The Academy has revised its guidance for use of palivizumab (Synagis) for respiratory syncytial virus (RSV) prophylaxis based on a systematic review of recent and older peer-reviewed literature. The focus of the review by the AAP Committee on Infectious Diseases and the Clinical Practice Guideline Subcommittee on Bronchiolitis Evidence Working Group has been on publications that delineate children at risk of serious RSV disease.

Palivizumab was licensed by the Food and Drug Administration in June 1998, largely on the basis of results of the IMpact-RSV trial conducted during the 1996-’97 RSV season. A second randomized, double-blind, placebo-controlled trial conducted between 1998-2002 evaluated prophylaxis among children with hemodynamically significant congenital heart disease.

The palivizumab package insert states, “Synagis is indicated for the prevention of serious lower respiratory tract disease caused by RSV in children at high risk of RSV disease.” In the absence of a specific definition of “high risk,” the Academy has endeavored to provide updated guidance for determining who is at increased risk since palivizumab was licensed.

Since the last AAP guidance on this topic was published in the 2012 Red Book, new information has become available in the following areas:

  • seasonality of RSV circulation,

  • more accurate data regarding risk of RSV hospitalization based on degree of prematurity,

  • palivizumab pharmacokinetics,

  • overall decline in incidence of hospitalization for bronchiolitis in the United States,

  • data demonstrating no difference in RSV attack or hospitalization rates between African-American and white children,

  • lower mortality rates than previously estimated in children hospitalized with laboratory-confirmed RSV,

  • demonstration of a statistically significant but clinically limited reduction of wheezing episodes among recipients of palivizumab prophylaxis,

  • evidence of limited benefit from palivizumab prophylaxis among patients with cystic fibrosis or Down syndrome,

  • description of palivizumab-resistant RSV isolates from hospitalized patients who receive prophylaxis, and

  • no evidence of excess morbidity in countries that use more restrictive guidance for use of palivizumab than the United States.

In addition, analyses conducted by independent investigators consistently demonstrate the cost of palivizumab prophylaxis far exceeds the economic benefit of hospital avoidance, even among infants at highest risk. Some experts suggest the statistically significant but minimal clinical reduction in RSV hospitalizations and reduction in wheezing episodes associated with palivizumab prophylaxis are not of sufficient clinical and societal importance to justify the cost and feel that palivizumab should not be recommended for any group of infants.

Health expenditures should be based not only on cost and benefit but also on the intervention’s benefit relative to the expenditure. High-cost interventions may be appropriate if highly beneficial. Because the high cost of palivizumab prophylaxis is associated with minimal health benefit (i.e., reducing a small number of hospitalizations without evidence of impact on mortality, intensive care admission or long-term health benefit), this intervention cannot be considered as high-value health care for any group of infants.

Following is a summary of the revised guidance. For a complete discussion of the basis for each change and references, see the updated AAP policy statement (

) and technical report (
), both titled Updated Guidance for Palivizumab Prophylaxis Among Infants and Young Children at Increased Risk of Hospitalization for Respiratory Syncytial Virus Infection.

  • In the first year of life, palivizumab prophylaxis is recommended for infants born before 29 weeks, 0 days’ gestation.

  • Palivizumab prophylaxis is not recommended for otherwise healthy infants born at or after 29 weeks, 0 days’ gestation.

    • Previously, prophylaxis was recommended for preterm infants born before 32 weeks’ gestation. Infants with certain risk factors born at 32 weeks, 0 days to 34 weeks, 6 days also were eligible.

  • In the first year of life, palivizumab prophylaxis is recommended for preterm infants born before 32 weeks, 0 days’ gestation with chronic lung disease of prematurity defined as greater than 21% oxygen for at least 28 days after birth.

    • Previously, no definition of chronic lung disease was provided.

  • Clinicians may administer palivizumab prophylaxis in the first year of life to certain infants with hemodynamically significant heart disease. In addition, consultation with a cardiologist for decisions about prophylaxis is recommended for patients with cyanotic heart disease.

    • Previously, prophylaxis also was recommended in the second year of life for certain infants with hemodynamically significant heart disease.

  • Clinicians may administer up to a maximum of five monthly doses of palivizumab during the RSV season to infants who qualify for prophylaxis in the first year of life (including those in Florida). Qualifying infants born during the RSV season will require fewer doses. For example, infants born in January would receive their last dose in March.

    • Previously, fewer than five monthly doses were recommended for some infants.

  • Palivizumab prophylaxis is not recommended in the second year of life except for children who require at least 28 days of supplemental oxygen after birth and who continue to require medical intervention (supplemental oxygen, chronic corticosteroid or diuretic therapy).

    • Previously, two seasons of prophylaxis were recommended.

  • Monthly prophylaxis should be discontinued in any child who experiences a breakthrough RSV hospitalization.

    • Previously, continued prophylaxis was recommended in a child who experienced a breakthrough RSV hospitalization.

  • Children with pulmonary abnormality or neuromuscular disease that impairs the ability to clear secretions from the lower airways may be considered for prophylaxis in the first year of life.

    • Previous recommendation was for two years of prophylaxis.

  • Children younger than 24 months of age who will be profoundly immunocompromised during the RSV season may be considered for prophylaxis.

    • Similar to previous recommendation.

  • Insufficient data are available to recommend palivizumab prophylaxis routinely for children with cystic fibrosis or Down syndrome.

    • Previously, the recommendation for children with cystic fibrosis was similar; children with Down syndrome were not addressed.

  • The burden of RSV disease in certain remote areas may result in a broader use of palivizumab for RSV prevention in Alaska Native populations and possibly in other selected Native American populations.

    • Present recommendations allow for greater flexibility for Alaska Native and Native American populations.

  • Palivizumab prophylaxis is not recommended for prevention of RSV nosocomial disease.

    • Similar to previous recommendation.

Detailed input regarding this revised guidance was solicited from 21 AAP committees, councils, sections and advisory groups as well as from organizations outside the Academy. Outside groups that contributed to and concur with the updated guidance include the American Academy of Family Physicians, American College of Chest Physicians, American College of Emergency Physicians, American Thoracic Society, Emergency Nurses Association, National Association of Neonatal Nurses and Society of Hospital Medicine. In addition, all data presented by the manufacturer of palivizumab were evaluated.