Performance of a Multianalyte 'Rule-Out' Assay in Pregnant Individuals With Suspected Preeclampsia.

Background: The ability to diagnose preeclampsia clinically is suboptimal. Our objective was to validate a novel multianalyte assay and characterize its performance, when intended for use as an aid to rule-out preeclampsia.

Methods: Prospective, multicenter cohort study of pregnant individuals presenting between 28 and 36 weeks' with preeclampsia-associated signs and symptoms.

Evaluation of a novel screening method for fetal aneuploidy using cell-free DNA in maternal plasma.

Objective: To evaluate the test performance of a novel sequencing technology using molecular inversion probes applied to cell-free DNA screening for fetal aneuploidy.

Methods: Two cohorts were included in the evaluation; a risk-based cohort of women receiving diagnostic testing in the first and second trimesters was combined with stored samples from pregnancies with fetuses known to be aneuploid or euploid. All samples were blinded to testing personnel before being analyzed, and validation occurred after the study closed and results were merged.

Factors affecting levels of circulating cell-free fetal DNA in maternal plasma and their implications for noninvasive prenatal testing.

Objective: Sufficient fetal DNA in a maternal plasma sample is required for accurate aneuploidy detection via noninvasive prenatal testing, thus highlighting a need to understand the factors affecting fetal fraction.

Method: The MaterniT21™ PLUS test uses massively parallel sequencing to analyze cell-free fetal DNA in maternal plasma and detect chromosomal abnormalities. We assess the impact of a variety of factors, both maternal and fetal, on the fetal fraction across a large number of samples processed by Sequenom Laboratories.

Non-invasive prenatal chromosomal aneuploidy testing--clinical experience: 100,000 clinical samples.

Objective: As the first laboratory to offer massively parallel sequencing-based noninvasive prenatal testing (NIPT) for fetal aneuploidies, Sequenom Laboratories has been able to collect the largest clinical population experience data to date, including >100,000 clinical samples from all 50 U.S. states and 13 other countries.

Noninvasive prenatal screening for fetal trisomies 21, 18, 13 and the common sex chromosome aneuploidies from maternal blood using massively parallel genomic sequencing of DNA.

Objective: The objective of this study was to validate the clinical performance of massively parallel genomic sequencing of cell-free deoxyribonucleic acid contained in specimens from pregnant women at high risk for fetal aneuploidy to test fetuses for trisomies 21, 18, and 13; fetal sex; and the common sex chromosome aneuploidies (45, X; 47, XXX; 47, XXY; 47, XYY).

Study Design: This was a prospective multicenter observational study of pregnant women at high risk for fetal aneuploidy who had made the decision to pursue invasive testing for prenatal diagnosis. Massively parallel single-read multiplexed sequencing of cell-free deoxyribonucleic acid was performed in maternal blood for aneuploidy detection.

Noninvasive prenatal detection of aneuploidy.

Noninvasive prenatal testing (NIPT) uses cell-free fetal DNA from the plasma of pregnant women to provide valuable information about the potential risks for fetal aneuploidy. This article provides a historical overview of both invasive diagnostic testing and serum screening approaches, both biochemical and the newer molecular noninvasive prenatal testing assays, used to identify patients who would be best served by invasive testing.

Maternal plasma DNA testing for aneuploidy in pregnancies achieved by assisted reproductive technologies.

Purpose: We sought to compare measurements of circulating cell-free DNA as well as Down syndrome test results in women with naturally conceived pregnancies with those conceived using assisted reproductive technologies.

Methods: Data regarding assisted reproductive technologies were readily available from seven enrollment sites participating in an external clinical validation trial of nested case/control design. Measurements of circulating cell-free fetal and total DNA, fetal fraction (ratio of fetal to total DNA), chromosome-specific z-scores, and karyotype results were available for analysis.

Noninvasive prenatal detection of sex chromosomal aneuploidies by sequencing circulating cell-free DNA from maternal plasma.

Objective: Whole-genome sequencing of circulating cell free (ccf) DNA from maternal plasma has enabled noninvasive prenatal testing for common autosomal aneuploidies. The purpose of this study was to extend the detection to include common sex chromosome aneuploidies (SCAs): [47,XXX], [45,X], [47,XXY], and [47,XYY] syndromes.

Method: Massively parallel sequencing was performed on ccf DNA isolated from the plasma of 1564 pregnant women with known fetal karyotype.

DNA sequencing of maternal plasma to identify Down syndrome and other trisomies in multiple gestations.

Objective: Studies on prenatal testing for Down syndrome (trisomy 21), trisomy 18, and trisomy 13 by massively parallel shotgun sequencing (MPSS) of circulating cell free DNA have been, for the most part, limited to singleton pregnancies. If MPSS testing is offered clinically, it is important to know if these trisomies will also be identified in multiple pregnancies.

Method: Among a cohort of 4664 high-risk pregnancies, maternal plasma samples were tested from 25 twin pregnancies (17 euploid, five discordant and two concordant for Down syndrome; one discordant for trisomy 13) and two euploid triplet pregnancies [Correction made here after initial online publication.

DNA sequencing of maternal plasma reliably identifies trisomy 18 and trisomy 13 as well as Down syndrome: an international collaborative study.

Purpose: To determine whether maternal plasma cell-free DNA sequencing can effectively identify trisomy 18 and 13.

Methods: Sixty-two pregnancies with trisomy 18 and 12 with trisomy 13 were selected from a cohort of 4,664 pregnancies along with matched euploid controls (including 212 additional Down syndrome and matched controls already reported), and their samples tested using a laboratory-developed, next-generation sequencing test. Interpretation of the results for chromosome 18 and 13 included adjustment for CG content bias.

DNA sequencing of maternal plasma to detect Down syndrome: an international clinical validation study.

Purpose: Prenatal screening for Down syndrome has improved, but the number of resulting invasive diagnostic procedures remains problematic. Measurement of circulating cell-free DNA in maternal plasma might offer improvement.

Methods: A blinded, nested case-control study was designed within a cohort of 4664 pregnancies at high risk for Down syndrome.

Fetal RHD genotype detection from circulating cell-free fetal DNA in maternal plasma in non-sensitized RhD negative women.

Objective: To examine the performance of the SensiGene Fetal RHD Genotyping Laboratory Developed Test (RHD Genotyping LDT) using circulating cell-free fetal DNA (ccff DNA) extracted from maternal plasma.

Methods: ccff DNA was extracted from maternal blood from non-sensitized women with singleton pregnancies in two cohorts, one with a serotype reference (11-13 weeks' gestation) and one with the reference source (6-30 weeks' gestation). The presence of three RHD exon sequences (exons 4, 5, 7), the psi-pseudogene, three Y-chromosome sequences (SRY, DBY and TTTY2), and the X/Y-chromosome TGIF gene control were determined using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry-the RHD Genotyping LDT.

Noninvasive detection of fetal trisomy 21 by sequencing of DNA in maternal blood: a study in a clinical setting.

Objective: We sought to evaluate a multiplexed massively parallel shotgun sequencing assay for noninvasive trisomy 21 detection using circulating cell-free fetal DNA.

Study Design: Sample multiplexing and cost-optimized reagents were evaluated as improvements to a noninvasive fetal trisomy 21 detection assay. A total of 480 plasma samples from high-risk pregnant women were employed.

Fetal sex determination using circulating cell-free fetal DNA (ccffDNA) at 11 to 13 weeks of gestation.

Objective: To examine the performance of a mass spectrometry-based detection platform using three Y-chromosome sequences for fetal sex determination from circulating cell-free fetal DNA (ccffDNA) in maternal blood in the first trimester of pregnancy.

Methods: We extracted ccffDNA for the determination of fetal sex from stored maternal plasma obtained at 11 to 13 weeks' gestation from singleton pregnancies with documented fetal gender. Mass spectrometry was used to examine 236 specimens for the presence of three Y-chromosome sequences (SRY, DBY and TTTY2).

The suitability of matrix assisted laser desorption/ionization time of flight mass spectrometry in a laboratory developed test using cystic fibrosis carrier screening as a model.

We designed a laboratory developed test (LDT) by using an open platform for mutation/polymorphism detection. Using a 108-member (mutation plus variant) cystic fibrosis carrier screening panel as a model, we completed the last phase of LDT validation by using matrix-assisted laser desorption/ionization time of flight mass spectrometry. Panel customization was accomplished via specific amplification primer and extension probe design.

Fetal cardiac scanning performed immediately following an abnormal nuchal translucency examination.

Objective: To study the implications of early fetal cardiac scanning immediately following an abnormal nuchal translucency (NT) examination.

Methods: Fetal cardiac scanning was performed immediately after an increased NT was observed. Scans were performed transvaginally at 11 to 14 weeks.

Preventing needlestick injuries in obstetrics and gynecology: how can we improve the use of blunt tip needles in practice?

Surgical needlestick injuries are common in obstetrics and gynecology and can cause transmission of viral diseases including hepatitis and acquired immunodeficiency syndrome (AIDS). Strategies to reduce the rate of needlestick injuries include using instruments rather than fingers to retract tissue and grasp needles, double gloving, using surgical staplers for skin closure, and substituting blunt tip surgical needles for sharp tip needles where applicable. Studies have shown the use of blunt tip surgical needles to be remarkably effective in reducing needlestick injuries.

A randomized clinical trial comparing the effect of maternal intravenous hydration and placebo on the amniotic fluid index in oligohydramnios.

Objective: To compare the treatment of acute intravenous hydration with placebo in term pregnant women manifesting oligohydramnios.

Methods: All patients with oligohydramnios who met the inclusion criteria were offered participation in this randomized, double-blind, placebo-controlled study. After ruling out rupture of membranes and maternal and fetal complications, we recruited 44 women with third trimester singleton pregnancies having an amniotic fluid index (AFI) of less than 6.

Screening for structural fetal anomalies during the nuchal translucency ultrasound examination.

Objective: The purpose of this study was to evaluate the ability to screen for structural fetal anomalies during the nuchal translucency (NT) ultrasound examination, without performing a complete anatomic fetal scan, by using the sagittal views of the fetus.

Study Design: In a prospective study, we evaluated all the suspected structural findings observed during the NT examinations performed in our Division of Maternal-Fetal Medicine in 2004-2005. The purpose of the examination was to screen for fetal chromosome abnormalities by using the fetal NT measurements.

Ethnicity and other factors that may affect the prevalence of echogenic intracardiac foci in the fetus.

Purpose: To study ethnicity and other possible factors that may affect the incidence of echogenic intracardiac foci (EIF) when detected via sonographic examination.

Materials And Methods: Patients were referred to our institution for sonographic evaluation from a wide range of practice formats, including both private obstetric practices as well as community outpatient clinics. The study protocol included presence or absence of EIF, maternal age, ethnicity, gestational age during the examination, optimal versus suboptimal scans, presence of other fetal malformations and sonographic markers, and presence of chromosomal anomalies.

Characteristics of patients with abnormal glucose challenge test and normal oral glucose tolerance test results: comparison with normal and gestational diabetic patients.

Objective: The purpose of this study was to evaluate the characteristics and outcomes of patients who had abnormal glucose challenge test results and subsequent normal oral glucose tolerance test results and to assess whether such patients are at a greater risk than normal pregnant patients for adverse perinatal outcome.

Study Design: In this retrospective cohort study that was conducted between June and December 2003, 101 pregnant women (group A) had an abnormal glucose challenge test result and a normal oral glucose tolerance test result. Data were also collected on 2 control groups: 100 pregnant women with normal glucose challenge test results (group B) and all 76 pregnant women who were diagnosed with gestational diabetes mellitus during this period of time (group C).