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Geralyn M Lambert-Messerlian

Publications and source records attributed to Geralyn M Lambert-Messerlian.

13 recordsLinked to original sources
PubMed2006

Stability of first- and second-trimester serum markers after storage and shipment.

OBJECTIVE: The purpose of this study was to examine the levels of first- and second-trimester maternal serum markers used in Down syndrome screening in relation to the time between sample collection and arrival at the laboratory. METHODS: The FASTER trial, designed to compare first- and second-trimester screening tests for aneuploidy, has recently been completed, having recruited more than 38,000 patients. According to the trial protocol, all blood samples were drawn in serum separator tubes, centrifuged within 30 min and stored at 4 degrees C until shipment by air express. To examine the effect of delayed shipment, serum marker levels (expressed as multiple of the median--MoM) were evaluated in the first- and second-trimester samples and stratified by the number of days between serum collection and laboratory receipt. RESULTS: Under specified collection and shipment conditions, first and second-trimester screening marker mean levels and degrees of variance were stable for up to 9 days, with the exception of unconjugated estriol, which was stable for up to 6 days. CONCLUSION: The levels of first- and second-trimester Down syndrome screening markers can be measured reliably when the sample is centrifuged, refrigerated until shipment and received in the laboratory within a week of being drawn. A conservative approach would be to restrict testing to within 6 days of draw, with the intent to keep shipping delays to a minimum.

Biomarkers↗
PubMed2006

Total activin A in maternal blood as a marker of preterm delivery in low-risk asymptomatic patients.

OBJECTIVES: To retrospectively evaluate whether increased serum levels of total activin A (t-activin A) are found in women who subsequently experience preterm delivery (PTD). METHODS: Data on maternal serum t-activin A concentrations were available from a total of 84 singleton pregnant women and included 14 PTD pregnancies, each matched for gestational age and length of freezer storage, with 5 control pregnancies having term delivery (TD). Analyte values were expressed as multiple(s) of the control median. RESULTS: The median t-activin A for controls and cases was 1.00 +/- 0.45 and 1.27 +/- 0.53 MoM, respectively. Univariate analysis of the MoM values was performed using the Kaplan-Meier algorithm. Differences in the rate of delivery using a t-activin A MoM cut-off of > or = 1 SD (equivalent to 1.26 MoM) were analysed using the log rank test. The cumulative rate of PTD (< 37 weeks) was significantly higher for women with t-activin A concentrations > or = 1.26 MoM than those with t-activin A concentrations below this cut-off (40% vs.. 10%, p-value = 0.0218 log rank test). CONCLUSIONS: T-activin A concentration is higher in women who will develop PTD in a low-risk population. T-activin A values are inversely proportional to the time elapsed from blood test to delivery. Prospective studies would determine the precise discriminability of this marker for PTD and the best week for performing the blood test, allowing for a proper calculation of the detection rate and a positive predictive value.

Activins↗
PubMed2006

Comparison of serum markers in first-trimester down syndrome screening.

OBJECTIVE: To estimate patterns of total hCG and inhibin A levels in the late first trimester of Down syndrome pregnancies, compare them with that of free beta-hCG, and assess screening performance of these markers individually and in combination with pregnancy-associated plasma protein-A (PAPP-A) and nuchal translucency. METHODS: Seventy-nine matched case-control sets of maternal serum samples (each Down syndrome case matched to 5 controls) from 11 through 13 completed weeks of gestation were taken from the sample bank of the First and Second Trimester Evaluation of Risk Consortium, a population-based study, and assayed for levels of free beta-hCG, total hCG, and inhibin A. Distribution characteristics and correlations of the multiples of the median values were estimated in cases and controls. Screening performance for each marker, alone and in combination with PAPP-A, nuchal translucency, and maternal age, was calculated. RESULTS: Median multiples of the median levels of free beta-hCG, total hCG, and inhibin A in cases were more elevated as gestation increased from 11 to 13 weeks, with univariate detection rates of 31%, 23%, and 29%, respectively, at a 5% false-positive rate. At 12 weeks, the multivariate detection rates at a 5% false-positive rate for nuchal translucency and PAPP-A (with maternal age) with either free beta-hCG, total hCG, or inhibin A were 84%, 83%, and 85%, respectively. The improvement in performance from nuchal translucency and PAPP-A to any of the three-marker tests was significant, while performance of any of the three-marker combinations was not significantly different from each other. CONCLUSION: Although levels of free beta-hCG in affected pregnancies were higher earlier than the levels of either total hCG or inhibin A, there was no significant difference in screening performance when either of the three markers was used with nuchal translucency and PAPP-A at 11-13 weeks of pregnancy. LEVEL OF EVIDENCE: II-2.

Adult↗
PubMed2005

Cell-free fetal DNA levels in pregnancies conceived by IVF.

BACKGROUND: Increased second-trimester levels of maternal serum HCG in IVF conceptions lead to an increased false-positive rate in Down syndrome screening. Increased levels of cell-free fetal DNA (cffDNA) in maternal plasma have been correlated with increased HCG levels. Our aim was to determine whether cffDNA levels are elevated in IVF pregnancies compared with natural pregnancies. METHODS: Sixteen archived second-trimester serum samples from IVF pregnancies were matched with five control samples from naturally conceived pregnancies per case, all carrying a singleton male fetus. cffDNA concentrations were measured by real-time PCR amplification of a Y chromosome sequence and compared with four standard second trimester serum screening markers (alpha-fetoprotein, estriol, HCG and inhibin A). RESULTS: Mean cffDNA levels for cases and controls were 57.9 and 57.1 genome equivalents/ml, respectively (P = 0.95). Mean observed rank (from 1 to 6) of cffDNA was 3.625 in the IVF conceived group, compared with an expected value of 3.5 (P = 0.53). No significant correlations were observed between cffDNA and serum markers. CONCLUSIONS: IVF does not affect levels of cffDNA, which appears to be independent of traditional screening markers (e.g. HCG). Therefore, cffDNA can be used as an additional serum marker (e.g. Down syndrome screening) without adjustment for IVF pregnancies.

Biomarkers↗
PubMed2005

Quad screen as a predictor of adverse pregnancy outcome.

OBJECTIVE: To estimate the effect of second-trimester levels of maternal serum alpha-fetoprotein (AFP), human chorionic gonadotrophin (hCG), unconjugated estriol (uE3), and inhibin A (the quad screen) on obstetric complications by using a large, prospectively collected database (the FASTER database). METHODS: The FASTER trial was a multicenter study that evaluated first- and second-trimester screening programs for aneuploidy in women with singleton pregnancies. As part of this trial, patients had a quad screen drawn at 15-18 6/7 weeks. We analyzed the data to identify associations between the quad screen markers and preterm birth, intrauterine growth restriction, preeclampsia, and fetal loss. Our analysis was performed by evaluating the performance characteristics of quad screen markers individually and in combination. Crude and adjusted effects were estimated by multivariable logistic regression analysis. Patients with fetal anomalies were excluded from the analysis. RESULTS: We analyzed data from 33,145 pregnancies. We identified numerous associations between the markers and the adverse outcomes. There was a relatively low, but often significant, risk of having an adverse pregnancy complication if a patient had a single abnormal marker. However, the risk of having an adverse outcome increased significantly if a patient had 2 or more abnormal markers. The sensitivity and positive predictive values using combinations of markers is relatively low, although superior to using individual markers. CONCLUSION: These data suggest that components of the quad screen may prove useful in predicting adverse obstetric outcomes. We also showed that the total number and specific combinations of abnormal markers are most useful in predicting the risk of adverse perinatal outcome.

Adolescent↗
PubMed2004

Placenta growth factor levels in second-trimester maternal serum in Down syndrome pregnancy and in the prediction of preeclampsia.

OBJECTIVES: To determine the levels of placenta growth factor (PlGF) in second-trimester maternal serum samples from pregnancies affected with fetal Down syndrome and from those that developed preeclampsia and to assess the utility of PlGF as a screening tool for these conditions. METHODS: Residual second-trimester maternal serum samples were retrieved from freezer storage for 39 cases of Down syndrome and 44 pregnancies that later developed preeclampsia. Each case was matched to 5 control samples for gestational age at collection and duration of freezer storage. PlGF levels were measured in each sample by enzyme-linked immunosorbent assay (ELISA). RESULTS: PlGF levels increased with gestational age between 15 and 20 gestational weeks. After adjusting for gestational-age effects, the median level of PlGF was 1.01 MoM in Down syndrome pregnancy and 0.74 MoM in pregnancies that developed preeclampsia, which were not significantly different from matched controls. The duration between sampling and onset of preeclampsia did not have an effect on the PlGF level. CONCLUSION: PlGF levels are not significantly altered in second-trimester maternal serum samples from cases of Down syndrome or in pregnancies that develop preeclampsia.

Biomarkers↗
PubMed2004

Clinical application of inhibin a measurement: prenatal serum screening for Down syndrome.

Inhibin A is secreted in significant quantities by the corpus luteum and fetoplacental unit, suggesting a role in fertility and pregnancy. Negative feedback regulation of follicle-stimulating hormone during pregnancy is one expected function of inhibin A, but the complete repertoire of actions of this hormone in pregnancy, including paracrine and autocrine actions, is yet to be fully understood. Inhibin A levels have been carefully described throughout normal pregnancy and studied in association with maternal and fetal complication such as intrauterine growth restriction, preterm labor or delivery, and preeclampsia. The first clinical application of inhibin A measurement in pregnancy has been its use as a second-trimester maternal serum marker for Down syndrome. Our laboratory was among the first, in 1998, to implement Quad marker screening, inhibin A measurement in conjunction with alpha-fetoprotein, unconjugated estriol, and human chorionic gonadotropin, to assess patients' risk of having a Down syndrome baby. The test performance of the Quad test has been validated by several large studies, detecting about 80% of Down syndrome pregnancies at a 5% false-positive rate. The present review describes Down syndrome and the use of inhibin A in second-trimester prenatal screening. We also address the method used for inhibin A measurement, the biology of inhibin A in Down syndrome pregnancy, and the effects of covariates and other fetal abnormalities on inhibin A levels.

Down Syndrome↗
PubMed2003

Prenatal screening for Down syndrome: current and future methods.

Second-trimester serum screening for Down syndrome has had a relatively long clinical life, beginning in the mid-1980s and continuing to the present day. In the past few years, however, new screening methods that involve testing just a few weeks earlier and the integration of first-trimester and second-trimester markers have been proposed and are being used. These improved methods have begun the transition to better and, hopefully, safer prenatal screening. In the past, as many as 1 in 10 pregnant women learned that they were at increased risk of having a baby with a serious birth defect and had to decide whether to have an invasive diagnostic procedure. Now, screening methods are at the point where as few as 1 in 50 or 1 in 100 pregnant women are found to be at increased risk. The ultimate goal in screening is to make noninvasive testing methods so safe that only those few women who are found to be at the very highest risk will need to face the uncertainty of invasive procedures. In the next few years, that goal will probably be achieved.

Adult↗
PubMed2003

Prenatal screening, epidemiology, diagnosis, and management of preeclampsia.

The cause of preeclampsia remains unknown. The disease manifests itself across a broad clinical spectrum from mild to severe, conferring vastly different morbidities and suggesting possibly different disease processes. Oxidative stress, endothelial dysfunction, maternal-fetal immune incompatibility, and abnormal placental implantation are among the suggested causes. The need for a marker or set of markers that allow for definitive diagnosis and assessment of future risk of preeclampsia is tremendous. Ultrasound techniques and several markers have been identified that are increased among patients with preeclampsia, but no test is highly sensitive. In the future, a combination of markers likely will be used to assess risk and, establish the diagnosis, and test treatment strategies. Such an approach would allow for more refined treatment studies of patients who are at highest risk for preeclampsia.

Adult↗
PubMed2003

Concentrations of serum total activin A and inhibin A in preterm and term labor patients: a cross-sectional study.

OBJECTIVE: To compare maternal serum levels of total activin A and inhibin A in preterm and term patients who are in labor or not in labor. METHODS: A cross-sectional study compared activin A and inhibin A in the following groups of patients: preterm and in labor (n = 65), preterm and not in labor (n = 96), term and in labor (n = 65), and term and not in labor (n = 65). Preterm was defined as 23-34 weeks' gestation and term as 37-42 weeks' gestation. Labor was defined as regular contractions with progressive cervical change or an initial examination revealing cervical dilation of 1-3 cm with 50% effacement or more. Follistatin levels were analyzed in a subset of 12 patients from each group. Analytes were measured by two-site enzyme-linked immunosorbent assays. RESULTS: Activin A levels were higher in the preterm labor group (median 1.38 multiples of the median [MoM], interquartile range [IQR] 1.01 MoM) compared with the preterm nonlabor group (median 1.0 MoM, IQR 0.78 MoM, P <.05) and in the term labor group (median 1.37 MoM, IQR 1.74 MoM) compared with the term nonlabor group (median 1.0 MoM, IQR 0.87 MoM, P <.05). Inhibin A levels were higher in the preterm labor group (median 1.27 MoM, IQR 0.73 MoM) compared with the preterm nonlabor group (median 1.0 MoM, IQR 0.58 MoM, P <.05). Post-hoc analysis of activin A and inhibin A elevations in the preterm labor group revealed a significant effect only during 31-34 weeks' gestation. The total activin A:follistatin ratio, an indirect measure of free activin A, was similar between labor and nonlabor gestational age-matched patient groups. CONCLUSIONS: Levels of total activin A and inhibin A were increased in patients during labor; however, based on the moderate degree and narrow gestational age range of the increased levels, these analytes are not likely to be clinically useful in predicting preterm labor.

Activins↗
PubMed2003

Evaluation of cell-free fetal DNA as a second-trimester maternal serum marker of Down syndrome pregnancy.

BACKGROUND: Second-trimester cell-free fetal DNA (studied only in pregnancies with male fetuses) is higher in maternal serum samples from women carrying Down syndrome fetuses than in unaffected pregnancies. In this study we evaluated the potential performance of fetal DNA as a screening marker for Down syndrome. METHODS: Data on maternal serum fetal DNA concentrations and the corresponding concentrations of the quadruple serum markers were available from 15 Down syndrome cases, each matched for gestational age and length of freezer storage, with 5 control samples. Analyte values were expressed as multiple(s) of the control or population median. Screening performance of fetal DNA, both alone and when added to estimates of quadruple marker performance, was determined after modeling using univariate and multivariate gaussian distribution analysis. RESULTS: The median fetal DNA concentration in Down syndrome cases was 1.7 times higher than in controls. In univariate analysis, fetal DNA gave a 21% detection rate at a 5% false-positive rate. When added to quadruple marker screening, fetal DNA increased the estimated detection rate from 81% to 86% at a 5% false-positive rate. CONCLUSIONS: Cell-free fetal DNA, measured in maternal serum, can modestly increase screening performance above what is currently available in the second trimester. If and when maternal serum fetal DNA can be measured in pregnancies with both male and female fetuses, the utility and cost-effectiveness of adding it as a Down syndrome screening marker should be assessed.

Biomarkers↗
PubMedDate not supplied

Mechanism of increased maternal serum total activin a and inhibin a in preeclampsia.

OBJECTIVE: To determine whether increased levels of maternal serum total activin A and inhibin A in preeclampsia are related to total blood volume, urinary clearance, or placental production. STUDY DESIGN: Activin A and inhibin A levels were measured in preeclamptic subjects and matched normotensive gravidas. In a subset of preeclamptic subjects (n = 21) and controls (n = 30), we performed blood volume studies. In an overlapping subset of preeclamptic subjects (n = 56), creatinine clearance results were available. Placental tissue was obtained from six preeclamptics and matched normotensive gravida for analysis of activin A and inhibin A mRNA expression. RESULTS: Maternal serum levels of inhibin A but not activin A were significantly negatively correlated with blood volume in preeclampsia (r(2) =.26, P =.017, and r(2) =.02, P =.44, respectively). Levels of both proteins were negatively correlated to creatinine clearance (r(2) =.29, P <.0001, and r(2) =.15, P =.003, respectively). Placental mRNA expression for both the alpha and betaA subunits was increased in preeclampsia (P =.038 and.049, respectively). CONCLUSION: Although placental mRNA expression of the subunits for both analytes is increased in preeclampsia, the increased levels of activin A appear to be more specifically a reflection of increased placental production than do the increased levels of inhibin A.

Activins↗