From the Journals

RSV-related risk of hospitalization higher in Down syndrome patients



Children with Down syndrome (DS) have a nine times higher risk both of hospitalization and mortality associated with respiratory syncytial virus (RSV) infection, reported Andrea Beckhaus, MD, and Jose Castro-Rodriguez, MD, PhD, at the Pontificia Universidad Católica de Chile in Santiago.

Dr. Craig Lyerla/CDC

Because DS is the most common chromosomal disorder, affecting 1 in every 800 children born worldwide, and respiratory infections are the leading cause of hospitalization in children with DS, especially during the first year of life, the results of this study are important and have considerable consequences for public health, the authors observed.

The economic burden on families of children with DS and the health care systems that treat them is, not surprisingly, significantly higher given their sevenfold higher need for supplemental oxygen therapy, threefold likely increased risk of ICU admission, fivefold higher likely need for ventilator support, and average increased length of hospital stay by nearly 5 days.

In the 15 years from 1997 to 2012, RSV-related hospital charges for infants with DS increased by nearly 80% from $10,141 (US dollars) to $18,217, compared with charges for infants not at high risk, which increased by more than 60% from $6,983 to $11,273 during the same period, according to a study (PLoS One. 2016;11[4]:e0152208).

Dr. Beckhaus and Dr. Castro-Rodriguez conducted their systematic review and meta-analysis to evaluate RSV-associated morbidity in children with DS. Following a search of four electronic data bases, a total of 12 studies published between 2004 and 2017 across 10 different countries were identified, including six in Europe, three in Asia, two in the United States, and one in Latin America. Altogether, 3,662 children with DS and 1,145,509 without DS were included in the review.

“Any potential strategy to reduce RSV infection (e.g., prophylaxis with monoclonal antibodies or new vaccines) in children with DS could decrease their morbidity and mortality,” the authors noted. Specifically, they cited the humanized monoclonal antibody palivizumab, which is used for prophylaxis against RSV. Palivizumab is known to reduce hospitalizations in children at high risk from comorbid conditions, including chronic lung disease, hemodynamically significant congenital heart disease (CHD), neuromuscular disease, immunodeficiency, and prematurity. At present, palivizumab is not recommended by the American Academy of Pediatrics for routine use to prevent RSV infection in patients with DS who are not already qualified for other reasons because there are insufficient data to recommend routine prophylactic use of the drug in children with Down syndrome.

The authors cited recent studies in Canada and Japan that may warrant further reconsideration of the AAP’s recommendations, however. A fourfold lowering of RSV-related hospitalizations was observed during the first 2 years of life among 532 children with DS receiving palivizumab who were included in a recent prospective Canadian study. The drug also was found to be safe and effective for preventing lower respiratory tract infections caused by RSV in a recent Japanese multicenter postmarketing surveillance study that evaluated palivizumab prophylaxis for RSV infection in 138 children with DS who did not have hemodynamically significant CHD; only 2 of the children treated required hospitalization.

“More cost-utility studies used to determine the efficacy of RSV immunoprophylaxis in this specific high-risk patient population need to be done,” Dr. Beckhaus and Dr. Castro-Rodriguez recommended.

The review was not without limitations. Not all of the studies included subgroups of participants with DS with CHD and without CHD or other additional risk factors. However, when only those studies were considered that had data for participants with DS without other risk factors, almost all results were similar.

One key strength of the study concerned the study methodology. Using the Newcastle–Ottawa scale, the risk of bias among the 12 studies was generally low, the total number of participants was considerably high, and the outcomes selected had importance for the patients and also public health implications. “It is important to remark that the vast majority of the outcomes that were analyzed had no or unimportant bias,” they said.

Dr. Beckhaus and Dr. Castro-Rodriguez had no relevant disclosures to disclose.

SOURCE: Beckhaus A et al. J Pediatrics. 2018;142(3):e20180225.

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