Prediction of preterm pre-eclampsia at midpregnancy using a multivariable screening algorithm.

BACKGROUND: Competing risk models used for midpregnancy prediction of preterm pre-eclampsia have shown detection rates (DR) of 85%, at fixed false-positive rate (FPR) of 10%. The full algorithm used between 19+0 and 24+6  weeks includes maternal factors, mean arterial pressure (MAP), mean uterine artery pulsatility index (UtAPI), serum placental growth factor (PlGF) level in multiples of the median (MoM), and soluble Fms-like tyrosine kinase-1 (sFlt-1) level in MoM. AIMS: To assess performance of the Fetal Medicine Foundation (FMF) algorithm at midpregnancy to screen for preterm (<37 weeks) pre-eclampsia. The outcome measured was preterm pre-eclampsia. MATERIALS AND METHODS: This is a prospective study including singleton pregnancies at 19-22 weeks gestation. Maternal bloods were collected and analysed using three different immunoassay platforms. Maternal characteristics, medical history, MAP, mean UtAPI, serum PlGF MoM and serum sFlt-1 MoM were used for risk assessment. DR and FPR were calculated, and receiver operating characteristic curves produced. RESULTS: Five hundred and twelve patients were included. Incidence of preterm pre-eclampsia was 1.6%. Using predicted risk of pre-eclampsia of one in 60 or more and one in 100 or higher, as given by the FMF predictive algorithm, the combination with the best predictive performance for preterm pre-eclampsia included maternal factors, MAP, UtAPI and PlGF MoM, giving DRs of 100% and 100%, respectively, and FPRs of 9.3 for all platforms and 12.9-13.5, respectively. Addition of sFlt-1 to the algorithm did not appear to improve performance. sFlt-1 MoM and PlGF MoM values obtained on the different platforms performed very similarly. CONCLUSIONS: Second trimester combined screening for preterm pre-eclampsia by maternal history, MAP, mean UtAPI and PlGF MoM using the FMF algorithm performed very well in this patient population.

Midpregnancy testing for soluble fms-like tyrosine kinase 1 (sFlt-1) and placental growth factor (PlGF): An inter-assay comparison of three automated immunoassay platforms.

We performed an inter-assay comparison among three immunoassay platforms for midpregnancy testing of sFlt-1, PlGF and the sFlt-1/PlGF ratio, which are established markers for pre-eclampsia. Maternal blood was collected 19-22 weeks' gestation. Raw data values were converted to multiples of the median (MoM). PlGF and sFlt-1 values among platforms were highly correlated (p < 0.001). There was significant variation in raw data values for PlGF and sFlt-1 among platforms, eliminated following conversion to MoM. When directly comparing raw data values among platforms, platform-specific reference ranges values should be used. MoM values were equivalent among platforms, allowing direct inter-assay result comparison.

Midpregnancy prediction of pre-eclampsia using serum biomarkers sFlt-1 and PlGF.

OBJECTIVES: Pre-eclampsia remains a significant cause of morbidity and mortality. Placental biomarkers soluble Fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) have been investigated previously for their ability to predict pre-eclampsia. We compared the performance of these biomarkers for midpregnancy pre-eclampsia prediction using three different immunoassay platforms. STUDY DESIGN: Prospective study including singleton pregnancies 19-22 weeks' gestation. Maternal bloods were collected at recruitment. Screening performances using receiver operating characteristic (ROC) curves for PlGF and sFlt-1/PlGF ratio raw data and MoM values in isolation were evaluated for three immunoassay platforms using selected cut-off values. MAIN OUTCOME MEASURES: Pre-eclampsia was defined as early-onset (<34 weeks' at delivery) and preterm (<37 weeks' at delivery). RESULTS: For prediction of preterm pre-eclampsia, PlGF MoM and sFlt-1/PlGF ratio MoM performed similarly, with areas under the curve (AUC), detection rates (DR) and false positive rates (FPR) for PlGF MoM and sFlt-1/PlGF ratio MoM being 0.77-0.79 and 0.71-0.74, 62.5% for both and 9.7-14.9 and 10.7-17.7, respectively. For the prediction of early-onset pre-eclampsia, sFlt-1/PlGF ratio raw data and MoM values performed similarly, with AUC, DR and FPR being 0.92-0.97 and 0.93-0.96, 100% for both, and 4.13-16.9 and 9.4-12.2, respectively. CONCLUSIONS: For midpregnancy prediction of preterm pre-eclampsia, PlGF MoM for all three platforms and sFlt-1/PlGF ratio MoM for the two platforms that tested sFlt-1 performed similarly. For midpregnancy prediction of early-onset pre-eclampsia at midpregnancy, sFlt-1/PlGF ratio raw data and MoM values using the early-onset cut-off for the two platforms that tested sFlt-1 gave similar performance from a clinical perspective.

Accuracy of second trimester prediction of preterm preeclampsia by three different screening algorithms.

AIM: To compare the performance of three different screening methods (National Institute for Health and Clinical Excellence (NICE) guidelines, American College of Obstetricians and Gynecologists (ACOG) recommendations and Fetal Medicine Foundation (FMF) algorithm) for second trimester prediction of preeclampsia. METHODS: This was a prospective non-intervention study in singleton pregnancies, including women attending for second trimester morphologic ultrasound at 19-22 weeks. Maternal characteristics, medical history, mean arterial pressure and mean uterine artery Doppler pulsatility index were recorded and used for risk assessment. Outcomes measured were preeclampsia with delivery before 34, before 37 and after 37 weeks gestation. Detection rates, false positive rates and positive likelihood ratios were calculated, and receiver operating characteristic curves were produced. RESULTS: We screened 543 women during the study. The incidence of preeclampsia before 34, before 37 and after 37 weeks was 0.5, 1.4 and 3.4%, respectively. Detection rates for prediction of preterm preeclampsia were 75% (95% CI 34.9-96.8), 87% (95% CI 47.3-99.6), 100% (95% CI 63.0-100) and 100% (95% CI 63.0-100) for NICE guidelines, ACOG recommendations, FMF algorithm with a 1:100 cut-off and FMF algorithm at 1:60 cut-off, respectively. False positive rates were, 22, 67, 19 and 12% for NICE guidelines, ACOG recommendations, FMF algorithm with a 1:100 cut-off and FMF algorithm at 1:60 cut-off, respectively. CONCLUSION: Second trimester combined screening for preterm preeclampsia by maternal history, mean arterial pressure and mean uterine artery Doppler pulsatility index (FMF algorithm) was superior to screening by maternal factors alone (NICE guidelines and ACOG recommendations).

Biomarker Immunoassays in the Diagnosis of Preeclampsia: Calculating the sFlt1/PlGF Ratio Using the Cobas®e 411 Analyser.

Preeclampsia is a relatively common pregnancy-related condition associated with serious maternal and fetal morbidity and mortality. It is now well established that anti-angiogenic sFlt1 is upregulated in preeclampsia and binds PlGF and VEGF, causing an imbalance in angiogenic factors with subsequent endothelial injury and dysfunction. Measurement of placental growth factor (PlGF) and the sFlt1/PlGF ratio have both been validated in other countries for screening and diagnosis of preeclampsia and the differentiation of preeclampsia from other hypertensive disorders of pregnancy. There are several automated, commercially available immunoassays capable of measuring PlGF and the sFlt1/PlGF ratio for preeclampsia diagnosis. Here we outline the methodology for using the Roche Cobas ® e 411 immunoassay platform to determine the sFlt1/PlGF ratio.

Uterine Papillary Serous Carcinoma: A Single-Institution Review of 62 Cases.

OBJECTIVE: Uterine papillary serous carcinoma (UPSC) is a rare variant of endometrial carcinoma responsible for up to 40% of endometrial cancer deaths. Controversy remains regarding optimal adjuvant therapy for UPSC, with lack of randomized trials to date. The objective of this retrospective study was to evaluate clinicopathological factors and determine event-free survival and overall survival (OS) in patients with UPSC managed within a single institution. MATERIALS AND METHODS: Medical and pathological records between 1987 and 2004 were reviewed at the Royal Women's Hospital, Melbourne, Australia. Cox regression analysis was used to analyze effects of clinical and histopathological variables on patient survival and survival times following adjuvant therapy. Event-free survival and OS were analyzed using the Kaplan-Meier survival curve. RESULTS: Sixty-two patients were included; 96.8% were managed surgically and 56.5% were completely surgically staged. Myoinvasion was present in 72.6% (n = 45) of the patients.In patients with stage I disease, recurrence rate was 41.4% with a 5-year OS of 46%. In stage II, recurrence rate was 20% with a 5-year OS of 67%. In stage III, recurrence rate was 58.8% with a 5-year OS of 34%. In stage IV, recurrence rate was 71.4% with a 5-year OS of 29%.There was no significant difference in survival based on the presence of positive peritoneal cytology, positive lymphovascular space invasion or positive lymph nodes at diagnosis, and no significant difference in survival based on the type of adjuvant therapy administered. Depth of myometrial invasion was a significant determinant of poor prognosis (P = 0.027). CONCLUSIONS: Uterine papillary serous carcinoma is an aggressive variant of endometrial cancer associated with a high proportion of advanced-stage disease at diagnosis, high recurrence rates, and low OS. In our patients, prognosis was determined by myometrial invasion and International Federation of Gynecology and Obstetrics stage at diagnosis. Randomized trials in this area are required to clarify optimal adjuvant therapy for patients with UPSC.

Normal vaginal delivery in a patient with autosomal recessive limb-girdle muscular dystrophy.

The limb-girdle muscular dystrophies (LGMDs) are a group of genetically determined disorders of skeletal muscle, predominantly affecting the pelvic and shoulder-girdle musculature. The clinical course is variable but steadily progressive. Type 2A LGMD is the most frequent form, accounting for approximately 30% of identified cases. There are few reports of patients with Type 2A LGMD undergoing pregnancy and delivery. This case outlines a successful vaginal delivery in a woman with this condition.