Prenatal Diagnosis Of Down Syndrome Research Articles

Prenatal Experiences and Desires With Early Intervention for Families of Children With Down Syndrome

Part C early intervention (EI) starts no earlier than birth, even with a prenatal diagnosis resulting in automatic eligibility. Despite other early home visiting programs beginning prenatally and the increasing likelihood of uncovering certain diagnoses prenatally, pregnant families cannot access EI. This study sought to understand families’ perspectives on their desire for prenatal EI and how EI could support them. Seventeen primarily White non-Hispanic mothers with a prenatal diagnosis of Down syndrome shared their prenatal experiences through retrospective, qualitative interviews. Three themes emerged: (1) prenatal period as a time to connect to EI, (2) different families, different prenatal desires, and (3) postnatal EI experiences, prenatal EI hopes. Families saw benefits to starting prenatally to enroll in and understand EI, and prepare for their baby’s arrival through individualized outcomes. Families appreciated their postnatal EI and envisioned similar supports prenatally. Participants’ shared experiences are discussed in relation to pre- and postnatal EI.

Prenatal diagnosis of Down syndrome combined with transient abnormal myelopoiesis in foetuses with a GATA1 gene variant: two case reports

BackgroundDown syndrome myeloid hyperplasia includes transient abnormal myelopoiesis (TAM) and the myeloid leukemia associated with Down syndrome (ML-DS). The mutation of GATA1 gene is essential in the development of Down syndrome combined with TAM or ML-DS. Some patients with TAM are asymptomatic and may also present with severe manifestations such as hepatosplenomegaly and hydrops.Case presentationWe report two cases of prenatally diagnosed TAM. One case was a rare placental low percentage 21 trisomy mosiacism, resulting in the occurrence of a false negative NIPT. The final diagnosis was made at 36 weeks of gestation when ultrasound revealed significant enlargement of the foetal liver and spleen and an enlarged heart; the foetus eventually died in utero. We detected a placenta with a low percentage (5–8%) of trisomy 21 mosiacism by Copy Number Variation Sequencing (CNV-seq) and Fluorescence in situ hybridization (FISH). In another case, foetal oedema was detected by ultrasound at 31 weeks of gestation. Two foetuses were diagnosed with Down syndrome by chromosomal microarray analysis via umbilical vein puncture and had significantly elevated cord blood leucocyte counts with large numbers of blasts. The GATA1 Sanger sequencing results suggested the presence of a [NM_002049.4(GATA1):c.220G > A (p. Val74Ile)] hemizygous variant and a [NM_002049.4(GATA1):c.49dupC(p. Gln17ProfsTer23)] hemizygous variant of the GATA1 gene in two cases.ConclusionIt seems highly likely that these two identified mutations are the genetic cause of prenatal TAM in foetuses with Down syndrome.

Families’ experiences with supports after receiving a prenatal diagnosis of down syndrome

In the United States, families whose infants or toddlers have a diagnosis that results in a high likelihood of developmental delay or disability are automatically eligible for early intervention (EI). When families know prenatally of this diagnosis, they are not eligible for EI until their baby is born despite other developmental programs starting during pregnancy. Seventeen families who had a prenatal diagnosis of Down syndrome shared their experiences with formal, intermediate, and informal resources during their pregnancy. Findings centered on families’ appraisals of those resources to meet their desire for a positive, hopeful pregnancy and parenting vision. Implications are discussed for early childhood prenatal home visitors, early childhood professionals overall, and EI systems and professionals.

Amniotic Fluid Ischemia Modified Albumin as a Novel Prenatal Diagnostic Marker for Down Syndrome: A Prospective Case-Control Study

Aims: There is no study in the literature about ischemia-modified albumin (IMA) and hepatocyte growth factor (HGF) levels in amniotic fluid for Down syndrome cases. The aim of this study was to investigate the changes of IMA and HGF in Down syndrome cases at 16-20 weeks of gestation compared to normal fetuses. Methods: For this prospective case-control study, following reaching the number of 20 women (study group) who had the prenatal diagnosis of Down syndrome, maternal and gestational age-matched pregnant women with normal constitutional karyotype were selected for the control group (n = 74) from the stored amniotic fluid samples. Results: Mean women and gestational ages were comparable between the two groups. Amniotic fluid IMA (1.32 ± 0.13 vs. 1.11 ± 0.11 ABSU, respectively, p < 0.001) and HGF (2743.53 ± 1389.28 vs. 2160.12 ± 654.63 pg/mL, respectively, p = 0.008). Levels were significantly higher in pregnant women having Down syndrome fetuses compared with women having normal fetuses. The amniotic fluid IMA levels for the diagnosis of Down syndrome, and the sensitivity and specificity were calculated as 95.0% and 71.6% for the limit value 1.171 cm3, respectively. Conclusion: In cases with suspected Down syndrome, the diagnosis of Down Syndrome may be made in approximately 1 hour with high sensitivity and specificity by measuring the IMA level in the amniotic fluid sample taken for fetal karyotyping.

Neonatal mortality and morbidity in Down syndrome in the time of prenatal aneuploidy testing: a retrospective cohort study

The total uptake of prenatal aneuploidy screening for Down syndrome (DS) is increasing worldwide. As a result of increasing prenatal diagnosis of DS and subsequent termination of pregnancy, livebirth prevalence of DS is decreasing. The aim of this study is to explore the impact of an increasing uptake of prenatal aneuploidy screening on the neonatal mortality and morbidity in DS. This is a retrospective cohort study of 253 neonates with DS born between 2012 and 2018 that were seen at the outpatient clinic of five hospitals in the Netherlands. The medical files were reviewed for maternal and neonatal characteristics and neonatal morbidities. The Dutch national birth registry (Perined) provided mortality numbers of neonates with DS. The results were interpreted in the context of other published studies. Neonatal mortality in DS remained stable, ranging from 1.4 to 3.6%. A congenital heart defect (CHD) was found in 138 of the 251 neonates (55.0%) with atrial septal defect, atrioventricular septal defect, and ventricular septal defect being the most common. The type of CHD in DS did not change over time. Gastro-intestinal defects were present in 22 of the 252 neonates with DS (8.7%), with duodenal atresia as the most reported anomaly. Persistent pulmonary hypertension of the neonate (PPHN) was found in 31 of the 251 infants (12.4%). Conclusions: Although uptake of prenatal aneuploidy screening increased, neonatal mortality and morbidity in DS appears to be stable. An increased incidence of PPHN was found.What is Known:• The total uptake of prenatal aneuploidy screening for Down syndrome is increasing worldwide.• As a result of increasing prenatal diagnosis of Down syndrome and subsequent termination of pregnancy, the livebirth prevalence of Down syndrome is decreasing.What is New:• Although uptake of prenatal aneuploidy screening increased, neonatal mortality and morbidity in Down syndrome appears to be stable.• An increased incidence of persistent pulmonary hypertension of the neonate was found.

Health Supervision for Children and Adolescents With Down Syndrome.

Health Supervision for Children and Adolescents With Down Syndrome.

“I had to think: This is not a child.” A qualitative exploration of how women/couples articulate their relation to the fetus/child following termination of a wanted pregnancy due to Down syndrome

ObjectiveTermination of a wanted pregnancy due to fetal anomaly may generate complex feelings of grief and loss. The aim of this study was to explore the different ways that women/couples articulated their relation to the fetus/child following a termination of pregnancy due to a prenatal diagnosis of Down syndrome. MethodQualitative interview study with 21 women/couples who had recently terminated a wanted pregnancy. Data were analyzed using thematic analysis. ResultsThe analysis identified how some women detached themselves from the fetus/child following the diagnosis by mentally separating from the fetus/child, by acting as if they were not pregnant (e.g., by drinking wine), or by deliberately using the term ‘fetus’ to designate the fetus/child as a biological entity. The analysis also identified accounts of attachment such as singing a lullaby to the fetus/child or using the term ‘our child’ or ‘my baby’. However, accounts of detachment and attachment often intermingled and changed over time. Following the termination, many women/couples felt ambiguous about the sonogram as a symbol of the potential child. Overall, the analysis showed that the relation to and the meaning of the fetus/child was ambiguous and open to reinterpretation. ConclusionThe main contribution of this study is the identification of how articulations of attachment and detachment are not mutually exclusive but coexist and may change over time. Furthermore, we argue that detachment does not equal indifference. Thus, healthcare professionals must support the couple in finding a terminology and a narrative that are meaningful for them.

Quantitative proteomic analysis of down syndrome biomarkers in maternal serum using isobaric tags for relative and absolute quantification (iTRAQ)

Prenatal diagnosis of Down syndrome (DS) is based on calculated risk involving maternal age, biochemical and ultrasonographic markers, and, more recently, cell-free DNA (cfDNA). The present study was designed to identify Down Syndrome biomarkers in maternal serum. We quantified the changes in maternal serum protein levels between 10 non-pregnant women, 10 pregnant women with healthy fetuses, and 10 pregnant women with DS fetuses using isobaric tags for relative and absolute quantification (iTRAQ). We subsequently conducted a Gene Ontology (GO) analysis. A total of 470 proteins were identified, 11 of which had significantly different serum levels between the DS fetus group and Healthy fetuses group. Our data shows the identified proteins may be relevant to DS and constitute potential DS biomarkers.

Segmental Duplications as a Complement Strategy to Short Tandem Repeats in the Prenatal Diagnosis of Down Syndrome.

Quantitative fluorescence-polymerase chain reaction (QF-PCR) is an inexpensive and accurate method for the prenatal diagnosis of aneuploidies that applies short tandem repeats (STRs) as a chromosome-specific marker. Despite its apparent advantages, QF-PCR is not applicable in all cases due to the presence of uninformative STRs. This study was carried out to investigate the efficiency of a method based on applying segmental duplications (SDs) in conjunction with STRs as an alternative to stand-alone STR-based QF-PCR for the diagnosis of Down syndrome. Fifty amniotic fluid samples from pregnant women carrying Down syndrome fetuses, 9 amniotic fluid samples with 1 or without any informative STR marker (inconclusive), and 100 normal samples were selected from Shiraz, Iran, between October 2015 and December 2016. Analysis was done using an in-house STR-SD-based multiplex QF-PCR and the results were compared. Statistical analysis was performed using MedCalc, version 14. All the normal, Down syndrome, and inconclusive samples were accurately identified by the STR-SD-based multiplex QF-PCR, yielding 100% sensitivity and 100% specificity. Karyotype analysis confirmed all the cases with normal or trisomic results. The STR-SD-based multiplex QF-PCR correctly identified all the normal and trisomy 21 samples regardless of the absence of informative STR markers. The STR-SD-based multiplex QF-PCR is a feasible and particularly useful assay in populations with a high prevalence of homozygote STR markers.

Receiving a prenatal diagnosis of Down syndrome by phone: a qualitative study of the experiences of pregnant couples

ObjectivesTo examine how pregnant couples experience receiving a prenatal diagnosis of Down syndrome (DS) by phone—a practice that has been routine care in the Central Denmark Region for years.DesignQualitative interview...

‘Prenatal screaming’ decision-making following a prenatal diagnosis of Down syndrome

‘Prenatal screaming’ decision-making following a prenatal diagnosis of Down syndrome

Multicentre study “Prenatal diagnosis of Down syndrome in Russia 2005–2015”. II. Ultrasound markers

Objective: to study the effectiveness of the use of ultrasound markers for Down syndrome (DS) in the fetus during ultrasound examinations at 11–14 and 18–21 weeks of gestation based on the results of multicentre analysis in the regions of Russia in 2005–2015 years. Materials. The analysis was based on data from a questionnaire on prenatal diagnosis of DS in 30 regions and cities of Russia in 2015. The data from the questionnaire survey of 12 regions in 2005 and 23 regions in 2010 for analyse the dynamic of prenatal diagnosis of DS in our country was obtained. The questionnaire included the questions about the number of births and pregnant women registered in the region; the total number of cases of DS registered in prenatal and postnatal periods; structures of diagnosed cases of DS depending on the detection period; indications for prenatal karyotype; the number of fetuses with DS and the increase of nuchal translucency in 11–14 weeks of gestation; ultrasound markers of DS in the II trimester of gestation and perinatal outcome in cases of prenatal diagnosis of DS. Results. In the course of the multicentre analysis it was established that the accuracy of identification of DS in the prenatal period in our country was 30,9% in 2005, 38,4% in 2010 and significantly increased to 59,7% in 2015. In 2005, only 17,2% of cases of DS were detected in 11–14 weeks of gestation, in 2010 — 38,2% and increased to 72,1 % (7,6–100%) in 2015. In 24 from 30 regions the proportion of diagnosed cases of trisomy 21 at 11–14 weeks of gestation was 50% or more, and in 11 regions — 90–100%. Increase of nuchal translucency thickness was detected on average in 76,3 % fetuses with DS with a range from 28,1 to 100 %. The most prenatal ultrasound markers in fetuses with DS in the second-trimester were congenital malformations and hypoplasia / absence of nasal bones — 64,9 and 65,5 %, respectively. Further, as the frequency of detection decreased: prenasal thickness (27,6 %), echogenic intracardiac focus (27,1%), pyelectasis (22%), nuchal fold (19,7%), short humerus/femur (17,5%), hyperechogenic bowel (14,6%), ventriculomegaly (11,2%), choroid plexus cysts (7,3%). Conclusion. Ultrasound examination is powerful method for identification the fetuses with DS. Therefore, it is necessary to continue the development of new ultrasound markers of DS for improving its prenatal diagnosis.

Termination of pregnancy following a prenatal diagnosis of Down syndrome: A qualitative study of the decision-making process of pregnant couples.

In Denmark, first trimester screening has a very high uptake (>90%). If Down syndrome is diagnosed, termination rates are high (>95%). The aim of this study was to investigate the timing of the decision to terminate pregnancy following a diagnosis of Down syndrome and the factors influencing this decision. Semi-structured, qualitative interview study with 21 couples who had received a prenatal diagnosis of Down syndrome and decided to terminate the pregnancy. Participants were recruited from obstetric departments between February 2016 and July 2017. Data were analyzed using thematic analysis. Five themes were identified: "initial decision-making", "consolidating the decision", "reasons and concerns shaping the termination of pregnancy decision", "the right decision is also burdensome", and "perceived influences in decision-making". For most couples, the initial decision to terminate pregnancy was made before or during the diagnostic process, but it was re-addressed and consolidated following the actual diagnosis. Imagining a family future with a severely affected Down syndrome child was the main factor influencing the termination of pregnancy decision. The decision was articulated as "right" but also as existentially burdensome for some, due to fear of regret and concern about ending a potential life. The decision to terminate pregnancy was considered a private matter between the couple, but was refined through interactions with clinicians and social networks. All couples made an initial decision prior to receiving the Down syndrome diagnosis. Knowledge of the couple's initial decision may facilitate patient-centered communication during and after the diagnostic process. Couples may benefit from counseling to deal with grief and existential concerns.

Prenatal diagnosis of Down syndrome

Down syndromes are the most commonly recognized genetic cause of mental retardation. The risk of trisomy 21 is directly related to maternal age, neuchal translucency, nasal bone, tricuspid valve regurgitation and fetal heart rate. Also, maternal serum markers must be included to increase the sensitivity and specificity of the ultrasound screening of Down syndrome.

Application of droplet digital PCR for prenatal screening of Down syndrome

Background: This study was proposed to explore the feasibility of droplet digital PCR (ddPCR) analysis for non-invasive prenatal diagnosis of Down syndrome. Materials and Methods: The authors studied maternal plasma samples from 465 pregnant women carrying euploid and trisomy 21 (T21) fetuses. A methylation-sensitive restriction endonuclease, BstUI, was used to digest the hypomethylated holocarboxylase synthetase (HLCS) gene. The authors quantified digestion-resistant HLCS gene on chromosome 21 and fetal-specific rs6636 SNP allele on chromosome 14 by droplet digital PCR analysis. Maternal plasma DNA analysis was performed by comparing the ratio of hypermethylated HLCS to fetal-specific rs6636 SNP allele between two groups. Results: Using a rs6636 SNP allele on chromosome 14 as the reference marker, the authors analyzed 78 euploid and 28 T21 plasma samples. The ratios of the numbers of positive hypermethylated HLCS and the fetal-specific C allele in the euploid and T21 samples were significantly different ( p p Conclusions: The study demonstrated that ddPCR approach can be applied for prenatal screening of trisomy 21.

Modified methylated DNA immunoprecipitation protocol for noninvasive prenatal diagnosis of Down syndrome.

Methylated DNA immunoprecipitation real-time quantitative polymerase chain reaction (MeDIP-real-time qPCR) has been introduced as noninvasive prenatal test that has shown absolute detection rate in the screening of Down syndrome. Herein, we aimed to propose a novel modification of MeDIP-qPCR and assess its potential to alleviate the overall cost of the test, being used in very early weeks of pregnancy, and develop it to a noninvasive prenatal diagnosis biosensor in future researches. Cell-free fetal DNA (cffDNA) isolated from 60 pregnant women, including 29 normal and 31 trisomy 21 pregnancies, were analyzed using proposed MeDIP protocol. Enriched methylated DNA sequences were amplified through real-time qPCR using eight fetal-specific primer pairs. The status of samples was determined through the calculation of D-value with the cutoff point of zero. The sensitivity and specificity of the MeDIP protocols using nanoparticles were 100% and 100%, respectively. Remarkable decrease in the price of MeDIP test per each patient would be a reasonable factor to confirm it on larger sample size. Moreover, the high detection rate of screening and the availability of the required instruments around the world make satisfactory reasons to be tested in earlier weeks of pregnancy, thanks to the high sensitivity of gold shell nanoparticles.

Prenatal diagnosis of Down syndrome: A 13-year retrospective study

ObjectiveThe aim of this study is to summarize the experience on prenatal diagnosis of Down syndrome. Materials and methodsThe study includes a retrospective data analysis of 157 prenatally detected cases of Down syndrome, routinely diagnosed among 6448 prenatal investigations performed during a 13-year period (2002–2014) in a single tertiary center. ResultsThe prevalence of diagnosed Down syndrome cases was 2.4%. Maternal age alone was indication for prenatal diagnosis in 47 cases (45.2%), increased first-/second-trimester biochemical screening test in 34 cases (21.7%), abnormal ultrasound examination in 69 cases (43.9%), positive familial history for chromosomal abnormalities in four cases, and high risk for trisomy 21 revealed by cell-free DNA testing in three cases. Ultrasound anomalies were present in total of 94 fetuses (59.8%). The most common abnormality was cystic hygroma found in 46 cases (29.3%). A regular form of Down syndrome (trisomy 21) was found in 147 cases (93.6%), Robertsonian translocation in six cases (3.8%), and mosaic form in four cases (2.6%). ConclusionIn prenatal diagnosis of Down syndrome noninvasive screening methods are important for estimation of individual risks, in both, young population of woman and older mothers, while conventional and molecular cytogenetic methods are essential for definite diagnosis and proper genetic counseling.

Prenatal neurogenesis induction therapy normalizes brain structure and function in Down syndrome mice

Down syndrome (DS) caused by trisomy of chromosome 21 is the most common genetic cause of intellectual disability. Although the prenatal diagnosis of DS has become feasible, there are no therapies available for the rescue of DS-related neurocognitive impairment. A growth inducer newly identified in our screen of neural stem cells (NSCs) has potent inhibitory activity against dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) and was found to rescue proliferative deficits in Ts65Dn-derived neurospheres and human NSCs derived from individuals with DS. The oral administration of this compound, named ALGERNON (altered generation of neurons), restored NSC proliferation in murine models of DS and increased the number of newborn neurons. Moreover, administration of ALGERNON to pregnant dams rescued aberrant cortical formation in DS mouse embryos and prevented the development of abnormal behaviors in DS offspring. These data suggest that the neurogenic phenotype of DS can be prevented by ALGERNON prenatal therapy.

Эффективность пренатальной диагностики синдрома Дауна в шести областях Центрального и Юго-Восточного регионов Украины

Chromosomal aneuploidy (CA), having an incidence rate of 6-8 per 1000 live births, holds a special place in the structure of congenital and hereditary pathology. Among the common CA, trisomy 21 chromosomes (T21) is the most frequently found (its incidence rate in the general population amounts to 1:700–800 live births). The objective: to study the efficiency of prenatal screening of CA (Down’s syndrome, DS) in the areas under the Center’s operational activity in the period of 2010-2015; To estimate the actual prevalence of DS in terms of born and prenatally diagnosed, eliminated fetuses with T21; On the basis of retrospective analysis of indications for prenatal karyotyping, in all detected cases of DS, to specify their structure and incidence rate; Based on data from medical literature, to make a comparative analysis with similar studies in different countries around the world. Patients and methods. Over the six years (2010–2015) we have performed 3,137 invasive prenatal interventions, among which are 720 chorionic villus biopsies, 929 placententesises, and 1,488 amniocentesis of pregnant women having a high risk of CA, who were seeking medical help from our center whose operational activity covers 6 provinces (oblasts). Results. From 3,137 prenatally karyotyped studies, there have been found only 558 cases of fetal CA, including 288 fetuses with T21. A retrospective analysis of the structure of indications for invasive prenatal diagnosis in 288 pregnant women, having fetuses with prenatally detected DS, is presented as follows: – separate: only 40-aged and above mothers – 4 (1.38%); Ultrasound (US)-findings (anomalies and markers of CA) – 192 (69.5%); High biochemical risk of CA – 2 (0.7%). – combined: the mother’s age is 40 and above + US findings – 36 (13%); The mother’s age is 40 and above + US and biochemical (BC) markers – 8 (2.8%); Ultrasound findings + positive BC test – 32 (11.5%). Delivery of the previous child with DS by a pregnant woman under 40 years with no ultrasound and BC markers – 1 (0.34%). In total, ultrasound findings (anomalies and markers of CA) were found in 97.5% of cases of prenatally detected fetuses with DS. The index of prenatal detection of fetuses with Down syndrome of all registered karyotyped cases of T21 (pre- and postnatal) in the Dnepropetrovskaya oblast corresponds to the average European level - 65%, (in the areas of the center’s operational activity – 37.7%). Taking into account 242 cases of DS in fetuses aborted prior 22 weeks of gestation, the actual prevalence of T21 in case of their birth would be 1:766 (13 per 10.000 infants). Conclusions. Prevalence of Down syndrome among newborns in the Dnepropetrovskaya oblast as a result of prenatal diagnosis of chromosomal abnormalities makes 1: 1257, which is 1.8 times lower than the incidence in the average population (1:700); In other areas covered by the center’s consulting and diagnostic activity this rate is 1.1–1.55 times lower than that of the population one. In the absence of the existing system of prenatal diagnosis of Down syndrome, its average prevalence in these provinces would correspond to that of the general population 1:766 newborns. Key words: сhromosomal abnormalities, Down syndrome, prenatal screening strategies, ultrasound diagnosis, invasive prenatal diagnosis, ultrasound markers.

Proteomic profile of serum of pregnant women carring a fetus with Down syndrome using nano uplc Q-tof ms/ms technology

Introduction: Prenatal diagnosis of Down syndrome (DS) is based on the calculated risk of maternal age, biochemical and ultrasonographic markers and recently by cfDNA. Differences in proteomic profiles may give an opportunity to find new biomarkers.Objective: Characterize proteome of serum of mothers carrying DS fetus.Material and methods: Blood serum samples of three groups of women were obtained, (a) 10 non-pregnant, (b) 10 pregnant with healthy fetus by ultrasound evaluation, (c) nine pregnant with DS fetus. Sample preparation was as follows: Albumin/IgG depletion, desalting, and trypsin digestion; the process was performed in nanoUPLC MS/MS. Data analysis was made with Mass Lynx 4.1 and ProteinLynx Global Server 3.0, peptide and protein recognition by MASCOT algorithm and UNIPROT-Swissprot database.Results: Each group showed different protein profiles. Some proteins were shared between groups. Only sera from pregnant women showed proteins related to immune and clot pathways. Mothers with DS fetus had 42 specific proteins.Conclusions: We found a different serum protein profile in mothers carrying DS fetuses that do not reflect expression of genes in the extra chromosome. Further studies will be necessary to establish the role of these proteins in aneuploid fetus and analyze their possible use as potential biomarkers.