Judith Arnon

The outcome of pregnancy in 689 women exposed to therapeutic doses of antidepressants. A collaborative study of the European Network of Teratology Information Services (ENTIS)

The European Network of the Teratology Information Services (ENTIS) has collected and evaluated data on 689 pregnancies in which exposure to tricyclic and nontricyclic antidepressants occurred. Data were collected prospectively from the time of in utero exposure and all the cases were followed up to the first few weeks of postnatal life using standardized procedures. In most cases, no longer term follow-up data were available. Approximately two-thirds of the mothers were on multidrug therapy, and of those, half took a benzodiazepine. About 95% of the patients were exposed during the first trimester. The most striking feature of the pregnancy outcomes is that 97% of live-born babies were morphologically normal. The incidence of spontaneous abortion and late fetal/neonatal deaths were within the normal range. Fourteen live-born babies and one fetus had either major or minor malformations, and six had minor anomalies. However, there was no increase in either a particular type of malformation or a specific pattern of defects. Another 31 infants without malformations had neonatal problems; these were usually associated with chronic multidrug therapy, especially near term. Elective termination of pregnancy occurred more frequently in the multidrug groups (86 out of 488) than in the monotherapy groups (20 out of 201), but data concerning the condition of the fetus are not available in the majority of the cases. Overall, no causal relationship could be established between in utero exposure to antidepressants and adverse pregnancy outcome.

Is benzodiazepine use during pregnancy really teratogenic

Benzodiazepines (BDs) have a widespread use among people suffering from anxiety. These drugs easily cross the placenta and may affect the developing embryo and fetus. The literature is divided as to whether BD may cause an increase in spontaneous abortions or congenital anomalies. From the years 1988 to 1996, 756 women called the Israeli TIS concerning exposures to BD prior to or during pregnancy. Of 599 women who called us during pregnancy, we have follow-up information on 460 pregnancies (76.6%). The incidence of congenital anomalies (3.1%) was not different from that found in 424 control pregnancies (2.6%). There was a significantly higher incidence of induced abortions (14.1% vs. 4.7%, P = 0.00) and of spontaneous abortions (8.7% vs. 5.2%, P = 0.01). From an examination of our results, it does not appear that BD during pregnancy caused an increase in the incidence of birth defects. There was no specific defect in the offspring. The increase in the rate of induced abortions is probably related to the counseling of the callers, and the increase in spontaneous abortions seems to be a result of the lower gestational age at the time of counseling in the women exposed to BD. It is unknown whether BD could be responsible for developmental or behavioral problems, which are observed only at a later stage.

The effect of bezafibrate and long-chain fatty acids on peroxisomal activities in cultured rat hepatocytes

Peroxisomal activities have been evaluated in cultured rat hepatocytes in the presence of bezafibrate or long-chain fatty acids added to the culture medium. All activities decreased continuously over a time period of 100 h in culture but selected activities were relatively increased as a function of the added effectors. This relative increase in peroxisomal activities was dose-dependent, discernible within the first 24 h in culture and consisted of activities related specifically to peroxisomal fatty acyl beta-oxidation, e.g., cyanide-insensitive palmitoyl-CoA oxidation, H2O2-forming palmitoyl-CoA oxidase and heat-labile enoyl-CoA hydratase. Peroxisomal catalase or mitochondrial fatty acyl beta-oxidation (cyanide-sensitive) remained relatively unchanged. The relative increase in peroxisomal activities was accompanied by a respective increase in the number of peroxisomes as well as in thymidine incorporation rate.

Primary versus Nonprimary Cytomegalovirus Infection during Pregnancy, Israel

We examined prospectively the outcome of primary and nonprimary maternal cytomegalovirus (CMV) infection during pregnancy among 88 and 120 women, respectively. The risk for vertical transmission was 1.83× higher for primary infection than for nonprimary infection. Nonetheless, congenital CMV disease was diagnosed in both infection groups at similar rates.

Pregnancy outcome after gestational exposure to the new macrolides: a prospective multi-center observational study.

OBJECTIVES To determine whether the use of the new macrolides (azithromycin, clarithromycin, roxithromycin) during the first trimester of pregnancy is associated with an increased risk of major malformations. STUDY DESIGN In a prospective multi-center study, pregnancy outcome was compared between pregnant women exposed to one of the new macrolides during the first trimester of pregnancy and two comparison groups one exposed to other antibiotics and the other to other non-teratogenic medications. All women enrolled in the study called one of the three participating teratogen information services (TIS). Group 1 macrolides (n=161), group 2 other antibiotics (n=213) and group 3 non-teratogens (n=740). RESULTS A total of 161 women exposed to the new macrolides (118 were exposed in the first trimester of pregnancy) and 953 from a comparison groups were followed up. The rate of major malformations in the study group was 4.1% compared to 2.1% in the other antibiotics exposed group (OR=1.41, 95% CI 0.47-4.23) and 3.0% in the non-teratogens exposed group. The rate of elective terminations of pregnancy was significantly higher in the exposed group in compare to both comparison groups. CONCLUSION Our study, although relatively small sized, suggests that the use of the new macrolides during the first trimester of pregnancy does not represent an increased risk for congenital malformations strong enough for an induced abortion after such an exposure. Elective terminations of pregnancy because of early exposure to these medications should be reconsidered.

Clofibrate does not induce peroxisomal proliferation in human hepatoma cell lines PLC/PRF/5 and SK-HEP-1

The potential of fibrate drugs to induce peroxisomal proliferation in human liver cells was evaluated in athymic nude mice transplanted with human hepatoma cells and treated by clofibrate in vivo as well as in cultured human hepatoma cells in the presence of fibrate drugs added to the culture medium. Clofibrate did not induce peroxisomal activities and neither acted as a peroxisomal proliferator in human PLC/PRF/5 or SK-HEP-1 heterotransplants under conditions of induction of peroxisomal activities in the host rodent liver. Similarly, clofibric acid or bezafibrate did not induce peroxisomal activities in cultured human PLC/PRF/5 or SK-HEP-1 cells under conditions of induction of peroxisomal activities in cultured primary rat liver cells. The lack of response of the human cells to peroxisomal proliferators of the fibrate type may indicate a species specificity with respect to induction of peroxisomal activities by xenobiotic peroxisomal proliferators.