Mortality In Down Syndrome Research Articles

Nationwide hospitalizations of patients with down syndrome and congenital heart disease over a 15-year period

Down syndrome is one of the most common genetic diseases, generally associated with an increased probability of congenital heart diseases. This increased risk contributes to escalated levels of morbidity and mortality. In this study, we sought to analyze nationwide data of pediatric and adult patients with Down syndrome and congenital heart disease over a 15-year period. Data obtained from the hospital discharge form between 2001 and 2016 of patients diagnosed with Down syndrome in Italy and at least one congenital heart disease were included. Information on 12362 admissions of 6527 patients were included. Age at first admission was 6.2 ± 12.8 years and was a predictor of mortality (HR = 1.51, 95% CI 1.13–2.03, p = 0.006). 3923 (60.1%) patients underwent only one admission, while 2604 (39.9%) underwent multiple (> 1) admissions. There were 5846 (47.3%) admissions for cardiac related symptoms. Multiple admissions (SHR: 3.13; 95% CI: 2.99, 3.27; P < 0.01) and cardiac admissions (SHR: 2.00; 95% CI: 1.92, 2.09; P < 0.01) were associated with an increased risk of additional potential readmissions. There was an increased risk of mortality for patients who had cardiac admissions (HR = 1.45, 95% CI: 1.08–1.94, p = 0.012), and for those who underwent at least 1 cardiac surgical procedure (HR = 1.51, 95% CI 1.13–2.03, p = 0.006).Conclusions: A younger age at first admission is a predictor for mortality in patients with Down syndrome and congenital heart disease. If patients undergo more than one admission, the risk of further readmissions increases. There is a pivotal role for heart disease in influencing the hospitalization rate and subsequent mortality.What is Known:• Down syndrome individuals often face an increased risk of congenital heart diseases.• Congenital heart diseases contribute significantly to morbidity and mortality in Down syndrome patients.What is New:• This study analyzes nationwide data covering a 15-year period of pediatric and adult patients in Italy with Down syndrome and congenital heart disease.• It identifies a younger age at first admission as a predictor for mortality in these patients, emphasizing the criticality of early intervention.• Demonstrates a correlation between multiple admissions, particularly those related to cardiac issues, and an increased risk of further readmissions, providing insights into the ongoing healthcare needs of these individuals.

The role of type I interferon on trisomy 21 endothelial angiogenesis

Rationale: Down syndrome (DS), resulting from Trisomy 21 (T21), is the most common chromosomal disorder worldwide. Cardiopulmonary complications are a leading cause of morbidity and mortality in DS. Pulmonary disorders include pulmonary hypertension and pulmonary capillaritis, which can result from a dysregulated lung endothelium. One of the major pathways consistently activated in DS is the type I interferon (IFN-I) pathway. High IFN-I inhibits VEGF induced development of capillary like structures, thus playing an anti-angiogenic role. Therefore, we aim to characterize the effects of IFN-I on T21 and euploid iPSC-derived endothelial cells (iPSC-ECs). Methods: Endothelial cell populations from single cell sequencing data of age matched T21 and Non-T21 prenatal lungs were carefully analyzed. Four iPSC lines were derived from age and sex matched T21 and non-T21 human fetal lung fibroblasts and used for endothelial cell differentiation using standardized kits and protocols from Stem Cell Technologies. FACs analysis confirmed endothelial cell purity and differentiation success: CD31+CD34+CD144+CD45-. For angiogenesis assays, endothelial cells were plated onto Cultrex in Ibidi angiogenesis 96-well plates with varying concentrations (0 to 10 4 pM) of IFNβ for 24 hours. Phase contrast images were taken with a 2.5X lens and analyzed in FIJI with the polygon shape tool to measure continuous mesh areas (CMA), defined here as a continuous endothelial cell layer undisrupted by branching structures. Results: Pathway analysis from our scRNAseq data demonstrated an upregulation of the IFN-I pathway across T21 endothelial clusters. T21 and non-T21 iPSC lines exhibited markers of pluripotency (OCT4, NANOG, SOX2, LIN28) and successfully generated pure populations of endothelial cells (~98% CD31+CD34+CD144+CD45-) by passage 2. Quantification demonstrated that at baseline T21 iPSC-ECs consistently had a significantly larger mean CMA than that of non-T21 iPSC-ECs (p&lt; 0.01, n=4). High concentrations of IFN treatment (10 4 pM) resulted in an increased CMA in non-T21 cultures (p=0.14; n=4), trending towards baseline T21 cultures (p=0.28, n=4). Additionally, we observed a significant increase in the CMA of T21 cultures treated with 10 4 pM IFNβ (p=0.04, n=4). Conclusion: Our data suggest decreased angiogenesis in T21 iPSC-ECs may be caused by hyperactive IFN-I signaling. Further studies are needed to determine the mechanisms by which IFN-I regulates angiogenesis in T21 lungs. NIH/NHLBI/OD HL155104-01A1, NIH/NHLBI HL141856, NIH/NHLBI R21HL165411-01, NIH/NICHD 2R24HD000836-52 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

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.

Individuals with Down syndrome hospitalized with COVID-19 have more severe disease

PurposeRare genetic conditions like Down syndrome (DS) are historically understudied. Infection is a leading cause of mortality in DS, along with cardiac anomalies. Currently, it is unknown how the COVID-19 pandemic affects individuals with DS. Herein, we report an analysis of individuals with DS who were hospitalized with COVID-19 in New York, New York, USA.MethodsIn this retrospective, dual-center study of 7246 patients hospitalized with COVID-19, we analyzed all patients with DS admitted in the Mount Sinai Health System and Columbia University Irving Medical Center. We assessed hospitalization rates, clinical characteristics, and outcomes.ResultsWe identified 12 patients with DS. Hospitalized individuals with DS are on average ten years younger than patients without DS. Patients with DS have more severe disease than controls, particularly an increased incidence of sepsis and mechanical ventilation.ConclusionWe demonstrate that individuals with DS who are hospitalized with COVID-19 are younger than their non-DS counterparts, and that they have more severe disease than age-matched controls. We conclude that particular care should be considered for both the prevention and treatment of COVID-19 in these patients.

Differences in morbidity and mortality in Down syndrome are related to the type of congenital heart defect.

Morbidity and mortality in Down syndrome (DS) are mainly related to congenital heart defects (CHDs). While CHDs with high prevalence in DS (typical CHDs), such as endocardial cushion defects, have been extensively described, little is known about the impact of less common CHDs (atypical CHDs), such as aortic coarctation and univentricular hearts. In our single-center study, we analyzed, in observational, retrospective manner, data regarding cardiac features, surgical management, and outcomes of a cohort of DS patients. Literature review was performed to investigate previously reported studies on atypical CHDs in DS. Patients with CHDs were subclassified as having typical or atypical CHDs. Statistical analysis was performed for comparison between the groups. The study population encompassed 859 DS patients, 72.2% with CHDs, of which 4.7% were atypical. Statistical analysis showed a significant excess in multiple surgeries, all-cause mortality and cardiac mortality in patients with atypical CHDs (p = .0067, p = .0038, p = .0001, respectively). According to the Kaplan-Meier method, survival at 10 and 40 years was significantly higher in typical CHDs (99 and 98% vs. 91 and 84%, log rank <0.05). Among atypical CHDs, it seems that particularly multiple complex defects in univentricular physiology associate with a worse outcome. This may be due to the surgical difficulty in managing univentricular hearts with multiple defects concurring to the clinical picture or to the severity of associated defects themselves. Further studies need to address this specific issue, also considering the higher pulmonary pressures, infective complications, and potential comorbidities in DS patients.

Celiac disease and Down syndrome mortality: a nationwide cohort study

BackgroundIndividuals with Down syndrome (DS) have increased mortality and are also at increased risk of celiac disease (CD). It is unknown if CD influences mortality in DS. In this study we examined the risk of death in individuals with DS according to celiac status.MethodsIn this nationwide population-based cohort study, we first identified individuals with CD (diagnosed 1969–2008) through small intestinal biopsy report data showing villous atrophy (Marsh stage III) from Sweden’s 28 pathology departments. Celiac individuals were then matched with up to five reference individuals from the general population. In these cohorts we identified individuals with DS using International Classification of Disease codes (ICD) registered in the Swedish Patient Register (includes inpatients and hospital-based outpatients), the Medical Birth Register, and the Register of Congenital Malformations. Of 29,096 individuals with CD, 201 (0.7%) had DS compared to 124 of the 144,522 reference individuals (0.09%). Data on mortality were obtained from the Swedish Cause of Death Registry. Hazard ratios (HRs) for death were calculated using Cox regression.ResultsDuring follow-up, there were seven deaths among individuals with DS and CD (7/201, 3.5%) as compared with 14 deaths among DS individuals without a record of CD (14/124, 11.3%). Adjusting for potential confounders, CD did not influence the risk of death in DS (HR = 1.36; 95%CI = 0.33–5.59). Cardiovascular death occurred in two individuals with CD and three individuals without CD, while death from malignancy occurred in one individual with CD and two individuals without CD.ConclusionWhile both DS and CD have been linked to increased risk of death, this study found no excess mortality in DS patients with a concurrent diagnosis of CD, however confidence intervals were wide.

Congenital Visceral Malformations in Children with Down Syndrome (DS) Followed in the Pediatric Unit of the CNHU, Cotonou, Bénin

Introduction: Mortality in Down syndrome (DS) remain high and often in relation with visceral malformations. The aim of this work was to describe the congenital visceral malformations associated with DS in children followed in the pediatric unit of National Health Teaching Hospital of Cotonou, in order to improve their management.Patients and methods: It was a prospective and descriptive survey conducted on children who were treated for DS at the pediatric unit of the National Health Teaching Hospital of Cotonou from October 2015 through July 2016. All children had a diagnosis of DS based on karyotype with trisomy 21 and underwent heart, gastrointestinal and kidney ultrasonographies.Results: A total of 36 children were included. The sex ratio was 1.25 and infants under 12 months were the most represented age group (55.56 %). The mean age at diagnosis was 18.8 months. The majority of mothers were aged than 35 years. Clinical features were dominated by up slanting palpebral fissures and hypertelorism. The visceral malformations were observed only in heart with a frequency of 55.55%. Atrio-ventricular septal defect (27.78%) and patent ductus arteriosus (16.76%) were predominant. Nondisjunction trisomy 21 was found in all children.Conclusion: Congenital visceral malformations associated to DS in children at pediatric unit of the National Health Teaching Hospital of Cotonou were exclusively cardiac with atrioventricular septal defect as major type. Early diagnosis of DS with malformations screening are essential for better management of affected children.

Rising infant mortality in down syndrome in Chile from 1997 to 2013

Down syndrome (DS) is associated with higher child mortality especially due to cardiac malformations. To describe the trend in Chilean infant mortality in DS in the period 1997-2013 as compared to the general population without DS. Raw data on infant deaths were extracted from the yearbooks of vital statistics of the National Institute of Statistics. The mortality risk associated to DS, relative to population without DS was estimated. There were 456 deaths in infants with DS during the study period (59 early neonatal deaths, 70 late neonatal deaths and 327 post-neonatal deaths). The trend in infant mortality rate in DS was ascending (r: 0.53, p = 0.03), with an average annual percentage change of 4.6% (95% confidence interval (CI) 0.4-9.0%; p < 0.01). Compared to the population without DS, the risk of early neonatal death was lower in DS (Odds ratio (OR) 0.14, 95% CI 0.11-0.19; p < 0.01) whereas the risk of post-neonatal death was higher (OR 4.74, 95% CI 3.85-5.85; p < 0.01). Infant mortality in Down syndrome has an increasing trend. We postulate that these children are not accessing timely cardiac surgery, the main therapeutic tool to reduce the death risk in the first year of life.

Risk factors for mortality in Down syndrome.

Down syndrome is a genetic condition that contributes to a significantly shorter life expectancy compared with the general population. We investigated the most common comorbidities in a population of acute hospital patients with Down syndrome and further explored what the most common risk factors for mortality are within this population. From our database of one million patients admitted to National Health Service (NHS) Trusts in northern England, we identified 558 people who had Down syndrome. We compared this group with an age- and gender-matched control group of 5580 people. The most prevalent comorbid diseases within the Down's population were hypothyroidism (22.9%) and epilepsy (20.3%). However, the conditions that had the highest relative risks (RRs) in the Down's population were septal defects and dementia. Respiratory failure, dementia and pneumonia were the most significantly related comorbidities to mortality in the Down syndrome population. In the control population, respiratory failure, dementia and renal failure were the most significant disease contributors. When these contributors were analysed using multivariate analysis, heart failure, respiratory failure, pneumonia and epilepsy were the identified risk factors for in-hospital mortality in the Down syndrome population. Respiratory failure was the sole risk factor for mortality in the Down syndrome population [RR = 9.791 (1.6-59.9) P ≤ 0.05], when compared with the risk factors for mortality in the control population. There is significant medical morbidity in Down syndrome. This morbidity contributes to the lower life expectancy. Respiratory failure is a risk factor for mortality in Down syndrome. We need to thoroughly investigate people with Down syndrome to ensure any treatable illnesses are well managed.

Should we mend their broken hearts? The history of cardiac repairs in children with Down syndrome.

* Abbreviation: AVSD — : atrioventricular septal defect In May 2014, Evans et al1 reported that children with Down syndrome had lower rates of in-hospital death after cardiac surgery, compared with children without Down syndrome. Forty years ago, these results would have been unthinkable, as heart defects were not repaired in the majority of children with Down syndrome. However, as the field of cardiac surgery evolved, equal postoperative outcomes were reported between children with Down syndrome and those without. The historical question of whether we ought to offer cardiac repairs to infants with Down syndrome was influenced by a complex web of ethical, social, and legal considerations that changed over time, resulting in the current standard of care in which children with and without Down syndrome have the same opportunity for cardiac repair. Complex intracardiac surgery in infants was not routinely performed until the early 1970s, and Pediatrics published the first report on cardiac repairs in infants with Down syndrome in 1976.2 The authors concluded that overall surgical mortality in Down syndrome was high, especially in atrioventricular septal defects (AVSD), the most common heart defect associated with Down syndrome. Critical appraisal reveals only a minority of the children in the cohort received cardiac repairs, and of those, many were not suitable for full repairs because they had developed pulmonary hypertension by the time of surgery. In a 1978 Letter to the Editor,3 Feingold suggested that children with Down syndrome did poorly because they did not receive prompt surgical repairs, and not because of their Down syndrome. Over the following years, cardiac surgical techniques in infants developed rapidly, with improved outcomes in all children. The advent of … Address correspondence to: Chantelle R. Champagne, BMSc, MD, Department of General Pediatrics, 3rd Floor, Edmonton Clinic Health Academy, University of Alberta, 11405-87 Ave NW, Edmonton, AB, Canada T6G 2J3. E-mail: cchampag{at}ualberta.ca

Changes in mortality and causes of death in the Swedish Down syndrome population

During the past few decades age at death for individuals with Down syndrome (DS) has increased dramatically. The birth frequency of infants with DS has long been constant in Sweden. Thus, the prevalence of DS in the population is increasing. The aim of the present study was to analyze mortality and causes of death in individuals with DS during the period 1969-2003. All individuals with DS that died between 1969 and 2003 in Sweden, and all individuals born with DS in Sweden between 1974 and 2003 were included. Data were obtained from the Swedish Medical Birth Register, the Swedish Birth Defects Register, and the National Cause of Death Register. Median age at death has increased by 1.8 years per year. The main cause of death was pneumonia. Death from congenital heart defects decreased. Death from atherosclerosis was rare but more frequent than reported previously. Dementia was not reported in any subjects with DS before 40 years of age, but was a main or contributing cause of death in 30% of the older subjects. Except for childhood leukemia, cancer as a cause of death was rare in all age groups. Mortality in DS, particularly infant mortality, has decreased markedly during the past decades. Median age at death is increasing and is now almost 60 years. Death from cancer is rare in DS, but death from dementia is common.

Survival Analysis of Down Syndrome Cohort in a Tertiary Health Care Center in India

To identify the major causes of death in Down Syndrome (DS), the ages at which mortality rates are the highest and recognize factors associated with it. The prospective cohort-based study was carried out in a tertiary health care center. Children with DS (n = 543) counseled at the Center of Medical Genetics, Sir Ganga Ram Hospital from 2005 through 2009 were followed up in year 2010. Survival curves and Cox's proportional hazards regression analysis were used to determine the effect of different variables on survival. Total mortality was 13 %, of which 80.3 % was in children less than 2 y of age. Presence of congenital heart disease (CHD) increased the risk of mortality by 5.7 folds (p = 0.001). A definitive survival benefit after cardiac intervention was noted, although it differed with the type of CHD. Sex, maternal age at time of birth and karyotypes did not show a significant correlation with survival. The higher DS infant mortality observed in the present study could be attributed to financial constraints of the families and misconceptions amongst health professionals. It is recommended that a nation-wide DS registry be created to study the morbidity and mortality in Down syndrome from birth. The findings of this study will help clinicians in making management decisions and enable better counseling.

Cancer mortality in Down syndrome in California

Cancer in Down syndrome (DS) is characterized by a well known and marked excess of leukaemia whereas few cohort studies are available on solid tumours in this population. Objective: To study the cancer mortality of DS in California. Study group: 16,808 DS cases (contributing 129,076 person-years) among 210,155 persons having received annual evaluations from the California Department of Developmental Services over the period 1988-2002 were followed. Methods: Cancer mortality in DS was compared with the Californian general population using age-standardized mortality ratios (SMRs) computed for various cancer sites (ICD-9 codes 140-208). Results: An excess of overall cancer mortality (SMR 2.6, 95% CI 2.0-3.2) was found with overall SMR for neoplasms of the lymphatic and hematopoietic system at 10.3 (CI 7.5-13.9) [lymphomas: 3.7 (1.3-8.0), lymphoid leukemias: 27.6 (17.5-41.4), other specified leukemias: 51.1 (1.3-285.0) and unspecified leukemias: 25.4 (13.1-44.3)]. Liver [5.6 (1.8-13.1)] and testicular cancer [12.5 (1.5-45.1) were also more common in DS. No cancer deaths from lip, oral cavity, or pharynx were reported in DS. Other sites showed no significant differences. Excluding neoplasms of lymphatic and hematopoietic systems, the SMR for remaining cancers was 1.2 (0.8-1.7). Conclusion: Our findings do not support the hypothesis of a decreased risk of solid tumours in general in DS and confirm increased risk of testis and liver cancers. Further studies taking into account hormonal and genetic factors are needed to better understand the specific tumour profile in DS.

Changes in incidence of cystic fibrosis

Prevalence, Neonatal Characteristics, and First-Year Mortality of Down Syndrome: A National StudyThe Journal of PediatricsVol. 152Issue 1PreviewTo determine the prevalence, neonatal characteristics, and first-year mortality in Down syndrome (DS) among children in the Netherlands. Full-Text PDF Is Down Syndrome a Disappearing Birth Defect?The Journal of PediatricsVol. 152Issue 1PreviewTo assess trends in the prevalence of Down syndrome (DS) from 1986 to 2004 in Victoria, Australia (population ∼5 million). Full-Text PDF Time Trends in Birth Incidence of Cystic Fibrosis in Two European Areas: Data from Newborn Screening ProgramsThe Journal of PediatricsVol. 152Issue 1PreviewTo determine the incidence of cystic fibrosis (CF) and its time trends over a 16-year period (1990 to 2005) in 2 European regions with a long history of newborn screening (NBS) for CF, and to investigate the impact of some external factors. Full-Text PDF How Far Can Prenatal Screening Go in Preventing Birth Defects?The Journal of PediatricsVol. 152Issue 1PreviewThe ideal screening program would have perfect sensitivity and specificity in detecting the condition of interest, the health condition being detected would be of substantial clinical and public health importance, once detected there would be effective and acceptable action to prevent the adverse outcome, and the health care community and public would fully embrace the strategy. Although screening for serious birth defects that result from single gene defects may not attain that standard of perfection, they come closer than perhaps any other health condition. Full-Text PDF

Prevalence, Neonatal Characteristics, and First-Year Mortality of Down Syndrome: A National Study

To determine the prevalence, neonatal characteristics, and first-year mortality in Down syndrome (DS) among children in The Netherlands. The number of DS births registered by the Dutch Paediatric Surveillance Unit (DPSU) in 2003 was compared with total live births (reference population) and perinatal registrations. The prevalence of DS was 16 per 10,000 live births. Compared with the reference population, the 182 children with trisomy 21 had a gestational age of 38 weeks versus 39.1 weeks (P < .001), a birth weight of 3119 g versus 3525 g in males (P < .001) and 2901 g versus 3389 g in females (P < .001), and mothers with a parity of > or = 4.17% versus 5% (P < .001) and a mean age of 33.6 years versus 31 years (P < .001) and 33% (n = 54) > or = 36 years). The mean age of DS diagnosis was 10.2 days in nonhospital deliveries and 1.8 days in hospital deliveries (P < .001). Children with DS were less often breast-fed (P < .05), and 86% (n = 156) were hospitalized after birth. Neonatal and infant mortality were higher in DS, 1.65% versus 0.36% (P < .02) and 4% versus 0.48% (P < 0.001), respectively. The prevalence of DS in The Netherlands exceeds previously reported levels and is influenced by the mother's age. Neonatal and infant DS mortality have declined, but still exceed those in the reference population.

Elevated Plasma β-Amyloid Peptide Aβ42 Levels, Incident Dementia, and Mortality in Down Syndrome

Deposition of the beta-amyloid peptide Abeta(42) is thought to be an important initial step in the pathogenesis of Alzheimer disease (AD). Individuals with Down syndrome have increased levels of beta-amyloid peptides and an increased risk for AD.To examine the relation of plasma levels of Abeta(42) and Abeta(40) to the risk of dementia in nondemented participants and all-cause mortality in adults with Down syndrome.Prospective, community-based longitudinal cohort study.State and voluntary service providers in New York State.Adults with Down syndrome (N = 204).Plasma Abeta(42) and Abeta(40) levels were measured at initial examination. Participants were assessed for cognitive and functional abilities, behavioral/psychiatric conditions, and health and vital status at 14- to 18-month intervals for 4 cycles of data collection.Among participants who were nondemented at baseline, those in the middle and highest tertiles of plasma Abeta(42) levels were more than 2 times as likely to develop AD as those in the lowest tertile. Compared with participants without AD, participants with prevalent AD had higher levels of plasma Abeta(42) but not Abeta(40). Among all participants, those in the highest tertile of plasma Abeta(42) level at baseline were more than twice as likely to die during the study period as those in the lowest tertile, whereas there was no difference in risk of death between those in the middle and lowest tertiles of plasma Abeta(42) level.Elevations in plasma Abeta(42) peptide levels are associated with earlier onset of AD and increased risk of death.

O2-06-01: Elevated plasma amyloid β-peptide Aβ42, incident dementia and mortality in down syndrome

O2-06-01: Elevated plasma amyloid β-peptide Aβ42, incident dementia and mortality in down syndrome

Incidence, survival, and mortality in Down syndrome in Denmark

The incidence of Down syndrome (DS) has been studied intensively for the two periods 1960-1972 and 1980-1985. The age distribution of birth-giving mothers has changed to older age at child birth from the first to the second period. Non-disjunction studies were carried out in 328 families. Most cases were first maternal meiotic division failures (43%). Nearly 12% were paternal meiotic failures, half of them in first meiosis and half in second. Both newborn infants and fetuses were studied. There was an excess of males, especially among newborn DS children, which was related to a failure at paternal first meiosis. A positive sex ratio was found in all newborn infants as well as in free trisomics as in those with de novo translocations. Survival was studied in the cohort of 278 infants born 1980 to 1985. The highest death-rate occurred between 22 days to 1 year (10.4%), 30 times more than the death probability in the Danish population. There was a significant difference between DS cases with congenital heart defect and those without. The probability of infants without heart disease of reaching the first year was 93.1% and the age of 6 years 88.0%. The probability of survival of children with congenital heart defect was 71.7% and 45.2%, respectively, reflecting also the increasing number of infants born prematurely with low birth weight or small-for-date infants. The predominant heart problems were atrio-ventricular canal defects. Infections and malformations added to the high mortality rate. Three cases of leukemia were significantly more than expected.

Maternal and neonatal factors and mortality in children with Down syndrome born in 1973-1980 and 1995-1998.

To investigate maternal and neonatal factors in Down syndrome (DS) at birth, the impact of a congenital heart defect (CHD) on these factors and changes over time. Medical data of children with DS born in northern Sweden in the periods 1973-1980 (n = 219) and 1995-1998 (n = 88) obtained from the Swedish Medical Birth Register were compared. A comparison with the general population on a group level was also made. The main finding was a reduction in infant mortality in DS, from 14.2% to 2.3% in 1995-1998 (p < 0.001), but this was still significantly higher than in the general population. The rate of Caesarean sections increased over time (from 14.5% to 27.3%, p < 0.05) even after adjustment for increased maternal age. No change over time was detected in the following rates: premature birth (gestational age < or = 36) (25%); asphyxia (5-min Apgar score < or = 6) (8%); low birthweight (< 2500 g) (14%); or small for gestational age (SGA) (14%); all rates were significantly higher than those of the general population. A CHD did not seem to influence the rates of these factors in a logistic regression model. Infant mortality decreased substantially over time in the DS group, whereas there was no reduction in the rate of asphyxia, SGA, low birthweight or prematurity. The presence of a CHD did not influence any of the neonatal factors studied.

Down syndrome in Israel

The incidence of Down syndrome was studied in Jerusalem for the years 1964-1970 showing an overall incidence rate of 2.43 per 1,000 live births. A National Down Syndrome Register was established in 1978 and data on annual incidence and mortality rates from 1979-1997 is presented. The incidence in 1997 was 1.0 per 1,000 live births, but 2.32 per 1,000, when live births and terminated pregnancies are summed. Infant mortality has generally decreased in the past 20 years in Israel, and a decrease in infant mortality in Down syndrome has also been noted. This is due to better medical treatment and increased parental involvement in the care for infants with Down syndrome.