Background Death of people with intellectual disabilities is considered to be earlier than for the general population. Methods Databases were searched for key words on intellectual disabilities and death. Strict inclusion/exclusion criteria were used. Information was extracted from selected papers, tabulated and synthesized. Prospero registration number: CRD42015020161. Results Of 19,111 retrieved articles, 27 met criteria. Death was earlier by 20 years. It has improved in recent decades; however, the same inequality gap with the general population remains. More severe intellectual disabilities, and/or additional comorbidities rendered it shortest. Standardized mortality rates showed a greater inequality for women than men. Respiratory disease and circulatory diseases (with greater congenital and lesser ischaemic disease compared with the general population) were the main causes of death. Cancer was less common, and cancer profile differed from the general population. Some deaths are potentially avoidable. All research is from high-income countries, and cause of death is surprisingly little investigated. Conclusions Improved health care, including anticipatory care such as health checks, and initiatives addressing most relevant lifestyle behaviours and health risks are indicated.

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Early death and causes of death of people with intellectual disabilities: A systematic review.

People with Down syndrome show signs of chronic immune dysregulation, including a higher prevalence of autoimmune disorders, increased rates of hospitalization during respiratory viral infections, and higher mortality rates from pneumonia and sepsis. At the molecular and cellular levels, they show markers of chronic autoinflammation, including interferon hyperactivity, elevated levels of many inflammatory cytokines and chemokines, and changes in diverse immune cell types reminiscent of inflammatory conditions observed in the general population. However, the impact of this immune dysregulation in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and CoV disease of 2019 (COVID-19) remains unknown. This Perspective outlines why individuals with Down syndrome should be considered an at-risk population for severe COVID-19. Specifically, the immune dysregulation caused by trisomy 21 may result in an exacerbated cytokine release syndrome relative to that observed in the euploid population, thus justifying additional monitoring and specialized care for this vulnerable population.

Down Syndrome and COVID-19: A Perfect Storm?

Down syndrome is the most common chromosomal abnormality among live-born infants. Through full or partial trisomy of chromosome 21, Down syndrome is associated with cognitive impairment, congenital malformations (particularly cardiovascular) and dysmorphic features. Immune disturbances in Down syndrome account for an enormous disease burden ranging from quality-of-life issues (autoimmune alopecia) to more serious health issues (autoimmune thyroiditis) and life-threatening issues (leukaemia, respiratory tract infections and pulmonary hypertension). Cardiovascular and pulmonary diseases account for ∼75% of the mortality seen in persons with Down syndrome. This review summarises the cardiovascular, respiratory and immune challenges faced by individuals with Down syndrome, and the genetic underpinnings of their pathobiology. We strongly advocate increased comparative studies of cardiopulmonary disease in persons with and without Down syndrome, as we believe these will lead to new strategies to prevent and treat diseases affecting millions of people worldwide.

https://err.ersjournals.com/content/errev/26/143/160098.full.pdf

What people with Down Syndrome can teach us about cardiopulmonary disease.

The prevalence of airway problems in children with Down's syndrome.

Background and Aims
Infants with Down syndrome (DS) or Trisomy 21, are at high risk for developing pulmonary arterial hypertension (PAH), but mechanisms that increase susceptibility are poorly understood. Laboratory studies have shown that early disruption of angiogenesis during development impairs vascular and alveolar growth and causes PAH. Human chromosome 21 encodes known anti-angiogenic factors, including collagen18a1 (endostatin, ES), s-amyloid peptide (BAP) and Down Syndrome Critical Region 1 (DSCR-1). Therefore, we hypothesized that fetal lungs from subjects with DS are characterized by early over-expression of anti-angiogenic factors and have abnormal lung vascular growth in utero.

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Increased Lung Expression of Anti-Angiogenic Factors in Down Syndrome: Potential Role in Abnormal Lung Vascular Growth and the Risk for Pulmonary Hypertension

Respiratory disease is a common cause of morbidity and mortality in children with Down's syndrome (DS). Causes range from those problems common to many children with DS, such as a narrow airway or impaired immunity, to rare structural lesions, such as tracheal bronchus. Additionally, other organ systems or extrinsic factors may play a role. A thorough understanding of the range of potential problems will aid in the evaluation and management of children with DS and respiratory symptoms.

https://adc.bmj.com/content/archdischild/98/10/812.full.pdf

An overview of respiratory problems in children with Down's syndrome

The negative impacts of COVID 19 on children's holistic development have been reported by researchers around the world. This qualitative study explored teachers' and parents' perspectives on the impact of physical/social distancing and school closure policies on children's socioemotional development. The study was conducted in fall 2020. The sample included four U.S. Preschools teachers (for 4-year-olds), four international preschool teachers (for 4, 5-year-olds), three U.S. Kindergarten teaches (for 5-year-olds), and 4 U.S. parents of 4 and 5-year-olds. Interviews were conducted over Zoom. Participants shared that the social deprivation experienced by children such as lack of friendships, absence of peer learning and peer communication, loss of play time, and lack of socialization impacted their children's socialization skills, higher order thinking development, mental health, and activity levels. Participants also shared that their children exhibited externalizing behaviors such as acting out, throwing tantrums, seeking negative attention, aggressiveness, lying, and showing disrespect. Participants reported children's life skills acquisition issues such as their over reliance on parents and difficulty in performing routine tasks. Participating teachers who taught 5-years-olds reported lower levels of fine motor skills among their students. The findings of the study suggest that although children have experienced severe academic learning loss during the pandemic, the post-pandemic ECE curriculum must keep a strong socio-emotional and practical life skills focus which contributes to children's overall well-being. Future studies may adopt a mixed method design in multi-country contexts to evaluate the impact of interventions implemented by early childhood programs on children's socioemotional health. 

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Rachel Watts

Papers

An overview of respiratory problems in children with Down's syndrome

Perspectives of Parents and Teachers on the Impact of the COVID-19 Pandemic on Children’s Socio-Emotional Well-Being