The contraceptive vaginal ring in women with renal and liver transplantation: analysis of preliminary results.

INTRODUCTION: Vaginal administration seems to be the best route to achieve steady and precise doses of contraceptive hormones, resulting in stable serum concentrations and low exposure. The aim of this study was to evaluate the contraceptive efficacy, cycle control, tolerability and acceptability of a contraceptive vaginal ring (NuvaRing) in renal and liver transplant recipients. MATERIAL AND METHODS: Renal or liver transplant recipients, asking for contraception, were enrolled into the study. The duration of treatment was 12 cycles, with each vaginal ring releasing an average of 120 mg etonogestrel and 15 mg ethinylestradiol daily. Study visits were scheduled at screening, in the first week following cycles 3, 6, and 12 (172 cycles). RESULTS: Among 17 females included into the study: were 9 renal (mean age, 30 +/- 7.2 years) and 8 liver transplant recipients (mean age, 32.6 +/- 6.6 years). At the onset of therapy all patients showed at least 6 months of stable graft function with no signs of allograft rejection. The mean posttransplant follow-up was 4 +/- 3.6 and 5.3 +/- 2.1 years for women with renal and hepatic transplantations respectively (P = NS). The immunosuppressive therapy was not changed for any patient. We demonstrated good cycle control: 162 cycles did not exhibit any bleeding; 7 cycles, only spotting episodes, whereas 2 cycles had 1 bleeding episode during the ring period. The estrogen-related adverse events (nausea and breast tenderness) were reported in 2 patients. One patient experienced significant bleeding related to thrombocytopenia. DISCUSSION: Nuvaring, in our preliminary findings, may be considered to be an highly effective contraceptive method for female transplant recipients that additionally regulate menstrual bleeding and seems to positively influence well-being. Vaginal administration may diminish the chance of drug interactions and therefore be safer for patients.

Pregnancy and renal transplantation: a case report of the risk of antibody induction against partner antigens.

Renal transplantation has provided women of childbearing age with increased fertility and the possibility of successful pregnancy outcomes. Approximately 14,000 births among women with transplanted organs have been reported worldwide, but pregnancy complications have been frequent: spontaneous or therapeutic abortion, preterm birth, low birth weight, and intrauterine growth restriction. Herein we have described a case of an acute rejection episode in a renal transplant recipient, occurring 6 months after successful delivery, despite the fulfillment of all European best practice guidelines criteria and the maintenance of adequate immunosuppression. Our case demonstrated that even a presumably low-risk patient can face worsening of renal function during or after pregnancy. Acute immune activation is uncommon but may occur in late-onset fashion. Despite adequate levels of maintenance immunosuppression, there is a risk of developing antibodies against the partner or the donor, causing acute renal immune damage.

Human papilloma virus infection and cervical intraepithelial neoplasia in transplanted patients.

Progress in diagnosis and treatment has led to an increased number of transplantation patients who consequently have immunological depression and emergence of tumors. The incidence of cervical neoplasia, according to previous studies, is 11%; this tumor is the only one that can be investigated by screening before and after a graft. Our purpose was to evaluate whether transplanted patients showed an increased incidence of genital human papilloma virus (HPV) infection and whether this infection produced greater progression of disease in cases of low-risk HPV infections. Our study involved 151 transplant patients who underwent Papanicolaou (Pap) and HPV tests. Patients listed for grafts underwent Pap and HPV tests 6 months before and 6 months after transplantation. All patients had negative Pap tests before their grafts. After their grafts 16 patients (10.59%) had negative Pap tests, but positive viral typing. Eleven patients (7.28%) showed positive Pap tests, 6 of whom had low-grade squamous intraepithelial lesion (SIL) and 5 patients high-grade SIL. The final HPV infection incidence (15.23%) was consistent with the literature. The incidence of lower female genital tract intraepithelial lesions (7.28%) was higher than the healthy population or analogous studies (4.5%-8.5%). We showed a constant association between high-risk HPV infection and gynecologic intraepithelial neoplasia, whereas there was no association between low-risk broods HPV infection and neoplasia. In conclusion, screening should start at almost 6 months before grafting to avoid an irreversible situation that is difficult to treat.

Extremely low ventricular rate in a fetus with an isolated non-autoimmune complete congenital heart block. Case report.

Congenital complete heart block (CCHB) is an uncommon disorder with an incidence of about 1/20,000 in liveborn infants. It can occur in the setting of structurally normal heart or with structural disease; it is associated with high mortality and morbidity and requires a high index of suspicion for early diagnosis and therapy. Isolated CCHB in a fetus is usually associated with the presence of autoantibodies to SSA (Ro) and SSB (La) antigens in the maternal circulation. Such antibodies cross into the fetal circulation and cause inflammation of the conduction tissues; the causal mechanism is not known. Although the prognosis for the majority of fetuses is good, it is less favourable in fetuses with a ventricular rate <55 bpm in early pregnancy or with a decrease in the ventricular rate by >5 bpm during pregnancy. It is not known if the same prognostic criteria apply for fetuses with isolated non-autoimmune CCHB. This article reports authors' experience in managing a pregnancy with an extremely low fetal heart rate (47 bpm) in a single fetus with an isolated non-autoimmune CCHB in which the outcome was favorable.

Variations in fibrinolytic parameters and inhibin-A in pregnancy: related hypertensive disorders.

BACKGROUND: The mechanisms leading to pregnancy-related hypertensive disorders, and pregnancy-induced hypertension (PIH) and pre-eclampsia (PE) in particular, are still not clear. Diagnostic criteria are clinical because specific markers of the condition are lacking. A role of the fibrinolytic system has been suggested. OBJECTIVES: We aimed to evaluate the behavior of tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor type 1 (PAI-1), PAI-2, and the placental hormone inhibin-A in women with a normal pregnancy vs. women with pregnancies complicated by PIH or PE. METHODS: Blood samples were drawn between the 25th and 30th gestational week (GW) and between the 31st and 36th GW in order to assay t-PA, PAI-1, PAI-2 and inhibin-A; routine biochemical exams, ultrasonography umbilical artery pulsatility index (PI), placental weight and newborn weight were measured. RESULTS: In pregnancies complicated by hypertensive disorders, PAI-1 levels were higher than in controls and increased significantly after the 25th GW, especially in PE, as did inhibin-A. PAI-2 levels were significantly lower after the 30th GW in patients with PIH and PE. The PAI-1/PAI-2 ratio was significantly higher in PE patients than in controls as of the 25th GW, but only after the 30th GW in patients with PIH. Inhibin-A was significantly correlated with fibrinolytic parameters, and inversely with newborn weight. Receiver-operator characteristic curves for PAI-1 and inhibin-A showed a high sensitivity and specificity for PE. PAI-2 correlated with newborn and placental weight, and inversely with PI of the umbilical artery. CONCLUSIONS: Fibrinolytic tests (especially PAI-1) and inhibin-A monitoring during pregnancy may help in the early diagnosis of pregnancy-related hypertensive disorders.

Early detection by magnetic resonance imaging of fetal cerebral damage in a fetus with hydrops and cytomegalovirus infection.

We discuss the use of magnetic resonance imaging (MRI) to reveal early fetal neurological involvement of cytomegalovirus (CMV) infection. A woman presented at 21 weeks of pregnancy with active CMV infection. Cerebral ultrasound examination had been normal. An MRI scan revealed a thickened germinal matrix, which was histologically confirmed, associated with underdevelopment of the gyri. Brain MRI proved particularly useful in identifying the findings not disclosed by routine ultrasound during pregnancy and subsequently confirmed at histology.

Hypertrophic obstructive cardiomyopathy and pregnancy: anesthesiological observations and clinical series.

Hypertrophic obstructive cardiomyopathy represents a genetic disorder characterized by hypertrophy, usually asymmetrical, of the ventricular musculature at the base of the septum in the left ventricular efflux tract. Patients suffering from this disorder can be extremely sensitive to small alterations in ventricular volumes, arterial pressure, cardiac frequency and rhythm. This disorder is found in pregnancy with an incidence of 0.1-0.5% and, because of its gravity, represents a contraindication which is often absolute to pregnancy. Hemodynamic variations such as those found in pregnancy, labor and delivery have complex influences on hypertrophic cardiomyopathy. Our clinical series includes 2 pregnant patients suffering from hypertrophic obstructive cardiomyopathy who both underwent caesarian section in general anesthesia, the first due to the gravity of cardiac obstruction and the second due to the emergent need to proceed after the beginning of labor. The small number of clinical cases in the literature, especially in the last few years, clearly underlines the difficulty of defining both the most correct method for delivery and the most appropriate anesthesiological techniques. In accordance with the literature and our clinical experience, we can conclude that a carefully managed pregnancy can proceed without complications in patients with moderate obstruction and that a regional anesthesiological approach is also possible with careful hemodynamic monitoring. General anesthesia, however, remains the safest method and has fewer risks for patients with serious obstruction or with worsening of their clinical condition during pregnancy.

The management of feto-maternal alloimmune thrombocytopenia: report of three cases.

We report herein three cases of severe fetal thrombocytopenia due to anti-human platelet antigen (HPA)- 1a maternal antibodies. The first and the third cases were diagnosed on the basis of previously affected siblings and treated successfully by maternal intravenous human immunoglobulins and corticosteroids. In the second case an unexpected neonatal thrombocytopenia was found after birth without previously affected siblings and treated subsequently with intravenous immunoglobulins. Our experience supports a switch from an invasive management, including early FBS (fetal blood sampling) and platelet transfusions, to a more cautious approach. Also in severe HPA-1a alloimmunization and in 'high risk' fetuses, prenatal maternal treatment could be performed, without previous FBS, only on the basis of a risk score defined by sibling history and parents' genotypes.

Efficacy of an acidic vaginal gel on vaginal pH and interleukin-6 levels in low-risk pregnant women: a double-blind, randomized placebo-controlled trial.

BACKGROUND: Increased interleukin-6 (IL-6) levels and a vaginal pH of > 4.7 are associated with obstetric complications such as preterm delivery and low birth weight. Topical treatments, able to maintain a physiological vaginal pH, could help in the prevention of vaginal infections. STUDY AIM: In a randomized, double-blind, placebo-controlled trial, we evaluated the effects of an acidic buffering vaginal gel (Miphil) on vaginal pH and IL-6 levels in pregnant women. PATIENTS AND METHODS: Seventy low-risk women pregnant with a singleton (second trimester) were enrolled in the trial. Thirty-five were randomized to the acidic gel, 2.5 g every 3 days for 12 weeks, and 35 to the corresponding placebo. Vaginal pH and vaginal IL-6 level were measured at baseline and after 12 weeks. Women were then followed until delivery. The main outcome measures were vaginal pH, vaginal pH normalization (pH < 4.5) and vaginal IL-6 levels. RESULTS: Vaginal pH at baseline was 4.6 +/- 0.4 and 4.4 +/- 0.3 in the acidic gel and the placebo group, respectively. At baseline, a total of 40% (14/35) and 22% (8/35) of women in each group, respectively, had a vaginal pH of > or = 4.7. At week 12, the vaginal pH was 4.3 +/- 0.3 in the acidic gel group and 4.3 +/- 0.3 in the placebo group (NS). The acidic gel normalized the vaginal pH in ten out of 14 women (p = 0.04) in comparison with only one out of eight women in the placebo group (NS). The acidic gel induced a significant (p < 0.02) reduction of vaginal IL-6 from 12.0 +/- 7 to 8.9 +/- 5 pg/l (-36%). In the placebo group, IL-6 increased from 9.0 +/- 5 to 13.5 +/- 6.8 pg/l (+50%) (p = 0.05). Birth weight was 2978 +/- 700 g in the placebo group and 3241 +/- 477 g in the acidic gel group (p = 0.06). CONCLUSIONS: The use of the acidic gel in low-risk pregnant women is able to maintain a physiological vaginal ecosystem and prevents the increases of vaginal pH and vaginal IL-6. Prospective and controlled trials are warranted to evaluate whether this acidic gel can reduce obstetric complications linked to vaginal inflammation during pregnancy.

Biochemical markers for the prediction of spontaneous pre-term birth.

OBJECTIVES: The aim of this study was to identify predictive biochemical markers for preterm labor. METHODS: In this prospective study we included 225 asymptomatic Caucasian women consecutively enrolled at 24 weeks of gestation. The following data were collected only once at 24 weeks of gestation: vaginal pH, vaginal fFN, cervical and serum concentration of IL-6, IL-8 and TNFalpha, maternal blood serum, ferritin. Student's t-test, the chi(2)-test and multiple linear regression were used as statistical methods. RESULTS: There were no differences between the age of patients, parity and gestational age at sampling between women who delivered at term and those who delivered pre-term (<37 weeks' gestation). There was a significant increase of cervical IL-6 (pre-term 608+/-1595 pg/l vs. at term 58.9+/-112 pg/l) and serum ferritin (pre-term microg/l 74.4+/-1.1 vs. at term 26.3+/-56.5 microg/l) in pregnant women who delivered pre-term (P<0.05). No differences in cervical IL-8 and cervical TNFalpha between pre-term and term deliveries were found. Multiple linear regression confirmed that the vaginal pH value and cervical fFN test were the best predictive biochemical markers of pre-term birth (standardized coefficient Beta=0.33 and 0.22, respectively). CONCLUSIONS: In order to evaluate pregnancies for pre-term labor, the presence of pH>4.5 and a positive fFN test seems to be predictive of subsequent pre-term delivery.

Activated protein C resistance in normal and pre-eclamptic pregnancies.

OBJECTIVES: A lower ratio in the classic activated protein C resistance (APC-R) test has been reported during pregnancy, which has been called 'acquired' APC-R. However, little is known about the cause of the lowered ratio, and whether or not there is a correlation with blood coagulation activation. The primary objective of our study was to determine changes in APC-R levels in each of the trimesters of normal pregnancy. The secondary objective was to confirm whether APC-R levels were lower in pregnancies complicated by pre-eclampsia than in a control group. Finally, this prospective study was performed to investigate the prevalence of APC-R among pregnant women and to elucidate its obstetric consequences. METHODS: We enrolled 35 healthy pregnant women and 47 pregnant women affected by pre-eclampsia in our study. The following laboratory tests were performed: prothrombin time, partial thromboplastin time, fibrinogen levels, antithrombin III, plasmatic fibronectin (as a marker of endothelial damage), haptoglobin (as a marker of intravascular haemolysis), a functional test for APC-R and analysis of factor V Leiden mutation by polymerase chain reaction. RESULTS: The activated protein C sensitivity ratio was lower in the pathological group than in the control group (p = 0.008 and p = 0.02, respectively). Plasmatic fibronectin was found to be higher in the pathological group than in the control group (p = 0.05). Finally, the overall prevalence of factor V Leiden mutation was 5.4%, i.e. 2/35 women (5.7%) in the control group and 3/47 women in the pathological group (6.38%). CONCLUSIONS: The APC ratio decreased after 20 weeks of gestation until week 42. This decrease was most pronounced in the third trimester, in which resistance was demonstrated in 34.2% of control group patients. In pre-eclampsia, we found a greater reduction of the APC ratio than in controls. We hypothesise that this is due to a decrease in the plasmatic levels of coagulation inhibitors and an increase in coagulatory factors.

Viral load in HCV RNA-positive pregnant women.

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.

The effects of epidural analgesia and uterine contractions on fetal oxygen saturation during the first stage of labour.

The aim of this study was to investigate the effects of (1) maternal epidural analgesia and (2) uterine contractions on fetal oxygen saturation. After informed consent 18 women were included in our prospective, non-blinded, observational study. After 30 min of monitoring fetal oxygen saturation and uterine contractions, all the parturients, at cervical dilatation >/= 3 cm, received epidural analgesia for labour: a Pajunk epidural catheter was passed through a 17-gauge Tuohy needle and left in the lumbar epidural space (insertion level L3-4 or L2-3). Sufentanil 10 microg and 0.1% ropivacaine 15 mL were injected into the epidural catheter. A second and third 15-mL epidural dose of 0.1% ropivacaine were administered on patient demand. Fetal oxygen saturation was unaffected by epidural analgesia and there was no change in fetal SpO(2)following an uncomplicated epidural top-up. SpO(2)values (%) 30 s before, during and after contraction were 47.6 +/- 2.4, 52.5 +/- 5.3 and 42.9 +/- 7.2 respectively. These changes were significant. A contraction appeared to inject a bolus of oxygenated blood into the fetus, causing an initial increase in fetal oxygenation followed by a decline. The lowest SpO(2)values observed occurred 120 s after the start of contractions.

Hepatitis C virus, hepatitis B virus and human immunodeficiency virus infection in pregnant women in North-East Italy: a seroepidemiological study.

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.

[Comparative analysis of premature labor markers]. / Analisi comparativa dei marcatori di parto pretermine.

We compared the diagnostic value of foetal fibronectin (fFN), phosphorilated insulin-like growth factor protein binding-1 (Birth test) and insulin-like growth factor protein binding-1 (PROM test) as markers of premature rupture of membrane (PROM) and in prediction of preterm labor with intact membranes. The study population included 120 asymptomatic women (group 1), with gestation of 24-34 weeks; we also considered 21 patients with clinically confirmed PROM (group 2) and 26 patients with suspected PROM with gestation between 15 and 24 weeks (group 3) (as measured by sonography data). From our data, it seems that only the predictive value of each test is related to the characteristics of the population considered. The fFN test and the Birth test prove to be highly predictive in pregnant women without PROM, on the contrary the use of the PROM test is optimal in pregnant women with suspected PROM or with PROM, regardless of risk factor or with contractile activity.

[Pregnancy in women infected with the hepatitis C virus]. / La gravidanza in donne affette dal virus dell'epatite C.

The prevalence of HCV-RNA positivity in pregnant women goes from 1.2% to 4.5% in different countries. The aim of our study is to show pregnancy outcome, vertical/perinatal transmission rate, the viral load and the tramnsaminases trend during pregnancy and after delivery. The study involved 11,681 pregnant women screened in the Obstetric Department for High Risk Pregnancy at the University of Padua between 1992 and 1999. We evaluated the markers of HCV, HBV, HIV, the viral load and genotype and AST/ALT in the mothers and positivity and viral load of HCV-RNA in the newborns at birth and at 3rd, 6th, 9th, 12th month. Of the 11,681 pregnant women, 135 (1.15%) tested positive for the presence of anti-HCV antibodies and of the 135 anti-HCV antibody-positive mothers, 80 were found to be positive for HCV-RNA. Of 80 pregnancies that were HCV-RNA positive, 4 termined in abortion, 1 in stillborn, 1 in neonatal death, 18 in preterm delivery and 56 were carried to term. We came to the conclusion that HCV infection does not increase the risk of obstetric complications and does not influence the fetal-neonatal status at delivery; the pregnancy evolution may be complicated by the onset of cholestatsis in the 2nd and 3rd trimester; vertical transmission of the infection develops in few cases (4.8%), more likely at delivery.

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).