A prospective study of fifty-three consecutive calcium heparin treated pregnancies in patients with antiphospholipid antibody-related fetal loss.

OBJECTIVE: In this study the efficacy and safety of calcium heparin administered alone for the prevention of fetal loss related to antiphospholipid antibodies (aPL) were evaluated. METHODS: Fifty-three consecutively ascertained pregnancies were followed in 53 patients who had a history of at least 2 consecutive miscarriages during the first trimester and/or 1 fetal death during the second or third trimesters. In addition, all patients had at least 2 positive aPL tests more than 8 weeks apart before pregnancy, or a positive aPL test at the beginning of pregnancy. They were treated with calcium heparin alone, self-administered subcutaneously 3 times daily at dosages varying between 15,000 and 37,500 units. Treatment was started soon after a sonogram demonstrated a live embryo and was continued throughout pregnancy until the end of puerperium. RESULTS: All pregnancies terminated favourably between the 25th and 40th weeks (mean +/- SD: 36.69 +/- 2.91) with planned caesarean section in 27 cases and vaginal delivery in 26. Delivery was brought forward due to maternal and/or fetal complications in 18 cases (33.96%). Calcium heparin was associated with intravenous immunoglobulin therapy in 2 patients with fetal problems unresponsive to anticoagulant treatment alone. The newborns, 30 females and 25 males, had a mean birth weight of 2,828.3 g +/- 706.5 and a mean Apgar score at 5 minutes of 9.60 +/- 0.68. No malformations were observed. Thirty of the 37 examined placentas (81.08%) showed signs of thrombotic events. Only minor side effects of calcium heparin were observed during treatment. CONCLUSION: Our study suggests that calcium heparin administered alone using the dosages and timing described here is effective in achieving the delivery of viable infants, and that it is well tolerated.

The effect of fetal infection with human immunodeficiency virus type 1 on birthweight and length of gestation. SIGO Study Group of HIV Infection in Pregnancy.

We sought to evaluate the effect of vertical transmission of human immunodeficiency virus type 1 (HIV-1) on birthweight and length of gestation. For this purpose we used maternal and pregnancy data of 559 HIV-1-seropositive pregnant women delivered at 13 Italian centers from 1985 to 1991. The mother-to-child transmission rate of HIV infection was 18.2% (84/461). After adjustment for potential confounders with multiple linear regression analysis, there were no differences in birthweight, gestational age, and proportion of expected birthweight (observed birthweight/expected birthweight) between infected and uninfected children. Intravenous drug abuse during current pregnancy was the factor which correlated best with a reduction in birthweight (mean reduction, 214.4 g; 95% confidence interval (CI), 61.7-367.1), length of gestation (mean reduction, 9.3 days; 95% CI, 3.9-14.7) and proportion of expected birthweight (mean reduction, 12.1%; 95% CI, 4.7-19.5%). In our population, HIV-1 infection of the fetus has little effect on length of gestation and birthweight.

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.

Estrogen therapy in menopause and endometrial cancer.

The hormone dependency of endometrial cancer and the increase of its incidence seem to be generally accepted. The Authors expose the results of a four year retrospective epidemiological research aiming at verifying the possible role of menopausal estrogen assumption in the etiopathogenesis of the above mentioned disease. Two groups of post-menopausal patients were examined, who underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy: 168 were endometrial cancer free, 50 were affected. The percentages of estrogen users, the exposition time and type of therapy were carefully analyzed in them. No correlation could be found between estrogen consumption, which resulted much lower than in the U.S.A., and endometrial cancer incidence. The relatively short assumption times, the different drug associations, and the hypoestrogenic origin of the most disturbing menopausal symptoms can help to explain this finding which is however, in agreement with what emerges from studies carried out in different countries by several Authors.

Betamethasone administration to the mother and problems in foeto-placental monitoring.

The administration of betamethasone to the mother in order to accelerate maturation of foetal lungs induces significant modifications in the foeto-placental hormonal secretion. Both the total estriol and unconjugated estriol present a sharp fall in the days immediately following the administration and a rise 10-12 days later, depending on a rebound effect. The HPL levels do not variate except for a progressive and constant rising due probably to better cardiocirculatory maternal condition with, consequently, a higher utero-placental blood-flow. All these phenomena increase when the administration of betamethasone to the mother is repeated more then once. The AA. believe that the sharp fall of the estriol doesn't represent a danger for the foetus being only an effect of maternal and fetal adrenal depression. Consequently the AA. suggest to drive the management during and after the administration of betamethasone to the mother on the basis of other foeto-placental functional tests, as cardiotocography. The results were analysed.

A comparison of qualitative and quantitative evaluation of cardiotocogram in the monitoring of high-risk pregnancy.

85 high risk pregnant women were evaluated by RIA of total estriol, unconjugated estriol and HPL by ultrasonic measurement of foetal BPD and by NST and Fischer's score. In all, 277 evaluations were made. The Authors found a good correlation between results of the cardiotocographic tests and levels of HPL and measurements of foetal BPD. A low correlation was noticed between the levels of total and unconjugated estriol and the characteristics of cardiotocography. The evaluation of the cardiotocographic tests, according to Lee and Coll., resulted better than according to Fischer's score. The contemporary qualitative and quantitative evaluation of the cardiotocograms seems to reduce significantly the false-positive results and to half the false-negative results of the other tests for foeto-placental function. Result were analysed.

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.

Use of intramyometrial injection of prostaglandin F 2 alpha in the management of intractable hemorrhage due to uterine atony.

Prostaglandin F2 alpha, in doses varying from 1 to 5 mg was injected transabdominally, transvaginally or intraabdominally (during caesarean section) into the myometrium in ten patients affected by metrorrhagias not responsive to conventional uterotonic drugs. In all cases but one the result was excellent. Important side effects were observed in only one patient, because of the inadvertent intravascular injection of 5 mg Prostaglandin into the endocervix. An adequate treatment of this patient brought her to complete recovery in a short time. According to our experience, the intramyometrial injection of PGF2 alpha, in doses varying from 1 to 2 mg, is a simple, safe and effective method in the control of severe hemorrhage due to uterine atony not responding to conventional treatment.

Cardiotocographic modifications during continuous epidural anaesthesia in labour.

Cardiotocographic variations certainly attributable to epidural anaesthesia were studied over the period 1972-1980 on 716 patients in labour. Transitory side-effects due to both direct and indirect action of local anaesthetics appeared in 1.4% of the cases, without, however, subsequently creating any particular foeto-newborn problem. On the basis of the experience acquired, it seems justifiable to affirm that the correct use of continuous epidural block, affected by very small doses of bupivacaine (10-20 mg per administration) is almost risk-free. The only inconvenience therefore that may sometimes arise would only be due to the relevation of a concealed cava occlusion when the maintenance of a left lateral position is not observed.

Successful management of a pregnancy at high risk because of Eisenmenger reaction.

Informed medical care, appropriate maternal and fetal monitoring, and cooperation among experienced obstetricians, anesthesists cardiologists, particularly during delivery and the early puerperium associated with psychological preparation of the mother, were the bases of the successful management of a pregnant 28-year-old woman at high risk because of the Eisenmenger reaction.

Cyclosporin A in a pregnant patient affected with systemic lupus erythematosus.

Few data regarding the use of cyclosporin A (CyA) in pregnancy are available and those available refer mainly to transplant recipients and not to patients with connective tissue diseases. We report the case of a patient with systemic lupus erythematosus (SLE), taking CyA before, during and after her pregnancy at a dose of 4 mg/kg per day. CyA was effective in controlling SLE activity and no side effects were observed in mother or baby. The lack of teratogenicity in this case was in keeping with previous reports in experimental systems, animals and human transplant recipients. If our observation is confirmed by further studies, CyA might become useful in the treatment of pregnant patients with SLE.

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.

Trends in immunoglobulin G anticardiolipin antibodies in ten successful heparin-treated pregnancies.

The pregnancies of ten women, all with histories of at least two spontaneous abortions of unknown cause, were followed. All patients were positive for immunoglobulin (Ig) G anticardiolipin antibodies (aCL) and one also for IgM aCL, while none had lupus anticoagulant activity. During pregnancy, the patients were treated with calcium heparin in doses varying between 15,000 and 30,000 IU daily. IgG aCL were assayed on average at the 9th, 17th, 24th and 29th weeks of pregnancy and at the moment of delivery. Mean values of IgG aCL levels during the 10 pregnancies steadily fell as the pregnancies progressed, and this decrease was significant (r = 0.985, P = 0.002). All pregnancies terminated favourably, although delivery was brought forward in eight patients and six of the nine placentas examined showed signs of thrombotic events. We assume that a steady fall in IgG aCL levels during pregnancy may be considered as indicative of a favourable outcome.

Fibrinolytic pattern in recurrent spontaneous abortions: no relationship between hypofibrinolysis and anti-phospholipid antibodies.

Patients with antiphospholipid antibodies may suffer from thrombotic events and recurrent spontaneous abortions. A defective fibrinolytic potential has been described in women with recurrent fetal losses. We investigated the prevalence of anticardiolipin antibodies and of various fibrinolytic abnormalities in 64 females with a history of at least two abortions of unknown origin. Anticardiolipin antibodies were present in the serum of 31 patients (48.4%). The overall prevalence of fibrinolytic disorders was 67.2% (43 cases) and resulted significantly higher than that of aCL positivity (P = 0.03). In most of cases the impaired fibrinolytic potential after venous occlusion test was due to increased PAI-1 levels; only in a few instances a defective fibrinolytic response was due to reduced t-PA release, a combined defect or an intrinsic fibrinolytic deficiency. After division of patients in two groups on the basis of the aCL presence, the distribution of different fibrinolytic defects was similar in aCL positive and negative women, suggesting the lack of correlation between hypofibrinolysis and aCL antibodies. Plasminogen abnormalities resulted compatible with congenital hypoplasminogenemia in two aCL negative women, whereas in four aCL positive patients they were suggestive for acquired dysplasminogenemia. Our results indicate that patients with recurrent spontaneous abortions may present fibrinolytic disorders, which occur independently and more often than aCL positivity. An accurate investigation of the fibrinolytic potential, and, namely, of PAI-1 levels, should be included in the study of females suffering from repeated fetal losses.