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.

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.

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.

Fibronectin and antithrombin as markers of pre-eclampsia in pregnancy.

INTRODUCTION: The differential diagnosis between pre-eclampsia and chronic hypertension is not easy, but is essential to proper management of a pregnancy. Patients presenting pre-pregnancy hypertension can be treated conservatively, if not a superimposed pre-eclampsia occurs, controlling pressure pharmacologically and completing the pregnancy with a natural delivery. In pre-eclampsia, hypertension is merely the visible sign of a process of endothelial damage and coagulation cascade activation which is often destined to emerge clinically on a dramatic scale. MATERIALS AND METHODS: The study involved 18 women with physiological pregnancies, 19 with pre-eclampsia and 13 with chronic hypertension since superimposed pre-eclampsia. The following laboratory tests were performed: PT, PTT, AT-III, proteins C and S, platelet count, D-dimer, fibrinogen and plasma fibronectin. The three groups were compared using the Kruskall Wallis test, the median test and, for multiple comparisons, the Mann-Whitney test. A 'P' value of < 0.01 was considered as statistically significant. RESULTS: The values for plasma fibronectin were higher in the pre-eclampsia group (410 mg/l (253-727)) than in controls (262 mg/l (183-385)) (P < 0.01) and values for AT-III were lower in the pre-eclampsia group (73% (40-100)) than in controls (93% (80-126) (P < 0.01) (Table 2). The groups with chronic hypertension revealed no such significant differences, however, in relation to the control group (fibronectin = 296 mg/l (198-530), AT-III = 86% (75-103)). CONCLUSIONS: Measuring antithrombin and fibronectin to monitor any onset of pre-eclampsia can help the obstetrician to avoid important diagnostic and therapeutic errors.

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.

Coagulation and plasma fibronectin parameters in HELLP syndrome.

OBJECTIVES: HELLP syndrome (hemolysis, elevated liver enzymes and low platelets) has a high fetal mortality and maternal morbidity, partly due to its late diagnosis. In order to facilitate earlier diagnosis, we studied the changes occurring in natural coagulation inhibitors, fibronectin and haptoglobin as potential early markers of endothelial damage, coagulation cascade activation and intravascular hemolysis. METHODS: The study compared antithrombin (AT-III), protein C and S activity, plasma fibronectin, 'prothrombin time' and 'partial prothrombin time' (AST, ALT), lactate dehydrogenase (LDH), bilirubin and serum haptoglobin in 17 asymptomatic controls, 19 preeclampsia patients and 11 HELLP syndrome patients. RESULTS: HELLP syndrome patients had higher fibronectin and D-dimer values, lower AT-III and protein C activity, a lower platelet count and higher LDH than healthy controls; only 25% had raised bilirubin. Serum haptoglobin was lower in HELLP syndrome. CONCLUSIONS: Early on in HELLP syndrome, there is probably a pro-coagulatory imbalance in the placental microcirculation. Endothelial damage causes tissue thromboplastin release and coagulation cascade activation due to collagen exposure; the vascular lesion increases thromboplastin in the bloodstream and triggers distant coagulation processes, suggesting compensated disseminated intravascular coagulopathy. Measuring plasma fibronectin and coagulation inhibitors should be supported by testing haptoglobin as a marker of intravessel hemolysis to differentiate conventional preeclampsia from HELLP.

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.

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).

Primary abdominal pregnancy. A case report.

Abdominal pregnancies are very uncommon; in the United States they are seen once every 10,000 births and consist of approximately 1% ectopic gestations. We report one case with a primary pelvic-peritoneal ectopic pregnancy, diagnosed by chance at 11 gestational weeks complicated by hemoperitoneum and acute abdomen. This case is interesting because the early diagnosis of abdominal pregnancy is frequently difficult. In fact the clinical history, physical examination, laboratory and ultrasonographic findings are non specific. The physical examination is inconclusive in most patients. Findings such as abdominal tenderness, a closed uneffaced cervix, palpation of a pelvic mass distinct from the uterus are described as being suggestive of the abdominal pregnancy. Once the diagnosis of abdominal pregnancy is made, management of these patients requires a careful and further evaluation. Most clinicians agree that immediate operative intervention is indicated for those pregnancies prior to 23 to 24 weeks, because of the high incidence of maternal morbidity with significant risks of maternal mortality, in light of the poor prognosis for the fetus. In patients who present after 24 weeks, debate has arisen in the literature concerning the appropriateness of a more conservative approach.

Persistent foetal tachycardia as an early marker of chorion-amnionitis. Description of a clinical case.

Intra-amniotic infection (IAI) is uncommon in pregnancy (0.5-1%) and is rarely responsible for maternal mortality, but it does lead to a high rate of maternal and foetal morbidity, e.g. sepsis, septic shock, post-partum endometritis and neonatal sepsis. The diagnosis of IAI is immediate in the case of premature rupture of the membranes, whereas it is far more difficult to reach a correct and timely diagnosis when the amniotic sac is intact, as the mother's clinical symptoms are often scarce and non-specific. Foetal and maternal prognosis in IAI depends on the timely implementation of antibiotic treatment and induction of delivery in order to drain off the infected amniotic fluid. The clinical case described here not only illustrates the difficulty in diagnosing IAI, but also confirms that timely antibiotic therapy can prevent the onset of severe maternal and foetal complications.

Protein S deficiency and pregnancy: is there a case for ylaxis?

Pregnancy reduces protein S to 40-50% of normal levels, but it is not clear whether lower protein S levels raise the risk of developing thrombo-embolism during pregnancy. This case report describes a primigravida with a documented protein S deficiency who delivered at 38 weeks of gestation with no thrombo-embolic complications.

Contraception in diabetic women.

There is a very strong need for an effective and reliable method of contraception in the diabetic woman. An unplanned pregnancy that occurs when her diabetes is not under good control can have disastrous consequences, ranging from abortion to a congenitally malformed fetus. The most important factor in the contraceptive decision for the diabetic patient, especially the IDDM patient, is that the choice be made not by the clinician alone or the patient alone, but through a carefully through-out process that involves both patient and physician.

PIP: Diabetic women are in special need of effective, reliable contraception. A pregnancy that occurs when the diabetes is not under control is at risk of congenital fetal malformations. Since diabetic women require a method with a minimum risk of failure, their choices are limited largely to the IUD and oral contraceptives (OCs). In women with insulin-dependent diabetes mellitus, OC use does not appear to disrupt diabetes control and may require only a mild alteration of insulin requirements. Low-dose monophasic OCs that limit the amount of androgenic activity of the progestin may be the best choice for women with a history of gestational diabetes or insulin-dependent diabetes mellitus.

[Diabetic nephropathy and pregnancy]. / Nefropatia diabetica e gravidanza.

Diabetes mellitus (or type 1) is a long-lasting disease (even twenty years or more) which causes kidney disease and, in the event of pregnancy, it can make differential diagnostic difficult even fort the most expert clinician. Metabolic changes caused by this type of diabetes (e.g., hypoglycemia, hyperglycemia, ketoacidosis) and their difficult compensation can often lead to the onset of eclampsia or convulsion. The diagnostic suspicion of diabetes is supported by the finding of proteinuria, edema and hypertension that are strictly correlated with the evolution of diabetic disease and sometimes exist prior to pregnancy. This cas report focuses on the diagnostic importance of clotting tests, especially in clarifying diagnostic doubts.

Chronic recurrent pancreatitis in pregnancy.

This report describes a case of chronic recurrent pancreatitis due to gallstones arising in the first trimester of pregnancy. Total parental nutrition produced a normalization of pancreatic enzymes and a rapid regression of symptoms. Following another relapse of acute pancreatitis, a laparoscopic cholecystectomy was performed. The pregnancy continued normally and the patient had a spontaneous delivery at the 37th week.

Portal hypertension in a pregnant woman.

We report a case of a patient with long-standing prehepatic portal hypertension. The patient (a 43-year-old parous 2012 female with a history of 2 full-term pregnancies and normal deliveries, plus a spontaneous abortion) incurred spontaneous abortion at the 7th week of gestation. An early, spontaneous abortion avoided this patient running severe risks in late pregnancy. The overall estimated risk of bleeding in patients with portal hypertension, reported in the literature, is 400 times greater than in normal pregnancy. The association with aneurysm of splenic artery increases the likelihood of bleeding because intra-abdominal pressure adds to the risk of rupture of the aneurysms. In our opinion, a patient of fertile age, with pre-hepatic hypertension and associated chronic liver disease, should be treated with contraceptives to avoid any pregnancy-induced risk of complications.

Congenital or torsion-induced absence of Fallopian tubes. Two case reports.

Unilateral absence of a uterine tube is an extremely rare finding, for which there are two possible etiopathogenic causes: in some cases it is due to haemorrhage filling of the cavity and its reabsorption as a result of asymptomatic torsion of the uterine tube during adult life, in pediatric age or even during intrauterine life; alternatively, the absence may be congenital, associated with developmental alterations of the mesonephric and paramesonephric ducts. The article presents two cases of fallopian tube absence: a congenital monolateral absence and a tubal torsion during pregnancy. The symptomatology of the torsion of the fallopian tube in pregnancy can be milder than in the classic description with peritoneal reaction and severe clinical alteration. The main risk factors for tubal torsion are: adhesions and inflammatory processes, ovarian cysts, usually of dermoid type, menstrual period, pregnancy, abnormal long mesosalpinx and/or mesovarium, pelvic congestion induced by constipation and disturbed venous blood flow from the adnexa. A congenital defect of the mesonephric duct is followed by a homolateral defect of the paramesonephric duct. The resulting anomaly is characterized by the absence of the uterine tube, uterus-tube angle, kidney and ureter. Partial or total unilateral defects of a paramesonephric duct are more common than aplasia of both ducts. Some authors have suggested that an inadequate blood supply during the descent into the pelvis of the caudal part of the paramesonephric duct might feasibly lead to incomplete tube development.

Congenital heart disease in pregnancy.

The clinical cases of three patients affected respectively by Eisenmerger's syndrome, Marfan syndrome, coarctation of the aorta are described. All patients belonged to NYHA class I or II. During pregnancy contact with cardiologists, anaesthetists, neonatologists was maintained and this allowed accurate management. Both pregnancy and delivery evolved without any complication and with a positive outcome for mother and newborn.

Acute pancreatitis and deep vein thrombosis associated with HELLP syndrome.

The HELLP syndrome (HS) belongs to the list of obstetric complications believed to be associated with coagulation disorders. It was formerly thought that chronic intravascular clotting (DIC) in the placental vessels was the main cause. A hypercoagulable state has been reported in cases of severe HS associated with microvascular abnormalities that may involve cerebral, placental, hepatic and renal vessels. A case of acute pancreatitis and DVT of inferior cava in a pregnant woman, presenting with HS at 29 weeks, who was found to have a R506Q mutation, is reported. Preeclampsia-associated pancreatitis and DVT have rarely been reported. It is hypothesized that APC-R and Factor V Leiden mutation may prove to be new and more important markers capable of predicting a more significant maternal morbidity associated with HS. Thrombosis prophylaxis may be considered during pregnancy in order to reduce hazardous multiorgan failure (MOF) in women who are heterozygous for Factor V Leiden mutation.

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.