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.

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.

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.

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.

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.

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.

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.

Disturbance of cerebral neuronal migration following congenital parvovirus B19 infection.

Objective: We describe the clinical course of an infant who presented with severe fetal anemia and fetal hydrops following congenital parvovirus B19 infection before 16 gestational weeks. The fetus was treated by cordocentesis and intrauterine transfusion at 18 weeks.

Results: The infant demonstrated mild unilateral ventriculomegaly on antenatal magnetic resonance imaging, and polymicrogyria and heterotopia on postnatal magnetic resonance imaging.

Maternal decision to terminate pregnancy in case of Down syndrome.

Objective: This study explores decisional processes regarding termination of pregnancy because of Down syndrome and aims to identify possibilities for improving counseling.

Study Design: Seventy-one women completed questionnaires 4 months after termination of pregnancy for Down syndrome, including motivations for the decision, reasons for doubt, perceived influence and/or pressure at decision-making, and satisfaction with the received health care.

Results: Child-related motivations to the termination were the most frequently mentioned, but almost all women indicated also motives of self-interest.

Non-invasive prenatal detection of achondroplasia in size-fractionated cell-free DNA by MALDI-TOF MS assay.

Achondroplasia is the most common form of short-limbed dwarfism in humans and is caused by mutations in the FGFR3 gene. Currently, prenatal diagnosis of this disorder relies on invasive procedures. Recent studies have shown that fetal single gene point mutations could be detected in cell-free DNA (cf-DNA) from maternal plasma by either the matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) assay with single allele base extension reaction (SABER) approach or the size fractionation of cf-DNA in maternal plasma.

Use of bi-allelic insertion/deletion polymorphisms as a positive control for fetal genotyping in maternal blood: first clinical experience.

Amplification of fetal DNA in maternal plasma is a new way for non-invasive fetal genotyping in pregnancies at risk for disorders where the presence of a paternal DNA sequence contributes to the risk status of the fetus. We describe the use of a panel of 10 bi-allelic highly polymorphic markers to ascertain the presence and amplification of fetal DNA in case the fetus is negative for the targeted paternal "disease" sequence.

Psychological consequences of termination of pregnancy for fetal anomaly: similarities and differences between partners.

Objective: We examined the psychological responses to termination of pregnancy (TOP) for fetal anomaly from both men and women. The aim was to find risk factors for poor psychological outcome both for the individuals and for the couple.

Methods: A cross-sectional study was performed in 151 couples 2-7 years after TOP.