Prenatal Diagnosis Of Down Syndrome Research Articles

Analyse du parcours de dépistage prénatal des femmes ayant donné naissance en France à un enfant atteint de trisomie 21

ObjectiveThe main objective of this study was to screen the prenatal follow-up of women with live birth trisomy 21 child in order to evaluate the proportion of prenatal screening failure versus cases where the women refused either the screening or the prenatal diagnosis of Down syndrome. This study covers the period of time from 2009 to 2012 when the national prenatal screening policy changed from second to first trimester and allows for a comparative assessment of the nationwide efficiency of the various maternal serum marker based strategies. MethodAll authorized cytogenetic laboratories sent required data for all cases of trisomy 21 diagnosed in FRANCE in new-borns (less than 1-year-old) from January 2010 to July 2013. ResultsA total of 1253 cases of trisomy 21 were diagnosed before 1 year of age whose mother did not had prenatal diagnosis. For 861 of them, information on the prenatal follow-up was available, with 72% of cases where a prenatal screening was organized either by maternal serum marker or by ultrasound. Results of the screening strategy was positive with maternal serum marker in 28% of cases (calculated risk≥1/250), positive because of abnormal ultrasound in 5% and negative with maternal marker screening (whatever the strategy used) in 67% of cases. Detection rate over the period of the study was 82%, with similar efficiency of first and second trimester strategies (83%) but significantly lower with sequential association of first trimester Nuchal translucency measurement and second trimester serum screening (70%). ConclusionSwitching from second trimester to first trimester screening strategy, with as many trisomy 21 foetuses diagnosed with half invasive procedures fulfilled national health policy objectives. Analysis of these data gives useful insights to elaborate a future screening policy involving cell-free foetal DNA sequencing.

Research on articulation problems of Turkish children who have Down syndrome at age 3 to 12

AbstractBackground:Articulation is a process that allows air to pass through vocal cords and then form words and syllables using the tongue, teeth, mentum and palatine tonsils. A person who has pronunciation problems produces, syllables or words inaccurately so; the auditoria have got difficulty to understand what did say, such that the listener has difficulty in understanding what is being said. Due to being genetically different the Down syndrome individual has difficulty with speech due to structural defects in the mouth and problems with the mouth-tongue muscles.Aim:Here the determination of the articulation (pronunciation) problems and the probable causes of the determined problems have been studied.Methods:This study involved children without hearing loss problems; 17 females and 23 males who have Down syndrome and were ages between 3 and 12 years. The Ankara articulation test (AAT) was applied to the individuals. The articulation (pronunciation) ages have been determined according to the ATT. By the detailed assessment of the ATT, it was determined which voices were uttered correctly or not. Through a family interview survey, the information that affected the development of the Down syndrome child’s speech and academic development was obtained. Through a patient identification survey, the education and health information that may effect the speech development were obtained. Through an oral motor assessment survey, the information regarding the competence of oral motor skills that may effect articulation problems were collected. The data were analyzed. Using a family survey, child identification survey and an oral motor assessment survey the correlation between articulation age and articulation defects were viewed.Results:It has been detected that the articulation age of Down syndrome children between 3 and 12 years of age are quite a bit lower when compared to the chronological age according to the ATT. Moreover, in terms of results from the ATT, children with Down syndrome whose cronological age is 8 years 7 months have a 3 year 5 months’ articulation age according to the ATT. They have some difficulties with Turkish vowels such as (/a/, /e/, /ı/, /i/). Also they have some difficulties with consonants such as (/r/, /j/, /z/, /ş/, /z/, /l/, /s/, /n/). Articulation defects at various levels have been detected for all Down syndrome children. Articulation (pronunciation) problems were encountered less in children from highly educated and more concerned families. It has been shown that articulation (pronunciation) problems are less children who receive early treatment, therapy and education services.Conclusion:Significant correlation between the level of articulation usage by individuals and frequency of the articulation problem were detected. For this reason, attaching importance to oral motor studies are considered. Raising parental awareness is required on prenatal diagnosis of Down syndrome. By treating the problems of the speech organs at an early age and including the children who have Down syndrome into the early education programs around 0–3 years and accurate intervention during critical periods, the articulation problems can be reduced. Using a wider age range and having more participants, it is considered that more efficient results may be obtained.

Accuracy of ultrasonography compared to laboratory in fetal screening, which one is more reliable?

Background: The aim of this study is to compare the efficacy of nuchal translucency (NT) measurement with laboratory screening tests in prenatal diagnosis of Down syndrome (DS) and neonatal outcomes. Materials and Methods: In this cross-sectional-descriptive study, data were collected from 260 pregnancy files. Ages of pregnant women were 20–34 year old who referred for prenatal care. NT was measured by ultrasound at 11–13 + 6 and quad marker tests at 15–18 gestational week. Data analysis was performed by SPSS 21 (IBM, USA) that was considered significant with P

A Qualitative Study of Factors Influencing Decision-Making after Prenatal Diagnosis of down Syndrome.

Previous research has identified twenty-six factors that may affect pregnancy management decisions following prenatal diagnosis of DS; however, there is no consensus about the relative importance or effects of these factors. In order to better understand patient decision-making, we conducted expansive cognitive interviews with nine former patients who received a prenatal diagnosis of DS. Our results suggest that patients attached unique meanings to factors influencing decision-making regardless of the pregnancy outcome. Nineteen of the twenty-six factors previously studied and four novel factors (rationale for testing, information quality, pregnancy experience, and perception of parenting abilities and goals) were found to be important to decision-making. We argue that qualitative studies can help characterize the complexity of decision-making following prenatal diagnosis of DS.

Why do pregnant women accept or decline prenatal diagnosis for Down syndrome?

To investigate if actual knowledge of Down syndrome (DS), influences the decision to accept or decline prenatal diagnosis (PND). Secondary aims were to elucidate reasons for accepting or declining PND and investigate differences between the accepting and declining group in perceived information, knowing someone with DS and thoughts about decision-making. A questionnaire was completed by 76 pregnant women who underwent invasive testing and 65 women who declined tests for chromosomal aberrations in Uppsala, Sweden. Apart from one question no significant differences were found in knowledge of DS between women declining or accepting PND for DS. Both groups had varying and in several respects low levels of knowledge about DS and its consequences. Most common reasons to accept PND were 'to ease my worries' and 'to do all possible tests to make sure the baby is healthy'. Corresponding statements declining PND were 'termination of pregnancy is not an option' and 'because invasive tests increase the risk of miscarriage'. More women declining PND knew someone with DS. Knowledge of DS at these levels is not a major factor when women decide to accept or decline PND for DS. Their choice is mostly based on opinions and moral values.

Amniocentesis increases level of anxiety in women with invasive prenatal diagnosis of Down syndrome

Backgound <br />Invasive prenatal diagnosis (PND) through amniocentesis and chorionic villus sampling (CVS) can detect Down syndrome. Pregnant women usually experience a variety of psychological responses associated with invasive PND. This study is intended to assess depression, anxiety and stress levels and the factors related to their psychological responses in pregnant women with invasive prenatal diagnosis of Down syndrome.<br /><br />Methods <br />A cross sectional study was conducted at Kandang Kerbau Women’s and Children’s Hospital, Singapore. The psychological responses of 70 women undergoing PND were assessed by Depression Anxiety Stress Scale 21 (DASS 21) questionnaire. A multiple linear regression analysis was used to analyze association between knowledge and perceived risk with psychological responses (CI 95% and significance value p<0.05).<br /><br />Results <br />More than half of the participants had normal anxiety (55.7%), stress (72.8%), depression levels (65.8%). The results revealed significantly higher level of anxiety in women with gestational age >13 weeks who had pursued amniocentesis. Women with no previous children had higher levels of depression and stress. Women who pursued amniocentesis had significantly higher anxiety scores compared to women undergoing CVS (p=0.015).<br /><br />Conclusions <br />Women’s psychological responses are associated with gestational age, type of procedure and parity. The level of anxiety increased in women who underwent amniocentesis for diagnosis of Down syndrome. Knowledge and perceived risk of having a baby with Down syndrome do not seem to have psychological effects to women.

Chloe's Law: A Powerful Legislative Movement Challenging a Core Ethical Norm of Genetic Testing.

Since the early 1970s, the ethical norm governing counselors involved in testing and screening for genetic conditions related to reproduction has been strict neutrality. Counseling about reproductive genetics was to be patient centered but nondirective. Many advocates for people with Down syndrome believe that high abortion rates following a diagnosis of this condition show an unfounded bias against those with Down syndrome. These advocates have succeeded in enacting federal and state legislation that requires women who receive a prenatal diagnosis of Down syndrome to receive positive information about the condition, thereby ending the nominal goal of value-neutral counseling and setting the stage for further normative shifts in clinical reproductive genetics as counseling expands because of cell-free testing.

Estimates of the live births, natural losses, and elective terminations with Down syndrome in the United States

The present and future live birth prevalence of Down syndrome (DS) is of practical importance for planning services and prioritizing research to support people living with the condition. Live birth prevalence is influenced by changes in prenatal screening technologies and policies. To predict the future impact of these changes, a model for estimating the live births of people with DS is required. In this study, we combine diverse and robust datasets with validated estimation techniques to describe the non-selective and live birth prevalence of DS in the United States from 1900-2010. Additionally, for the period 1974-2010, we estimate the impact of DS-related elective pregnancy terminations (following a prenatal diagnosis of DS) on the live births with DS. The live birth prevalence for DS in the most recent years (2006-2010) was estimated at 12.6 per 10,000 (95% CI 12.4-12.8), with around 5,300 births annually. During this period, an estimated 3,100 DS-related elective pregnancy terminations were performed in the U.S. annually. As of 2007, the estimated rates at which live births with DS were reduced as a consequence of DS-related elective pregnancy terminations were 30% (95% CI: 27.3-31.9) for the U.S. as a whole. Our results and our model provide data on the impact of elective pregnancy terminations on live births with DS and may provide a baseline from which future trends for live births with DS can be estimated.

Prenatal genetic counseling in Klinefelter syndrome: comments on the article by Lalatta et al. [2013] and a proposal of a new approach.

We read with great interest the article “Counseling parents beforeprenataldiagnosis:Doweneedtosaymoreaboutthesexchromo-someaneuploidies?”byLalattaetal.[2013].Wewouldliketowidenthe discussion about the importance of an appropriate geneticcounseling, focusing the attention particularly on the Klinefeltersyndrome (KS).In our Pediatric Department at “Universita` Sapienza di Roma”we are trying to improve our method of counseling to parentsofchildrenwithKS.Ifprenataltestingidentifiesthepresenceofanychromosomalanomalyinthefetus,future parentsfindthemselvesconfronted with the decision to continue or terminate the preg-nancy [Marteau et al., 2002].Weselected,over10years(September2002toSeptember2012)agroup of couples with a child with Klinefelter Syndrome andquestioned them.A questionnaire has been created, using open-ended ques-tions, to present to the 50 couples (Fig. 1). The questionnaireaimed to evaluate what the parents experienced. The questionsare divided into two groups. The first group is formed by threequestions evaluating the initial experience of these coupleswith the gynecological counseling. This part, which providesfor parents to meet with the physician, has as objective tounderstandthedegreeofinformationofparentsonKS,discoversources from which parents have learned the information and,eventually, fill in any gaps. We use this part also to facilitatethe parents towards a correct and accurate understanding ofthe syndrome by changing erroneous beliefs and to propose thepossible observational approach in the case of continuation ofthe pregnancy. The presence of the geneticist is very importantto become a guide to which refer, both for the counseling andthe management of the child during the growth. The consultanthasalwaystoexpresspurelymedical opinions, avoiding toexpress personal opinions or to influence the parents’ decision.Thesecondgroupinvolvestheadministrationofananonymousquestionnaire to both parents, formed by three questions aim-ing to understand if our approach influenced the idea that theparents had about the syndrome and about the future of theirchild. The questionnaire was administered at the end of eachconsult, providing parents all the time needed to compile it.Afterourgeneticcounseling,thepercentageofabortionwasonly4.2%;infact,among50coupleswithaprenataldiagnosisofKS,onlytwo couples decided to terminate pregnancy. None of the termi-natedpregnanciespresentedafetalabnormalityatultrasound,butone was a couple with previous therapeutic abortion for prenataldiagnosis of Down syndrome and the other one was previouslyinformed by the gynecologist, that KS presents mental retardationand congenital anomalies. Maternal age and year of test did notinfluence parental decisions (Table I).Ourstudydemonstratedthat,withapropergeneticcounseling,parents can decide being fully aware of what having an extra sexchromosome can mean in the development of their child. Theytypically express fears about sexual orientation of their child,dimensionsofhispenis,riskofimpotence,feminineaspectassoci-ated with the presence of one or more X chromosomes andjudgment by their family and by others. Also, there is a markedworry about when to inform the patient about his condition.

Prenatal diagnosis of Down syndrome using cell-free fetal DNA in amniotic fluid by quantitative fluorescent polymersase chain reaction

Backgroud Amniotic fluid (AF) supernatant contains cell-free fetal DNA (cffDNA) fragments. This study attempted to take advantage of cffDNA as a new material for prenatal diagnosis, which could be combined with simple quantitative fluorescent polymerase chain reaction (QF-PCR) to provide an ancillary method for the prenatal diagnosis of trisomy 21 syndrome. Methods AF supernatant samples were obtained from 27 women carrying euploid fetuses and 28 women carrying aneuploid fetuses with known cytogenetic karyotypes. Peripheral blood samples of the parents were collected at the same time. Short tandem repeat (STR) fragments on chromosome 21 were amplified by QF-PCR. Fetal condition and the parental source of the extra chromosome could be determined by the STR peaks. Results The sensitivity of the assay for the aneuploid was 93% (26/28; confidence interval, CI: 77%-98%) and the specificity was 100% (26/26; CI: 88%-100%). The determination rate of the origin of the extra chromosome was 69%. The sensitivity and the specificity of the assay in the euploid were 100% (27/27). Conclusions Trisomy 21 can be prenatally diagnosed by the QF-PCR method in AF supernatant. This karyotype analysis method greatly reduces the requirement for the specimen size. It will be a benefit for early amniocentesis and could avoid pregnancy complications. The method may become an ancillary method for prenatal diagnosis of trisomy 21.

Differentially expressed microRNAs in maternal plasma for the noninvasive prenatal diagnosis of Down syndrome (trisomy 21).

Objectives. Most developmental processes are under the control of small regulatory RNAs called microRNAs (miRNAs). We hypothesize that different fetal developmental processes might be reflected by extracellular miRNAs in maternal plasma and may be utilized as biomarkers for the noninvasive prenatal diagnosis of chromosomal aneuploidies. In this proof-of-concept study, we report on the identification of extracellular miRNAs in maternal plasma of Down syndrome (DS) pregnancies. Methods. Using high-throughput quantitative PCR (HT-qPCR), 1043 miRNAs were investigated in maternal plasma via comparison of seven DS pregnancies with age and fetal sex matched controls. Results. Six hundred and ninety-five miRNAs were identified. Thirty-six significantly differentially expressed mature miRNAs were identified as potential biomarkers. Hierarchical cluster analysis of these miRNAs resulted in the clear discrimination of DS from euploid pregnancies. Gene targets of the differentially expressed miRNAs were enriched in signaling pathways such as mucin type-O-glycans, ECM-receptor interactions, TGF-beta, and endocytosis, which have been previously associated with DS. Conclusions. miRNAs are promising and stable biomarkers for a broad range of diseases and may allow a reliable, cost-efficient diagnostic tool for the noninvasive prenatal diagnosis of DS.

Placental methylation markers in normal and trisomy 21 tissues

The objective of this study is to combine multiplex ligation-dependent probe amplification (MLPA) and bisulfite sequencing to determine DNA methylation markers for noninvasive prenatal diagnosis of Down syndrome. DNA methylation ratios (MR) of four fragments (CGI149, CGI045, HLCS-1, and HLCS-2) on chromosome 21 were evaluated in blood cells from 13 nonpregnant women, 15 euploidies, and 11 Down Syndrome (DS) placentae. Ratios were measured by bisulfite sequencing and methylation-specific (MS)-MLPA. The MS-MLPA and bisulfite sequencing results were concordant. CGI149, CGI045, and HLCS-2 were unmethylated in all nonpregnant blood cells. CGI149, CGI045, HLCS-1, and HLCS-2 were methylated in most of the euploid (13, 11, 15, and 15, respectively) and DS placentae (10, 11, 11, and 11, respectively). The median placental DNA MR in CGI149 was 0.4578 (interquartile range, 0.3568-0.5169) and 0.5918 (interquartile range, 0.5618-0.6659) in euploid and DS placentae, respectively (p = 0.001). Using placental MR at 0.5390 as a threshold, we detected DS at 90.9% sensitivity and 93.3% specificity. The MS-MLPA is an effective alternative to bisulfite sequencing in assessing placental MR. CGI149 is a potential marker for the noninvasive diagnosis of Down syndrome.

¿Cómo reciben los padres la noticia del diagnóstico de su hijo con síndrome de Down?: what do the parents think?

Having a child with Down syndrome (DS) is usually unexpected and stressful.To describe the experiences of parents of children with DS at the time of diagnosis.A self-administered survey was answered by 345 parents (62% women) with an offspring with DS.Eighty four percent of parents received a postnatal diagnosis of DS, 32.3% were informed of the diagnosis in the presence of his or her partner and 19.3%o received some form of printed material regarding DS. Fifty six percent of respondents considered that the delivery of the diagnosis was inadequate. Factors associated with an overall positive experience were prenatal diagnosis (Odds Ratio (OR) 3.91 (95% Confidence Intervals (CI) 2.06-7.44)) and the presence of both parents at the time of the delivery of the diagnosis (OR 1.84 (95%> CI 1.16-2.91)). Fifty three percent of respondents believe that prenatal diagnosis of DS is preferable.The majority of parents are unsatisfied with the way the diagnosis of DS is delivered. Efforts should be made to educate health personnel regarding the delivery of the diagnosis of SD, to foster opportunities for prenatal diagnosis and to improve the delivery of printed material.

Author's response regarding “MeDIP‐qPCR approach for non‐invasive prenatal diagnosis of Down syndrome: accuracy and reproducibility”

Author's response regarding “MeDIP‐qPCR approach for non‐invasive prenatal diagnosis of Down syndrome: accuracy and reproducibility”

Prenatal diagnosis of Down syndrome in dizygotic twin pregnancy

We present a case of a 33-year-old pregnant woman who had a transvaginal ultrasound performed at week 9 of gestation. A dichorionic diamniotic twin pregnancy with symmetrically developing fetuses, was confirmed. Chromosomal defect markers (NT NB, DV TV) were analyzed in the first genetic test, performed according to the Fetal Medicine Foundation (FMF) criteria, and the double marker test was performed (PAPP-A protein and free beta-hCG concentrations in patient serum were determined). In the subsequent diagnostic procedures, the patient was offered and consented to amniopuncture after week 15 of gestation. The material obtained in the course of that invasive procedure allowed to identify a normal male karyotype - 46, XY in the first fetus (Fetus I). Cytogenetic analysis of the material from the second fetus (Fetus II) resulted in the diagnosis of an abnormal female karyotype - 47, XX, +21. Based on the analyzed clinical case, we present the difficulties of performing prenatal diagnosis in a dizygotic twin pregnancy The results prove the applicability and efficacy of prenatal diagnostics tests based on the FMF criteria also in twin pregnancies.

Current Resources for Evidence‐Based Practice January/February 2013

Current Resources for Evidence‐Based Practice January/February 2013

Prenatal diagnosis and termination of pregnancy: perspectives of South African parents of children with Down syndrome

This study aims to evaluate the attitudes of a group of South African parents with a preschool child with Down syndrome (DS) towards prenatal diagnosis (PND) and termination of a Down syndrome-affected pregnancy (TAP). This study employs a qualitative phenomenological approach with the use of semi-structured interviews. Twelve participants were recruited from two state sector hospitals in Cape Town, South Africa. Thematic analysis was used to interpret the data. The participants had a positive attitude towards PND and felt that it was every parent's right to have the option. They considered a benefit of PND the fact that it allowed parents time to prepare for the arrival of a baby with DS. The induced miscarriage risk associated with invasive prenatal testing procedures caused major negative feelings. They were totally opposed to the termination of a Down syndrome-affected pregnancy due to their personal experience, moral, ethical or religious convictions. South African parents of preschool children with Down syndrome are comfortable with PND for Down syndrome; however, they do not support TAP. These findings will provide health care providers with further insight into the motivations behind the decisions their patients make.

Non‐invasive prenatal diagnosis for Down syndrome: no paradigm shift, just better testing… and it is already here!

Non‐invasive prenatal diagnosis for Down syndrome: no paradigm shift, just better testing… and it is already here!

Noninvasive Prenatal Diagnosis of Down Syndrome in Samples from Southwest Chinese Gravidas Using Pregnant Plasma Placental RNA Allelic Ratio

The purpose of this research was to attempt a preliminary study of noninvasive prenatal diagnosis of Down syndrome in Southwest Chinese gravidas by using the plasma placental RNA allelic ratio. The genotypes of the single-nucleotide polymorphisms (SNPs) located in the transcribed regions of the gene PLAC4 were detected in population samples collected in Southwest China by using polymerase chain reaction-restriction fragment length polymorphism, and SNPs with a higher heterozygosity were selected. Mass spectrometer analysis was adopted, and cases with the heterozygous SNPs on PLAC4 mRNA in maternal plasma were selected from 29 pregnancies with a euploid fetus and from 21 pregnancies with a trisomy-21 fetus, and then their RNA-SNP allelic ratios were further determined for noninvasive prenatal diagnosis of Down syndrome. Of all 50 singleton pregnancies, 37 gravidas were found with at least one heterozygous SNP on PLAC4 mRNA in maternal plasma. Among them, 13 pregnancies with a trisomy-21 fetus were detected by the analysis of the RNA-SNP allelic ratio. The plasma placental RNA allelic ratio can be used for noninvasive prenatal diagnosis of Down syndrome, if SNPs on PLAC4 mRNA in maternal plasma are heterozygous.

Noninvasive prenatal diagnosis of Down syndrome: current knowledge and novel insights

The noninvasive prenatal diagnosis of trisomy 21 (Down syndrome) is an actively researched area of prenatal medicine, as this is the most common aneuploidy compatible with life and a major cause of mental retardation. The isolation of intact fetal cells, and most importantly, the successful detection of fetal-origin nucleic acids (cell-free fetal DNA and RNA), in maternal plasma even from the early stages of pregnancy has inspired scientists to develop discriminative genetic markers for the prenatal detection of aneuploidy. In the near future, the development of epigenetic fetal-specific markers will possibly allow the universal application of a cell-free fetal DNA-based diagnostic test regardless of the gender of the fetus or its polymorphic status. Other promising approaches rely upon the detection of free placentally derived RNA transcribed from genes located on chromosome 21 and the application of highly sensitive techniques, such as digital polymerase chain reaction and high-throughput shotgun sequencing. However, irrespective of which strategy is selected for isolating or distinguishing fetal genetic material in maternal plasma, the small quantity of fetal origin nucleic acids poses severe technical challenges. In this review article, we present an overview of the current knowledge in the field of noninvasive prenatal assessment of fetuses with Down syndrome and the future perspectives regarding new fetal markers and novel molecular techniques that may eventually be applied in the clinical setting as a valid and safe option for women who opt for noninvasive accurate prenatal diagnosis.