Labour induction at term: clinical, biophysical and molecular predictive factors.

PURPOSE: The aim of this multicentric study is to compare clinical, biophysical and molecular parameters in the prediction of the success of labour induction with prostaglandins. METHODS: We included 115 women, who underwent to labour induction at term with vaginal prostaglandin gel. We evaluated the diagnostic efficiency of endocervical phosphorylated insulin-like growth factor-binding protein (phIGFBP-1), cervicovaginal interleukins 6 (IL-6) and 8 (IL-8). We analyzed the transvaginal sonographic measurement of cervical length. A receiver-operating characteristics (ROC) curve was used to determine the most useful cut-off point. A multivariate logistic regression model was used to analyze the combination of significant predictive variables following univariate analysis. We analyzed all the data searching for the parameters that best predict the beginning of the active phase of labour within 12 h. RESULTS: 36.5 % of the patients delivered within 12 h. The Bishop score was >4 in the 43 % of patients with an active phase. The best cut-off values at ROC curves for cervical length, IL-6 and IL-8 were respectively 22 mm, 5 mg/dl and 20,237 mg/dl. At univariate analysis, all predictors of success, with the exception of IL-6, were significantly associated with the beginning of the active phase. Multivariate analysis of the Bishop score (OR 2.3), phIGFBP-1 test (OR 11.2) and IL-8 (OR 6.6) showed that the variables were independent and therefore useful in combination to predict the success of labour induction. CONCLUSION: The phIGFBP-1 test is a fast and easy test that can be used with Bishop score and IL-8 to reach an high positive predictive value in the prediction of the success of labour induction with prostaglandins.

Combination of biochemical markers in predicting pre-term delivery.

PURPOSE: The aim of this study was to evaluate the predictive performances of some biochemical markers in predicting pre-term delivery in asymptomatic women. METHODS: We included 491 asymptomatic women at 24 weeks' gestation, who underwent the endocervical phosphorylated insulin-like growth factor binding protein (phIGFBP-1) test, cervico-vaginal interleukins 6 (IL-6) and 8 (IL-8), and serum C-reactive protein (CRP). A receiver-operating characteristics (ROC) curve was used to determine the most useful cut off point. A multivariate logistic regression model was used in order to analyze the combination of significant predictive variables for pre-term delivery following univariate analysis. RESULTS: ROC curves indicated that 33 µg/l was the optimal cut off value for phIGFBP-1 test, 21.3 ng/l for IL-6, 324 ng/l for IL-8, and 8.42 mg/l for CRP in predicting pre-term delivery. The univariate logistic regression analyses revealed an odds ratio of 3.04 for phIGFBP-1 test, 4.82 for IL-6, and 3.08 for CRP. The multivariate analysis of phIGFBP-1 test, IL-6, and CRP showed that they were independent variables and therefore useful in combination for predicting pre-term delivery. CONCLUSIONS: The phIGFBP-1 test, the cervico-vaginal IL-6, and the serum CRP are independent variables that can be used together to predict pre-term delivery in asymptomatic women.

Biochemical markers predicting pre-term delivery in symptomatic patients: phosphorylated insulin-like growth factor binding protein-1 and fetal fibronectin.

PURPOSE: The aim of this study was to evaluate the efficacy of the phosphorylated insulin-like growth factor-binding protein (phIGFBP-1) and of the fetal fibronectin test (fFN) in predicting pre-term delivery in symptomatic women. METHODS: We included 210 symptomatic women at 24-34 weeks' gestation, who underwent the phIGFBP-1 and fFN test. We analyzed the prevalence of pre-term delivery in these patients within 7 days upon admission, before the 34th and the 37th weeks' gestation. RESULTS: The 3.8% of women delivered within 7 days upon the admission, the 7.6% before 34 weeks and the 16.2% before 37 weeks' gestation. The phIGFBP-1 and fFN test had a high specificity and a high negative predictive value in predicting pre-term delivery within 7 days, before 34 and before 37 weeks' gestation. The logistic regression of phIGFBP-1 was statistically significant in predicting pre-term delivery with an odds ratio of 10.08 <34 weeks' gestation. The multivariate analysis showed that the phIGFBP test had a higher OR <34 weeks' gestation (p < 0.001) and that the two variables were independent and useful in combination to predict pre-term delivery (<37 weeks' gestation). CONCLUSION: The phIGFBP-1 test may be better that the fFN test in predicting pre-term delivery before 34 weeks' gestation.

Pulmonary hypertension during pregnancy: management of two cases.

PURPOSE: The aim of this article is to describe two cases of pulmonary hypertension during pregnancy to highlight the major issues associated with the obstetric and anesthesiological management of such patients who, despite the medical advice, decided to continue their pregnancy and gave birth to healthy babies. METHODS AND RESULTS: In our first case, there has been the need for a general anesthesia because of the detachment of the placenta, whereas in the second case elective surgery under spinal anesthesia was performed, thus avoiding the anesthesiological and surgical problems associated with an emergency. CONCLUSIONS: Pregnancy is contraindicated in case of pulmonary hypertension, a highly morbid disease affecting young women of childbearing age. Therefore, in such cases, a multidisciplinary approach is indispensable to plan optimal treatment for patients who wish to pursue a pregnancy even though their heart disease exposes them to a high level of risk.

GB virus C infection in pregnancy: maternal and perinatal importance of the infection.

OBJECTIVES: The more effective way of transmission of GB virus C (GBV-C) is parenteral, but sexual and vertical transmission seem to be the main way of spreading. We evaluated the prevalence and the effect of GBV-C infection on pregnant women, vertical transmission and viral effects on the newborn. STUDY DESIGN: This study has consecutively enrolled 879 pregnant women. All patients had blood sampling to determine GBV-C RNA, serologic tests for chronic viral infections and seric tests of hepatic damage. The newborns from infected mothers had blood sampling to detect the presence of GBV-C at birth, and after 3 and 6 months. Positive babies were checked until 18 months. RESULTS: 36 (4.1%) women resulted GBV-C positive. Among the positive patients none presented complications during pregnancy. Neither embryonic-fetal abnormalities nor relevant differences in fetal birth weight and week of gestation at delivery were found. 20 out of 36 babies had a follow-up. At birth, 13 (65%) babies were positive. 4 out of 9 vaginal deliveries (44%) and 9 out of 11 cesarean sections (82%) resulted positive to GBV-C RNA. The risk of GBV-C vertical transmission was not significantly increased by type of delivery (p=0.274). At 3 months, 13 babies were GBV-C positive (65%) and 7 were negative (35%). At the end of the follow-up, 9 babies were positive (45%), while 11 were negative (55%). CONCLUSION: The percentage of patients positive to GBV-C RNA was comparatively high (4.1%). This prevalence, in a population without particular risk factors, confirms that common ways of transmission, such as the sexual and vertical ones, might have an important role in viral diffusion. Our data suggest that the infection does not influence the course of pregnancy. The rate of transmission found in our study is high. Type of delivery does not seem to be actually involved in vertical transmission and the protective role of cesarean section has not been confirmed.

Endogenous interferon-alpha level is increased in hepatitis C virus (HCV)-positive pregnant women.

BACKGROUND: Mother-to-child transmission of hepatitis C virus (HCV) has been reported in around 5% of cases, and is much more likely to occur in case of coinfection with HIV. However, other cofactors influencing the vertical transmission are still debated. AIM: To assess the serum concentration of endogenous interferon (IFN) during pregnancy, and its eventual role on the vertical transmission of HCV. METHODS: Forty-seven HCV-infected pregnant women, and 3 control groups: (1) 75 HCV-negative pregnant women; (2) 29 HCV-positive nonpregnant women; (3) 29 HCV-negative nonpregnant women entered into the study. Endogenous IFN was assayed by enzyme-linked immunosorbent assay. The following parameters were also analyzed: viral load, HIV infection, risk factors for acquiring HCV, parity, gestational age, mode and course of delivery. RESULTS: Vertical transmission of HCV was observed in 2 cases (4.3%). Plasma levels of IFN were significantly higher in HCV-positive pregnant women compared with either HCV-positive and HCV-negative nonpregnant women. The 2 mothers who transmitted the infection had IFN levels within the same range as the women who did not transmit the infection. CONCLUSIONS: In HCV-positive pregnant women, there is an increased production of endogenous IFN-alpha. Further studies are warranted for clarifying the mechanisms of this cytokine in the prevention of HCV transmission.

Investigation of endothelin-1 type A receptor gene polymorphism (-231 G > A) in preeclampsia susceptibility.

OBJECTIVE: Preeclampsia is considered as a multifactorial disorder with a genetic predisposition. Alterations in the endothelin-1 (ET-1) system are considered to take part in triggering the vasoconstriction seen in preeclampsia. METHODS: In order to investigate the possible association of the -231 G > A polymorphism in the endothelin-1 type A receptor gene (EDNRA), previously shown to be associated with other conditions characterized by vasospasm, we examined 77 Caucasian preeclamptic women and 67 matched controls including normotensive subjects without history of thromboembolic event, abnormalities in blood pressure, proteinuria, edema and preeclampsia. The genotype was assessed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) on genomic DNA extracted from blood samples. Case vs. control allele frequencies and genotype distributions were compared. RESULTS: No significant differences were found when considering both genotype (chi(2) = 0.58, p = 0.75) and allelic frequencies (chi(2) = 0.08, p = 0.77). Furthermore, no significant genotype-related difference was found in relation to clinical features, such as gestational age at onset, systolic and diastolic blood pressure, proteinuria on admission and delivery week. CONCLUSIONS: No association between the -231 G > A polymorphism in the EDNRA gene and preeclampsia as well as any correlation with the main clinical features of the disorder were found, thus excluding a role for this polymorphism in susceptibility to preeclampsia.

Cervical phIGFBP-1 in the evaluation of the risk of preterm delivery.

BACKGROUND: To evaluate the accuracy of the decidual phosphorylated isoform of insulin-like growth factor binding protein-1 in endocervical secretions to predict premature delivery in symptomatic and asymptomatic pregnant women. METHODS: The study included 332 pregnant women: 109 symptomatic patients (study group) and 223 asymptomatic women (control group). For all women, qualitative and quantitative assessment of the decidual phosphorylated isoform of insulin-like growth factor binding protein-1 in endocervical secretions was carried out, but the quantitative assay was finally performed in 282 of 332. Student's test, the chi2 test, and Fisher's exact test were used as appropriate. RESULTS: The phosphorylated insulin-like growth factor binding protein-1 qualitative test was positive in 35 of 301 women (11.6%) and 11 (31.4%) of them delivered before 37 weeks; in the remaining 266 women with a negative test, there were 11 (4.7%) premature deliveries (relative risk = 5.8; 95% CI = 3.3-10.3). The mean values of quantitative phosphorylated isoform of insulin-like growth factor binding protein-1 were 56.9 microg/l (95% CI = 40.7-73.1) in cases of a positive qualitative test and 6.1 microg/l (95% CI = 4.0-8.3; p = 0.0001) in women with a negative result. The sensitivity, specificity, positive predictive value, and negative predictive value for phosphorylated isoform of insulin-like growth factor binding protein-1 test in symptomatic patients were 69.2%, 90.5%, 50%, and 95.6% respectively, while in the asymptomatic patients they were 22.2%, 91.8%, 11.8%, and 96% respectively. CONCLUSIONS: The phosphorylated isoform of insulin-like growth factor binding protein-1 in cervical secretions is a potential specific marker for preterm delivery occurring before 37 weeks. This test may have an important role in the management of women presenting with symptoms suggestive of preterm labour.

Hypoplastic left heart syndrome with intact atrial septum: case report.

OBJECTIVES: Hypoplastic left heart syndrome (HLHS) with an intact atrial septum (IAS) is a rare finding, reported in only 1% of pathologic specimens with hypoplasia of the aortic tract complex. In newborns with left heart obstruction, the existence of an interatrial communication is very important for oxygenated blood to be distributed to the body and to prevent pulmonary congestion. The ability to predict prenatally restriction of the atrial defect may allow earlier surgery to be planned. METHODS: We report a case of prenatal diagnosis of HLHS with a complete premature closure of the foramen ovale that was not detected by prenatal echocardiography. RESULTS AND CONCLUSION: The management of neonates with HLHS in the first days of life is crucial to the results of the first stage of the Norwood procedure. We suggest that delivery of the mother close to surgical centre and avoiding neonatal transfer improve the results, but stabilisation with prostaglandins and balancing of the systemic and pulmonary resistances are also important. A restrictive or closed atrial septal defect may contribute to haemodynamic instability in the first days of life. The ability to predict this complication prenatally may help in the immediate postnatal management of the affected infant.

C-reactive protein in hypertensive disorders in pregnancy.

Hypertension is the most frequent medical complication of pregnancy. A recent report demonstrates the flogistic pathogenesis of pregnancy-induced hypertension. Because C-reactive protein (CRP) is a marker of inflammation, it can be used in the differential diagnosis of hypertensive disorders of pregnancy. A total of 322 pregnant women at 24 to 32 weeks' gestation were enrolled. The control group (A) comprised 190 women. Sixty-three women had preeclampsia (PE, group B), 31 women presented transient hypertension (TH, group C), 19 had HELLP syndrome (HS, group D) and 19 had chronic hypertension (CH, group E). CRP serum concentrations were significantly higher in groups B, C, and D in comparison with the group A. In the whole population, systolic and diastolic pressure value inversely correlate with weight at delivery and weeks of gestation at delivery. CPR levels in patients with PE and HS inversely correlate with birth weight and gestational week at delivery. Normal plasma levels of CRP may be an important marker of differential diagnosis between TH and CH. In TH, PE, and HS, CRP levels were higher than in the control and CH groups, suggesting that inflammation may be the common pathogenetic cause of TH and PE. Finally CRP levels in preeclampsia are believed to correlate with preeclamptic process severity.

Ballantyne syndrome: a case report.

Ballantyne syndrome (also called mirror syndrome or triple edema) describes the unusual association of fetal and placental hydrops with maternal preeclampsia. This is a case report illustrating a 37-year-old patient who was referred to our clinics at 28 weeks of gestation (wg) because of fetal hydrothorax. On examination, the woman did not show signs of preeclampsia. The fetal ultrasound examination revealed bulky hydrothorax, generalized subcutaneous edema, placental edema, and polyhydramnios. It was not possible to find the cause of the fetal hydrops. At 29 weeks and 4 days of gestation, the fetal hydrothorax was removed by two pleuro-amniotic shunts, but at the moment of our intervention anasarca was already present. In the following 3 days, despite observing bed rest, the mother developed edema of hands and face, while blood pressure remained normal. At 30 wg the patient underwent cesarean section because fetal movements ceased and the fetal heart rate monitoring showed loss of variability and decelerations. Before dying, the neonate lived for 20 days in a state of deep hypotension.

Recent progress in the therapeutic management of pre-eclampsia.

Pre-eclampsia is a pregnancy-specific syndrome of unknown aetiology, observed in 3 - 5% of all pregnancies, associated with pathological vascular lesions in multiple organs, activation of the coagulation system, and maternal multisystemic and fetal complications. Clinically, pre-eclampsia is characterised by the onset of hypertension, proteinuria and oedema, usually beginning in the third trimester. Conventionally, antihypertensive agents are the main pharmacological treatment. Recently, some studies have shown that the treatment of pre-eclampsia with antithrombin concentrate corrects the hypercoagulability and improves the fetal status and the perinatal outcome. No clear evidence supports the use of heparin. A conservative treatment of moderate- to- severe pre-eclampsia, based on the administration of antithrombin concentrate, may allow a significant prolongation of pregnancy and a better neonatal outcome, as well as fewer maternal complications.

Efficacy of AT in pre-eclampsia: a case-control prospective trial.

Pre-eclampsia is an extremely severe condition. It is associated with vasospasm, activation of the coagulation system and abnormal haemostasis. In pre-eclamptic patients increased plasmatic concentrations of fibronectin, laminin, von Willebrand factor (VWF) and endothelin are observed. Experimental studies on rats have also shown that the doses of antithrombin III (AT) needed to mediate anti-inflammatory processes are much higher than those required to obtain the anti-coagulant effect. The study aimed to evaluate the clinical efficacy of treatment with high AT doses (HD) in comparison with standard doses (SD). The primary endpoint was the prolongation of pregnancy defined as time (in days) from enrollment to delivery and to assess the maternal bleeding at and after delivery. The secondary endpoint was to demonstrate a role for AT in controlling haemostasis at conventional doses, and the inflammatory state at higher doses. The biochemical parameters assessed were: AT activity (%), Fibronectin (Fn), Fibrinogen, D-dimer, Uricemia, Proteinuria 24h, Protein C Reactive (PCR), Granulocyte Elastase and Endothelin. This study included 23 pre-eclamptic women. Patients were randomly subdivided into two groups: 10 patients ("cases") were treated with high doses of AT (6 vials: 3000 units) once daily for 5 days, or until delivery, while 13 women ("controls") were treated with doses of AT sufficient to maintain at least 80% of the activity. High-dose therapy was associated with prolongation of pregnancy by 2.5 days more when compared with controls (p = 0.03; Mann-Whitney test). The incidence of clinical significant bleeding was lower in cases than in controls (mean 550 mL vs. 650 mL, respectively). Preventive- and conservative-type treatment of moderate-severe pre-eclampsia, based on the administration high doses of AT, allows a significant prolongation of pregnancy, and thus a better neonatal outcome, as well as less maternal intra- and post-operative bleeding. Fn, PCR and elastase levels (markers of inflammation) decrease in the HD group in comparison with SD group. In the HD group, the AT plasma levels were obviously higher both at the end of the treatment (p < 0.0001) and after delivery (p = 0.03), in comparison with SD group. The fibrinogen and D-dimer levels were above the reference interval in both groups. TPA and PAI 1 were found to be significantly raised in the course of pre-eclampsia. In conclusion, the bio-chemical findings support a role for AT in controlling the haemostasis at conventional doses, and the inflammatory state at higher doses.

Acute hepatic failure in pregnancy.

Severe liver dysfunction in late pregnancy is an unusual but dramatic event because it can progress very rapidly to fulminating disease and also because two lives, that of the mother and foetus, are involved. We report a descriptive study of a pregnant woman presenting with severe liver dysfunction.

Prenatal diagnosis of vein of Galen aneurysmal malformations.

Vein of Galen aneurysmal malformations are rarely seen intracranial malformations. They represent less than 1% of the cerebral arteriovenous malformations. Prenatal diagnosis of an arteriovenous fistula malformation may be achieved by real-time and Doppler sonography with color flow imaging, by identifying dilated veins and arteriovenous shunts with turbulent flow. In addition, an elevated cardiac output may be observed and correlated with the magnitude of the cerebral arteriovenous shunt. The high incidence of cardiomegaly in neonates with arteriovenous malformations also suggests that high-output cardiac failure is already present in a significant number of cases during the 3rd trimester, and, therefore, treatment in utero may need to be considered to improve the hemodynamic status. In our case, all the above cardiovascular features were present during prenatal ultrasonography. The information on outcome compiled from the literature suggests that when an arteriovenous malformation is large enough to be detected prenatally, as in our case, it is likely to lead to cardiac failure either during the antenatal period or soon after birth. In this paper, we present the management of a case of 3rd-trimester diagnosis of a vein of Galen aneurysm associated with cardiac decompensation.

Anhydramnios and maternal thrombocytopenia after prolonged use of nimesulide.

Prostaglandin synthesis inhibition have been proposed as an effective alternative to prevent preterm labour. This case report shows a pregnancy with anhydramnios and maternal thrombocytopenia, as side effects of the nimesulide therapy.

Sex hormone profile and endometrial cancer risk in primary biliary cirrhosis: a case-control study.

OBJECTIVE: To investigate the sex hormone profile and endometrial histology in primary biliary cirrhosis (PBC). STUDY DESIGN: A prospective case-control study. Twenty-two females with PBC and 22 sex- and age-matched healthy controls underwent complete gynaecological examination including endometrial biopsy and a sex hormone serological profile including: oestrone, 17-beta oestradiol, testosterone, progesterone, dehydroepiandrosterone sulphate (DHEA-S) and sex hormone binding protein (SHBG). The sex hormone profile was evaluated with respect to the body mass index (BMI), anthropometric measurements and endometrial histological/cytological patterns in each case. Statistical analysis was done with the chi-squared method, Student's t-test for unpaired data, linear regression analysis, Spearman's rank correlation test and stepwise multiple regression analysis. RESULTS: The BMI was comparable in the two groups, while PBC cases had significantly smaller subscapular, waist, bicipital, tricipital and calf fold measurements than controls. Testosterone serum levels were significantly lower in PBC cases than in controls (0.9+/-0.6 versus 1.4+/-0.7 mmol/l, P<0.03), whereas SHBG was significantly higher than in controls (88.6+/-72.1 versus 63.6+/-27.6, P<0.005). No significant differences between the two groups were found for oestrone, 17-beta oestradiol, DHEA-S, and progesterone levels. No difference patterns were observed in endometrial histological/cytological patterns. Multiple regression analysis identified SHBG as an independent variable associated with PBC. CONCLUSIONS: Changes in sex hormone profile are secondary to hepatic dysfunction in PBC. Females with PBC do not appear to carry a higher risk of endometrial cancer.

Intra-hepatic cholestasis of pregnancy in hepatitis C virus infection.

BACKGROUND: Aims of this study were to investigate whether hepatitis C virus infection influences the incidence and natural history of intrahepatic cholestasis of pregnancy (ICP) and whether ICP has different characteristics in hepatitis C virus (HCV) positive women from ICP in HCV negative women. METHODS: A prospective study for the prevalence of the HCV infection and for the incidence of ICP was carried out in the 5840 patients admitted to the Prenatal Department of Padua University, Italy, between January 1996 and January 1999. Testing was done for HCV by the enzyme linked immunosorbent assay (ELISA 3), recombinant immuno blot assay (RIBA 3) and polymerase chain reaction (PCR). The diagnosis of ICP was made on clinical grounds based on the occurence of pruritus with onset during pregnancy, persisting up to the time of delivery and disappearing after delivery, supported by demonstrating an elevation of both serum ALT and total serum bile acids. The Student's t-test, one way anova and chi-square tests were used for statistical analysis. RESULTS: During the study period, 56 of 5840 patients developed ICP (0.96%). Of these, 12 were also HCV-RNA positive. The rate of ICP was observed more commonly in HCV-RNA positive women than in HCV-RNA negative women (20.33% or 12/59 versus 0.78% or 44/5767, P = 0.001 CONCLUSIONS: Occurrence of ICP during the third trimester should be an indication to investigate the HCV status of the patient. Although the diagnosis of ICP is not confirmed by specific tests, we confirmed a higher risk of HCV infection in this condition. Therefore, occurence of ICP during the third trimester should be an indication to investigate the HCV status of the patient. Broader studies are necessary to assess the impact of infection on the perinatal outcome of ICP.