Where does the money go to? Cost analysis of gynecological patients with a benign condition.

OBJECTIVES: The impact of benign gynecological conditions on life of women and on costs for the society is high. The purpose of this study is to gain knowledge and understanding of costs of the treatment of these disorders in order to be able to improve the clinical care processes, gain insight into feasible savings opportunities and to allocate funds wisely. METHODS: The healthcare processes of 311 women attending university or community hospitals in the Helsinki and Uusimaa Hospital District between June 2012 and August 2013 due to a benign gynecological condition were followed up for two years and treatment costs analysed. RESULTS: Total direct hospital costs averaged 689€ at six months and 2194€ at two years. The most expensive treatment was that of uterine fibroids in the short term and that of endometriosis and fibroids later on. Costs did not depend on hospital size. Surgical operations caused nearly half of hospital costs. Productivity loss caused biggest expenses outside of the hospital. LNG-IUD (levonorgestrel-releasing intrauterine device) accounted for the largest pharmaceutical costs for patients. Hospital treatment was associated with a reduced need for outpatient services during follow-up. CONCLUSIONS: A majority of direct hospital costs arise over time. This stresses the need for prolonged healthcare management. To control costs, the need for repetitive doctors' appointments, monitoring tests, and ward treatments should be carefully evaluated. Procedures not needing an operation theatre (for example hysteroscopy for polypectomy), should be done ambulatorily.

Intrapartal cardiotocographic patterns and hypoxia-related perinatal outcomes in pregnancies complicated by gestational diabetes mellitus.

AIMS: In previous reports, cardiotocographic (CTG) fetal heart rate (FHR) monitoring has shown only limited benefits in decreasing adverse perinatal outcomes in pregnancies complicated by gestational diabetes mellitus (GDM). The aim of the present study was to evaluate whether an association exists between the recently reported ZigZag pattern (FHR baseline amplitude changes of > 25 bpm with a duration of 2-30 min) and asphyxia-related neonatal outcomes in GDM pregnancies. METHODS: Intrapartal CTGs were recorded in a one-year cohort of 5150 singleton childbirths. The following CTG changes were evaluated: ZigZag pattern, saltatory pattern, late decelerations, episodes of tachycardia and bradycardia, reduced variability, and uterine tachysystole. The cohort was divided into three groups: women with GDM, women with normal oral glucose tolerance test (OGTT), and women with no OGTT performed. Umbilical artery (UA) blood gases, Apgar scores, neonatal respiratory distress, and neonatal encephalopathy were used as outcome variables. RESULTS: GDM was diagnosed in 624 (12.1%), OGTT was normal in 4115 (79.9%), and OGTT was not performed in 411 (8.0%) women. Hypoxia-related ZigZag patterns (OR 1.94, 95% CI 1.64-2.34) and late decelerations (OR 1.65, 95% CI 1.27-2.13) of FHR, as well as a greater risk of fetal asphyxia (UA pH < 7.10 and/or UA BE < -12.0 meq/L and/or Apgar scores < 7 at 5-min) (OR 6.64, 95% CI 1.84-12.03) were observed in those with GDM compared with those without GDM. CONCLUSIONS: GDM is associated with intrapartal ZigZag pattern and late decelerations, cord blood acidemia and low 5-min Apgar scores at birth indicating increased occurrence of fetal hypoxia in GDM pregnancies.

The health-related quality of life of patients with a benign gynecological condition: a 2-year follow-up.

Aim: To assess health-related quality of life (HRQoL) of patients with benign gynecological disorders. Materials & methods: Prospective 2-year follow-up with the 15D HRQoL-instrument of 311 women treated in Helsinki-area hospitals in 2012-2013. Results: The initially impaired HRQoL regarding excretion, discomfort and symptoms, and vitality and sexual activity improved after treatment. However, only sexual activity reached similar levels as in the general population. Treatment of endometriosis, fibroids and polyps resulted in best and that of unspecific pelvic pain and bleeding disorders in worst HRQoL scores. Results were independent of hospital size. Conclusion: The impaired HRQoL dimensions were improved by treatment but HRQoL still remained poorer than in the general female population. Treatment of unspecific pelvic pain and bleeding disorders needs further evaluation.

Tweetable abstract Benign gynecological conditions markedly impact women's quality of life including physical, sexual and mental well-being. Two-year follow-up of patients in this new study found quality of life to be partly improved by treatment, but was still lower than in the general female population.

Factors associated with intrapartum ZigZag pattern of fetal heart rate: A retrospective one-year cohort study of 5150 singleton childbirths.

OBJECTIVES: Recent studies suggest that intrapartum ZigZag pattern of fetal heart rate (FHR) is significantly associated with cord blood acidaemia and neonatal complications. For the clinical significance of this pattern, it is mandatory that ZigZag episodes in cardiotocographic (CTG) recording are correctly identified. The aim of the present study was to examine maternal, fetal and delivery-related factors that could explain the occurrence of ZigZag pattern of FHR during the last 2 h of labour in a large obstetric cohort. STUDY DESIGN: CTG recordings from 5150 singleton childbirths at ≥33 weeks of gestation during one year were evaluated retrospectively and blinded to pregnancy and neonatal outcomes in a university hospital in Helsinki, Finland. All women in the cohort were in the active phase of labour with regular uterine contractions. ZigZag FHR pattern was defined as FHR baseline amplitude changes of >25 bpm with a duration of 2-30 min. The following maternal, fetal and labour/delivery-related variables were determined: maternal age, obesity (prepregnancy BMI ≥ 30.0 kg/m2), parity, preeclampsia, maternal fever ≥38.0 °C, smoking, gestational age at delivery, fetal sex, birth weight z-score, mode of delivery, and type of onset of labour. RESULTS: ZigZag pattern occurred in 582/5150 (11.3 %) cases, and only in childbirths after 37 weeks of gestation. Fetal male gender (OR 3.29; 95 % CI 2.70-4.02), nulliparous pregnancy (OR 2.60; 95 % CI 2.15-3.15) and post-term gestational age (≥42 weeks) (OR 1.92; 95 % CI 1.47-2.48) were independently associated with the occurrence of ZigZag pattern. Among the three significant risk factors, clustering of two or three factors was associated with an increase of the ZigZag pattern occurrence risk to 5.0-16.4-fold (95 % CI 3.16-31.60). CONCLUSIONS: ZigZag pattern occurred in term pregnancies after 37 weeks of gestation only. Fetal male gender, nulliparity and post-term pregnancy are significantly associated with ZigZag FHR pattern during the last two hours of labour. Identification of maternal, fetal and delivery-related variables are imperative in order to interpret correctly the findings of CTG and to prevent adverse neonatal outcome.

Intrapartum zigzag pattern of fetal heart rate is an early sign of fetal hypoxia: A large obstetric retrospective cohort study.

INTRODUCTION: The aim of the present study was to identify possible associations of fetal heart rate (FHR) patterns during the last 2 hours of labor with fetal asphyxia expressed by umbilical artery acidemia at birth and with neonatal complications in a large obstetric cohort. MATERIAL AND METHODS: Cardiotocographic recordings from 4988 singleton term childbirths over 1 year were evaluated retrospectively and blinded to the pregnancy and neonatal outcomes in a university teaching hospital in Helsinki, Finland. Umbilical artery pH, base excess and pO2 , low Apgar scores at 5 minutes, need for intubation and resuscitation, early neonatal hypoglycemia, and neonatal encephalopathy were used as outcome variables. According to the severity of the neonatal complications at birth, the cohort was divided into three groups: no complications (Group 1), moderate complications (Group 2) and severe complications (Group 3). RESULTS: Of the 4988 deliveries, the ZigZag pattern (FHR baseline amplitude changes of >25 bpm with a duration of 2-30 minutes) occurred in 11.7%, late decelerations in 41.0%, bradycardia episodes in 52.9%, reduced variability in 36.7%, tachycardia episodes in 13.9% and uterine tachysystole in 4.6%. No case of saltatory pattern (baseline amplitude changes of >25 bpm with a duration of >30 minutes) was observed. The presence of the ZigZag pattern or late decelerations, or both, was associated with cord blood acidemia (odds ratio [OR] 3.3, 95% confidence interval [CI] 2.3-4.7) and severe neonatal complications (Group 3) (OR 3.3, 95% CI 2.4-4.9). In contrast, no significant associations existed between the other FHR patterns and severe neonatal complications. ZigZag pattern preceded late decelerations in 88.7% of the cases. A normal FHR preceded the ZigZag pattern in 90.4% of the cases, whereas after ZigZag episodes, a normal FHR pattern was observed in only 0.9%. CONCLUSIONS: ZigZag pattern and late decelerations during the last 2 hours of labor are significantly associated with cord blood acidemia at birth and neonatal complications. The ZigZag pattern precedes late decelerations, and the fact that normal FHR pattern precedes the ZigZag pattern in the majority of the cases suggests that the ZigZag pattern is an early sign of fetal hypoxia, which emphasizes its clinical importance.

Treatment of gynecological malignancies: long-term follow-up of health-related quality of life and healthcare costs.

Aim: To assess long-term health-related quality of life (HRQoL) and treatment-related costs in gynecological cancer patients, and to compare HRQoL between cancer types and to age-standardized general female population. Materials & methods: A prospective 8-10-year follow-up of 218 patients treated in Helsinki University Hospital in 2002-2004. Results: The most common malignancies were uterine, ovarian and cervical cancers. The mean HRQoL scores were 0.880 (baseline), 0.885 (6 months) and 0.884 for survivors in the end of the study. Depression, vitality and sexual activity were impaired at baseline but improved during follow-up. Total secondary healthcare costs during the follow-up averaged EUR 41342. Conclusion: The long-term HRQoL of surviving gynecological cancer patients was good and similar to that of age-standardized general female population.

Prediction of pre-eclampsia and its subtypes in high-risk cohort: hyperglycosylated human chorionic gonadotropin in multivariate models.

BACKGROUND: The proportion of hyperglycosylated human chorionic gonadotropin (hCG-h) to total human chorionic gonadotropin (%hCG-h) during the first trimester is a promising biomarker for prediction of early-onset pre-eclampsia. We wanted to evaluate the performance of clinical risk factors, mean arterial pressure (MAP), %hCG-h, hCGß, pregnancy-associated plasma protein A (PAPP-A), placental growth factor (PlGF) and mean pulsatility index of the uterine artery (Uta-PI) in the first trimester in predicting pre-eclampsia (PE) and its subtypes early-onset, late-onset, severe and non-severe PE in a high-risk cohort. METHODS: We studied a subcohort of 257 high-risk women in the prospectively collected Prediction and Prevention of Pre-eclampsia and Intrauterine Growth Restriction (PREDO) cohort. Multivariate logistic regression was used to construct the prediction models. The first model included background variables and MAP. Additionally, biomarkers were included in the second model and mean Uta-PI was included in the third model. All variables that improved the model fit were included at each step. The area under the curve (AUC) was determined for all models. RESULTS: We found that lower levels of serum PlGF concentration were associated with early-onset PE, whereas lower %hCG-h was associated with the late-onset PE. Serum PlGF was lower and hCGß higher in severe PE, while %hCG-h and serum PAPP-A were lower in non-severe PE. By using multivariate regression analyses the best prediction for all PE was achieved with the third model: AUC was 0.66, and sensitivity 36% at 90% specificity. Third model also gave the highest prediction accuracy for late-onset, severe and non-severe PE: AUC 0.66 with 32% sensitivity, AUC 0.65, 24% sensitivity and AUC 0.60, 22% sensitivity at 90% specificity, respectively. The best prediction for early-onset PE was achieved using the second model: AUC 0.68 and 20% sensitivity at 90% specificity. CONCLUSIONS: Although the multivariate models did not meet the requirements to be clinically useful screening tools, our results indicate that the biomarker profile in women with risk factors for PE is different according to the subtype of PE. The heterogeneous nature of PE results in difficulty to find new, clinically useful biomarkers for prediction of PE in early pregnancy in high-risk cohorts. TRIAL REGISTRATION: International Standard Randomised Controlled Trial number ISRCTN14030412 , Date of registration 6/09/2007, retrospectively registered.

First trimester serum placental growth factor and hyperglycosylated human chorionic gonadotropin are associated with pre-eclampsia: a case control study.

BACKGROUND: To study whether maternal serum hyperglycosylated human chorionic gonadotropin (hCG-h) improves first trimester prediction of pre-eclampsia when combined with placental growth factor (PlGF), pregnancy-associated plasma protein-A (PAPP-A) and maternal risk factors. METHODS: Gestational-age-adjusted concentrations of hCG, hCG-h, PlGF and PAPP-A were analysed in serum samples by time-resolved immunofluorometric assays at 8-13 weeks of gestation. The case-control study included 98 women who developed pre-eclampsia, 25 who developed gestational hypertension, 41 normotensive women with small-for-gestational-age (SGA) infants and 177 controls. RESULTS: Of 98 women with pre-eclampsia, 24 women developed preterm pre-eclampsia (diagnosis < 37 weeks of gestation) and 13 of them had early-onset pre-eclampsia (diagnosis < 34 weeks of gestation). They had lower concentrations of PlGF, PAPP-A and proportion of hCG-h to hCG (%hCG-h) than controls. In receiver-operating characteristics (ROC) curve analysis, the area under the curve (AUC) for the combination of PlGF, PAPP-A, %hCG-h, nulliparity and mean arterial blood pressure was 0.805 (95% confidence interval, CI, 0.699-0.912) for preterm pre-eclampsia and 0.870 (95% CI 0.750-0.988) for early-onset pre-eclampsia. Without %hCG-h the AUC values were 0.756 (95% CI 0.651-0.861) and 0.810 (95% CI 0.682-0.938) respectively. For prediction of gestational hypertension, the AUC for %hCG-h was 0.708 (95% CI 0.608-0.808), but for other markers the AUC values were not significant. None of the AUC values were significant for the prediction of SGA infants in normotensive women. CONCLUSIONS: First trimester maternal serum %hCG-h tended to improve prediction of preterm and early-onset pre-eclampsia when combined with PlGF, PAPP-A and maternal risk factors.

[Pregnancy contraception (Current Care Guideline)]. / KÄYPÄ HOITO -SUOSITUS (Tiivistelmä). Raskauden ehkäisy.

There are no age limits for the start or use of contraception. Prior gynecological examination or cervical smear is not needed. Condom is the only method that protects from sexually transmitted diseases. An increase in the risk of venous thromboembolism (VTE) is associated only with combined contraceptives. However, the risk is remarkably higher with pregnancy, puerperium or with smoking. The most effective reversible methods are intrauterine devices (IUD) and implants, as these do not depend on daily memory. Natural family planning methods are not reliable, and effective contraception should be easily available for all at all times.

The Salivary Scavenger and Agglutinin (SALSA) in Healthy and Complicated Pregnancy.

Pre-eclampsia is a leading cause of maternal and perinatal morbidity and mortality worldwide. The etiology is not clear, but an immune attack towards components of placenta or fetus has been indicated. This involves activation of the complement system in the placenta. We have previously described the presence of the complement-regulating protein salivary scavenger and agglutinin (SALSA) in amniotic fluid. In this study we investigated the potential role of SALSA in pregnancy by analyzing its presence in amniotic fluid and placental tissue during healthy and complicated pregnancies. SALSA levels in amniotic fluid increased during pregnancy. Before 20 weeks of gestation the levels were slightly higher in patients who later developed pre-eclampsia than in gestation age-matched controls. In the placenta of pre-eclamptic patients syncytial damage is often followed by the formation of fibrinoid structures. SALSA was found clustered into these fibrinoid structures in partial co-localization with complement C1q and fibronectin. In vitro analysis showed direct protein binding of SALSA to fibronectin. SALSA binds also to fibrin/fibrinogen but did not interfere with the blood clotting process in vitro. Thus, in addition to antimicrobial defense and epithelial differentiation, the data presented here suggest that SALSA, together with fibronectin and C1q, may be involved in the containment of injured placental structures into fibrinoids.

[Current Care Guideline: Eating disorders]. / Syömishäiriöt.

Early diagnosis with intervention is linked to better outcome. In primary care patients in risk for eating disorder should be screened and actively asked about eating disorder symptoms. Treatment is mainly out-patient care and should first be focused on gaining a normal nutritional status. It is important to involve the patient's family in the treatment. A confidential relationship between health care professionals and the patient is important. The patient's own motivation and readiness for recuperation are essential. Different therapeutic and psychosocial approaches are central in the treatment, as the disorders are psychiatric. Medical treatment may bring additional help in treating binge-eating disorder or bulimia nervosa, but it is seldom of help in treating anorexia nervosa.

[Update on Current Care Guidelines: Ectopic pregnancy]. / Ektooppinen (kohdunulkoinen) raskaus.

Ectopic pregnancy should be suspected it a woman of fertile age has lower abdominal pain and irregular vaginal bleeding. Symptoms range from almost none to shock. The diagnosis is based on a quantitative serum pregnancy test (hCG) and transvaginal ultrasound. An acute situation requires emergency surgery, whereas patients with mild symptoms should be treated policlinically by follow-up or a single intramuscular dose (1 mg/kg) of methotrexate. No folic acid supplementation is needed. In later pregnancies their location should be verified by transvaginal ultrasound done by the seventh gestational week at the latest.

[How do I evaluate and utilize information provided by observational study]. / Miten arvioin ja hyödynnän havainnoivan tutkimuksen tuottamaa tietoa?

The strength of observational study is the utilization of large materials in order to evaluate the risk factors and prognosis of disease, rare adverse effects of treatments and their everyday effectiveness. Observational studies are, however, associated with a higher risk of bias as compared with randomized controlled studies. Whereas the effectiveness of individual interventions under ideal conditions must be resolved in randomized studies, the effectiveness of treatment chains under routine healthcare conditions can be assessed only through observational studies.

[Principles and pitfalls of randomized controlled study]. / Satunnaistetun kontrolloidun tutkimuksen periaatteita ja sudenkuoppia.

Randomized controlled study is a central tool in the study of the prevention and treatment of diseases and effect of rehabilitation. Whereas prevention of bias resulting from potential differencies in study groups is a great advantage of the randomized study design, pitfalls are also involved in these studies. The task of the reader of the study is to evaluate the validity of the results, their clinical significance and possible applicability to one's own treatment decisions.

Serum hyperglycosylated human chorionic gonadotrophin at 14-17 weeks of gestation does not predict preeclampsia.

INTRODUCTION: Low first-trimester serum concentrations of hyperglycosylated human chorionic gonadotrophin (hCG-h) predict later preeclampsia. We studied whether serum hCG-h at 14-17 weeks of pregnancy also predicts preeclampsia alone or combined with placental growth factor (PlGF) and soluble vascular endothelial growth factor 1 (sVEGFR-1). METHODS: We conducted a nested case-control study comprising 55 women with subsequent preeclampsia, 21 with gestational hypertension, 30 with a small-for-gestational-age infant, and 83 controls. Serum concentrations of hCG-h, proportion of hCG-h to hCG (%hCG-h), PlGF, and sVEGFR-1 were converted to multiples of the medians (MoMs) adjusted for gestational age. RESULTS: Concentrations of hCG-h or %hCG-h did not differ between women with subsequent preeclampsia and controls. In women with subsequent preeclampsia, PlGF was lower (0.62 MoM) than in controls (P < 0.001). In receiver-operating characteristics curve analysis for the prediction of preeclampsia, the area under the curve for hCG-h or %hCG-h was not significantly different from 0.5, whereas that for PlGF was 0.746 (95% confidence interval, 0.656-0.836; P < 0.001). Combining hCG-h or %hCG-h with PlGF did not improve the prognostic value. CONCLUSIONS: Serum hCG-h did not improve prediction of preeclampsia in the second trimester.

Cost-effectiveness of hysterectomy for benign gynecological conditions: a systematic review.

The objective of this study was to assess the cost-effectiveness of hysterectomy performed for benign indications. Hysterectomy remains the most common major gynecological operation in the Western world. Rates of hysterectomy have not declined as expected with the introduction of new treatment options. Furthermore, use of laparoscopic techniques varies widely within the Nordic countries. We designed a systematic review in a University Central Hospital. The sample included all published studies regarding the cost-effectiveness of hysterectomy performed for benign indications (n = 1666). Medline, Cochrane Library, PsycINFO, CINAHL, and Nursing databases were searched. Inclusion criteria were the availability of pre- and post-intervention health-related quality of life measures (HRQoL) and data on costs. HRQoL, costs, and cost-effectiveness of treatment were the main outcome measures. Studies (n = 24) focused on treatment of symptomatic fibroids (n = 8), treatment of heavy menstrual bleeding (n = 10), various surgical techniques (n = 5) and the effect of various indications for hysterectomy (n = 2). Follow-up periods varied from 4 months to over 10 years. SF/RAND-36 or EQ-5D measures and societal cost perspective were most commonly used. Only 11 studies used individual patient data. HRQoL following hysterectomy was generally good but costs were high. The cost-effectiveness depended on indication, age, and duration of follow-up. The cost-effectiveness of hysterectomy has been surprisingly poorly studied. Conclusions are difficult to draw due to different study designs, indications, follow-up times, and HRQoL instruments used. Rates of hysterectomy have declined less than expected with the introduction of new treatment modalities. Costs of surgery are high. Laparoscopic hysterectomy seems to be the least cost-effective, although further data from original patient cohorts with long-term follow-up are needed.

[Update on current care guidelines: ovarian cancer]. / Munasarjasyöpä.

Ovarian cancer is the most lethal gynaecological cancer. It appears that seemingly ovarian or primary peritoneal carcinomas, in fact, originate from fimbriae. BRCA1/2 mutation carriers are recommended for the removal of ovaries and fimbriae, to reduce the risk of cancer. Treatment of epithelial ovarian cancer is based on the combination of surgery and chemotherapy. The residual tumour volume at the primary operation is the most important predictive factor of survival. The best response at the primary treatment is observed with combination chemotherapy with taxane and platinum. Adding bevacitzumab to first line chemotherapy may improve survival.

Significant decrease in maternal serum concentrations of angiopoietin-1 and -2 after delivery.

OBJECTIVE: To characterize the physiological distribution of angiopoietins (Ang)-1 and Ang-2 and soluble endothelial cell-specific tyrosine kinase receptor-2 (Tie-2) at term and following delivery. DESIGN: A prospective, descriptive study. SETTING: Helsinki University Central Hospital. POPULATION: Twenty healthy term pregnant women undergoing elective cesarean delivery and their newborns. METHODS: The concentrations were analysed by enzyme-linked immunosorbent assay in maternal antepartum and the first postpartum day sera, umbilical serum, amniotic fluid and maternal and newborn urine. MAIN OUTCOME MEASURES: Concentrations of Ang-1, Ang-1 and Tie-2. Results. Concentrations of maternal serum Ang-1 and Ang-2 decreased after delivery {[median (range)]: Ang-1, from 33 (25-51) to 30 (18-49) ng/mL, p= 0.017; and Ang-2, from 5.4 (1.8-18) to 1.4 (0.7-4.6) ng/mL, p < 0.0001}, whereas Tie-2 concentrations remained stable [23 (13-41) vs. 25 (14-29) ng/mL, p= 0.107]. Compared with maternal antepartum serum, umbilical serum concentrations of Ang-1 [46 (28-59) ng/mL, p < 0.0001] and Tie-2 [45 (21-71) ng/mL, p < 0.0001] were higher and those of Ang-2 similar [5.4 (1.8-18) vs. 4.2 (2.9-6.0) ng/mL; p= 0.067]. Low concentrations of Ang-1 [1.2 (0.1-2.2) ng/mL], Ang-2 [1.1 (0.3-4.1) ng/mL] and Tie-2 [0.4 (0.08-0.9) ng/mL] were observed in amniotic fluid, but they were undetectable in newborn urine and in most of the maternal urine samples. CONCLUSIONS: Maternal Ang-1 and Ang-2 concentrations decreased following delivery. Umbilical concentrations of Ang-1 and Tie-2 were higher than the maternal concentrations.

Maternal serum angiopoietin-1 and -2 and tie-2 in early pregnancy ending in preeclampsia or intrauterine growth retardation.

CONTEXT: The antiangiogenic growth factor angiopoietin-2 (Ang-2) antagonizes, whereas angiopoietin-1 (Ang-1) activates the endothelial cell-specific tyrosine kinase receptor-2 (Tie-2). In preeclampsia, circulating concentrations of Ang-1 are increased and those of Ang-2 and Tie-2 are decreased. OBJECTIVE: We wanted to study whether maternal serum concentrations of Ang-1, Ang-2, and Tie-2 are altered at gestational wk 12-15 or 16-20 in women with subsequent preeclampsia or intrauterine growth retardation (IUGR). DESIGN: This was a case-control study. SETTING: The study was conducted in Helsinki University Central Hospital, a tertiary referral center. PATIENTS: This study comprised 124 pregnant women, of whom 49 developed preeclampsia and 16 gave birth to infants with IUGR, and 59 healthy women served as controls. MAIN OUTCOME MEASURES: Serum concentrations of Ang-1, Ang-2, and Tie-2 were assessed by ELISA. Data were combined with our earlier data on soluble VEGF receptor (sVEGFR)-1. RESULTS: At gestational wk 12-15, the median concentrations of Ang-1, Ang-2, or Tie-2 were all similar between the study groups. At 16-20 wk, Ang-2 concentrations were higher in women with subsequent preeclampsia [25.0 ng/ml, 19.3-39.5 ng/ml; median, interquartile range (IQR)] than in the controls (17.7 ng/ml, 10.8-27.4 ng/ml, P = 0.006). The odds ratio of high Ang-2 concentrations for subsequent preeclampsia was 4.2 (95% confidence interval 1.4-12.6; P = 0.011) and high Ang-2 combined with high sVEGFR-1, 6.4 (95% confidence interval 2.2-18.7; P = 0.001). CONCLUSION: Maternal serum Ang-2 concentrations are increased prior to preeclampsia. High concentrations of both Ang-2 and sVEGFR-1 indicate subsequent disease.

Maternal serum endostatin at gestational weeks 16-20 is elevated in subsequent pre-eclampsia but not in intrauterine growth retardation.

OBJECTIVE: Endostatin, an important anti-angiogenic factor produced by endothelial cells, is elevated in established pre-eclampsia. We measured maternal serum endostatin concentrations in early pregnancy associated with later pre-eclampsia and intrauterine growth retardation (IUGR). DESIGN: Retrospective case-control study. SETTING: University Central Hospital. SAMPLE: Serum samples were collected at 12-15 and 16-20 gestational weeks from a total of 124 pregnant women of whom 49 developed pre-eclampsia, 16 gave birth to infants with IUGR without pre-eclampsia, and 59 remained normotensive giving birth to healthy, normal-weight infants. METHODS: Enzyme-linked immunosorbent assay. MAIN OUTCOME MEASURES: Endostatin concentrations in serum. RESULTS: At 12-15 gestational weeks, there was no difference in median endostatin concentrations between the groups. At 16-20 gestational weeks, the median endostatin concentration was higher in the women with subsequent pre-eclampsia (p=0.026), especially preceding a later severe form of the disease (p=0.041), than in the controls. The results were further confirmed by receiver operating characteristic (ROC) analysis showing an area under the curve (AUC) of 0.64 (95% confidence interval: 0.50-0.81) for endostatin to identify subsequent pre-eclampsia, and 0.71 (0.53-0.89) in cases of severe pre-eclampsia. Optimal cut-off values were determined and used for calculations of sensitivity and specificity, which were 80 and 52% (cut-off value = 58.0 microg/L) in pre-eclampsia, and 80 and 65% (cut-off value = 65.5 microg/L) in the severe form of the disease. CONCLUSIONS: The concentrations of endostatin in maternal serum at 16-20 weeks' of gestation are associated with an increased risk of pre-eclampsia but not IUGR.