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OBJECTIVES: The risk of hepatitis C virus (HCV) infection in the newborn is estimated to be around 5%, but becomes very high in the case of coinfection with HIV. One of the main factors associated with the vertical transmission of HCV is the viral load. Our objective was to investigate the behavior of HCV viral load during pregnancy in relation to HIV coinfection, liver enzymes, and vertical transmission. METHODS: Three thousand seven hundred forty-eight women seen consecutively in their first trimester of pregnancy were screened for HCV infection. Sixty-five were found to be anti-HCV+/HCV RNA+ and were followed up with clinical and serological assessment (i.e., transaminases and quantitative polymerase chain reaction [PCR] for viral load) in their second and third trimesters and 6 months after delivery. All were anti-HIV and hepatitis B surface antigen negative. HCV RNA was 12.0+/-19.9 x 10(6) copies/ml in the first trimester and 10.9+/-13.3 x 10(6) in the second, but increased to 19.5+/-25.1 x 10(6) in the third trimester. Six months after delivery the viral load returned to the baseline levels; the changes in viral load did not reach any statistical significance, however. Transaminases tended toward a reduction from the baseline during the second and third trimesters, and then an increase in both AST and ALT was recorded 6 months after delivery. However, when the group whose AST/ALT were found abnormal at the first test was considered, no significant changes were recorded during the follow-up. The overall rate of vertical transmission was 4.6 CONCLUSIONS: With HCV+ mothers monitoring transaminases during pregnancy is unnecessary, and testing liver enzymes at the beginning of pregnancy is sufficient. Qualitative PCR should be done once during the pregnancy, but any staging of the liver disease should be taken after delivery. Quantitative PCR testing is expensive and pointless. Any decision for elective cesarean section in HCV RNA+ mothers should be confirmed by other studies.

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A heterogeneous population of 4396 consecutive pregnant women (86.6% indigenous, 13.4% immigrants) attending the Department of Obstetrics and Gynecology of the University of Padua (north-east Italy) were counselled and tested for HIV infection between September 1995 and December 1997. Sociodemographic and sanitary data were collected on each case. Anti-HIV prevalence was 0.57%. Intravenous drug use and foreign birth accounted for 28% and 24%, respectively, of the anti-HIV positive cases; 44% of the HIV-positive subjects reported no risk factors. In the logistic regression HIV positivity proved independently associated with intravenous drug use (adjusted OR 76. 6), sexually transmitted diseases (adjusted OR 13.2), unmarried status (adjusted OR 4.8), birth outside the European Union (EU) (adjusted OR 3.1) and age (adjusted OR 1.1). Heterosexual HIV spread appears to be a major concern. The monitoring of trends in HIV infection among subgroups should be continued in order to control the AIDS epidemic appropriately both by promoting HIV counselling and individual care, and by watching for changes in the social background.

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BACKGROUND: Pregnant women can be considered a sentinel population, because they are a relatively unselected population whose prevalence data may be extended to the general population. METHODS: A seroepidemiological study was carried out in Padua (North-East Italy) to assess the epidemiological aspects of HCV. HBV and HIV infection in 2059 pregnant women consecutively seen at the Department of Obstetrics and Gynaecology during 1996. Out of them, 1804 (87.2%) were indigenous and 255 (12.8%) immigrants. Sociodemographical and sanitary data were collected for each woman. RESULTS: The overall prevalence of anti-HCV was 1.9% (42.5% with detectable HCV-RNA); HBsAg was found in 1.0%: the prevalence of anti-HIV was 0.3%. Findings are substantially consistent with the epidemiological picture of such infections in the general population of our geographic area. A parenteral risk factor for HCV infection was found in 19 subjects (47.5%): 18 were intravenous drug users and 1 a blood transfusion recipient. HBsAg seroprevalence was higher in immigrants than in autochthonous (3.1% vs. 0.7% respectively, p < 0.01). One of the 6 anti-HIV positive women was intravenous drug user. Logistic regression analysis was carried out for each viral agent to determine which characteristics were independently associated with infection: anti-HCV prevalence resulted independently associated to Italian origin (OR: 3.7), unmarried status (OR: 2.7), unemployed condition (OR: 6.1) and history of previous abortion (OR: 2.8). HBsAg prevalence was independently associated to unemployed condition (OR: 10.8), whereas HIV positivity was significantly related to the unmarried status (OR: 18.5). CONCLUSION: Our study pinpoints the need of screening all pregnant women for HCV and HIV infection, in addition to the HBsAg screening which is compulsory in Italy.

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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.

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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).

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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OBJECTIVES: To evaluate the clinical aspects of hepatitis C virus (HCV) liver disease in anti-HCV+ve mothers, both during pregnancy and six months after delivery, and to assess the outcome of pregnancy. SETTING: Obstetric department for high risk pregnancies of the University of Padova, Italy. PARTICIPANTS: Seventeen hundred consecutive pregnant women were studied. METHODS: Each woman underwent the following: 1. serological screening for hepatitis surface antigen (HBsAg), antibodies to HCV (anti-HCV), antibodies to human immunodeficiency virus type 1 (HIV1) within the first trimester of pregnancy; and 2. clinico-biochemical assessment in order to ascertain previous or active liver disease and risk factors for viral infections. RESULTS: Twenty-nine (1.7%) of the 1700 women were found anti-HCV positive. Eight of them had an associated positivity for HIV infection. HCV-RNA was positive in 64.2% of anti-HCV positive women. Liver function tests (included transaminases) were within the normal range in 27 mothers (both during and six months after delivery). Only 2/29 women had a slight increase in AST/ALT; liver biopsy in these cases was compatible with mild chronic active chronic active hepatitis. In all women the outcome of pregnancy was favourable (12/29 anti-HCV positive mothers underwent caesarean delivery for causes independent from HCV infection). CONCLUSIONS: A substantial proportion of anti-HCV positive pregnant mothers, even if asymptomatic, have circulating HCV-RNA. The pregnancy does not induce a deterioration of liver disease, and vice versa, HCV infection does not increase the risk of obstetric complications.

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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.

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In this cross-sectional study of 178 pregnant women between the 7th and 42nd week of pregnancy, we analyzed correlations between erythropoietin (EPO) and vitamin B12 (B12) in different stages of pregnancy and in relation to hemoglobin (Hb) levels. Patients with hypertension, fetal growth retardation and severe systemic diseases were excluded. EPO (by ELISA), B12 (by RIA) and Hb were assayed in the same blood sample taken on admission. On the basis of weeks of pregnancy, EPO levels and B12 levels, the 178 subjects were found to fall into two clusters, before and after the 27th week of gestation. The correlation coefficient between EPO and B12 was highly significant in the first group but not in the second (R = -0.33; p < 0.01). When the patients were divided on the basis of Hb levels (< or = or > 11 g/dl), a significant correlation was found only in the 88 patients with Hb > 11 g/dl (R = -0.44; p < 0.001) and not in the 72 anemic subjects. Moreover, in the former group the correlation between EPO and B12 was high before and after the 27th week, unlike in the latter group for which no significant correlation was found. These results suggest that EPO and B12 act together to establish normal erythropoiesis in pregnancy.

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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.

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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.

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