Prenatal Visualization of the Pulmonary and Aortic Valves and Leaflets Is Feasible Using 4-Dimensional Sonography.

Objectives: The purpose of this study was to determine whether the morphologic characteristics and area of the semilunar valves in healthy fetuses and fetuses with cardiac defects can be visualized by using spatiotemporal image correlation (STIC).

Methods: Spatiotemporal image correlation volumes from 74 healthy fetuses were recorded in 5 examinations between the 15th and 36th weeks of pregnancy. Second, we recorded STIC volumes from 64 fetuses with various cardiac defects.

When is a post-mortem skeletal survey of the fetus indicated, and when not?

Objective: Radiography after fetal or perinatal death has become a routine part of post-mortem diagnostics. However, only a selected subset of these babygrams or fetal post-mortem skeletal surveys (FPSSs) provides useful information. We investigated the indication for a FPSS.

Women's and healthcare professionals' preferences for prenatal testing: a discrete choice experiment.

Objective: This study evaluates pregnant women's and healthcare professionals' preferences regarding specific prenatal screening and diagnostic test characteristics.

Method: A discrete choice experiment was developed to assess preferences for prenatal tests that differed in seven attributes: minimal gestational age, time to test results, level of information, detection rate, false positive rate, miscarriage risk and costs.

Results: The questionnaire was completed by 596 (70.

Small biparietal diameter and head circumference are part of the phenotype instead of independent prognostic markers in fetuses with spinal dysraphism.

Objective: The aim of this retrospective study was to assess the fetal biparietal diameter (BPD) and head circumference (HC) in the second trimester of pregnancy in fetuses with open spinal dysraphism.

Methods: BPD and HC were measured at 16-26 weeks in 74 fetuses with open spinal dysraphism and compared with reference values.

Results: BPD was smaller in fetuses with open spinal dysraphism.

The consequences of implementing non-invasive prenatal testing in Dutch national health care: a cost-effectiveness analysis.

Objective: Non-invasive prenatal testing (NIPT) using cell-free fetal DNA in maternal plasma has been developed for the detection of fetal aneuploidy. Clinical trials have shown high sensitivity and specificity for trisomy 21 (T21) in both high-risk and average-risk populations. Although its great potential for prenatal medicine is evident, more information regarding the consequences of implementing NIPT in a national programme for prenatal screening is required.

Size-based molecular diagnostics using plasma DNA for noninvasive prenatal testing.

Noninvasive prenatal testing using fetal DNA in maternal plasma is an actively researched area. The current generation of tests using massively parallel sequencing is based on counting plasma DNA sequences originating from different genomic regions. In this study, we explored a different approach that is based on the use of DNA fragment size as a diagnostic parameter.

The effectiveness of multifetal pregnancy reduction in trichorionic triplet gestation.

Objective: The objective of the study was to assess in trichorionic triplet pregnancies the effectiveness of elective reduction to twins.

Study Design: This was a nationwide retrospective cohort study. We compared the time to delivery and perinatal mortality in trichorionic triplet pregnancies electively reduced to twins with ongoing trichorionic triplets and primary dichorionic twins.

Evaluation of the introduction of the national Down syndrome screening program in the Netherlands: age-related uptake of prenatal screening and invasive diagnostic testing.

Objective: To study the effect of different government prenatal screening (PNS) policies on the uptake of PNS and prenatal diagnostic testing (PND) over the periods 2001-2003 (PNS on request), 2004-2006 (permission to offer the first-trimester combined test (FCT) to women of advanced maternal age (AMA), with women aged <36 years informed on explicit request) and 2007-2010 (introduction of population screening) and to evaluate whether trends in uptake are related to maternal age. The indication AMA for PND is still warranted, and the costs for FCT are only reimbursed for AMA women.

Study Design: Analysis of data on the first- and second-trimester screening program (n=41,600) for Down syndrome (DS) and on PND (n=10,795) performed from 2001 to 2010 in the region North-Holland of the Netherlands.

Validation of correction factors for serum markers for first-trimester Down syndrome screening in singleton pregnancies conceived with assisted reproduction.

Objective: To validate previously computed correction factors for free β-human chorionic gonadotrophin (fβ-hCG) and pregnancy-associated plasma protein-A (PAPP-A) in in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) pregnancies with hormone treatment and to determine the effect on false-positive rate (FPR).

Methods: Retrospective study on 249 IVF and 250 ICSI cases and 20,190 controls. Correction factors 1.

Reliable noninvasive prenatal testing by massively parallel sequencing of circulating cell-free DNA from maternal plasma processed up to 24h after venipuncture.

Objectives: Circulating cell-free fetal DNA (ccffDNA) in maternal plasma is an attractive source for noninvasive prenatal testing (NIPT). The amount of total cell-free DNA significantly increases 24h after venipuncture, leading to a relative decrease of the ccffDNA fraction in the blood sample. In this study, we evaluated the downstream effects of extended processing times on the reliability of aneuploidy detection by massively parallel sequencing (MPS).

Monochorionic dizygous twins presenting with blood chimerism and discordant sex.

Monochorionic dizygous twins are probably more frequent than considered previously as many cases remain unrecognized, especially when the children have the same sex. Here we present a pair of dizygous, sex-discordant monochorionic twins who were conceived after artificial insemination. Histological examination of the placenta and extensive genetic studies of the healthy boy and girl clearly proved that they indeed were monochorionic dizygous twins with a fully joined blood circulation.

Women's Attitudes towards the Option to Choose between Karyotyping and Rapid Targeted Testing during Pregnancy.

Objectives. Pregnant women, referred because of an increased risk of fetal Down syndrome, who underwent an invasive prenatal procedure were offered a choice between karyotyping and rapid targeted testing. This study aims to assess women's attitudes and experiences towards what option to choose.

Why do parents prefer to know the fetal sex as part of invasive prenatal testing?

Objectives. The aim of this study was to determine whether prospective parents, primarily referred for prenatal diagnosis to exclude Down syndrome, prefer to know the fetal sex as part of invasive testing. Methods.

ADAM12s and PP13 as first trimester screening markers for adverse pregnancy outcome.

Background: The aim of the study was to assess the screening performance of first trimester maternal serum measurements of A-disintegrin-and-metalloprotease 12-s (ADAM12s) and placental protein 13 (PP13) for preeclampsia (PE), gestational hypertension (GH) and small-for-gestational-age (SGA) fetuses.

Methods: In this retrospective case-control study 220 pregnant women were matched for gestational and maternal age at sampling. Results were expressed as multiples of the median (MoM) and compared using Kruskal-Wallis and Mann-Whitney U-test.

Non-invasive prenatal diagnosis of fetal aneuploidies using massively parallel sequencing-by-ligation and evidence that cell-free fetal DNA in the maternal plasma originates from cytotrophoblastic cells.

Blood plasma of pregnant women contains circulating cell-free fetal DNA (ccffDNA), originating from the placenta. The use of this DNA for non-invasive detection of fetal aneuploidies using massively parallel sequencing (MPS)-by-synthesis has been proven previously. Sequence performance may, however, depend on the MPS platform and therefore we have explored the possibility for multiplex MPS-by-ligation, using the Applied Biosystems SOLiD(™) 4 system.

Non-targeted whole genome 250K SNP array analysis as replacement for karyotyping in fetuses with structural ultrasound anomalies: evaluation of a one-year experience.

Objective: We evaluated both clinical and laboratory aspects of our new strategy offering quantitative fluorescence (QF)-PCR followed by non-targeted whole genome 250K single-nucleotide polymorphism array analysis instead of routine karyotyping for prenatal diagnosis of fetuses with structural anomalies.

Methods: Upon the detection of structural fetal anomalies, parents were offered a choice between QF-PCR and 250K single-nucleotide polymorphism array analysis (QF/array) or QF-PCR and routine karyotyping (QF/karyo).

Results: Two hundred twenty fetal samples were included.

Performance of first-trimester combined test for Down syndrome in different maternal age groups: reason for adjustments in screening policy?

Objective: To evaluate the performance of the first-trimester combined test (FCT) in different maternal age groups and to discuss whether adjustments in screening policies should be made.

Methods: In this retrospective study data (n = 26 274) from a fetal medicine center on FCT (maternal age, fetal NT, free β-human chorionic gonadotrophin, pregnancy-associated plasma protein-A) were studied.

Results: 70.

Spatiotemporal image correlation artifacts in an in vitro model.

An experimental in vitro setting with a latex miniature balloon was designed to test the accuracy of volumetric measurements by spatiotemporal image correlation. Two-dimensional images clearly showed the round balloon as a thin echogenic ring in a translucent area. Four-dimensional reconstructed images, however, showed a severely distorted balloon.

Noninvasive prenatal diagnosis of fetal trisomy 18 and trisomy 13 by maternal plasma DNA sequencing.

Massively parallel sequencing of DNA molecules in the plasma of pregnant women has been shown to allow accurate and noninvasive prenatal detection of fetal trisomy 21. However, whether the sequencing approach is as accurate for the noninvasive prenatal diagnosis of trisomy 13 and 18 is unclear due to the lack of data from a large sample set. We studied 392 pregnancies, among which 25 involved a trisomy 13 fetus and 37 involved a trisomy 18 fetus, by massively parallel sequencing.

Expectant management in twin pregnancies with discordant structural fetal anomalies.

Objective: Routine obstetric ultrasound increasingly leads to the detection of structural fetal anomalies. In twin pregnancies with one anomalous twin, counseling on management strategies is complicated.

Patients And Methods: Twin pregnancies (n = 212) were referred to a tertiary center between January 2007 and July 2009.

Aberrant lymphatic development in euploid fetuses with increased nuchal translucency including Noonan syndrome.

Objective: Increased nuchal translucency in the human fetus is associated with aneuploidy, structural malformations and several syndromes such as Noonan syndrome. In 60–70% of the Noonan syndrome cases, a gene mutation can be demonstrated. Previous research showed that aneuploid fetuses with increased nuchal translucency (NT) demonstrate an aberrant lymphatic endothelial differentiation.

Non-invasive prenatal assessment of trisomy 21 by multiplexed maternal plasma DNA sequencing: large scale validity study.

Objectives: To validate the clinical efficacy and practical feasibility of massively parallel maternal plasma DNA sequencing to screen for fetal trisomy 21 among high risk pregnancies clinically indicated for amniocentesis or chorionic villus sampling.

Design: Diagnostic accuracy validated against full karyotyping, using prospectively collected or archived maternal plasma samples.

Setting: Prenatal diagnostic units in Hong Kong, United Kingdom, and the Netherlands.

Non-invasive aneuploidy detection using free fetal DNA and RNA in maternal plasma: recent progress and future possibilities.

Background: Cell-free fetal DNA (cff DNA) and RNA can be detected in maternal plasma and used for non-invasive prenatal diagnostics. Recent technical advances have led to a drastic change in the clinical applicability and potential uses of free fetal DNA and RNA. This review summarizes the latest clinical developments in non-invasive prenatal diagnosis in the context of the latest technical developments.