Abstract
Children with Down syndrome (DS) are at high risk of respiratory tract infections (RTIs) due to anatomical variations, comorbidities, and immune system immaturity. Evidence on interventions to reduce this risk is incomplete. This study aims to quantify the effect of antibiotics prescribed for RTIs in primary care on the subsequent risk of RTI-related hospitalization for children with DS versus controls. We conducted a retrospective cohort study of 992 children with DS and 4874 controls managed by UK National Health Service General Practitioners (GPs) and hospitals as identified in CALIBER (Clinical disease research using LInked Bespoke studies and Electronic health Records), 1997-2010. Univariate and multivariate logistic regression were undertaken. In children with DS, the prescription of antibiotics following an RTI-related GP consultation did not significantly reduce the risk of RTI-related hospitalization in the subsequent 28 days (risk with antibiotics, 1.8%; without, 2.5%; risk ratio, 0.699; 95% confidence interval, 0.471-1.036). Subgroup analyses showed a risk reduction only in infants with DS, after adjustment for covariates. There was no reduction in risk for controls, overall or across subgroups. In conclusion, while prescription of antibiotics following RTI-related GP consultations were effective for infants with DS in reducing subsequent RTI-related hospitalization, this was not the case for older children with DS. We would encourage further high-quality cohort and randomized controlled trials to interrogate this finding, and to examine the impact of antibiotics on other endpoints, including symptom duration.
Highlights
In the overall population of children with Down syndrome (DS), without adjustment for covariates, the prescription of antibiotics following an respiratory tract infections (RTIs)‐related General Practitioners (GPs) consultation did not show any significant evidence for reduction in the risk of RTI‐related hospitalization in the subsequent 28 days (risk, 1.8% (95% confidence interval [CI], 1.3%–2.3%), and 2.5% respectively; risk ratio [RR], 0.699; 95% CI, 0.471–1.036)
A 2007 study used CPRD primary care data to assess the effect of antibiotics in preventing serious complications following RTIs in the general population, and found a limited benefit, with an number needed to treat (NNT) of over 4000.15 That study did not link primary to secondary care data, thereby potentially underestimating complication rates and overestimating the NNT
This study indicates that other than in infancy children with DS do not receive an observable benefit with regard to hospitalization after being prescribed antibiotics for RTIs in primary care
Summary
With an incidence of 1 in 1000 live births, and prevalence of 6.3 in 10,000 people, Down syndrome (DS) is one of the most common genetic conditions in the UK.[1,2] As of 2011, an estimated 37,090 people were living with DS in England and Wales, of whom approximately 10,438 were aged 0–18.3 It has been projected that the number of children with DS is increasing in the UK, with one analysis projecting 11,592 children 0–15 to be living in England and Wales by 2020.4 In addition, life expectancy of people with DS has doubled in the past six decades, increasing from 30 to 60 years,[5,6] alongside advances in medical and surgical treatment, improved social inclusion and support, and general quality of life.[5,6]Children with DS are thought to be at an increased risk of frequent and severe respiratory tract infections (RTIs) due to anatomical variations (such as a narrow upper airway), complications from comorbidities (including congenital heart disease and reflux), and immune system immaturity.[7,8] A study of 22 children with DS age‐matched to 22 healthy siblings found children with DS had a significantly higher frequency of lower RTIs (LRTIs) compared to their siblings alongside observed immune parameter differences.[7]. This study aims to quantify the effect of antibiotics prescribed for RTIs in primary care on the subsequent risk of RTI‐related hospitalization for children with DS versus controls. Results: In children with DS, the prescription of antibiotics following an RTI‐related GP consultation did not significantly reduce the risk of RTI‐related hospitalization in the subsequent 28 days (risk with antibiotics, 1.8%; without, 2.5%; risk ratio, 0.699; 95% confidence interval, 0.471–1.036). Conclusions: In conclusion, while prescription of antibiotics following RTI‐related GP consultations were effective for infants with DS in reducing subsequent RTI‐ related hospitalization, this was not the case for older children with DS. We would encourage further high‐quality cohort and randomized controlled trials to interrogate this finding, and to examine the impact of antibiotics on other endpoints, including symptom duration
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