Impact of Palivizumab in Preventing Severe Acute Lower Respiratory Infection in Moderate-to-Late Preterm Infants: A Nationwide Cohort Study

Abstract

Background: Respiratory syncytial virus (RSV) prophylaxis using palivizumab effectively reduces RSV-associated morbidity in preterm infants. In Korea, national insurance coverage for palivizumab was implemented in October 2016 for moderate-to-late preterm (MLPT) infants born during the RSV season (October-March) who have older siblings. However, no large-scale studies have investigated the changes in the incidence and risk of severe acute lower respiratory infections (ALRIs) after insurance coverage implementation for MLPT infants.

Methods: This large-scale retrospective cohort study used data from the Korean National Health Insurance Service between October 2013 and December 2019. MLPT infants (32 0/7-35 6/7 weeks of gestation) with older siblings were stratified into pre-insurance period (PIP; October 2013-September 2016) and insurance period (IP; October 2016-March 2019) groups based on the date of birth with respect to initial insurance palivizumab implementation. Severe ALRI outcomes (hospitalization, respiratory support, and intensive care unit admission) were evaluated up to 1 year of age using multivariable logistic regression models.

Results: Of the 11,722 MLPT infants included in the study, 6,716 and 5,006 infants were included in the IP and PIP groups, respectively. The incidences of ALRI-hospitalization and ALRI-respiratory support were significantly lower in the IP group than that in PIP group (24.0% vs. 26.0% and 3.1% vs. 4.0%, respectively). Additionally, ALRI-respiratory support risk was significantly lower in the IP group (adjusted odds ratio 0.771, 95% confidence interval 0.626-0.949, P = 0.014) than that in the PIP group. Among infants born during the RSV season, the risk of ALRI-hospitalization and ALRI-respiratory support were significantly lower in the IP group than that in the PIP group. However, no significant differences were observed between the IP and PIP groups for infants born during the non-RSV season.

Conclusion: The risks of severe ALRI outcomes decreased in Korea following the 2016 insurance implementation of palivizumab prophylaxis for MLPT infants born during the RSV season with older siblings.

Keywords: Infant, Premature; Palivizumab; Prophylaxis; Respiratory Syncytial Virus; Respiratory Tract Infection.

Fig. 1. Flowchart.

BPD = bronchopulmonary dysplasia, CHD = congenital heart disease, GA = gestational age, RSV = respiratory syncytial virus.

Fig. 2. Incidence of acute lower respiratory infection-related outcomes between pre-insurance and insurance periods.

ALRI = acute lower respiratory infection, ALRI-H = acute lower respiratory infection-related hospitalization, ALRI-ICU = acute lower respiratory infection-related intensive care unit admission, ALRI-RS = acute lower respiratory infection-related respiratory support, IP = insurance period, PIP = pre-insurance period, RSV = respiratory syncytial virus. The incidence rates are derived from the entire study population, regardless of palivizumab prophylaxis status. ^*P < 0.05, ^**P < 0.01, ^***P < 0.001.

Fig. 3. Incidence of gestational age-dependent acute lower respiratory infection-related outcomes between pre-insurance and insurance periods among RSV season birth infants.

ALRI = acute lower respiratory infection, ALRI-H = acute lower respiratory infection-related hospitalization, ALRI-ICU = acute lower respiratory infection-related intensive care unit admission, ALRI-RS = acute lower respiratory infection-related respiratory support, IP = insurance period, PIP = pre-insurance period. The incidence rates are derived from the entire study population, regardless of palivizumab prophylaxis status. ^*P < 0.05, ^**P < 0.01, ^***P < 0.001.