Pregnancy outcomes and prognostic factors in patients with intrahepatic cholestasis of pregnancy.

The aim of this study was to describe maternal and fetal characteristics associated with intrahepatic cholestasis of pregnancy (ICP) and to determine clinical and biochemical predictors of fetal complications. A total of 89 singleton pregnancies with ICP were analysed, retrospectively. All data concerning laboratory results, symptom onset time, treatment response, delivery time and infant information were recorded in the study protocol. The mean gestational age at diagnosis was 32.6 ± 3.4 weeks; mean time of delivery was 36.8 ± 1.9 weeks. Binary logistic regression revealed that gestational age at diagnosis was predictive of preterm delivery (OR = 2.3, 95% CI: 1.5-3.3, p = 0.001). The incidence of respiratory distress syndrome (RDS), fetal growth restriction, fetal distress and preterm delivery were significantly higher in patients who were diagnosed before 30 weeks than after 34 weeks' gestation (p < 0.01). Gestational age at diagnosis is an important independent factor predicting adverse perinatal outcomes in patients with ICP.

Neonatal morbidity mortality outcomes in pre-term premature rupture of membranes.

We present a retrospective review of 228 pre-term premature rupture of membranes (PPROM) singleton pregnancies followed-up in our clinic between 1996 and 2005. The most common neonatal morbidities in PPROM cases are respiratory distress syndrome (RDS), sepsis and intraventricular haemorrhage (IVH). The route of delivery does not affect newborn intensive care unit (NICU) requirements, perinatal asphyxia, sepsis and IVH rates in PPROM cases. NICU and PPV requirements, RDS, sepsis and IVH rates increase if the Apgar score is < 5. Neonatal morbidity and mortality rates increase as the latent period lengthens. C reactive protein (CRP) on admission, last CRP, birth weight and the 5 min Apgar score was found to be associated with NICU requirements; only the 5 min Apgar score was found to be associated with RDS; and last leukocyte count and maternal haemotocrit was found to be associated with sepsis and pneumonia, independently. In PPROM cases, CRP on admission, last CRP, birth weight, the 5 min Apgar score, last leukocyte count and maternal haemotocrit, should be considered to predict neonatal outcomes.

Characteristics and outcome of 102 fetuses with fetal cerebral ventriculomegaly: experience of a university hospital in Turkey.

The aim of this study was to evaluate the incidence of associated structural anomalies and the outcome of fetuses with ventriculomegaly. We retrospectively collected 102 cases of antenatally diagnosed ventriculomegaly examined between 2000 and 2008. Ventricular width measurements were 10-12 mm, 12.1-14.9 mm and ≥ 15 mm in 24.5%, 20.6% and 54.9% of the cases, respectively. Associated structural malformations were detected in 77.4% of the fetuses. Mortality rate of fetuses with associated malformations and isolated ventriculomegaly was 86.1% and 55.7%, respectively (p < 0.001). The mortality rate was significantly lower in mild (10-12 mm) than in moderate (12.1-14.9 mm) and severe (≥ 15 mm) cases (p < 0.05). All of the fetuses with mild isolated ventriculomegaly were alive at >12 months of age, without morbidity. Our results suggest that the prognosis of fetuses with ventriculomegaly mainly depends on the aetiology and on the presence of associated abnormalities. Fetuses with mild isolated ventriculomegaly have a favourable outcome.

Systemic lupus erythematosus and pregnancy.

We present a retrospective study of 42 consecutive cases of systemic lupus erythematosus (SLE) and pregnancy followed and delivered during the period 2002-2007 in our department. The mean patient age was 28.6 years and the nulliparity rate was 45.2%. Disease flare up occurred in 9.5% of patients. Lupus anticoagulants, anticardiolipin IgG and IgM antibodies were positive in 33%, 16.6% and 19% of patients, respectively. Mean gestational age at delivery was 36.9 +/- 4.2 and mean birth weight was 2,750 +/- 844 g. Stillbirth, fetal growth restriction, pre-eclampsia and pre-term delivery rates were 7.1%, 14.3%, 2.4% and 23.1%, respectively. Cases with uterine artery Doppler abnormalities had significantly poorer obstetric outcomes. Antiphospholipid antibodies, renal involvement and lupus activation did not have any significant influence on poor obstetric outcome. Multidisciplinary approach to the care of pregnant women with SLE is mandatory for good maternal and fetal outcomes. Uterine artery Doppler seems to be a good prognostic factor for adverse obstetric outcomes.

Placental apoptosis and adhesion molecules expression in the placenta and the maternal placental bed of pregnancies complicated by fetal growth restriction with and without pre-eclampsia.

The aim of the study was to examine the expression of adhesion molecules VCAM-1 and ICAM-3 in placental tissue samples and placental bed (maternal decidual tissue) biopsies of pregnancies complicated by pre-eclampsia (PE) and fetal growth restriction (FGR), and to determine whether PE and FGR are associated with an increase in placental apoptosis. We studied placentas and placental bed samples of 49 third trimester pregnancies complicated by FGR (26 with associated PE, 23 without PE) and 25 normotensive healthy pregnant women. Placental apoptosis was assessed by the TUNEL method. Immunohistochemistry was used to assess expression of the VCAM-1 and ICAM-3. There was no significant difference in the staining intensity of VCAM-1 in placentas (p=0.472) and placental bed biopsies (p=0.754) of women delivering appropriate for gestational age and growth restricted fetuses (with and without associated PE). The amount of lymphocytes staining positively with ICAM-3 was significantly higher in both placental and placental bed biopsies of women delivering growth restricted fetuses compared with control pregnancies (p<0.001). Fetal growth restricted pregnancies with associated PE showed higher staining of ICAM-3 in placental compared with placental bed samples (p=0.049). In fetal growth restricted placentas, apoptotic nuclei were more abundant compared with control placentas (p<0.001). Increased expression of ICAM-3 on lymphocyte surface of both maternal and fetal side, suggests lymphocyte overactivation in PE and FGR. Increased placental apoptosis may play an important role in the pathogenesis or sequelae of PE.

Circulating oxidized low-density lipoprotein and paraoxonase activity in preeclampsia.

Preeclampsia is one of the most frequent complications of pregnancy, however, little is known about its etiology. The objective of this study was to investigate the association of oxidized low-density lipoprotein (oxLDL) and paraoxonase (PON1) activity in women with either preeclampsia or normotensive (NT) pregnancy. The study groups included 41 pregnant women with preeclampsia and 33 normotensive pregnant women. In all patients maternal serum total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglycerides (TGs) were measured using enzymatic methods. Serum PON1 activities and malondialdehyde (MDA) concentrations were measured by spectrophotometric methods, and oxLDL was measured by enzyme-linked immunoassay (ELISA). Serum concentrations of lipid parameters (TC, LDL, VLDL, and TGs) were significantly higher in preeclampsia compared with NT controls (p < 0.001, p < 0.05, p < 0.05, and p < 0.001, respectively). Serum concentrations of MDA and oxLDL were significantly higher, while PON1 activity was significantly lower in preeclampsia compared with NT controls (p < 0.001, p < 0.001, and p < 0.001, respectively). A positive correlation was detected between oxLDL and MDA (r = 0.876), and a negative correlation was detected between both MDA and oxLDL and PON1 (r = -0.837 and r = -0.759, respectively). Our data demonstrate that preeclampsia is associated with increased oxLDL and decreased PON1 activity. Elevated oxidative stress, oxLDL, dyslipidemia and decreased PON1 activities may cause vascular endothelial damage and contribute to the pathophysiology of preeclampsia.

Prediction of preeclampsia with maternal mid-trimester placental growth factor, activin A, fibronectin and uterine artery Doppler velocimetry.

OBJECTIVE: To assess whether alterations in the serum levels of placental growth factor, activin A and fibronectin could be detected in patients before they become preeclamptic. And to evaluate and compare the clinical utility of these markers and uterine artery Doppler velocimetry in predicting preeclampsia. METHODS: One hundred and twenty-two normotensive women were prospectively included in the study. Peripheral venous blood samples were obtained and Doppler examination of the uterine arteries was performed between 21 and 26 weeks' gestation. Serum levels of placental growth factor, activin A and fibronectin were measured by enzyme-linked immunoassay and radial immundiffusion technic. RESULTS: Mid-trimester maternal serum activin A and fibronectin levels and average S/D ratios were significantly higher whereas placental growth factor levels were significantly lower in women who subsequently developed preeclampsia than remained normotensive (p<0.001). The best cut-off values for predicting preeclampsia of placental growth factor, activin A and fibronectin based on ROC curve analysis were 90 pg/ml, 14 ng/ml and 370 mg/l respectively. The areas under the curve equal to 0.993, 0.972, 0.872 and 0.813 for placental growth factor, activin A, fibronectin and uterine artery Doppler respectively were determined for the prediction of preeclampsia. CONCLUSION: Placental growth factor, activin A, fibronectin and uterine artery Doppler are all potentially useful as predictors of preeclampsia. Maternal serum midtrimester PGF has the highest predictive value and activin A with a compatible accuracy for early identification of preeclampsia.

Histomorphology of the placenta and the placental bed of growth restricted foetuses and correlation with the Doppler velocimetries of the uterine and umbilical arteries.

The aim of the present study was to evaluate the histomorphology of the placenta and the placental bed and to correlate this with the Doppler study of the uterine and umbilical arteries of intrauterine growth restricted pregnancies. The study group consisted of 47 women with intrauterine growth restricted foetuses. Twenty-five uneventful pregnancies with appropriate for gestational age foetuses were selected as controls. Doppler studies of umbilical and uterine arteries were performed within the last week before delivery. Placental bed biopsies were obtained at Caesarean section with direct visualization of the placental site. The incidence of pathologic bed biopsies in control, IUGR with normal uterine artery Doppler velocimetry and IUGR with abnormal uterine artery Doppler velocimetry was 0 per cent, 16.6 per cent and 79.3 per cent respectively (P< 0.001). Placentae from IUGR cases with abnormal umbilical artery Doppler velocimetries had a significantly increased number of villous infarcts, cytotrophoblast proliferation and thickening of the villous trophoblastic basal membrane (P=0.001, P=0.038 and P=0.02 respectively). Abnormal placental bed biopsy pathology was significantly associated with abnormal uterine artery velocimetry (OR 33.7, 6.5-173.6; P< 0.001). Abnormal placental pathology was significantly associated with abnormal umbilical artery Doppler velocimetry (OR 21.04, 3.8-115.9;P< 0.001). Women with both abnormal uterine and umbilical artery Doppler velocimetries were delivered earlier and their babies had lower mean birth and placental weight (P< 0.001). In conclusion, placental bed biopsy and placental pathologies are best reflected by abnormal uterine and umbilical artery velocity waveforms, respectively. The most severe clinical outcomes and perinatal mortality are present when both uterine and umbilical districts are altered.

The plasma and placental levels of malondialdehyde, glutathione and superoxide dismutase in pre-eclampsia.

The aim of the study is to investigate the plasma and placental levels of malondialdehyde, glutathione and superoxide dismutase in normotensive and pre-eclamptic pregnancies. Peripheral venous blood samples were collected before labour (35.3 +/- 1.1 and 34.2 +/- 3.4 weeks for normotensive and pre-eclamptic, respectively) and placental tissues was obtained after delivery from 34 pre-eclampsia and 33 normotensive pregnancies. The mean plasma and placental levels of malondialdehyde were significantly higher, glutathione and superoxide dismutase levels were significantly lower in pre-eclamptic compared with normotensive patients (P < 0.01). The plasma and placental levels of malondialdehyde significantly increased, glutathione and superoxide dismutase significantly decreased with the increments in diastolic blood pressure. As a conclusion maternal circulating and placental tissue levels of lipid peroxides increase whereas antioxidants decrease in pre-eclampsia. The magnitude of oxidative stress and antioxidant changes correlate well with diastolic blood pressure.

Spinal cord injury caused by gunshot wound during pregnancy.

We report a case of a pregnant woman with acute spinal cord injury (C5) caused by gunshot wound and discuss the respective maternal and fetal considerations. Neither decompressive surgery nor corticosteroid protocols were used. At 37 weeks, the patient delivered a normal female infant after induction of labor and epidural anesthesia, with no medical or obstetrical complications. With conservative management and rehabilitation, this patient had significant recovery of function.

Doppler assessment of umbilical artery, thoracic aorta and middle cerebral artery in the management of pregnancies with growth restriction.

BACKGROUND: The aim of the study was to determine the best use of information obtained from Doppler studies of umbilical artery, thoracic aorta and middle cerebral artery in the management of pregnancies with growth restriction. METHODS: The study group consisted of 100 pregnant women with intrauterine growth restricted fetuses. Doppler flow velocity waveforms were obtained from the umbilical artery, middle cerebral artery and thoracic aorta. The pregnancies were grouped according to the umbilical artery Doppler results. There were 29, 30 and 41 fetuses with normal and high PI (pulsatility index), and absent end-diastolic velocity (AEDV) in the umbilical artery, respectively. RESULTS: Birth weight and umbilical vein pH at birth significantly decreased and perinatal mortality rates significantly increased with the worsening of the diastolic flow in the umbilical artery (p<0.01). Increased umbilical artery PI was significantly associated with increased thoracic aorta PI and decreased middle cerebral artery PI (r=0.75 and -0.55, p<0.01 respectively). Perinatal mortality due to fetal asphyxia in fetuses with AEDV in the umbilical artery and in both the umbilical artery and thoracic aorta was 39.5% and 50%, respectively. Detection of AEDV in the thoracic aorta was found to be the most significant predictive factor of perinatal deaths. CONCLUSIONS: The degree of abnormality of the Doppler findings parallels the severity of fetal compromise. Growth restricted fetuses with AEDV detected both in the umbilical artery and thoracic aorta are severely compromised and time gained in utero has no benefit for these fetuses.

A case of prenatally diagnosed fetal neurenteric cyst.

The combination of a thoracic cystic mass with vertebral anomalies on prenatal ultrasound suggests a neurenteric cyst. The outcome of such cysts mostly depends on the extent of the displacement and functional impairment of the adjacent organs and of the associated central nervous system defects. We present a case of a neurenteric cyst diagnosed on prenatal ultrasound at 34 weeks of gestation which was treated successfully in the early neonatal period.

Detailed ultrasonographic findings in Greenberg dysplasia.

A case of Greenberg dysplasia [hydrops fetalis, ectopic calcifications, "moth-eaten" skeletal dysplasia (HEM)] is presented. Fetal ultrasonography at 20 weeks' gestation showed hydrops fetalis, severe micromelia, irregular hyperechogenic foci in the ribs and vertebral bodies, irregular hypo- and hyperechogenic areas and abnormal contour within the long bones, and flattened and "T"-shaped appearance of the vertebrae. Findings on postmortem histological and radiographic examination were consistent with Greenberg dysplasia.

Doppler dynamics: their clinical significance and relationship with fetal blood gases and pH measurements.

The aim of the study is to demonstrate the ability of abnormal Doppler indices to predict the acid-base status of the fetus. A pulsed Doppler study of umbilical artery, middle cerebral artery and thoracic aorta were assessed on 30 intrauterine growth restricted and 27 appropriate-for-gestational-age fetuses immediately before cordocentesis. All the fetuses with absent end diastolic velocity in the umbilical artery were found to be acidemic by cordocentesis. Thoracic aorta pulsatility index (PI) increased and middle cerebral artery PI decreased significantly with increased umbilical impedance (r = 0.702, r = -0.340, respectively). Umbilical artery and thoracic aorta PI significantly increased, whereas middle cerebral artery PI decreased with a decrease in umbilical blood pH (r = -0.760, r = -0.642, r = 0.292, respectively). Doppler findings have a very strong correlation with the acid-base status of the fetuses. Increased umbilical impedance is associated with progressive impairment of placental gas exchange and that by the time diastolic flow is lost hypoxaemia or acidaemia is usually present.

Correlation between placental bed biopsy findings, vascular cell adhesion molecule and fibronectin levels in pre-eclampsia.

OBJECTIVE: To determine the correlation between placental bed biopsy findings, and blood levels of the vascular cell adhesion molecule (VCAM-1) and fibronectin in pre-eclampsia/eclampsia, and to evaluate the relationship between these variables and severity of the disease. DESIGN: A prospective case-control study. SETTING: Department of Obstetrics and Gynaecology, Cerrahpasa Medical Faculty, Istanbul. SAMPLE: Thirty-five women with pre-eclampsia/eclampsia were compared with 25 healthy women with uncomplicated pregnancies. Twenty-one placental bed biopsies from pre-eclamptic pregnancies were compared with 17 from normal pregnancies. MAIN OUTCOME MEASURES: Peripheral venous blood levels of VCAM-1 and fibronectin, measured by enzyme-linked immunoassay and radial immune diffusion technique. RESULTS: In pre-eclampsia/eclampsia, blood VCAM-1 and fibronectin levels were higher than in normal pregnancy. Levels of both fibronectin and VCAM-1 correlated significantly with the diastolic blood pressure (r = 0.49 and r = 0.65, P < 0.001). There was also a significant direct linear correlation between plasma fibronectin and VCAM-1 levels (r = 0.57, P < 0.001). Normotensive women all had normal placental bed biopsy findings and the incidence of pathological placental bed biopsy findings increased with the severity of the pre-eclampsia. CONCLUSION: Inadequate trophoblastic invasion of spiral arteries, and elevated levels VCAM-1 and fibronectin were found in women with pre-eclampsia. The magnitude of defective trophoblastic invasion, and blood levels of VCAM-1 and fibronectin correlate with the clinical severity of pre-eclampsia.

Lipid peroxidation and antioxidants in preeclampsia.

OBJECTIVE: To determine the changes in plasma levels of lipid peroxide, vitamin E and vitamin C in women with preeclampsia and to investigate their relationship with diastolic blood pressure. STUDY DESIGN: Cross sectional study consisting of 22 preeclamptic and 21 healthy pregnant women. Fasting venous blood samples were collected during the antepartum period and plasma levels of malondialdehyde, alpha-tocopherol and ascorbic acid were measured. RESULTS: In the preeclamptic group malondialdehyde, a lipid peroxidation product, was significantly increased, while vitamins E and C were significantly decreased compared to healthy pregnant women. A strong correlation was detected between malondialdehyde and antioxidant factors (vitamins E and C) with blood pressure. CONCLUSION: Our findings are consistent with previous studies suggesting that lipid peroxidation is an important factor in the pathogenesis of preeclampsia. In preeclampsia, antioxidant nutrients are excessively utilised to counteract the cellular changes mediated by free radicals.