Unconjugated Estriol Research Articles

A Classification Model for Predicting Fetus with down Syndrome – A Study from Turkey

ABSTRACT The triple test is a screening test (blood test) used to calculate the probability of a pregnant woman having a fetus that has a chromosomal abnormality like Down Syndrome (DS). AFP (Alpha-Fetoprotein), hCG (Human Chorionic Gonadotropin), and uE3 (Unconjugated Estriol) values in the blood sample of pregnant women are computed and compared with the similar real records where the outputs (healthy fetus or a fetus with DS) are actually known. The likelihood of the indicators is used to calculate the probability of having a fetus with chromosomal abnormality like DS. However, high false positive rate of the triple test has been a problematic issue. One of the reasons of the high false positives is the differences in the norm values of indicators for the pregnant women from different geographical regions of a country. We use 81 patient records retrieved from Şahinbey Training and Research Hospital of Gaziantep University; Turkey. In our study, nine different classification algorithms were trained based on triple test indicators. Multilayer perceptron outperformed with 94.24% detection rate and 13% false positive rate. The multilayer perceptron can predict the outcome of triple test with a high level of accuracy and fewer patients are suggested for amniocentesis. This study is the first study using the MLP model for Turkish triple test data. Regional MLP models can eliminate the bias due to local biological differences.

Diagnostic accuracy of maternal serum multiple marker screening for early detection of gestational diabetes mellitus in the absence of a gold standard test

BackgroundGestational diabetes mellitus (GDM) is associated with adverse diabetic complications for both mother and child during pregnancy. The common Gold Standard (GS) for diagnosis of GDM is 75 g oral glucose tolerance test (OGTT) during 24–28 gestational weeks which seems a little late for any proper intervention. This study aimed to employ the Bayesian latent class models (LCMs) for estimating the early diagnostic power of combination of serum multiple marker in detecting GDM during 14–17 weeks of gestation.MethodsData from a sample of 523 pregnant women who participated in gestational diabetes screening tests at health centers affiliated to Shahid Beheshti University of Medical Sciences in Tehran, Iran from 2017 to 2018 were used. The beta-human chorionic gonadotropin (β-hCG), unconjugated estriol (uE3), and alfa-fetoprotein (AFP) values were extracted from case records for all participants. The Bayesian LCMs were applied for estimating sensitivity, specificity, and area under receiver operating characteristic curve (AUC) of combining the three biomarkers’ results in the absence of GS, adjusting for maternal age and body mass index.ResultsThe mean (standard deviation) maternal age of the participants was 28.76 (±5.33) years. Additionally, the mean (standard deviation) BMI was 24.57 (±3.22) kg/m2. According to the Bayesian model, the cSensitivity, cSpecificity, and cAUC for the optimal composite diagnostic test were estimated as 94% (95% credible interval (CrI) [0.91–0.99]), 86% (95% CrI [0.80–0.92]), and 0.92 (95% CrI [0.87–0.98]), respectively.ConclusionsOverall, the findings revealed that the combination of uE3, AFP, and β-hCG results might be considered as an acceptable predictor for detecting GDM with a rather high level of accuracy in the early second trimester of pregnancy without a GS.

Early pregnancy prediction of gestational diabetes mellitus risk using prenatal screening biomarkers in nulliparous women

AimsTo evaluate the clinical utility of first and second trimester prenatal screening biomarkers for early pregnancy prediction of gestational diabetes mellitus (GDM) risk in nulliparous women. MethodsWe conducted a population-based cohort study of nulliparous women participating in the California Prenatal Screening Program from 2009 to 2011 (n = 105,379). GDM was ascertained from hospital discharge records or birth certificates. Models including maternal characteristics and prenatal screening biomarkers were developed and validated. Risk stratification and reclassification were performed to assess clinical utility of the biomarkers. ResultsDecreased levels of first trimester pregnancy-associated plasma protein A (PAPP-A) and increased levels of second trimester unconjugated estriol (uE3) and dimeric inhibin A (INH) were associated with GDM. The addition of PAPP-A only and PAPP-A, uE3, and INH to maternal characteristics resulted in small, yet significant, increases in area under the receiver operating characteristic curve (AUC) (maternal characteristics only: AUC 0.714 (95% CI 0.703–0.724), maternal characteristics + PAPP-A: AUC 0.718 (95% CI 0.707–0.728), maternal characteristics + PAPP-A, uE3, and INH: AUC 0.722 (0.712–0.733)); however, no net improvement in classification was observed. ConclusionsPAPP-A, uE3, and INH have limited clinical utility for prediction of GDM risk in nulliparous women. Utility of other readily accessible clinical biomarkers in predicting GDM risk warrants further investigation.

Is maternal serum inhibin A a good predictor in preterm labor? - Experience from a community hospital in Taiwan

BackgroundWe aimed to determine whether inhibin A could be a reliable and accurate predictor of preterm birth, and discuss the possible pathogenic processes of inhibin A leading to preterm birth. MethodsA retrospective cohort study was conducted on consecutive singleton pregnant women who underwent the second-trimester quad screen test at a gestational age of 15–20 weeks at Keelung Chang-Gung Memorial Hospital from March 2011 to May 2015. Data including maternal characteristics and pregnancy outcomes were collected from an electric medical record database. Data regarding pregnancy terminations before a gestational age of 24 weeks and regarding pregnancies that involved chromosomal or congenital anomalies were excluded from this analysis. One-way analysis of variance was used to compare second-trimester α-fetoprotein, human chorionic gonadotropin, unconjugated estriol, and inhibin A in women with preterm deliveries versus those with term deliveries. ResultsAlthough a total of 935 women with singleton pregnancies were enrolled, pregnancy outcome and complete maternal data were obtained from only 770 (82.3%)of them. In total, 687 (89.2%) women delivered at or after 37 weeks of gestation and 83 (10.8%) women delivered before 37 weeks of gestation. The results showed that the inhibin A level was significantly increased in the preterm labor group (p = 0.009). A cutoff inhibin A value above 2.25 was identified statistical significantly in the preterm labor group. ConclusionsFrom our results, an inhibin A level above 2.25 multiples of the median in the quad screen test may be associated with preterm labor afterward. Closely monitoring for uterine contractions or cervical length measurement in the second trimester may be indicated in patients with unexplained elevated inhibin A levels.

He assessment of the perinatal outcomes of the patients who underwent quad screening test

Objective The aim of this study is to assess the correlation between the poor perinatal outcomes and the serum biochemical markers such as maternal serum alpha fetoprotein (AFP), human chorionic gonadotropin (hCG), unconjugated estriol (uE3) and inhibin-A (INH-A) checked during the quad screening test. Methods In this retrospective study, the results of 485 pregnant women who underwent quad screening test in the Outpatient Clinic of Gynecology and Obstetrics of Faculty of Medicine at Erciyes University, Kayseri, Turkey between January 2018 and January 2019 and met the inclusion criteria were analyzed. The primary result of the study was established as the development of poor perinatal outcomes. The poor perinatal outcomes were defined as gestational diabetes (GDM), gestational hypertension (GHT), preeclampsia, intrauterine growth restriction (IUGR), preterm labor, premature rupture of membranes (PRM), oligohydramnios, polyhydramnios, HELLP syndrome, and intrahepatic cholestasis of pregnancy (ICP). Results A total of 485 pregnant women, who met the inclusion criteria, were included in the study. A significant correlation was found between AFP MoM≥2 and GHT, PRM, preterm labor, and the development of IUGR (p=0.017, p=0.033, p=0.037, and p=0.038, respectively). It was seen that the risk increased 5.1 times for GHT, 3.2 times for preterm labor, and 3.8 times for the development of IUGR. There was a significant correlation between hCG MoM≥2 and the risk of GHT development (p=0.024); however, the risk of GHT development increased for 3.8 times above this value. A significant correlation was found between INH-A being MoM≥2 and the development of GHT and HELLP syndrome (p=0.009 and p=0.005, respectively). In these pregnant women, the risk increased 31 times for the development of HELLP syndrome, and 9.4 times for GHT. In the cases with uE3 MoM£0.5, there was a significant correlation for the development of preeclampsia and HELLP syndrome (p=0.033 and p=0.049, respectively). On the other hand, there was no significant correlation between GDM, ICP, polyhydramnios, and oligohydramnios and AFP MoM, beta-hCG MoM, uE3 MoM and INH-A MoM values. Conclusion In our study, we found correlation between poor perinatal outcomes and the changes in AFP, hCG, uE3 and INH-A levels.

The predictive value of maternal serum screening tests for adverse pregnancy outcomes

Aim: Free beta-human chorionic gonadotropin (Fβ-hCG), pregnancy-associated plasma protein-A (PAPP-A), alpha-fetoprotein (AFP), unconjugated estriol (uE3), and inhibin-A have been shown to be useful not only in identifying chromosomal abnormalities in the first and second trimesters, but also in predicting adverse pregnancy outcomes (APOs). In this study, we aimed to investigate the predictive value of maternal serum screening tests for various APOs including preeclampsia, intrauterine growth retardation (IUGR), preterm labor, and gestational diabetes mellitus (GDM).Material and Methods: The study was carried out at our clinics and included a total of 220 pregnant women who respectively underwent the double and quadruple marker testsduring the 11th to 14th and 15th to 22nd gestational weeksbetween January 2017 and December 2018. Patient data (maternal age, parity/gravidity, gestational age, history of infertility, use of in vitro fertilization, maternal/fetal complications, preterm labor, mode of delivery, birth weight, and length of stay in the neonatal intensive care unit) were reviewed retrospectively.Results: The AFP levels were statistically significantly higher in patients with IUGR (p=0.022),GDM (p=0.036), and preterm labor (p=0.021), compared to the control group with no APO. No significant correlation was found between preeclampsia and the serum markers.Conclusion: Our results show that elevated maternal serum AFP levels might be associated with various APOs,requiring closer patient follow-up for early diagnosis and treatment.

Predictive Power of Unconjugated Estriol in Diagnosis of Gestational Diabetes: A Cohort Study

Background: Gestational diabetes is the most common antenatal medical complication that is associated with adverse short- and long-term maternal, fetal, and neonatal outcomes. Reducing maternal and fetal complications requires the early diagnosis of gestational diabetes. Unconjugated Estriol (UE) has led to insulin resistance under in vitro conditions. Objectives: This study aimed to determine the predictive power of unconjugated estriol in the diagnosis of gestational diabetes in Tehran, Iran. Methods: The present historical cohort study was conducted on 523 pregnant women presenting to two university-affiliated hospitals in Tehran, Iran, 2017 - 2018. The level of unconjugated estriol was determined at the 14th - 17th week of pregnancy, and gestational diabetes was diagnosed at the 24th - 28th week of pregnancy using the oral glucose tolerance test with 75 grams of glucose. Data were collected through interviews and sampling was carried out using a convenience sampling method. Results: Out of 523 pregnant women examined, 63 (12%) were placed in the gestational diabetes group and 460 (88%) in the non-gestational diabetes group. The best cutoff point for unconjugated estriol was determined using the ROC curve as 0.965 MOM. We obtained 66.66% sensitivity, 54.78% specificity, 16.8% positive predictive value, and 92.30 negative predictive value for the UE test. Conclusions: Given the acceptable sensitivity (66.66%) and specificity (54.78%) obtained for the UE test and the area under the ROC curve of 0.60, it appears that the UE test can be considered a new, accessible, and reliable screening test for gestational diabetes.

P13.07: A pre‐eclampsia risk prediction model based on maternal characteristics and serum markers in twin pregnancy

The purpose of this study was to develop pre-eclampsia (PE) risk prediction model based on maternal characteristics and serum markers at the first and second trimester in the twin pregnancy. Between January 2005 and September 2017, we retrospectively reviewed medical records of 532 twin pregnant women who underwent maternal serum integrated test and gave birth at a Bundang CHA medical centre. Maternal serum pregnancy-associated plasma protein A (PAPP-A) was determined at 10+0 to 13+0 weeks and the serum alpha-fetoprotein (MSAFP), human chorionic gonadotrophin (hCG), unconjugated estriol (uE3) and inhibin A were assayed at 14+0 to 22+0 weeks. We reviewed all antenatal primary screening records and assessed the relationships of maternal characteristics and serum markers by using multiple logistic regression analysis. The study included 35 patients who diagnosed PE and a control group consisting of the other 497 patients in twin pregnancy. There were no significant differences in the maternal age and body mass index (BMI) between two groups. However, the gestational age and placenta weight at delivery were significantly different between groups (p < 0.001, p = 0.005, respectively). In the study group, median multiples of median (MoM) values of hCG and inhibin A were elevated significantly (all p < 0.05), but PAPP-A, MSAFP and uE3 did not differ significantly between two groups. Among the maternal serum markers, Inhibin A value was significantly higher in women with PE compared to those without PE (p < 0.001). In addition, we predicted the PE using maternal age, BMI, uE3, and inhibin A which were achieving an area under the curve of 0.73 overall, in a combined multivariate prediction model of PE in twin pregnancy. A risk prediction model of PE which combined maternal age, BMI, uE3, and inhibin A was better early predictors than any individual marker and these factors are more useful as there is no additional examination for early diagnosis women with PE in twin pregnancy. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

An Intelligent Prenatal Screening System for the Prediction of Trisomy-21 Using Triple Test Variables: The Hacettepe System

Objective: To introduce an intelligent prenatal screening system, using triple test variables.Study Design: In this study, we have used a backpropagation learning algorithm (a supervised artificial neural network) to develop an intelligent antenatal screening system (heretofore referred as Hacettepe System). Triple test variables were used as input variables, while “Down syndrome” and “non-Down syndrome” fetuses were the output of the algorithm. Unconjugated estriol (E3), beta-human chorionic gonadotropin, and α-feto protein with gestational week and maternal age (triple test) were used as input variables in the training and testing. Multiples of median values of the E3, α-feto protein, and beta-human chorionic gonadotropin were used in this study. The testing group of Hacettepe system consisted of 97 patients who were found to be high-risk (&gt;1/250) during the routine antenatal screening (triple test) and underwent amniocentesis for fetal karyotyping.Results: Amniocentesis was performed in 97 pregnancies with “high-risk” triple test results (&gt;1/250). Fetal karyotyping revealed trisomy 21 in about 9.3% (9/97) of the pregnancies. Our algorithm (Hacettepe System) detected 77.8% (7/9) of Down syndrome cases. Moreover, all of the normal fetal karyotypes were assigned as normal in the Hacettepe System.Conclusion: We have developed an intelligent system using the backpropagation learning algorithm (using triple test variables) to predict trisomy 21.

Detection and characterization of estradiol (E2) and unconjugated estriol (uE3) immunoassay interference due to anti-bovine alkaline phosphatase (ALP) antibodies

ObjectivesCompetitive immunoenyzmatic assays for estradiol (E2) and unconjugated estriol (uE3) on UniCel DxI 800 Access immunoassay systems (Beckman Coulter) utilize bovine alkaline phosphatase (ALP) for amplification. In these assays, rare ‘IND’ error flags indicate that a relative light unit (RLU) raw result is past the high or low end of the calibration curve but cannot be differentiated from an instrument error or analytical interference. The present studies were conducted to establish a protocol to identify analytical interference and to characterize its mechanism when present. Design and methodsMatrix and recovery studies were conducted to establish a protocol for interference identification. Spiking experiments with inactivated calf intestinal ALP were performed to determine whether interference could be blocked. Commercial anti-ALP antibodies (Abs) were spiked into human serum to model assay interference. Three E2 immunoassays which do not include ALP as a reagent component (cobas e602, Roche; Centaur XP, Siemens; ARCHITECT i2000SR, Abbott) were tested for comparative purposes. Results1:2 dilution of specimen into Access Sample Diluent A (Beckman) differentiated IND error flags due to true low results (e.g. less than the analytical measurement range; AMR) from those due to assay interference. Interferences were reduced by pre-incubation with inactivated ALP and could be replicated by spiking with commercial anti-ALP Abs. ConclusionsPatient anti-bovine ALP Abs can cause interference on DxI 800 E2 and uE3 assays. This model can be used to investigate interference risk with other ALP-dependent assays.

Risk of Severe Maternal Morbidity or Death in Relation to Prenatal Biochemical Screening: Population-Based Cohort Study

This study aimed to examine whether prenatal biochemical screening analytes are associated with an increased risk of severe maternal morbidity (SMM) or maternal mortality. This population-based cohort study includes all women in Ontario, Canada, who underwent prenatal screening from 2001 to 2011. Increasing fifth percentiles of the multiple of the median (MoM) for alphafetoprotein (AFP), total human chorionic gonadotropin, unconjugated estriol (uE3), dimeric inhibin-A (DIA), and pregnancy-associated plasma protein A were evaluated. An abnormally high concentration (>95th percentile MoM) for each analyte, individually and combined, was also evaluated. The main outcome assessed was the adjusted relative risk (aRR) of SMM or maternal mortality from 20 weeks' gestation up to 26 weeks thereafter. Among 748,972 pregnancies, 11,177 resulted in SMM or maternal mortality (1.5%). Except for uE3, the aRR of SMM or maternal mortality increased in association with increasing fifth percentiles of the MoM for all analytes. AFP (aRR: 2.10; 95% confidence interval [CI]: 1.97-2.25) and DIA (aRR: 2.33; 95% CI: 1.98-2.74) > 95th versus ≤ 5th percentile of the MoM were especially associated with SMM or death. Women with abnormally high concentrations of certain prenatal biochemical analytes may be at a higher risk of SMM or death in pregnancy or postpartum.

Impact of Material Serum Screening in Early Prenatal Diagnosis and Management of Congenital Anomalies

It was performed a case-control study, that included totally 187 pregnant women hospitalized in Obstetrical-Gynecology Department of Prof. Dr. Panait Sarbu Hospital, Bucharest, Romania. The selection criteria for case sample were: age over 30 years, history of malformative risk, clinical exam that emphasised malformations and ultrasound examination that suspicioned embrio-fetal morphological abnormalities. We determined the serum levels of alpha fetoprotein (AFP), human chorionic gonadotropin (hCG) and unconjugated estriol (uE3), by immunoenzymometry. As statistical analysis we determined the estimated median value. For each of the three parametres, the final curve was compared with the value obtained by spectrophotometry. The study revealed the predictive value of correlated use of these three parameters, together with ultrasound examination and cytogenetic investigations, in order to early prenatal diagnosis of congenital fetal anomalies.

The association between antiretroviral therapy and early placental function: a cohort study

Objective: To evaluate the association of antiretroviral therapy (ART) type and duration of exposure with early placental function using biomarkers of aneuploidy screening.Study design: Three hundred thirty-eight pregnant women living with HIV were enrolled in two Canadian centers. Multiple linear regressions were performed adjusting for confounding factors (race, age, gestational age, body mass index, parity, smoking, and fetal sex).Results: Women receiving ART had significantly increased second trimester alpha-fetoprotein (AFP) levels (β = 0.147, 95% CI = [0.067–0.227] for protease inhibitor-based ART and β = 0.176, 95% CI = [0.080–0.272] for ART without protease inhibitor) compared to women who received no treatment. However, there was no significant association between ART type and the levels of free β-human chorionic gonadotrophin (β-hCG), pregnancy-associated plasma protein-A (first trimester), unconjugated estriol, total hCG, and inhibin A (second trimester). No significant association was shown between biomarker levels and duration of ART exposure.Conclusion: Early placental function does not appear to be significantly affected by ART, except for AFP.

Normative Values of Second-Trimester Maternal Serum Markers Using an Automated Assay Platform for Down Syndrome Screening

Objective: Automated chemiluminescent immunoassay has several advantages over manual ELISA with comparable test performance. Few studies have reported the reference values of the second-trimester serum markers maternal serum alpha-fetoprotein (AFP), human chorionic gonadotropin (hCG), unconjugated estriol (uE3), and inhibin A (Inh A) by automated immunoassay in Asian population. Accordingly, this study aimed to determine the median values of second trimester serum markers as a function of gestational age (GA) in Thai population using an automated immunoassay. Methods: This prospective cross-sectional study of serum markers in healthy singleton second trimester (14-22 weeks) pregnant women was conducted at Siriraj Hospital from September 2012 to April 2015. Maternal serum AFP, hCG, uE3, and Inh A were analyzed by automated immunoassay. Predicted median values as a function of GA were calculated from best-fit regression equations. Results: A total of 1,526 women were included. Median values serum markers were constructed from the following optimal models: AFP (ng/mL) = 99.082 - 14.195 GA + 0.662 GA 2 , r 2 =0.995; hCG (mIU/mL) = 39, 0168.106 - 35 968.397GA + 876.708GA 2 , r 2 =0.972; uE3 (ng/mL) = -3.388 + 0.274 GA, r 2 =0.997; and, Inh-A (pg/mL) = 1,206.875 - 114.171 GA + 3.174 GA 2 , r 2 =0.882. Using the same platform analysis and maternal weight adjustment, the reference values in Thai population were shown to be different from those of other ethnicities. Conclusion: Median values of second-trimester serum markers for Thai population were determined. Maternal weight and the use of population-specific normal values have to be taken into account for Down syndrome screening in the second trimester.

Second Trimester Serum Biomarker Screen for Fetal Aneuploidies as a Predictor of Preterm Delivery: A Population-Based Study

Objective: To determine the association between second-trimester serum Down syndrome screening (alpha-fetoprotein [AFP] free beta-human chorionic gonadotropin [b-hCG] unconjugated estriol [uE3]) and preterm birth and to create predictive models for preterm birth. Methods: Secondary analysis on a prospective database of pregnancies undergoing second-trimester screen with complete follow-up. The multiples of medians (MoM) of the biomarkers were compared between the group of term, preterm (< 37 weeks), early preterm (< 34 weeks), and very early preterm (< 32 weeks) delivery. Predictive models were developed based on adjusted MoMs and logistic regression and diagnostic performances in predicting preterm birth were determined. Results: Of 20,780 pregnancies, 1,554 (7.5), 363 (1.7), and 158 (0.8%) had preterm, early preterm, and very early preterm birth respectively. High levels of AFP and b-hCG but low levels of uE3 were significantly associated with higher rates of preterm, early preterm and very early preterm delivery. The predictive models had diagnostic performance in predicting preterm birth with the areas under the ROC curve of 0.688, 0.534, 0.599, and 0.718 for AFP, b-hCG, uE3, and combined biomarkers respectively. Conclusion: The second trimester Down syndrome screening could also be used as a tool of risk identification of preterm birth in the same test, without extra-effort and extra-cost.

Down Syndrome Prediction Using a Cascaded Machine Learning Framework Designed for Imbalanced and Feature-correlated Data

Down syndrome (DS) caused by the presence of part or all of a third copy of chromosome 21 is the most common form of aneuploidy. The prenatal screening for DS is a key component of antenatal care and is recommended to be universally offered to women irrespective of age or background. The objective of this paper is to introduce a noninvasive and accurate diagnosis procedure for DS and to minimize social and financial cost of prenatal diagnosis. Recently, machine learning has received considerable attention in predictive analytics for medical problems. However, there is few its applications on DS prediction reported due to the difficulty of dealing with highly imbalanced and feature-correlated screening data. In this paper, we propose a cascaded machine learning framework designed for DS prediction based on three complementary stages: 1) pre-judgment with isolation forest technique, 2) model ensemble by voting strategy, and 3) final judgment using logistic regression approach. The experimental results show that the performance of this framework on maternal serum screening data set, when evaluated with different evaluation parameters, is superior to those of some machine learning methods. The best suggested combination of input features for DS screening is the group of alpha-fetoprotein, human chorionic gonadotropin, unconjugated estriol, and maternal age. In addition, our method has the potential to generate further accurate prediction for imbalanced and feature-correlated data, thereby providing a novel and effective approach for certain diseases analysis.

Alkaline phosphatase ınterference in an unconjugated estriol assay causing a false positive Down syndrome screening result

Abstract Objective Decreased unconjugated estriol (uE3) concentrations increase calculated risk of Down syndrome. Therefore, falsely low uE3, due to assay interference, have the potential to cause false-positive screening results. Here we present a 35 years old woman with a pregnancy of 17+2 weeks. Materials and methods Second-trimester screening test was performed on the UniCelDxI 800 (Beckman Coulter, Brea, CA, USA) analyzer and her uE3 level was 0.21 ng/mL (0.21 MoM). Risk calculated for DS was 1/8. Measurements were repeated on IMMULITE 2000 XPi (Siemens Healthcare Diagnostics Inc., USA). uE3 result was 0.614 ng/mL (0.97 MoM). The risk for DS was negative with this system. There was no sign of fetal anomaly on three-dimensional ultrasound examination and cell-free fetal DNA screening test. We suspected assay interference for uE3. Results Serial dilutions of serum samples revealed nonlinearity. 36.3% increase was observed with heterophile antibody blocking tubes. The post-polyethylene glycol treatment resulted approximately the same uE3 levels as IMMULITE system. Addition of alkaline phosphatase Scavenger to serum increased the result by 90% showing that falsely low E3 result was due to an interferent reacting on assay medium. Conclusion Laboratories should be aware that falsely low uE3 results due to interference may be obtained.

Quad Screen Test, A Multiplexed Biomarker Assay for Prenatal Screening to Assess Birth Defects: The Columbia University Experience Using the Beckman Access2 Immunoassay Analyzer and Benetech PRA.

In the prenatal quad screen, the levels of four analytes in maternal serum are used to calculate the risk of serious birth defects. The Beckman Access2 Immunoassay System is an automated analyzer that enables rapid measurement of alpha-fetoprotein, unconjugated estriol, human chorionic gonadotropin, and dimeric inhibin A. The Benetech PRA software package is used to convert maternal serum analyte concentrations to multiples of the median (MoM) and calculates the risks of particular birth defects. The results from this simple and minimally invasive screen determine the need for more sensitive, specific, and usually riskier diagnostic procedures. We present herein some recent data from our experience at Columbia University Medical Center in New York, NY, using the Beckman Access2 immunoassay analyzer and Benetech PRA software package.

Estrogen metabolism in menopausal hormone users in the women's health initiative observational study: Does it differ between estrogen plus progestin and estrogen alone?

The WHI found an unexpected reduced breast cancer risk in women using CEE alone. We hypothesized CEE alone induces estrogen hydroxylation along the 2-pathway rather than the competing 16-pathway, a pattern linked to reduced postmenopausal breast cancer risk. One thousand eight hundred and sixty-four women in a WHIOS case-control study of estrogen metabolism and ovarian and endometrial cancer were studied of whom 609 were current E + P users (351 used CEE + MPA), while 272 used E alone (162 used CEE). Fifteen EM were measured, and analyses were conducted for each metabolite, hydroxylation pathway (2-, 4-, or 16-pathway) and ratios of pathway concentrations using inverse probability weighted linear regression. Compared to E + P users, all EM were higher in E alone users (significant for unconjugated estrone, total/conjugated estradiol, total/unconjugated 2-methoxyestrone, 4-methoxyestrone and unconjugated estriol). The relative concentrations of 2- and 4-pathway EM did not differ between the MHT users (2-pathway EM comprised 15% and 4-pathway EM <2% of the total), but 16-pathway EM were lower in E alone users (p = 0.036). Ratios of 2- and 4-pathway EM compared to 16-pathway EM were significantly higher in E alone compared to E + P users. Similar but not significant patterns were observed in CEE-alone and CEE + MPA users. Our data suggest that compared to E + P users, women using E alone have more extensive metabolism via the 2- vs. the competing 16-pathway. This is consistent with epidemiologic evidence of reduced postmenopausal breast cancer risk associated with this metabolic profile and may provide a clue to the breast cancer risk reduction in CEE alone users during the WHI.

Plasma progesterone, estradiol, and unconjugated estriol concentrations in twin pregnancies: Relation with cervical length and preterm delivery.

The aim of this study was to examine the association between plasma hormone concentrations, cervical length, and preterm delivery in twin pregnancies, including the effect of progesterone treatment. This study included 191 women pregnant with twins from a randomized placebo-controlled trial. A baseline blood sample was collected at 18-24weeks before treatment with vaginal progesterone (n=95) or placebo pessaries (n=96), and 167 (87.4%) women had a second sample collected after 4-8weeks of treatment. At baseline, 155 (81.2%) women had their cervical length measured. Progesterone, estradiol, and unconjugated estriol concentration was measured, and the association between hormone concentrations, cervical length, and gestational age at delivery was examined. Hormone concentrations were compared in the placebo and progesterone group. Statistical analysis included Spearman's rho, Mann-Whitney U test, Cuzick's test for trends, and linear regression analyses. A short cervical length was associated with preterm delivery. Cervical length and hormone concentrations were not associated (Spearman's rho; progesterone -.05, estradiol .04, estriol .08). Decreasing gestational age at delivery was associated with higher progesterone and estradiol concentrations at baseline (P trend; progesterone 0.04, estradiol 0.02) but not in the second sample or in the weekly change between samples. Progesterone treatment did not increase the progesterone concentration. Plasma concentrations of progesterone, estradiol, and unconjugated estriol at 18-24weeks are not associated with cervical length or preterm delivery in twin pregnancies. Vaginal progesterone treatment does not increase the circulating progesterone concentration in twin pregnancies. Cervical length, but not hormone concentration, is predictive of preterm delivery in twin gestations.