Syndrome Live Births Research Articles

Down syndrome live births following assisted reproductive technology in Japan: a nationwide survey between 2007 and 2016.

The use of assisted reproductive technology (ART) and prenatal genetic testing have become more widespread in line with an increase in maternal age. However, the effect of the introduction of non-invasive prenatal testing (NIPT) in April 2013 on pregnancy outcomes in Japan, including the prevalence of Down syndrome live births following ART, has not been investigated. This study aimed to evaluate the trends in the prevalence of Down syndrome live births following ART in Japan. This population-based retrospective study used the Japanese nationwide ART registry. All clinical pregnancies resulting in live births, stillbirths, and termination of pregnancy (TOP) following ART from 2007 to 2016 were included. Pregnancy outcomes involving infants with Down syndrome were evaluated. Among 351,808 pregnancies, the proportion of mothers with advanced age increased significantly from 2007 to 2016 (from 49.5 to 62.4% and 8.9 to 17.8% for mothers aged ≥ 35 and ≥ 40years, respectively). The proportion of live births with Down syndrome was 77.3% in 2007, which remained consistent until 2012, but then decreased significantly to 45.1% after 2013 (P < 0.001). The prevalence of Down syndrome live births increased up to 2012 (19.5/10,000 live births), decreased significantly in 2013 (12.1/10,000 live births), and then remained almost stable (11.1-14.7/10,000 live births). The introduction of NIPT balanced the prevalence of Down syndrome live births following ART with recent increasing maternal age in Japan.

Outcome of publicly funded nationwide first-tier noninvasive prenatal screening

PurposeNoninvasive prenatal screening (NIPS) using cell-free DNA has transformed prenatal care. Belgium was the first country to implement and fully reimburse NIPS as a first-tier screening test offered to all pregnant women. A consortium consisting of all Belgian genetic centers report the outcome of two years genome-wide NIPS implementation. MethodsThe performance for the common trisomies and for secondary findings was evaluated based on 153,575 genome-wide NIP tests. Furthermore, the evolution of the number of invasive tests and the incidence of Down syndrome live births was registered. ResultsTrisomies 21, 18, and 13 were detected in respectively 0.32%, 0.07%, and 0.06% of cases, with overall positive predictive values (PPVs) of 92.4%, 84.6%, and 43.9%. Rare autosomal trisomies and fetal segmental imbalances were detected in respectively 0.23% and 0.07% of cases with PPVs of 4.1% and 47%. The number of invasive obstetric procedures decreased by 52%. The number of trisomy 21 live births dropped to 0.04%. ConclusionExpanding the scope of NIPS beyond trisomy 21 fetal screening allows the implementation of personalized genomic medicine for the obstetric population. This genome-wide NIPS approach has been embedded successfully in prenatal genetic care in Belgium and might serve as a framework for other countries offering NIPS.

Birth incidence, deaths and hospitalisations of children and young people with Down syndrome, 1990–2015: birth cohort study

ObjectiveTo investigate current Down syndrome live birth and death rates, and childhood hospitalisations, compared with peers.SettingGeneral community.ParticipantsAll live births with Down syndrome, 1990–2015, identified via Scottish regional cytogenetic laboratories, each...

Mortality Among Children with Down syndrome in Hong Kong: A Population-Based Cohort Study from Birth

To describe the mortality patterns, comorbidities, and attendance at accident and emergency departments among children with Down syndrome in Hong Kong. This is a population-based, retrospective cohort study of live births of children with Down syndrome delivered between 1995 and 2014, as identified from territory-wide hospitalization data in Hong Kong. The Kaplan-Meier product limit method was adopted to estimate the survival probabilities of children with Down syndrome by selected demographic and clinical characteristics. Cox regression analyses were conducted to examine associations of comorbidities and accident and emergency department accident and emergency departments attendances with mortality patterns. There were 1010 live births of children with Down syndrome in Hong Kong within the study period and the average rate of live births with Down syndrome was 8.0 per 10 000 live births (95% CI, 6.8-9.30). The rate of live births with Down syndrome over the past 2decades decreased from 11.8 per 10 000 live births in 1995 to 3.4 per 10 000 in 2014. Eighty-three patients with Down syndrome died during this period. The overall 6-month and 1- and 5-year survival probabilities were 95.8%, 94.4%, and 92.6%, respectively. There was a significant decrease in mortality rates over the study period, particularly among those born between 2000-2004 and 2005-2009 compared with those born between 1995 and 1999 (P<.05). Patients with Down syndrome without congenital cardiovascular anomalies and without low birth weight had lower mortality rates than those with these diagnoses. Over the past 2decades, the early life mortality of children with Down syndrome in Hong Kong has improved significantly along with a reduction in Down syndrome live births.

National screening guidelines and developments in prenatal diagnoses and live births of Down syndrome in 1973-2016 in Denmark.

Denmark was the first country in the world to implement a national, free-for-all offer of prenatal screening for Down syndrome to all pregnant women. It has a high uptake (>90%) compared to other countries. Thus, Denmark offers an interesting case for investigating the consequences of implementing comprehensive, national prenatal screening guidelines. The aim of this study was to describe the historical developments in invasive procedures, pre-/postnatal diagnoses of Down syndrome and Down syndrome live births in the period 1973-2016 in Denmark. Data on invasive procedures, pre- and postnatal Down syndrome diagnoses were retrieved from the Danish Cytogenetic Central Registry. From 1973 to 1993, screening based on maternal age and high-risk indications resulted in a constant increase in invasive procedures. After the introduction of the triple test in 1994, invasive procedures decreased for the first time in 20years. Following the introduction of an offer of combined screening to all pregnant women in 2004, the number of invasive procedures decreased markedly, while there was a concurrent increase in prenatal diagnoses of Down syndrome. Additionally, the number of Down syndrome live births decreased suddenly and significantly, but subsequently stabilized at 23-35 annual live births. Of these, the majority were diagnosed postnatally. Though prenatal screening technologies constantly improve, it was the introduction of and adherence to national guidelines that resulted in marked shifts in screening procedures and outcome in Denmark.

Comorbidities in Down syndrome livebirths and health care intervention: an initial experience from the birth defects registry in Southern Thailand.

Down syndrome (DS) is the most common chromosomal disorder causing mental retardation with a worldwide average prevalence of 1-2 cases per 1000 births. This study aimed to determine the comorbidities associated with DS and the coverage of health care services and developmental interventions for DS livebirths in Southern Thailand. A total of 149 livebirth DS infants, recruited through the prospective birth defects registry system during 2009-2013 in 3 provinces in Southern Thailand, were regularly followed-up every 3-6 months. The data collection form included the infants' demographic data, associated congenital anomalies, and developmental interventions. The DS infants were born at an average gestational age of 38.5±2.3 weeks with average birth weight of 2760±478 g, length 48.5±2.2 cm, and head circumference 32.7±1.2 cm. Congenital heart diseases, gastrointestinal defects and congenital hypothyroidism were found in 43.0%, 6.7%, and 12.1% of the cases, respectively. The percentage of DS infants who received developmental interventions in this current study were significantly greater than in a previous study covering the years 1992-2002: early stimulation program 90.0% vs. 65.6% (P<0.01), and speech training program 74.8% vs. 38.9% (P<0.01), respectively, and the infants in our study began intervention programs significantly earlier, 0.58±0.39 years vs. 1.69±0.66 years, respectively. Congenital heart disease was the most common comorbidity associated with DS. The coverage of health care services and developmental interventions for DS children has generally improved in Southern Thailand. One hundred percent coverage of health services and interventions for children with special needs is expected in the near future.

Uptake, outcomes, and costs of implementing non-invasive prenatal testing for Down’s syndrome into NHS maternity care: prospective cohort study in eight diverse maternity units

Objective To investigate the benefits and costs of implementing non-invasive prenatal testing (NIPT) for Down’s syndrome into the NHS maternity care pathway.Design Prospective cohort study.Setting Eight maternity units across the...

A cost-effectiveness analysis of cell free DNA as a replacement for serum screening for Down syndrome.

The aim of this article is to determine the cost effectiveness of cell free DNA (cfDNA) as a replacement for integrated screening using a societal cost perspective. This study used Monte-Carlo simulation with one-way and probabilistic sensitivity analysis. Cell free DNA is more effective and less costly than integrated screening. The incremental cost-effectiveness ratio for cfDNA relative to the integrated test was -$277 955 per case detected (95th percent confidence interval -$881 882 to $532 785). Cell free DNA screening is a cost-effective replacement for maternal serum screening when the lifetime costs of Down syndrome live births are considered. The adoption of cfDNA screening would save approximately $277 955 for each additional case detected over integrated screening.

Bosentan treatment for pulmonary arterial hypertension due to patent ductus arteriosus and Down's syndrome in an infant

Down's syndrome is the most common autosomal chromosome abnormality with an estimated incidence of approximately 1.1 per 1000 births [ [1] Morris J.K. Alberman E. Trends in Down's syndrome live births and antenatal diagnoses in England and Wales from 1989 to 2008: analysis of data from the National Down Syndrome Cytogenetic Register. BMJ. 2009; 339 Google Scholar ]. The prevalence of congenital heart disease (CHD) in the Down's population is 40–60% [ 2 D'Alto M. Romeo E. Argiento P. et al. Therapy for pulmonary arterial hypertension due to congenital heart disease and Down's syndrome. Int J Cardiol. 2013; 164: 323-326 Abstract Full Text Full Text PDF PubMed Scopus (39) Google Scholar , 3 Suzuki K. Yamaki S. Mimori S. et al. Pulmonary vascular disease in Down's syndrome with complete atrioventricular septal defect. Am J Cardiol. 2000; 86: 434-437 Abstract Full Text Full Text PDF PubMed Scopus (59) Google Scholar , 4 Rowe R.D. Uchida I.A. Cardiac malformation in mongolism: a prospective study of 184 mongoloid children. Am J Med. 1961; 31: 726-735 Abstract Full Text PDF PubMed Scopus (134) Google Scholar ] and patent ductus arteriosus (PDA) is a common congenital heart disease and makes up 5–10% of all heart disease in newborns at term [ 5 Yunfei L. Ke L. Qi A. et al. Transcatheter intervention following ambrisentan treatment in an adult patient with patent ductus arteriosus and severe pulmonary hypertension. Int J Cardiol. 2014; 173 (e16–7) Abstract Full Text Full Text PDF PubMed Scopus (6) Google Scholar , 6 Mitchell S.C. Korones S.B. Berendes H.W. Congenital heart disease in 56,109 births. Incidence and natural history. Circulation. 1971; 43: 323-332 Crossref PubMed Scopus (934) Google Scholar ]. Children with Down's syndrome may develop progressive pulmonary changes earlier than non-Down's counter-parts with similar congenital heart defects and harder to decrease the pressure [ [7] Soudon P. Stijns M. Tremouroux-Wattiez M. et al. Precocity of pulmonary vascular obstruction of Down's syndrome. Eur J Cardiol. 1975; 2: 473-476 PubMed Google Scholar ]. Here we are going to report an infant with pulmonary arterial hypertension due to patent ductus arteriosus and Down's syndrome.

The Impact of Down Syndrome Screening on Taiwanese Down Syndrome Births: A Nationwide Retrospective Study and a Screening Result from a Single Medical Centre

A retrospective analysis of the Taiwanese National Birth Defect Registration and Notification System was conducted in order to determine the live birth- and stillbirth rates in infants with Down syndrome, trisomy 18, trisomy 13 and Turner syndrome between 2001 and 2010. The objective was to investigate the impact of Down syndrome screening on the Taiwanese Down syndrome live birth rate. In addition, the results of first-trimester Down syndrome screening between 2006 and 2011, and of second-trimester quadruple testing between 2008 and 2011, were obtained from the National Taiwan University Hospital. All Taiwanese infants born between 2001 and 2010 were included in the first part of the analysis, and women receiving first-trimester Down syndrome screening or second-trimester quadruple testing from the National Taiwan University Hospital were included in the second part. The live birth rate of infants with Down syndrome, per 100 000 live births, decreased from 22.28 in 2001 to 7.79 in 2010. The ratio of liveborn DS to total DS was 48.74% in 2001, and then decreased to 25.88% in 2006, when first-trimester screening was widely introduced in Taiwan. This ratio dropped to 20.64% in 2008, when the second-trimester quadruple test was implemented. The overall positive rate in first-trimester screening in the National Taiwan University Hospital was 3.1%, with a Down syndrome detection rate of 100%; the quadruple test had values of 9.0% and 75%, respectively. The use of first-trimester screening and the second-trimester quadruple test may be responsible for the marked decrease in the Taiwanese Down syndrome live birth rate observed between 2001 and 2010.

Changes in yearly birth prevalence rates of children with Down syndrome in the period 1986-2007 in the Netherlands

The Netherlands are lacking reliable national empirical data in relation to the development of birth prevalence of Down syndrome. Our study aims at assessing valid national live birth prevalence rates for the period 1986-2007. On the basis of the annual child/adult ratio of Down syndrome diagnoses in five out of the eight Dutch cytogenetic centres, the national annual figures of the National Cytogenetic Network on total numbers of postnatal Down syndrome diagnoses were transformed into national figures on total numbers of postnatal Down syndrome diagnoses in newborn children only. In combination with the national annual data of the Working Group for Prenatal Diagnostics and Therapeutics on numbers of Down syndrome pregnancies not aborted after diagnosis, national figures on birth prevalence were constructed. For the period 1986-2007, results based on the data of the cytogenetic centres are almost similar to the theory-based model data of de Graaf et al., with a small discrepancy of approximately 4%. Down syndrome birth prevalence in the Netherlands shows an upward trend from around 11 per 10,000 births in the early 1990s to around 14 per 10,000 births nowadays. In spite of expansion of antenatal screening in the Netherlands, Down syndrome live birth prevalence has risen in the last two decades as a result of rising maternal age. This increase in Down syndrome birth prevalence is in contrast to studies from other European countries.

Demographic differences in Down syndrome livebirths in the US from 1989 to 2006

To explore demographic differences in Down syndrome livebirths in the United States. Using National Center for Health Statistics (NCHS) birth certificate data from 1989 to 2006 we analyzed Down syndrome livebirths after correcting for under-reporting. We created six subsets based on maternal age (15-34 and 35-49 years old); US regions, that is, Northeast, Midwest, South and West; marital status, (married, unmarried); education, ( ≤ 12 years, ≥ 13 years); race, (white, black); and Hispanic ethnicity, (non-Hispanic, Hispanic). We estimated expected Down syndrome livebirths assuming no change in birth certificate reporting. The percentage of expected Down syndrome livebirths actually born was calculated by year. There were 72 613 424 livebirths from 1989 to 2006. There were 122 519 Down syndrome livebirths expected and 65 492 were actually born. The Midwest had the most expected Down syndrome livebirths actually born (67.6%); the West was lowest (44.4%). More expected Down syndrome livebirths were born to women who were 15 to 34 years old (61 vs 43.8%) and to those with ≤ 12 years education (60.4 vs 46.9%), white race (56.6 vs 37%), unmarried (56.0 vs 52.5%), and of Hispanic ethnicity (55.0 vs 53.3%). The percentage of expected Down syndrome livebirths actually born varies by demographics.

Trends in Down's syndrome live births and antenatal diagnoses in England and Wales from 1989 to 2008: analysis of data from the National Down Syndrome Cytogenetic Register

Trends in Down's syndrome live births and antenatal diagnoses in England and Wales from 1989 to 2008: analysis of data from the National Down Syndrome Cytogenetic Register

849: Does the month prenatal care began influence Down syndrome livebirths?

849: Does the month prenatal care began influence Down syndrome livebirths?

595: Are there regional differences in Down syndrome livebirths?

595: Are there regional differences in Down syndrome livebirths?

Trends in Down’s syndrome live births and antenatal diagnoses in England and Wales from 1989 to 2008: analysis of data from the National Down Syndrome Cytogenetic Register

Objectives To describe trends in the numbers of Down’s syndrome live births and antenatal diagnoses in England and Wales from 1989 to 2008.Design and setting The National Down Syndrome Cytogenetic...

578: An update on trends in down syndrome livebirths in the U. S. from 1989 to 2005

578: An update on trends in down syndrome livebirths in the U. S. from 1989 to 2005

Predicted prevalence of Down syndrome live births in Japan, 1970–2006

Predicted prevalence of Down syndrome live births in Japan, 1970–2006

First- and Second-Trimester Evaluation of Risk for Down Syndrome

To investigate the differences in costs and outcomes of Down syndrome screening using data from the First and Second Trimester Evaluation of Risk (FASTER) Trial. Seven possible screening options for Down syndrome were compared: 1) Triple Screen-maternal serum alpha fetoprotein, estriol, and hCG; 2) Quad-maternal serum alpha fetoprotein, estriol, hCG, and Inhibin A; 3) Combined First-nuchal translucency, pregnancy-associated plasma protein A (PAPP-A), free beta-hCG; 4) Integrated-nuchal translucency, PAPP-A, plus Quad; 5) Serum Integrated-PAPP-A, plus Quad; 6) Stepwise Sequential-Combined First plus Quad with results given after each test; and 7) Contingent Sequential-Combined First and only those with risk between 1:30 and 1:1,500 have Quad screen. The detection rates for each option were used given a 5% false-positive rate except for Contingent Sequential with a 4.3% false-positive rate. Outcomes included societal costs of each screening regimen (screening tests, amniocentesis, management of complications, and cost of care of Down syndrome live births), Down syndrome fetuses identified and born, the associated quality-adjusted life years, and the incremental cost-utility ratio. Based on the screening results derived from the 38,033 women evaluated in the FASTER trial, the Contingent Sequential screen dominated (lower costs with better outcomes) all other screens. For example, the Contingent Sequential cost 32.3 million dollars whereas the other screens ranged from 32.8 to 37.5 million dollars. The Sequential strategy led to the identification of the most Down syndrome fetuses of all of the screens, but at a higher cost per Down syndrome case diagnosed ($719,675 compared with $690,427) as compared with the Contingent Sequential. Because of the lower overall false-positive rate leading to fewer procedure-related miscarriages, the Contingent Sequential resulted in the highest quality-adjusted life years as well. The Contingent Sequential remained the most cost-effective option throughout sensitivity analysis of inputs, including amniocentesis rate after positive screen, rate of therapeutic abortion after Down syndrome diagnosis, and rate of procedure-related miscarriages. Analysis of this actual data from the FASTER Trial demonstrates that the Contingent Sequential test is the most cost-effective. This information can help shape future policy regarding Down syndrome screening.

The relationship between utilization of prenatal care and Down syndrome live births

Objective. This study evaluated whether utilization of prenatal care, as measured by the Kessner index, affects the number of Down syndrome live births.Methods. A retrospective analysis of birth certificate data of Down syndrome live births comparing 1989 to 2001 by year, maternal age, gestational age at first prenatal visit, and adequacy of prenatal care according to Kessner categories of adequacy of prenatal care.Results. Down syndrome live births were inversely correlated with adequacy of prenatal care. Reductions in Down syndrome live births were seen in all categories of prenatal care in all age groups. In 2001 a minimum 30% reduction was seen in any category rising to a 58% reduction in women ≥35 years with adequate prenatal care. The largest reductions were seen in women ≥35 years of age.Conclusions. Reductions in Down syndrome live births occurred in all age groups between 1989 and 2001. Utilization of prenatal care as measured by the Kessner index was associated with reductions in Down syndrome live births, with a greater reduction in women ≥35 years of age.