[Transplacental teratogenesis]. / Teratogenesi transplacentare.

Exposure during pregnancy to drugs or environmental chemicals (named xenobiotics) may cause birth defects in the embryo. Little is known about the biochemical and molecular mechanisms of teratological susceptibility. Many embryotoxic xenobiotics are proteratogens when bioactivated by enzymes, such as cytochromes, peroxidases and prostaglandin synthase to reactive intermediary metabolites. These intermediates are free radicals or electrophiles, that oxidize or bind irreversibly to cellular macromolecules such as DNA, proteins and lipids, altering cellular function. Teratological susceptibility is determined by a balance among maternal xenobiotic elimination, embryonic bioactivation and detoxification of reactive intermediates, cytoprotection and repair of molecular lesions. The embryo is relatively susceptible to reactive intermediates due to immature pathways for the detoxification, cytoprotection and repair. In this way, teratogenesis can occur from exposure to therapeutic concentrations of drugs or low concentrations of environmental chemicals.

Predictive markers of pre-eclampsia in hypertensive disorders of pregnancy.

OBJECTIVE: The aim of this work is to assess the most widespread methods currently proposed and two new markers for predicting the development of pre-eclampsia in pregnant women with hypertension. METHODS: The study involved 212 pregnant Caucasian women: 104 normotensive, 68 pregnancy-induced hypertensive and 40 chronic hypertensive. Blood and urine were sampled between 28 and 30 weeks gestation. All 108 hypertensive pregnant women, at the time of sampling, demonstrated proteinuria below 0.3 g/24 h. The following laboratory tests were performed: fibronectin, antithrombin-III, alpha-1-microglobulin, U-N-acetyl-beta-glucosaminidase, uric acid and albumin excretion rate. Student's t-test, discriminant analysis and chi2 (chi-square) test were used as statistical methods. A P value less than 0.05 was considered significant. RESULTS: After discriminating analysis, only three of the six variables analyzed were able to discriminate patients who would develop pre-eclampsia from the remaining hypertensive pregnant women: microalbuminuria, uric acid and fibronectin (chi2 = 29.122, P < 0.01). CONCLUSIONS: In agreement with previous studies, albumin excretion rate appeared to be the best predictive test for pre-eclampsia in hypertensive pregnant women, giving a higher positive predictive value and specificity (87.5 and 98.9%, respectively).

[Endothelial damage and blood coagulation activation in preeclampsia]. / Danno endoteliale ed attivazione della coagulazione nella preeclampsia.

BACKGROUND: The aim of this study was the evaluation of the endothelial cell damage and of the likely activation of coagulative cascade in preeclampsia. METHODS: Forty-seven pregnant women of gestational age from 30 to 34 weeks of gestation were studied: 30 normal pregnancies (N) and 17 women suffering from preeclampsia (P). The plasma factors studied were the following: 1) plasma fibronectin and thrombomodulin as markers of endothelial cell damage; 2) beta-thromboglobulin as platelet activity markers; 3) VIII:C factor and fibrinopeptide A as coagulation activity markers; 4) coagulation inhibitors such as protein C and protein S activity; 5) tissue plasminogen activator (t-PA), plasminogen level and plasminogen activator inhibitors (PAI) as fibrinolytic activity markers. All hypertensive patients didn't use heparin. Data are presented as mean +/- 1SD. Mann-Whitney "U" -test was used for statistical analysis. A p value of < or = 0.05 was regarded as statistically significant. RESULTS: In preeclampsia the plasma fibronectin is increased (P: 115 +/- 64 ng/ml, N: 73 +/- 47 ng/ml; p = 0.023) as well as VIII:C factor activity (P: 151 +/- 13.5%, N: 117.2 +/- 23%; p = 0.0005). CONCLUSIONS: Endothelial cell damage (increase of plasma fibronectin) and a slight thrombin generation (increase of VIII:C factor activity) are to be found in preeclampsia. We can't say which event starts the process. Intravascular coagulative cascade activation with platelet consumption, fibrin production and fibrinolytic activation occurs only in a restricted number of preeclamptic patients, in a late and worsening stage of illness, as a consequence of massive endothelial damage at placental and systemic level.

Antenatal ambroxol treatment does not prevent the respiratory distress syndrome in premature infants.

UNLABELLED: The effectiveness of ambroxol in the prevention of neonatal respiratory distress syndrome and in reducing the need for intermittent mandatory ventilation and oxygen therapy was studied in 88 mothers whose infants was born between 24 and 34 weeks of gestation and who were randomized either for treatment with ambroxol (group A = 42) or served as control (group B = 46). There were no significant differences in the mean gestational age, birth weight or Apgar score between the two groups. We found no significant differences in occurrence of respiratory distress syndrome (55% vs 45%), in support by intermittent mandatory ventilation (71% vs 72%) or oxygen therapy (74% vs 75%) at 12 h of age between groups A and B. CONCLUSION: This study does not suggest the efficacy of antenatal ambroxol treatment both for the prevention of neonatal respiratory distress syndrome and for the reduction of its severity.

S-adenosylmethionine versus ursodeoxycholic acid in the treatment of intrahepatic cholestasis of pregnancy: preliminary results of a controlled trial.

OBJECTIVES: To evaluate the efficacy of S-adenosylmethionine (SAMe) and ursodeoxycholic acid (UDCA) in intrahepatic cholestasis of pregnancy (ICP). METHODS: Twenty patients in the last trimester of pregnancy were randomly assigned to receive either SAMe (1000 mg/day i.m.) or UDCA (450 mg/day) until delivery; the treatment lasted at least 15 days in all cases. RESULTS: After UDCA the women exhibited significantly lower levels of total bile acids (P < 0.02), but no significant differences were noted in AST, ALT, or alkaline phosphatase. All ten patients showed a complete resolution of pruritus. After SAMe no significant changes were noted in pruritus, total bile acids or liver function tests. No adverse reactions on mother or child were recorded during either UDCA or SAMe treatment and the outcome of pregnancy was favorable in both groups. CONCLUSIONS: These findings show that UDCA is more effective than SAMe in controlling pruritus and total bile acids, which are considered a prognostic parameter in ICP with respect to the fetus. Nevertheless, before UDCA is introduced as an effective and safe treatment for ICP, which also has a beneficial effect on fetal prognosis, we believe these results should be confirmed and extended in other clinical trials.

AIDS in Italy and proposals for a new therapeutic strategy.

In Italy, the number of AIDS cases reported up to September 1993 was 18,832. Of these, 3,544 were women (21%), mainly of fertile age. AIDS in pregnancy has aroused great interest in Italy, mainly due to the extent of the phenomenon, which is not equalled in other Western countries. In this contribution to the study of HIV infection in pregnancy, the Authors propose a new procedure for monitoring, asymptomatic HIV-positive pregnant women, using fetal Fibronectin as an indicator of aspecific chorionamnionitis and the threat of premature birth, both considered as a risk factors for transmission of the virus from mother to child.

Mineralocorticoid effector mechanism in preeclampsia.

Mineralocorticoid effector mechanisms were evaluated in 29 patients with preeclampsia and in 25 uncomplicated pregnancies by measurement of plasma aldosterone, levels of mineralocorticoid receptor (MR) in mononuclear leucocytes, and subtraction potential difference (SPD; rectal minus oral values). Mean values for plasma aldosterone were not different between the two groups, but significant differences were observed for MR (preeclampsia, 81 +/- 44 receptors/cell; controls, 306 +/- 168) and SPD (preeclampsia, 65 +/- 7 mV; controls, 12 +/- 5 mV). In six cases we determined MR, plasma aldosterone, and SPD in patients with preeclampsia before and 3 months after delivery. MR were reduced before delivery (96 +/- 27 receptors/cell), and SPD increased (64 +/- 8 mV), with both parameters normalizing after delivery (MR, 242 +/- 79; SPD, 14.0 +/- 4 mV). Aldosterone levels returned to normal nonpregnant values after delivery. These data suggest an important role for abnormalities in mineralocorticoid effector mechanisms in the etiology of preeclampsia and could be an useful marker for diagnosis.

The prevention of respiratory distress syndrome in premature infants: efficacy of antenatal aminophylline treatment versus prenatal glucocorticoid administration.

Antepartum administration of aminophylline (AF) to pregnant animals resulted in accelerated and increased pulmonary maturation as well as in decreased morbidity and mortality from RDS in premature offspring. The present study was undertaken to evaluate the effect of antenatal AF treatment on the frequency of RDS among premature infants born of women who were treated (18) and to compare this group with betamethasone (GC) treated group (16 women). No statistical significant differences were noted between the AF and GC groups in the incidence of RDS (AF = 11.0%; GC = 0%) and in the frequency of perinatal deaths (AF and GC = 0%). Only a significant difference was noted between the AF group and the GC group in the incidence of neonatal signs of infection (AF = 0%; GC = 50%). The authors conclude that antenatal AF treatment may be as effective as GC in the prevention of RDS in premature infants with, for the moment, no side effects.

Plasma prolactin in women with mastodynia.

Plasma prolactin was measured by radioimmunoassay during the luteal phase in 22 patients affected by moderate or severe mastodynia and results were compared to those of 43 control subjects. No consistent changes were seen during the course of the luteal phase in either group. No significant differences were noted between the prolactin levels of the two groups. No association was found between moderate or severe mastodynia and variations of plasma prolactin levels.

Total and unconjugated plasma estriol. A comparison.

Total and unconjugated plasma estriol levels from the 24th to the 40th gestational week in 161 normal and 44 pathological pregnancies were studied. A lack of correlation between the two fractions was observed at the different gestational ages, probably due to the different rates of the several metabolic steps which condition the levels of the hormone fractions also in quite physiological conditions. The onset of pregnancy complications further modifies the ratio between the two fractions, as they differently affect the single metabolic processes which are essential for estriol to be produced, conjugated, recovered and excreted. E.P.H. gestosis and poor intrauterine fetal growth can be better diagnosed by the assay of total than unconjugated estriol: the total fraction proved to have the higher sensitivity, predictive value and relative risk and should therefore be preferred for pregnancy monitoring, as it better corresponds to the clinical situation.

Two problems in oral contraception: arteriosclerotic cardiopathy and drug interactions.

The Authors examine two aspects of oral contraception: the risk of arteriosclerotic cardiopathy and the interaction with other drugs. The former is rather limited but increases significantly when other arteriosclerotic risk factors, first and foremost smoke, are present. The dose of both the estrogenic and the progestinic components also influences the risk. The Authors examine the most recent information on the interference of some drugs with the contraceptive effectiveness of synthetic, especially low-dose, estroprogestinics, which is mediated by changes of the intestinal absorption or metabolic clearance rate. Finally, they analyse the interference of contraceptive steroids with the kinetics of other drugs and, consequently, with the intensity of therapeutical and side effects.

PIP: 2 aspects of oral contraception (OC) were considered--the risk of arteriosclerotic cardiopathy and the interaction with other drugs. Opinions still diverge on the role of contraceptives in the etiology of myocardial infarction. In contrast to the British studies, the World Health Organization's (WHO) data and US statistics on death from cardiovascular diseases fail to show higher prevalence for OC users. Most likely the data of different countries cannot be compared due to the differing incidence of other cardiovascular morbidity and mortality risk factors such as hypertension, obesity, smoking, physical activity, and genetic predisposition. A recent study examined the prevalence of myocardial infarction in relation to the use of estroprogestinic contraceptives. Rosenberg et al. found that 156 out of 121,944 women (1.2%) had been hospitalized following myocardial infarction, and 23 of them used OCs. The authors concluded that OCs increased the risk of infarction by 1.8. Shapiro et al. studied 369 patients who suffered myocardial infarction and an adequate control group. The overall relative frequency was 4 times in OC users but it was 4.5 times in smokers and 3.9 times in nonsmokers. The smokers who did not use OCs showed a relative frequency of 7.8 times. The risk of arteriosclerotic cardiopathy depends upon the dose of both the estrogenic and progestinic components. When prescribing drugs, physicians should know whether their patients use OCs, since these hormonal steroids may interfere with the expected therapeutic effect. A phenomenon of enzymatic competition may occur which slows down the elimination of the drug, thus exposing the patient to a "relative overdose" despite the assumption of therapeutic doses. It has always been reported that the simultaneous administration of triacetiloleandomycin and OCs causes jaundice. Thus far 15 cases have been reported. OCs tend to enhance the effect of corticosteroids. Vitamin K antagonists, oral anticoagulants, are less effective in OC users. A research study conducted by Patwardhan et al. showed that caffeine is eliminated more slowly in OC users because of a mechanism of enzymatic competition with contraceptive steroids at the level of the hepatic oxygenase system linked to cytochrome P-450. ready been reported that the simultaneous administration of triacetiloleandomycin and OCs causes jaundice. Thus far 15 cases have been reported. OCs tend to enhance the effect of corticosteroids. Vitamin K antagonists, oral anticoagulants, are less effective in OC users. A research study conducted by Patwardhan et al. showed that caffeine is eliminated more slowly in OC users because of a mechanism of enzymatic competition with contraceptive steroids at the level of the hepatic oxygenase system linked to cytochrome P-450.

What are the most suitable fetoplacental tests in the monitoring of the third trimester of pregnancy?

The case-series of the Institute of Obstetrics and Gynaecology were examined to evaluate the suitability of urinary estriol, total plasma estriol, unconjugated plasma estriol, unconjugated plasma estetrol, plasma placental lactogen, plasma S.P.-1 glycoprotein, plasma alphafetoprotein and biparietal diameter in correctly forecasting the perinatal risk, when performed after the 25th week of pregnancy. In high-risk pregnancies, according to our results, S.P.-1 glycoprotein and urinary estriol are the most sensitive tests, while S.P.-1 glycoprotein, placental lactogen and biparietal diameter are found to have the highest predictive value. The repetition of the considered tests increases their sensitivity, but not their predictive value. In pregnancy mass screening the most suitable tests, on the basis of the "relative risk" are S.P.-1 glycoprotein (or even placental lactogen), estriol and biparietal diameter. For the last one a single measurement seems to be enough during the third trimester.