The American Academy of Pediatrics Committee on Infectious Diseases released a 2014 policy statement ( Pediatrics 2014:134;415-20 ) updating guidance on use of palivizumab in high-risk patients infected with respiratory syncytial virus (RSV). The policy statement was accompanied by a detailed technical report to explain the committee’s rationale for the changes made since the previous update in 2012.
Since 2012, several observational studies were published related to risk factors associated with the need for hospitalization for RSV infection. The Committee on Infectious Diseases (COID) referred to these observational studies, along with other historical studies, in its 2014 technical report.
Some aspects of the updated guidance have met with controversy because the new advice limits palivizumab use among premature infants. The 2014 COID policy asserts that preterm infants born at greater than 29 weeks’ gestational age (GA) do not benefit substantially from palivizumab dosing during RSV season. This assertion has met with controversy because the justification detailed in the technical report cites several observational studies that don’t appear to support that conclusion. What percentage of a cohort would need to be hospitalized for RSV infection to identify them as high risk? COID doesn’t draw that line for us. Because approximately 3% of the term birth cohort is hospitalized with RSV, should we use this as the “baseline” and predetermine a percentage of hospitalization beyond baseline to define “at increased risk”?
The 2014 technical report states that RSV hospitalization rates from Stevens et al. ( Arch. Pediatr. Adolesc. Med. 2000;154:55-61 ) were 7.5% and 4.4% for infants 28-30 weeks’ gestational age (GA) and 30-32 weeks’ GA, respectively. However, the rates quoted by COID were not the generalizable rates reported by Dr. T. P. Stevens and his team in their study. The authors calculated community-wide hospitalization rates for these groups to be 10% and 6.4%, respectively. These author-reported community-wide rates closely mirror rates reported in several other large observational studies, and still likely underestimate the true burden of RSV hospitalization based on the lower sensitivity of RSV detection testing done 15 years ago when that study was performed.
Similarly, the COID states that Dr. A.G. Winterstein’s study ( JAMA Pediatrics 2013;167:1118-24 ) shows hospitalization rates among 32-34 weeks’ GA infants of 3.1% and 4.5% in two states based on health care insurance claims. Because fewer than half of infants are ever tested for RSV as the possible cause of their lower respiratory tract infection, these claims data are most certainly an underestimate of true rates. When active testing for RSV is done among hospitalized infants in this same GA category, using sensitive and specific PCR-based technology, hospitalization rates are 9.1%. Dr. Winterstein and associates also reported that RSV hospitalization rates increase as gestational age decreases.
In Dr. Caroline Breese Hall’s 2013 observational study ( Pediatrics 2013;132:341-8 ) she and her associates recognized that hospitalization rates in children under 2 years of age were similar among term and preterm infants. The COID used these data in its 2014 technical report to suggest that preterm infants are no longer at high risk. The detail omitted from the report was that approximately 70% of eligible preterm infants in Dr. Hall’s study (according to the 2012 COID guidelines) had received palivizumab prophylaxis. This suggests that maintaining RSV prophylaxis according to the 2012 COID policy statement (and not the 2014 policy statement) can be successful in reducing the rate of RSV hospitalizations in preterm infants to that observed in term infants.
Finally, the technical report cites “overall declining incidence of hospitalizations for bronchiolitis in the United States” from the 2013 publication by Hasegawa et al. ( Pediatrics 2013:132:28-36 ) without defining this observation for the AAP readers. While Hasegawa did report such a decline, the decline was specific to term infants, as no such decline was observed in the higher-risk preterm infants.
Based on careful review of several of the manuscripts referenced by COID, it’s difficult to determine why the committee’s recommendations changed so dramatically in the most recent iteration. It appears that the data need another look.
Dr. Domachowske is professor of pediatrics and professor of microbiology and immunology at the State University of New York Upstate Medical University in Syracuse. He serves on the New York State American Academy of Pediatrics Chapter 1 executive committee, volunteers as his district’s immunization champion, and is an appointed member of the New York State Immunization Advisory Council. He is a Pediatric News Editorial Advisory Board member. Dr. Domachowske disclosed he does consulting for the vaccine divisions of GlaxoSmithKline, Medimmune, Pfizer, Merck, Sanofi Pasteur, and Novartis; he performs clinical trials with GlaxoSmithKline, Medimmune, Merck, and Novartis; and he does basic and translational research with GlaxoSmithKline. E-mail him at pdnews@frontlinemedcom.com .
