Appeal type: Medical necessity
Decision: Overturned

This is a patient with birth weight 1525 grams. Her neonatal period was complicated by respiratory distress syndrome, requiring nasal continuous positive airway pressure (CPAP) and supplemental oxygen, as well as suspected sepsis treated with antibiotics for 72 hours pending negative cultures. She received a dose of Synagis prior to discharge from the Neonatal Intensive-Care Unit (NICU). The current request is to continue administration of Synagis for the duration of the RSV season. The health plan's determination is overturned.
The American Academy of Pediatrics issued new guidelines for the administration of Synagis for RSV prophylaxis based on review of current peer-reviewed literature related to burden of RSV in infants and children with emphasis on those at highest risk of severe disease. The following groups of patients are considered at highest risk, with recommendations for administration of Synagis: infants born before 29 weeks' gestation younger than 12 months of age at the start of RSV season; infants with chronic lung disease of prematurity born before 32 weeks' gestation during the first year of life, with some consideration during the second year of life if continued medical support is necessary; infants 12 months of age or younger with hemodynamically significant congenital heart disease (excluding those with lesions adequately corrected by surgery unless medication is necessary for ongoing congestive heart failure); consideration for infants 12 months of age or younger with anatomic pulmonary abnormalities or neuromuscular disorders that have difficulty clearing secretions; consideration for infants less than 24 months of age that are profoundly immunocompromised; and consideration for infants with Down syndrome or cystic fibrosis that have evidence of other risk factors such as chronic lung disease or congenital heart disease. (1) Despite these published guidelines for administration, there remains significant debate among practitioners and experts in RSV illness about the use of Synagis in late preterm infants. The literature falls on both sides of the debate. One article recently published supports and substantiates the changes in administration guidelines made by the American Academy of Pediatrics (AAP). When looking at healthy preterm infants born between 29 and 36 weeks' gestation, this group found that the hospitalization rate was similar for those born at 29-32 weeks and those born at 33-36 weeks. There was a very small difference in hospitalization rate between infants in the 29-32 weeks cohort that received palivizumab and those that did not (1186 infants in this group, 1.9% difference amounting to 22 additional hospitalizations over a 3-year period). Interestingly, the overall hospitalization rate for infants with RSV disease has decreased compared to the initial studies of palivizumab. One finding in this study was that infants that received palivizumab prophylaxis had an increased hospitalization rate for bronchiolitis due to other causes. (2)  On the other side, Horn and Smout (2) analyzed retrospective data from 304 infants less than (<) 1 year of age with bronchiolitis or RSV pneumonia admitted to the hospital. Data were subdivided by gestational age (< 32 weeks, 33-35 weeks, > 36 weeks) and compared, looking at rates of intubation and ICU admission, as well as length of stay. They found that infants < 1 year of age born at 33-35 weeks gestation fared worse than those born more prematurely over all measures. "Our findings that 33 to 35 weeks GA [gestational age] infants have hospital outcomes at least as bad or worse than those of infants born at < 32 weeks GA might seem counterintuitive to some clinicians. One possible explanation could be that we know that true alveoli begin to form between 32 and 35 weeks GA, with all infants having alveoli by 36 weeks GA. Premature birth during this critical period of lung development (32-35 weeks GA) may result in significant alteration in lung function and physiology." Further, Carbonell-Estrany and colleagues (3) noted, "there is a growing body of evidence suggesting that infants born between 33 and 35 weeks GA [gestational age] may be equally at risk for RSV LRTI [lower respiratory tract infection] as infants born < 32 weeks GA. Interrupted lung development and an immature immune system have been linked with an increased susceptibility for RSV LRTI." Finally, Simoes and colleagues (4) have developed a model based on seven risk factors to predict which infants born between 32-35 weeks are at highest risk of severe RSV disease, as defined as need for hospitalization. These risk factors include the following: birth +/- 10 weeks at the start of the RSV season, birth weight, breast feeding for < 12 months, siblings > 2 years, family history of atopy, family history of wheezing, and gender. Regarding birth weight, an infant with a birth weight between 1500 and 2500 grams is 5 times more likely to die from RSV infection than an infant with a birth weight > 2500 grams. (5)
Taking all of the studies and data and guidelines into consideration, most practitioners err on the side of caution and administer Synagis to their late preterm patients, particularly if there are concerning risk factors (birth weight, hospital course, etc). In this case, this child was born at 34 weeks' gestation with respiratory distress syndrome requiring non-invasive ventilatory support with supplemental oxygen and birth weight 1525 grams, placing her at risk for development of severe disease should she become infected with RSV. Synagis is medically necessary and appropriate for the full duration of the RSV season based on the literature and the current standards of care.