Receiving the news of Down syndrome in the era of prenatal testing.

Objective: To explore the prenatal trajectory and the experiences of mothers of a child with Down syndrome (DS) at the time of receiving information or test results when participating in a nationwide prenatal screening program.

Methods: An online questionnaire study was completed by mothers of children with DS born between January 1, 2010 and February 28, 2016 (n = 212). Data were collected between February 15 and 28, 2016.

Induction of Labor for Maternal Indications at a Periviable Gestational Age; Survey on Management, Reporting and Auditing amongst Dutch Maternal-Fetal Medicine Specialists and Neonatologists.

 In cases of life-threatening maternal conditions in the periviable period, professionals may consider immediate delivery with fetal demise as a consequence of the treatment. We sought the opinion of involved medical professionals on management, reporting, and auditing in these cases.  We performed an online survey amongst all registered maternal-fetal medicine (MFM) specialists and neonatologists in the Netherlands.

Discordant NIPT result in a viable trisomy-21 pregnancy due to prolonged contribution to cfDNA by a demised trisomy-14 cotwin.

One of the confounders in noninvasive prenatal testing (NIPT) is the vanishing twin phenomenon. Prolonged contribution to the maternal Cell-free DNA (cfDNA) pool by cytotrophoblasts representing a demised, aneuploid cotwin may lead to a false-positive outcome for a normal, viable twin. We show that a vanishing trisomy-14 twin contributes to cfDNA for more than 2 weeks after demise.

Origin and clinical relevance of chromosomal aberrations other than the common trisomies detected by genome-wide NIPS: results of the TRIDENT study.

PurposeNoninvasive prenatal screening (NIPS) using cell-free DNA in maternal blood is highly sensitive for detecting fetal trisomies 21, 18, and 13. Using a genome-wide approach, other chromosome anomalies can also be detected. We report on the origin, frequency, and clinical significance of these other chromosome aberrations found in pregnancies at risk for trisomy 21, 18, or 13.

Subsequent pregnancy outcome after mid-trimester termination of pregnancy for preeclampsia.

Background: In this study we determined the outcome of subsequent pregnancies after termination of pregnancy for preeclampsia, with the purpose of presenting data useful for counselling these women on future pregnancies.

Study Design: The cohort consisted of 131 women with a history of termination of pregnancy for preeclampsia.

Results: Data of 79 pregnancies were available for analysis, including 13 women with chronic hypertension and 16 women with thrombophilia.

Women's Experience with Non-Invasive Prenatal Testing and Emotional Well-being and Satisfaction after Test-Results.

Increasingly, high-risk pregnant women opt for non-invasive prenatal testing (NIPT) instead of invasive diagnostic testing. Since NIPT is less accurate than invasive testing, a normal NIPT result might leave women less reassured. A questionnaire study was performed among pregnant women with elevated risk for fetal aneuploidy based on first-trimester combined test (risk ≥1:200) or medical history, who were offered NIPT in the nationwide Dutch TRIDENT study.

Sensitivity of fetal RHD screening for safe guidance of targeted anti-D immunoglobulin prophylaxis: prospective cohort study of a nationwide programme in the Netherlands.

Objective:  To determine the accuracy of non-invasive fetal testing for the RHD gene in week 27 of pregnancy as part of an antenatal screening programme to restrict anti-D immunoglobulin use to women carrying a child positive for RHD DESIGN:  Prospectively monitoring of fetal RHD testing accuracy compared with serological cord blood typing on introduction of the test. Fetal RHD testing was performed with a duplex real time quantitative polymerase chain reaction, with cell-free fetal DNA isolated from 1 mL of maternal plasma The study period was between 4 July 2011 and 7 October 2012. The proportion of women participating in screening was determined.

Trial by Dutch laboratories for evaluation of non-invasive prenatal testing. Part I-clinical impact.

Objective: To evaluate the clinical impact of nationwide implementation of genome-wide non-invasive prenatal testing (NIPT) in pregnancies at increased risk for fetal trisomies 21, 18 and 13 (TRIDENT study).

Method: Women with elevated risk based on first trimester combined testing (FCT ≥ 1:200) or medical history, not advanced maternal age alone, were offered NIPT as contingent screening test, performed by Dutch University Medical laboratories. We analyzed uptake, test performance, redraw/failure rate, turn-around time and pregnancy outcome.

Trial by Dutch laboratories for evaluation of non-invasive prenatal testing. Part II-women's perspectives.

Objective: To evaluate preferences and decision-making among high-risk pregnant women offered a choice between Non-Invasive Prenatal Testing (NIPT), invasive testing or no further testing.

Methods: Nationwide implementation study (TRIDENT) offering NIPT as contingent screening test for women at increased risk for fetal aneuploidy based on first-trimester combined testing (>1:200) or medical history. A questionnaire was completed after counseling assessing knowledge, attitudes and participation following the Multidimensional Measure of Informed Choice.

Absolute first trimester cell-free DNA levels and their associations with adverse pregnancy outcomes.

Objective: To study associations of first trimester cell-free fetal DNA levels (in this paper referred to as cell-free placental DNA (cfpDNA) levels) and preeclampsia (PE), pregnancy-induced hypertension (PIH), gestational diabetes (GDM) and spontaneous preterm birth (sPB).

Method: A nested case-control study was conducted in first trimester samples (gestational age 8 -13  weeks). A total of 226 cases and 301 controls were included.

Terminating pregnancy for severe hypertension when the fetus is considered non-viable: a retrospective cohort study.

Objective: To investigate frequency and practise of termination of pregnancy for early-onset hypertensive disorders where the fetus is considered to be non-viable.

Study Design: Retrospective cohort study in all Dutch tertiary perinatal care centres (n=10), between January 2000 and January 2014. All women who underwent termination of pregnancy, without fetal surveillance or intention to intervene for fetal reasons, for early-onset hypertensive disorders in pregnancy, were analyzed.

Fetal RHD genotyping after bone marrow transplantation.

Background: Fetal RHD genotyping allows targeted diagnostic testing, fetal surveillance, and eventually intrauterine treatment to D-alloimmunized pregnant women who carry an RHD+ fetus. However, false-positive and false-negative results of noninvasive prenatal fetal RHD genotyping have been described due to a variety of causes. In this case report we present two cases where noninvasive fetal RHD typing was complicated by a previous bone marrow transplantation (BMT).

Cell-free fetal DNA in the maternal circulation originates from the cytotrophoblast: proof from an unique case.

Noninvasive prenatal testing (NIPT) and direct karyotyping of cytotrophoblast were normal for a male fetus, but cultured chorionic villus mesenchymal cells and umbilical cord fibroblasts showed nonmosaic trisomy 18. This observation provides direct evidence for the cytotrophoblastic origin of cell-free fetal DNA and yields a biological explanation for falsely reassuring NIPT results.

Genomic futures of prenatal screening: ethical reflection.

The practice of prenatal screening is undergoing important changes as a result of the introduction of genomic testing technologies at different stages of the screening trajectory. It is expected that eventually it will become possible to routinely obtain a comprehensive 'genome scan' of all fetuses. Although this will still take several years, there are clear continuities between present developments and this future scenario.

Unexplained False Negative Results in Noninvasive Prenatal Testing: Two Cases Involving Trisomies 13 and 18.

Noninvasive prenatal testing (NIPT) validation studies show high sensitivity and specificity for detection of trisomies 13, 18, and 21. False negative cases have rarely been reported. We describe a false negative case of trisomy 13 and another of trisomy 18 in which NIPT was commercially marketed directly to the clinician.

Analysis of false-positive results of fetal RHD typing in a national screening program reveals vanishing twins as potential cause for discrepancy.

Objectives: We aim to elucidate causes of false-positive fetal RHD screening results obtained with cell-free DNA.

Methods: Fetal RHD screening was performed in 32,222 samples from RhD-negative women by multiplex real-time PCR in triplicate for RHD exons 5 and 7 using cell-free DNA isolated from maternal plasma obtained in the 27th gestational week. PCR results were compared with cord blood serology in 25,789 pregnancies (80.

Detection of fetal chromosomal anomalies: does nuchal translucency measurement have added value in the era of non-invasive prenatal testing?

Objectives: The objective of this study is to determine what percentage of fetal chromosomal anomalies remains undetected when first trimester combined testing is replaced by non-invasive prenatal testing for trisomies 13, 18, and 21. We focused on the added clinical value of nuchal translucency (NT) measurement.

Methods: Data on fetal karyotype, ultrasound findings, and pregnancy outcome of all pregnancies with an NT measurement ≥3.

Intrahepatic cholestasis of pregnancy: maternal and fetal outcomes associated with elevated bile acid levels.

Objective: The primary aim of this study was to investigate the correlation between pregnancy outcome and bile acid (BA) levels in pregnancies that were affected by intrahepatic cholestasis of pregnancy (ICP). In addition, correlations between maternal and fetal BA levels were explored.

Study Design: We conducted a retrospective study that included women with pruritus and BA levels ≥10 μmol/L between January 2005 and August 2012 in 3 large hospitals in the Netherlands.

Termination of pregnancy for maternal indications at the limits of fetal viability: a retrospective cohort study in the Dutch tertiary care centres.

Objective: Maternal morbidity, either pregnancy related or pre-existent, can become life threatening and of such severity as to warrant termination of pregnancy (TOP). In this situation, chances of fetal survival are usually poor, either because of low gestational age and/or because of the fetal effects of the maternal condition. Examples include severe growth restriction in pre-eclampsia and intrauterine infection due to the very early preterm prelabour rupture of membranes.

The influence of pregnancy termination on the outcome of subsequent pregnancies: a retrospective cohort study.

Objective: To compare the incidences of preterm delivery, cervical incompetence treated by cerclage, placental implantation or retention problems (ie, placenta praevia, placental abruption and retained placenta) and postpartum haemorrhage between women with and without a history of pregnancy termination.

Design:  A retrospective cohort study using aggregated data from a national perinatal registry.

Setting: All midwifery practices and hospitals in the Netherlands.

Factors determining uptake of invasive testing following first-trimester combined testing.

Objective: This study aims to analyze differences in characteristics between women who opted for invasive testing after first-trimester combined testing and those who did not.

Method: Follow-up was performed in 20 215 combined tests conducted between 2007 and 2011 in the central region of the Netherlands. Multivariate logistic regression analysis compared variables (Down syndrome risk estimate, maternal age, previous Down syndrome pregnancy, IVF/ICSI, parity and nuchal translucency measurement) between different groups.

Noninvasive fetal genotyping of human platelet antigen-1a.

We describe a reliable noninvasive fetal human platelet antigen (HPA)-1a genotyping assay on a real-time polymerase chain reaction (PCR) platform using cell-free fetal DNA isolated from maternal blood. Nonspecific amplification of maternal cell-free DNA is overcome by pre-PCR digestion of the cell-free DNA with the Msp1 restriction enzyme. Noninvasive fetal HPA-1a genotyping offers a safe method for alloimmunised pregnant women to determine whether their fetus is at risk of fetal or neonatal alloimmune thrombocytopenia (FNAIT) and whether interventions to prevent intracranial haemorrhage are required.

Noninvasive fetal blood group genotyping of rhesus D, c, E and of K in alloimmunised pregnant women: evaluation of a 7-year clinical experience.

Objective: To evaluate the diagnostic performance of noninvasive fetal blood group genotyping.

Design: Descriptive analysis.

Setting: Dutch national reference laboratory for pregnancies complicated by alloimmunisation.

Reliability of fetal sex determination using maternal plasma.

Objective: To determine the diagnostic accuracy of noninvasive fetal sex determination in maternal plasma.

Methods: All consecutive patients for whom fetal sex determination in maternal plasma was performed in our laboratory from 2003 up to 2009 were included in the study. Real-time polymerase chain reaction was performed for the SRY gene and multicopy DYS14 marker sequence.

Adjustment to termination of pregnancy for fetal anomaly: a longitudinal study in women at 4, 8, and 16 months.

Objective: We studied psychological outcomes and predictors for adverse outcome in 147 women 4, 8, and 16 months after termination of pregnancy for fetal anomaly.

Study Design: We conducted a longitudinal study with validated self-completed questionnaires.

Results: Four months after termination 46% of women showed pathological levels of posttraumatic stress symptoms, decreasing to 20.