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.

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.

Outcome of fifty-five newborns of antiphospholipid antibody-positive mothers treated with calcium heparin during pregnancy.

OBJECTIVE: The outcome of 55 infants born to 53 antiphospholipid antibody (aPL)-positive mothers treated during pregnancy with calcium heparin is described. METHODS: The clinical state of the children was evaluated immediately after delivery by a clinical examination, and a neonatological check-up was performed no later than 24 hours after birth. Neonates with problems were transferred to the neonatal intensive care unit. After their discharge from hospital the clinical state of the babies was followed by means of interviews with the pediatricians and mothers for a period varying between 1.33 and 5.66 years (mean 2.51 +/- 0.92 SD). RESULTS: The newborns comprised 30 females and 25 males, including 2 sets of twins, delivered between the 25th and 40th weeks of gestation (mean 36.69 +/- 2.91 SD). They had a mean birth weight of 2.828 g +/- 706.50 SD (range 800-4.000) and a mean Apgar score at 5 minutes of 9.60 +/- 0.68 SD (range 7-10). Soon after delivery, 12 children (21.81%) were admitted to the neonatal intensive care unit for periods varying between 2 and 120 days (mean 30.33 +/- 33.40 SD), after which the clinical course was normal. All of these neonates suffered from complications exclusively due to prematurity. Malformations and signs of thrombosis or other aPL-related disorders were not observed in any of the newborns. During the follow-up, none of the diseases suffered by the 55 children differed from those of the normal pediatric population; in particular, aPL-related manifestations were never observed. CONCLUSION: These data indicate the absence of aPL-related problems in the offspring of aPL-positive mothers treated during pregnancy with calcium heparin.

Erythropoietin and transferrin concentrations during pregnancy in relation to hemoglobin levels.

Serum levels of erythropoietin (EPO) were assayed by ELISA at the same time as red blood cells (RBC), hemoglobin (Hb), hematocrit (Hct), serum iron and transferrin in 136 pregnant women, divided on the basis of hemoglobin values (> or < or = 10.5 g/dl) and weeks of pregnancy (< or > or = 27th week). In the overall population, a parallel increase with weeks of pregnancy was shown by serum concentrations of EPO expressed as a logarithm (multiple R = 0.367, P < 0.0001), and transferrin levels (multiple R = 0.529, P < 0.0001). It was found that EPO levels did not differ significantly between anemic and non-anemic patients before the 27th week, but the difference became highly significant (P < 0.01) after the 27th week in favour of anemic patients. Before the 27th week, the correlations between log EPO and RBC, Hct, Hb and iron were not significant, whereas the correlation between log EPO and transferrin was significant (P < 0.01); after the 27th week, the correlations and significance of the regression found were: log EPO vs Hb (Pearson coefficient = -0.384; P < 0.001), vs Hct (Pearson coefficient = -0.370; P < 0.01), vs transferrin (Pearson coefficient = 0.392; P < 0.0001), vs iron (Pearson coefficient = -0.274, P < 0.05). In the population divided according to Hb levels, the correlation was positive and significant in both groups between log EPO and transferrin (Hb > 10.5 g/dl: Pearson coefficient = 0.524, P < 0.0001; Hb < or = 10.5: Pearson coefficient = 0.614, P < 0.0001), but was inverse and significant only in the group with Hb < or = 10.5 g/dl between log EPO and serum iron (Pearson coefficient = -0.481, P < 0.01). The variations in EPO were related to Hb levels after the 27th week of pregnancy and were closely correlated with transferrin over the whole period. The physiological mechanism of these changes is discussed.

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.

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.

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).

[Antineoplastic agents and pregnancy]. / Antineoplastici e gravidanza.

The current impossibility of establishing a definite causal relationship between the administration of antineoplastic drugs before and/or during pregnancy and possible modifications of the gestational attitude in the treated women is discussed after a review of the Literature. The data till now reported are often deficient as far as concerns the evaluation of either the fetal, perinatal and post-natal parameters and the past and current reproductive performance of the patients on study. The need for strict methodology in the study and report of feto-maternal parameters to provide a comprehensive answer to the questions raised by the use of antineoplastic drugs before and/or during pregnancy is discussed in detail.

[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.

Obstetric complications in Marfan's syndrome pregnancy.

Marfan syndrome is usually inherited as an autosomal dominant trait with high degree of penetrance. It is caused by an abnormal fibrillin gene located on chromosome 15q. Cardiovascular involvement in Marfan syndrome has been overstressed, although very little attention has been given to obstetric complications. Marfan syndrome may be responsible of cervical incompetence, abnormal placental site and post partum haemorrhagic complications. A 22-year-old woman with Marfan syndrome had mitral regurgitation since childhood. In addition aortic root dilatation was documented over six years by means of echocardiography and had been followed up regularly in a district hospital. Echocardiography six months before pregnancy had shown minimal mitral and aortic regurgitation and aortic root dilatation of 4.1 cm; left ventricular function was normal. Repeat echocardiography evaluations during pregnancy confirmed an aortic root dilatation. Routine booking and screening investigations were all within normal limits. At the 25th week, admission was necessary following a vaginal bleeding, without pain contraction. Echography showed a placenta praevia and cervical dilatation 2.8 cm of diameter. Bed rest and intravenous thocolitic therapy were immediately enhanced. A cervical cerclage, as described by McDonald, was placed. At the 37th week the patient was admitted and cerclage removed before the caesarean section. A healthy female of 2900 g was born. The postoperative period was favourable and patient was discharge after 7 days. In the present case, it is suggested that cervical incompetence and placenta praevia may be caused by an alteration of microfibrillar fibers.

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.

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.

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.

The significance of the relationship between serum levels of cobalamin and MCHC during pregnancy.

Cobalamin concentration and mean corpuscular haemoglobin concentration (MCHC) were found to have highly significant inverse correlation with the weeks of pregnancy (respectively -.278 P < .0001 and .342 P < .00001) in 205 pregnant women. Among all haematometric parameters cobalamin concentrations during pregnancy only correlates with MCHC (P < .01). This datum seems to indicate an influence of B12 on erythropoiesis which adequate the concentration of haemoglobin to circulatory modifications of pregnant women.

Iron balance in pregnancy in relation to anemia.

Blood levels of iron, transferrin and ferritin varied in the course of pregnancy (6th to 42nd week) in 136 women. Analysis of variance showed that the factor "weeks of pregnancy" (< or = 27 or > 27 weeks) was correlated differently with the variables "ferritin" and "iron" according to the presence or absence of anemia (Hb < or = or > or = 11 g/dl). In anemic women the correlation was significant (F-ratio = 5.90; P = 0.018) for iron (which decreased from initial low level until term) but not ferritin, whereas in non-anemic women the correlation was significant (F-ratio = 13.306; P = 0.0006) for ferritin (which decreased to less than 20 micrograms/ml around the 34th week) but not iron. In both anemic and non anemic subjects, transferrin levels increased with weeks of pregnancy. It is concluded that towards the end of pregnancy, some decrease in ferritin (> or = 15 micrograms/ml) is physiological, and in the absence of anemia (Hb > 11 g/dl) iron supplements are not necessary.

Modifications of the coagulation factors during normal and pathological pregnancies.

Levels of fibrinogen and fibrin/fibrinogen degradation products (F.D.P.) have been mesurated respectively by thrombin time and by staphylococcus clumping test in 33 pregnant patients, recovered in the Obstetric and Gynaecological Clinic - University of Padua, during the ninth month of pregnancy. A control group of 16 normal pregnancies, a second group of 12 hypertensive patients, and a third group of 15 pregnancies who had given birth to rather small babies for date, were considered. A significative increase (p less than 0,001) of the F.D.P. values was found both in the pregnant women with hypertension and in those with foetal insufficiency respect to the control group. The fibrinogen levels did not vary in any of the three groups.

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.

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.

Prenatal theophylline and necrotizing enterocolitis in premature newborn infants.

To determine whether prenatal theophylline therapy would increase the incidence of neonatal necrotizing enterocolitis (NEC) we studied bowel dysfunction in 59 consecutive premature infants (g.s. < 34 weeks), whose mothers were treated with theophylline as a tocolytic during the last trimester, or as surfactant synthesis inductor, for at least three days prior to premature labor (Group A). As case-control we considered the premature, matched for gestational age born immediately before, and whose was untreated with theophylline (Group B). NEC occurred in one patient from group A during the second postnatal week, and surgery was performed. First passage of meconium and start of enteral feeding were comparable in groups A and B, while gastric residuals lasting more than 4 days were found statistically increased (p < 0.03) in antenatally treated group A prematures. Furthermore, 18 out of 49 prematures postnatally treated with theophylline had gastric residuals (36%) with respect to 5 out of 69 untreated (7%) (p < 0.001). Also the premature infants treated ante and postnatally with theophylline showed a statistically significant increase of lasting gastric residuals with respect to the untreated, 13/16 vs 5/7, respectively (p < 0.03). Antenatal theophylline administered to high risk mothers, when maternal diseases do not allow the use of steroids, does not appear to later increase the risk of NEC in premature infants, and provides a chance to avoid the risks related to premature birth. Inhibitory activity on gut motility and gastric irritability are only detectable during the first postnatal days, enhanced by gut immaturity of preterm infants.