Epidemiology of respiratory symptoms in children with Down syndrome: a nationwide prospective web-based parent-reported study

Down syndrome (DS) is the most common genetic cause of developmental delay in humans, affecting approximately 1 in 700 liveborn infants in the Netherlands [1, 2]. Numerous health issues are related to DS. In newborns, hypotonia, facial characteristics and congenital heart disease (CHD) are variably present. Later in life, DS is associated with an increased incidence of hematological malignancies and auto-immune diseases, such as celiac disease, hypothyroidism and type 1 diabetes mellitus [3].

Respiratory complications and ear, nose and throat (ENT) diseases are a major contributor to morbidity and mortality in patients with DS. Up to 80% of all hospitalizations and admissions to a pediatric intensive care unit of children with DS is caused by lower respiratory tract infections [4, 5]. The risk of respiratory syncytial virus infection and viral induced wheezing, but not asthma, is increased in infants with DS [6‐11]. Moreover, up to 29% of deaths in DS are related to pneumonia, influenza and aspiration, with increased standardized mortality odds ratio of 3.00-4.15 in children with DS aged <20 years [12, 13]. In addition, we recently showed that parent-reported recurrent respiratory tract infections in 8-year-old children with DS are associated with more impaired mental and motor development, lower health related quality of life and more behavioral problems compared to children whose parents report no increased respiratory tract infections in their child [14].

In a retrospective Finnish chart study, up to 40% of children and young adults (aged <30 years) with DS have had at least one pneumonia, partly caused by aspiration [15]. Schieve et al. report that 27.6% of children with DS compared to 17.5% of children without DS or other cause of mental retardation had symptoms of head/chest cold in the 2 weeks prior to the conduction of the survey [9]. Another study showed that 17.6% of school-aged children with DS have a continual runny nose and that 12% have had more than 3 upper respiratory tract infections in the preceding year [16]. ENT diseases are more frequently found in children with DS and include ear infections, hearing impairment and obstructive sleep apnea syndrome, [17‐21] which can subsequently lead to behavioral problems and more developmental delay [22, 23].

Treatment, and especially prevention of recurrent respiratory tract infections is challenging. Anatomical and physiological changes in the respiratory and ENT tract in children with DS are inherent to the syndrome and leave little room for improvement, except adenotomy and/or tonsillectomy. The use of prophylactic antibiotics to decrease the frequency of respiratory infections has never been studied in children with DS (nor in healthy children). Also, although palivizumab is sometimes prescribed in children with DS to prevent severe RSV disease, there have been no studies to evaluate the effect of this treatment. At last, other – more active – diagnostics and treatment by ENT specialists may be beneficial since adenotomy and/or tonsillectomy do not help all children [24]. In order to evaluate treatment options there is a need for more data on the exact incidence of respiratory symptoms and their evolvement in time to define patient groups who may benefit from these therapies. In this paper we describe the construction of a web-based observational study of respiratory tract infections in children with DS.

Although respiratory tract and ENT diseases are frequently encountered in the care for children with DS, little is known about their epidemiology. We have designed a prospective web-based study, which allows us to describe the incidence of respiratory symptoms, as well as their relation to comorbidity, age and season. This information can help to evaluate the effect of future treatment options.

To our knowledge this is the first prospective study in patients with DS on epidemiological data of respiratory symptoms. Earlier studies were often based on retrospective chart reviews, which excludes complaints for which no medical attention was sought by the parents [5, 7, 15]. Also, there have been many studies based on a single questionnaire where parents were asked if complaints were present in the past year(s), which leads to recall bias [9, 11, 16, 21]. Other authors have therefore used both chart review and retrospective questionnaires to minimize the effect of recall bias [4, 6]. Some studies are based on hospital admission/discharge records or mortality records only, and all outpatient symptoms are missed [8, 12, 13]. We expect our study to give more insight in respiratory symptoms in children with DS, which may help DS specialists to improve health care for this group.