. Serious hemorrhage occurred in 1.4% of newborn infants, including five intraventricular bleeds and a total of nine intracranial hemorrhages, all in premature infants. Major congenital abnormalities occurred in 2.5% of infants. These findings signify that enoxaparin is well tolerated by pregnant women. In this review, adverse events could be accounted for by the study groups high-risk profile.