Single deepest vertical pocket or amniotic fluid index as evaluation test for predicting adverse pregnancy outcome (SAFE trial): a multicenter, open-label, randomized controlled trial.

OBJECTIVE: To determine whether the amniotic fluid index (AFI) or the single deepest vertical pocket (SDP) technique for estimating amniotic fluid volume is superior for predicting adverse pregnancy outcome. METHODS: This was a multicenter randomized controlled trial including 1052 pregnant women with a term singleton pregnancy across four hospitals in Germany. Women were assigned randomly, according to a computer-generated allocation sequence, to AFI or SDP measurement for estimation of amniotic fluid volume. Oligohydramnios was defined as AFI ≤ 5 cm or the absence of a pocket measuring at least 2 × 1 cm. The diagnosis of oligohydramnios was followed by labor induction. The primary outcome measure was postpartum admission to a neonatal intensive care unit. Further outcome parameters were the rates of diagnosis of oligohydramnios and induction of labor (for oligohydramnios or without specific indication), and mode of delivery. RESULTS: Postpartum admission to a neonatal intensive care unit was similar between groups (4.2% (n = 21) vs 5.0% (n = 25); relative risk (RR), 0.85 (95% CI, 0.48-1.50); P = 0.57). In the AFI group, there were more cases of oligohydramnios (9.8% (n = 49) vs 2.2% (n = 11); RR, 4.51 (95% CI, 2.2-8.57); P < 0.01) and more cases of labor induction for oligohydramnios (12.7% (n = 33) vs 3.6% (n = 10); RR, 3.50 (95% CI, 1.76-6.96); P < 0.01) than in the SDP group. Moreover, an abnormal cardiotocography was seen more often in the AFI group than in the SDP group (32.3% (n = 161) vs 26.2% (n = 132); RR, 1.23 (95% CI, 1.02-1.50); P = 0.03). The other outcome measures were not significantly different between the two groups. CONCLUSIONS: Use of the AFI method increased the rate of diagnosis of oligohydramnios and labor induction for oligohydramnios without improving perinatal outcome. The SDP method is therefore the favorable method to estimate amniotic fluid volume, especially in a population with many low-risk pregnancies. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Identification of a new hormone-binding site on the surface of thyroid hormone receptor.

Thyroid hormone receptors (TRs) are members of the nuclear receptor superfamily of ligand-activated transcription factors involved in cell differentiation, growth, and homeostasis. Although X-ray structures of many nuclear receptor ligand-binding domains (LBDs) reveal that the ligand binds within the hydrophobic core of the ligand-binding pocket, a few studies suggest the possibility of ligands binding to other sites. Here, we report a new x-ray crystallographic structure of TR-LBD that shows a second binding site for T3 and T4 located between H9, H10, and H11 of the TRα LBD surface. Statistical multiple sequence analysis, site-directed mutagenesis, and cell transactivation assays indicate that residues of the second binding site could be important for the TR function. We also conducted molecular dynamics simulations to investigate ligand mobility and ligand-protein interaction for T3 and T4 bound to this new TR surface-binding site. Extensive molecular dynamics simulations designed to compute ligand-protein dissociation constant indicate that the binding affinities to this surface site are of the order of the plasma and intracellular concentrations of the thyroid hormones, suggesting that ligands may bind to this new binding site under physiological conditions. Therefore, the second binding site could be useful as a new target site for drug design and could modulate selectively TR functions.

Blood flow velocity waveforms of the umbilical artery in a normal population: reference values from 18 weeks to 42 weeks of gestation.

PURPOSE: The aim of the present study was to calculate new Doppler reference ranges for systolic, intensity-weighted mean, and end-diastolic blood flow velocities (Vmax, Vmean, Vmin) and fetal heart rate and impedance indices (PI, RI) of the umbilical artery by automatic waveform analysis. MATERIALS AND METHODS: A cross-sectional prospective study of 1926 low-risk pregnancies was performed at 18 - 42 weeks of gestation. The measurements were carried out in the region of a free floating loop of cord. Reference ranges for the individual measuring parameters were constructed based on a growth function from a four-parameter class of monotonic continuous functions according to the smallest square principle. The intraobserver reliability was also assessed. RESULTS: A significant increase in umbilical blood flow velocity was observed at 18 - 42 weeks of gestation (Vmax = 33.7 cm/sec to 65 cm/sec (p < 0.001), Vmean = 18.2 cm/sec to 38.7 cm/sec (p < 0.001) and Vmin = 8.2 to 31 cm/sec (p < 0.001). Reference curves for the pulsatility and the resistance index were associated with significant decreases with increasing gestational age (PI: 18 weeks: 1.3; 28 weeks: 1.1; 42 weeks: 0.8 and RI: 18 weeks: 0.7; 28 weeks: 0.6; 42 weeks: 0.5). The fetal heart rate decreased from 147 - 134 bpm. The intraobserver reliability was low, but of no clinical relevance. CONCLUSION: The reference ranges for blood flow velocities and resistance indices in the umbilical artery calculated by the authors serve as the basis for Doppler ultrasound antenatal examinations in a normal patient population and enable the early diagnosis of fetal risk.

[Clinical and economic challenges of moderate preterm babies born between 32+0 and 36+6 weeks of gestation]. / Klinische und ökonomische Herausforderung der moderaten Frühgeburt zwischen 32+0 und 36+6 SSW.

BACKGROUND: Preterm births show a worldwide increasing incidence. The majority of preterm births occur between 32+0 and 36+6 weeks of gestation and are associated with an increased rate of maternal and neonatal morbidity. The focus of our research is the clinical and economical analysis of all preterm births between 32+0 and 36+6 weeks of gestation in a German level 1 perinatal centre over a period of 3 years. MATERIALS AND METHODS: A retrospective analysis of all preterm births between 32+0 and 36+6 weeks of gestation in the University Hospital Mainz from 2007 to 2009 was undertaken. Data were collected using our electronic documentation system. Gestational age at delivery, mode of birth, indication for delivery, duration of the peripartum treatment, treatment of the newborn in the children's hospital, birth weight and therapy costs were evaluated. RESULTS: We recorded 407 moderate preterm births in total; this amounts to a rate of of 10% of all births. Major causes of prematurity were PPROM, preterm labour and preeclampsia/HELLP. Maternal and fetal systemic diseases were more uncommon. Rates of Caesarean sections (62%) and of neonatal inpatient treatment needs (58.5%) were high. Maternal treatment costs were 332 Euro/day. The mean duration of maternal inpatient treatment was 13.15 days. DISCUSSION: Moderate preterm birth is associated with maternal morbidity frequently due to a high rate of Caesarean sections. Neonatal morbidity is also increased. In comparison with previous research, we saw an increased rate of pregnancy complications. This could be typical for a level 1 perinatal centre. Moderate preterm birth is seen as the cause of considerable treatment costs.

The IUGA/ICS classification of complications of prosthesis and graft insertion: a comparative experience in incontinence and prolapse surgery.

INTRODUCTION AND HYPOTHESIS: This is a presentation of case series after the use of alloplasic material in urogynaecology. METHODS: From 2004 to 2010, a total 179 patients with complications have been referred directly after the use of alloplastic material in incontinence and prolapse surgery. Of this total, 125 patients had a previous vaginal sling plasty because of urinary stress incontinence, while 54 patients underwent a prolapse surgery with mesh use. Symptoms and findings are expressed by the recently introduced International Urogynecological Association/International Continence Society (IUGA/ICS) terminology. RESULTS: The most frequent findings after vaginal sling plasty were bladder outlet obstruction, pain and tape exposure. The most frequent findings after prolapse surgery were pain and mesh erosion. The IUGA/ICS classification does not give the possibility to express functional disorders. Most revisions were done more than 2 months after surgery. After incontinence surgery, mostly the vaginal area of suture line was affected; after prolapse surgery, the vagina and the trocar passage were affected. CONCLUSIONS: Mesh complication and affected site after prolapse surgery do differ from those after incontinence surgery. The IUGA/ICS classification of mesh complication facilitates the comparison of mesh complication.

Pregnancy outcome in maternal Crigler-Najjar syndrome type II: a case report and systematic review of the literature.

OBJECTIVE: To report a case of maternal Crigler-Najjar syndrome (CNS) type II in pregnancy, systematically review the literature for similar case reports, and to evaluate whether pregnancy is safe in patients with the disease. Data sources included the PubMed and up to date databases. RESULTS: A 37-year-old mother with CNS type II was treated with phenobarbital during her pregnancy and her bilirubin levels were monitored. Her newborn had mild direct hyperbilirubinemia, did not require any treatment and his postnatal follow-up showed normal growth and development as well as normal hearing. CONCLUSION: CNS type II is rare, and only a few pregnancies with this condition have been reported. Maternal treatment with phenobarbital lowers the unconjugated bilirubin and avoids fetal and newborn sequelae.

Fetal urogenital sinus with consecutive hydrometrocolpos because of labial fusion: prenatal diagnostic difficulties and postpartal therapeutic management.

OBJECTIVE: To elucidate the differential diagnoses of tumorous dilations in the fetal pelvic region detected by prenatal ultrasound and the postnatal management demonstrated on a fetus with 29 weeks of gestation with a retrovesical located bottle-like cystic structure measuring 54 x 31 x 27 mm within the pelvis. Postnatal findings were a labial fusion and a consecutive hydrometrocolpos due to a urethrovaginal fistula. METHOD: Case report of a fetus affected by an intricate cloacal anomaly. RESULTS: The long-term prognosis for this nonsyndromic form of hydrometrocolpos without any other structural defects or organic failures after operative sanitation is excellent. Final reconstruction is planned at about 12 months of age. CONCLUSION: Prenatal diagnosis of tumorous dilations in the fetal pelvic region often involves difficulties because of numerous differential diagnoses and possible presentation in late pregnancy. Magnetic resonance imaging could be a useful complementary tool for assessing these anomalies when ultrasonography is inconclusive. In some cases, the final diagnosis cannot be confirmed until after delivery.

Role of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor type 1 (PAI-1) for prognosis in endometrial cancer.

BACKGROUND: Urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor type 1 (PAI-1) contribute to the invasiveness of many carcinomas. Here, we studied a possible association between cytosolic uPA and PA-1 concentrations in tumor tissue with prognosis in patients with endometrial cancer. METHODS: Cytosolic concentrations of uPA and PAI-1 were determined in 69 primary endothelial adenocarcinomas using an enzyme-linked immunoassay (ELISA). A possible influence of uPA and PAI-1 was studied by multivariate Cox regression adjusting for the established clinical prognostic factors FIGO-stage, grading, depth of invasion, diabetes mellitus and age. RESULTS: Both uPA (p=0.011) and PAI-1 (p=0.003) were associated with relapse free time using the multivariate proportional hazards model. Association with overall survival was less pronounced with p=0.021 for uPA and p=0.358 for PAI-1. Concentrations of PAI-1 increased with FIGO stage (p=0.003) and with histological grading (p=0.005). Both uPA and PAI-1 concentrations were negatively correlated with estrogen and progesterone receptor levels. CONCLUSION: The combination of high cytosolic concentrations of uPA (>5 ng/mg total protein) and high PAI-1 (>20 ng/mg total protein) may reveal a group of patients with increased risk of progression.