The High Diagnostic Yield of Prenatal Exome Sequencing Followed by 3400 Gene Panel Analysis in 629 Ongoing Pregnancies With Ultrasound Anomalies.

Background: The aim of this study was to evaluate the diagnostic yield of routine exome sequencing (ES) in fetuses with ultrasound anomalies.

Methods: We performed a retrospective analysis of the ES results of 629 fetuses with isolated or multiple anomalies referred in 2019-2022. Variants in a gene panel consisting of approximately 3400 genes associated with multiple congenital anomalies and/or intellectual disability were analyzed.

The role of confined placental mosaicism in fetal growth restriction: A retrospective cohort study.

Objective: To evaluate which cytogenetic characteristics of confined placental mosaicism (CPM) detected in the first trimester chorionic villi and/or placentas in terms of chromosome aberration, cell lineage involved and trisomy origin will lead to fetal growth restriction and low birthweight.

Methods: Cohort study using routinely collected perinatal data and cytogenetic data of non-invasive prenatal testing, the first trimester chorionic villi sampling and postnatal placentas.

Results: 215 CPM cases were found.

Prenatal counseling of an isolated fetal small head circumference during the second trimester expert ultrasound examination.

Objective: To evaluate perinatal and postnatal outcomes of fetuses with an isolated small head circumference (HC) on expert ultrasound examination in the second trimester for further recommendations in prenatal care.

Study Design: In a retrospective cohort we included singleton-pregnancies with a fetal HC > -3.0 SD and ≤ -1.

Clinical impact of additional findings detected by genome-wide non-invasive prenatal testing: Follow-up results of the TRIDENT-2 study.

In the TRIDENT-2 study, all pregnant women in the Netherlands are offered genome-wide non-invasive prenatal testing (GW-NIPT) with a choice of receiving either full screening or screening solely for common trisomies. Previous data showed that GW-NIPT can reliably detect common trisomies in the general obstetric population and that this test can also detect other chromosomal abnormalities (additional findings). However, evidence regarding the clinical impact of screening for additional findings is lacking.

Periconceptional maternal folate status and the impact on embryonic head and brain structures: the Rotterdam Periconceptional Cohort.

Research Question: Does periconceptional maternal folate status influence the size of human embryonic head and brain structures?

Design: The study population was selected from the Rotterdam Periconceptional Cohort conducted at the Erasmus MC. Three-dimensional (3D) ultrasound scans were performed at 9 and 11 weeks of gestational age. Using 3D ultrasound datasets, head volume, head circumference, diencephalon (DTD), mesencephalon (MTD) and left/right telencephalon (TTL/TTR) measurements were performed offline using a virtual reality technique and specialized 3D software.

A novel family illustrating the mild phenotypic spectrum of TUBB2B variants.

TUBB2B codes for one of the isotypes of β-tubulin and dominant negative variants in this gene result in distinctive malformations of cortical development (MCD), including dysgyria, dysmorphic basal ganglia and cerebellar anomalies. We present a novel family with a heterozygous missense variant in TUBB2B and an unusually mild phenotype. First, at 21 37 weeks of gestation ultrasonography revealed a fetus with a relatively small head, enlarged lateral ventricles, borderline hypoplastic cerebellum and a thin corpus callosum.

How to deal with uncertainty in prenatal genomics: A systematic review of guidelines and policies.

Exome sequencing (ES) enhanced the diagnostic yield of genetic testing, but has also increased the possibility of uncertain findings. Prenatal ES is increasingly being offered after a fetal abnormality is detected through ultrasound. It is important to know how to handle uncertainty in this particularly stressful period.

IVF with or without ICSI and the impact on human embryonic brain development: the Rotterdam Periconceptional Cohort.

Study Question: Does IVF with or without ICSI (IVF/ICSI) treatment impact the development of embryonic brain structures?

Summary Answer: Our results show associations between IVF/ICSI treatment, smoking and slightly increased sizes of early human embryonic brain structures.

What Is Known Already: The number of IVF/ICSI procedures is increasing worldwide and is associated with higher risks of obstetric and perinatal complications in pregnancies.

Study Design, Size, Duration: One hundred seventy-five women with a singleton pregnancy were included in the Rotterdam Periconceptional Cohort (Predict study).

The potential diagnostic yield of whole exome sequencing in pregnancies complicated by fetal ultrasound anomalies.

Introduction: The aim of this retrospective cohort study was to determine the potential diagnostic yield of prenatal whole exome sequencing in fetuses with structural anomalies on expert ultrasound scans and normal chromosomal microarray results.

Material And Methods: In the period 2013-2016, 391 pregnant women with fetal ultrasound anomalies who received normal chromosomal microarray results, were referred for additional genetic counseling and opted for additional molecular testing pre- and/or postnatally. Most of the couples received only a targeted molecular test and in 159 cases (40.

Growth trajectories of the human fetal brain in healthy and complicated pregnancies and associations with neurodevelopmental outcome in the early life course.

Background: There is a need for non-invasive prenatal markers of the brain to assess fetuses at risk for poor postnatal neurodevelopmental outcome. Periconceptional maternal conditions and pregnancy complications impact prenatal brain development.

Aims: To investigate associations between growth trajectories of fetal brain structures and neurodevelopmental outcome in children in the early life course.

Non-invasive prenatal testing (NIPT): societal pressure or freedom of choice? A vignette study of Dutch citizens' attitudes.

The introduction of the accurate and procedurally easy non-invasive prenatal test (NIPT) raises ethical concerns that public attitudes towards prenatal screening may change, leading to societal pressure to participate in aneuploidy screening. This study examined Dutch citizens' attitudes towards a pregnant woman's decision to (1) decline NIPT in the context of two different funding policies and (2) to terminate or continue a pregnancy affected by different disorders. The attitudes of 1096 respondents were assessed with the contrastive vignette method, using two pairs of vignettes about declining NIPT and termination of pregnancy.

Implementing non-invasive prenatal testing (NIPT) in the Netherlands: An interview study exploring opinions about and experiences with societal pressure, reimbursement, and an expanding scope.

The noninvasive prenatal test (NIPT) as the first trimester prenatal screening (FTS) for trisomies 21, 18, and 13 is offered to all pregnant women in the Netherlands. NIPT using genome sequencing allows for an expansion of the scope of FTS and the introduction of NIPT gives rise to ethical and societal concerns about deliberated decision-making, pressure to engage in screening, and possible lack of equal access due to the financial contribution (€175) to NIPT. We explored the opinions and experiences of pregnant women, who were offered FTS, about these concerns, and the possibility of a broadened scope.

Placental studies elucidate discrepancies between NIPT showing a structural chromosome aberration and a differently abnormal fetal karyotype.

Objective: Placental cytogenetic studies may reveal the origin of discordant noninvasive prenatal testing (NIPT). We performed placental studies to elucidate discordances between NIPT showing a structural chromosome aberration and the fetus having a different chromosome aberration in three cases.

Method: Diagnostic testing with genomic SNP microarray was performed in three cases with NIPT showing a duplication on 4q (case 1), a terminal deletion of 13q (case 2), and a terminal deletion of 15q (case 3).

Three-dimensional ultrasound imaging of fetal brain fissures in the growth restricted fetus.

Objectives: To examine differences in growth trajectories of fetal brain fissures in the growth restricted fetus (FGR) compared to controls.

Methods: We selected a subgroup of 227 women with a singleton pregnancy from the Rotterdam Periconceptional Cohort. Participants received three-dimensional ultrasound (3D-US) examinations of the fetal brain at 22, 26 and 32 weeks of gestational age (GA).

Termination of pregnancy for fetal anomalies: Parents' preferences for psychosocial care.

Objective: To investigate, from the perspective of women and partners, at what stage of a termination of pregnancy (TOP) for fetal anomalies psychosocial care (PSC) is most meaningful, what topics should be discussed, and who should provide PSC.

Method: A cross-sectional retrospective cohort study was conducted with a consecutive series of 76 women and 36 partners, who completed a semi-structured online questionnaire.

Results: Overall, women expressed a greater need for PSC than their partners.

Correction: Periconception Maternal Folate Status and Human Embryonic Cerebellum Growth Trajectories: The Rotterdam Predict Study.

[This corrects the article DOI: 10.1371/journal.pone.

Unexpected finding of uniparental disomy mosaicism in term placentas: Is it a common feature in trisomic placentas?

Objective: Non-invasive prenatal testing (NIPT) detects placental chromosome aberrations. When amniocentesis reveals a normal karyotype, confined placental mosaicism (CPM) may be assumed. In order to confirm this, placental cytogenetic studies were performed.

Accuracy of fetal sex determination in the first trimester of pregnancy using 3D virtual reality ultrasound.

Purpose: Early detection of fetal sex is becoming more popular. The aim of this study was to evaluate the accuracy of fetal sex determination in the first trimester, using 3D virtual reality.

Methods: Three-dimensional (3D) US volumes were obtained in 112 pregnancies between 9 and 13 weeks of gestational age.

Prenatal influence of congenital heart defects on trajectories of cortical folding of the fetal brain using three-dimensional ultrasound.

Objective: The objective of the study is to investigate the prenatal influence of congenital heart defects (CHD) on trajectories of fetal cortical folding using three-dimensional ultrasound (3D US).

Method: We included 20 CHD fetuses and 193 controls for studying the fetal brain at 22, 26 and 32 weeks' gestational age (GA). The Sylvian, insula and parieto-occipital fissure (POF) depths were measured using 3D US, and reliability was evaluated.

The influence of SNP-based chromosomal microarray and NIPT on the diagnostic yield in 10,000 fetuses with and without fetal ultrasound anomalies.

Prenatal diagnostics has been impacted by technological changes in the past decade, which have affected the diagnostic yield. The aim of this study was to evaluate the impact of SNP array and noninvasive prenatal testing (NIPT) on the diagnostic yield and the number of invasive tests in our center. The frequency of pathogenic fetal unbalanced chromosome aberrations was studied in 10,005 cases referred for prenatal testing in 2009-2015.