Mikko Loukovaara

Antenatal diagnosis of placenta accreta leads to reduced blood loss.

Objective. Placenta accreta is one of the most devastating pregnancy complications. We sought to compare outcomes between women with placenta accreta when diagnosed antenatally or intrapartum, and to define predictors of the antenatal diagnosis. Design. Retrospective case–control study. Setting. University teaching hospital. Population. Twenty‐four women with placenta accreta diagnosed antenatally and 20 women discovered intrapartum. Methods. Chart review of historical and delivery‐associated variables. Rates were compared between the groups. Main Outcome Measures. Placenta accreta diagnosed antenatally or intrapartum. Results. Women with antenatal diagnosis had a lower estimated blood loss of a median of 4500ml (range 100–15000ml) compared with 7800ml (range 2500–17000ml, p=0.012) and required fewer units of packed red blood cells transfused (median 7; range 0–27 compared with 13.5; range 4–31, p=0.026). Nineteen (79%) women diagnosed antenatally had balloon catheter occlusion carried out during the cesarean section. Five (21%) had the entire placenta left in situ. There was no difference in the rate of surgical complications or duration of hospitalization. The clinical diagnosis among women with antenatal diagnosis was more often placenta percreta (p=0.013). The risk factor profile of women with antenatal diagnosis of placenta accreta included higher gravidity (p=0.014) and parity (p<0.0001), history of cesarean section (p=0.004), and placenta previa in the current pregnancy (p<0.001). Conclusions. Antenatal diagnosis of placenta accreta may reduce peripartum blood loss and the need for blood transfusion. Women with antenatal diagnosis more often have placenta previa and history of previous cesarean section, and the clinical diagnosis is more often placenta percreta.

Regulation of sex hormone-binding globulin production by isoflavonoids and patterns of isoflavonoid conjugation in HepG2 cell cultures

The effect of the isoflavonoid phytoestrogens daidzein, equol, and genistein on sex hormone-binding globulin (SHBG) levels, SHBG mRNA transcript levels, and SHBG gene methylation was studied in HepG2 cell cultures by fluoroimmunometric SHBG assay and Northern and Southern hybridizations, respectively. The effect of 17 beta-estradiol on these parameters was studied as a control. The metabolism of isoflavonoids in HepG2 cells was determined by isotope dilution gas chromatography-mass spectrometry, after ion-exchange chromatography. Daidzein and equol increased SHBG levels in parallel intracellularly and extracellularly, whereas genistein increased SHBG levels only within the cells, resembling thus the effect of 17 beta-estradiol. The difference may originate from the fact that genistein has more hydroxyl groups than daidzein and equol. The regulation of SHBG production by phytoestrogens appears to occur at the post-transcriptional level. Firstly, daidzein, equol, or genistein did not have a clear effect on the steady-state SHBG mRNA levels. Secondly, no effect on SHBG gene methylation was observed by genistein. The findings applied also to 17 beta-estradiol. However, as the SHBG gene was more methylated in SHBG-negative MCF-7 cells than in SHBG-positive HepG2 cells, DNA methylation may play a role in the tissue-specific activation of this gene. The metabolism of isoflavonoids in HepG2 cells yielded mainly unconjugated and sulfated compounds. Similar metabolism in hepatocytes in vivo might retain their biological activity in tissues responsive to estrogens.

Comparative studies on the regulation of insulin-like growth factor-binding protein-1 (IGFBP-1) and sex hormone-binding globulin (SHBG) production by insulin and insulin-like growth factors in human hepatoma cells.

Production of insulin-like growth factor-binding protein-1 (IGFBP-1) by the liver is efficiently inhibited by insulin both in vivo and in vitro. Consequently, serum IGFBP-1 concentration reflects insulin bioactivity in portal vein. Sex hormone-binding globulin (SHBG) is another insulin-regulated liver-derived protein that has appeared promising in detecting individuals with portal hyperinsulinemia. We compared the regulation of IGFBP-1 and SHBG production by insulin and insulin-like growth factors (IGF-I and IGF-II) in human hepatoma cell cultures. Insulin equipotently inhibited IGFBP-1 and SHBG production, with maximal decrease in culture medium concentrations being about 35% for both proteins during 48 h of culture in serum-free medium. IGF-I and IGF-II also inhibited the IGFBP-1 and SHBG levels. We conclude that IGFBP-1 and SHBG are equally sensitive to ambient insulin concentrations in human hepatoma cell cultures, and the production of both proteins is also attenuated by the IGFs.

Serum highly sensitive C-reactive protein in preterm premature rupture of membranes

OBJECTIVE Low-grade inflammation may raise serum C-reactive protein (CRP) concentrations. We studied whether serum CRP is altered in preterm premature rupture of membranes (PPROM), which is frequently associated with an asymptomatic intrauterine infection. STUDY DESIGN CRP was quantitated with highly sensitive immunofluorometric (IFMA) and immunoenzymometric (IEMA) assays in 32 women with PPROM at 30.7+/-0.4 gestational weeks (mean+/-standard error of the mean) and in 27 gestational age-matched healthy women. The results were compared to those obtained by the conventional immunoturbidimetric method. RESULTS Twenty-three PPROM patients had a normal CRP value (</=12mg/l) by immunoturbidimetry. Their highly sensitive CRP value was not different from that of controls. During the observation period of 11+/-3 days after PPROM, an increase in the highly sensitive CRP was observed in patients whose immunoturbidimetric CRP remained normal (n=10). CONCLUSION The increase in the highly sensitive CRP in PPROM patients with constantly normal immunoturbidimetric CRP may reflect the presence of a subclinical inflammation.

Magnetic resonance imaging in the assessment of high-risk features of endometrial carcinoma: a meta-analysis.

Objective The aim of this study was to review the available literature on the reliability of contemporary magnetic resonance imaging (MRI) techniques in the assessment of high-risk features of endometrial carcinoma, that is, deep myometrial invasion, cervical stromal involvement, and lymph node metastasis. Methods The PubMed and Scopus databases were searched for studies published before March 2014. Studies on plain MRI were excluded. Results Fifty-two eligible studies were identified. For the assessment of deep (≥50%) myometrial invasion (50 studies, 3720 patients), the pooled sensitivity, specificity, positive predictive value, and negative predictive value were 80.7%, 88.5%, 77.6%, and 89.5%, respectively, by random-effects analysis. For predicting cervical stromal involvement (12 studies, 1153 patients), the pooled values were 57.0%, 94.8%, 68.7%, and 90.5%, respectively. For lymph node metastasis on a per-patient basis (10 studies, 862 patients), they were 43.5%, 95.9%, 66.3%, and 92.2%, respectively. In a meta-regression analysis, dynamic imaging was associated with a higher sensitivity in detecting deep myometrial invasion, as compared with contrast-enhanced imaging (P = 0.021). The improvement by diffusion-weighted imaging was of a borderline significance (P = 0.057). Significant small-study effects were found for the sensitivity of MRI in detecting deep myometrial invasion (P < 0.0001) and cervical stromal involvement (P = 0.049). Conclusions Considering the poor-to-moderate sensitivity of MRI in detecting high-risk features of endometrial carcinoma, patients with negative findings on MRI may not safely forgo surgical staging unless the findings are confirmed by a backup method. The high specificities allow the targeting of staging procedures by MRI alone in patients with positive findings. Compared with contrast-enhanced imaging, dynamic and diffusion-weighted imaging may be more reliable in the radiological staging of endometrial carcinoma.

Prediction of lymph node and distant metastasis in patients with endometrial carcinoma: A new model based on demographics, biochemical factors, and tumor histology

OBJECTIVE To develop a model that might predict the probability of lymph node and distant metastasis (stages IIIC-IV) in endometrial carcinoma. METHODS We studied 774 patients with endometrial carcinoma treated in a single institution. Demographic factors, biochemical factors and preoperative tumor characteristics, identified as potential risk factors for advanced carcinoma in unadjusted analyses, were used to create a logistic regression model with lymph node and distant metastasis as the dependent variable. Statistically significant odds ratios in the regression model were rounded to the nearest whole number. These rounded values were the estimated weights for each factor that were summed to generate a score that might predict the probability of stage IIIC-IV carcinoma. RESULTS Biochemical factors and preoperative tumor characteristics predicted lymph node and distant metastasis in the regression model, whereas demographic factors were without effect. The score combining weighted risk factors was: (2 × leukocytosis)+(3 × thrombocytosis)+(7 × elevated CA125)+(4 × high-risk histology). The area under curve (AUC) for this total score was 0.823, with 71.6% sensitivity, 75.2% specificity, 25.9% positive predictive value, and 95.7% negative predictive value, using 6 as cut-point. After excluding stage IV carcinomas from the dataset, the AUC was 0.813 for the total score in predicting nodal involvement (P=0.82 vs. total score in predicting stage IIIC-IV carcinomas in the complete dataset). CONCLUSIONS Based on the high negative predictive value, this prediction model could be applied for identifying patients who may not benefit from lymphadenectomy for endometrial carcinoma staging.

Amniotic fluid S100B protein and erythropoietin in pregnancies at risk for fetal hypoxia

OBJECTIVE S100B protein is a biochemical marker for brain injury, and high serum S100B levels have been observed in newborns with birth asphyxia. We hypothesized that the concentration of amniotic fluid erythropoietin, which increases in chronic fetal hypoxia, correlates with amniotic fluid S100B concentration. STUDY DESIGN Amniotic fluid samples in 35 pregnancies at high risk for chronic fetal hypoxia were obtained at cesarean section or by amniocentesis done within a median of 2 days before delivery. S100B and erythropoietin concentrations were measured by chemiluminescent immunoassays. RESULTS A positive correlation existed between the concentrations of S100B and erythropoietin in the amniotic fluid (r=0.57, p<0.0001). Amniotic fluid S100B concentration was higher (70 ng/l; 33-469, n=17) (median; range) in pregnancies with elevated amniotic fluid erythropoietin (>or= 50 IU/l) than in pregnancies with normal erythropoietin (34 ng/l; 20-340, n=18) (p<0.0001, Mann-Whitney U-test). S100B predicted an elevated amniotic fluid erythropoietin concentration in the study population with the sensitivity of 94% and specificity of 83%. CONCLUSION A strong positive correlation exists between amniotic fluid S100B and erythropoietin concentrations in pregnancies at high risk for chronic fetal hypoxia. This suggests that chronic fetal hypoxia increases the intrauterine release of S100B.

Fetal Hypoxia Is Associated with Elevated Cord Serum C-Reactive Protein Levels in Diabetic Pregnancies

Maternal diabetes increases the risk of intrauterine hypoxia. Inflammation may play a role in the pathogenesis of hypoxia-related neonatal complications. We studied correlations between levels of cord serum C-reactive protein (CRP), measured by a highly sensitive immunofluorometric assay, and indices of fetal hypoxia in diabetic pregnancies. Cord serum CRP correlated positively with amniotic fluid erythropoietin and umbilical artery pCO2. A negative correlation existed between cord serum CRP and umbilical artery pH and pO2. Amniotic fluid erythropoietin showed an independent effect on cord serum CRP in multiple regression analysis. These data suggest that the fetus responds to hypoxia by an inflammatory reaction.

Effect of maternal diabetes on phosphorylation of insulin-like growth factor binding protein-1 in cord serum.

Aims  The insulin‐like growth factor (IGF) system is considered important in the regulation of fetal growth. Binding of IGFs to specific binding proteins (IGFBPs) modifies their actions. In fetal blood, IGFBP‐1 is the primary IGF binding protein whose phosphorylation generates proteins with different affinities for IGF‐I. We studied cord serum IGFBP‐1 phosphoisoform profiles in normal pregnancies and in diabetic pregnancies, which are frequently complicated by macrosomia.

Concentration of cord serum placenta growth factor in normal and diabetic pregnancies

Objective  To investigate whether maternal diabetes or diabetes‐related complications, such as macrosomia and chronic fetal hypoxia, are associated with altered placenta growth factor (PlGF) levels in cord serum.