Christopher McPherson

Respiratory syncytial virus (RSV) is the leading cause of hospitalization in infancy in the United States. Nearly all infants are infected by 2 years of age, with bronchiolitis requiring hospitalization often occurring in previously healthy children and long-term consequences of severe disease including delayed speech development and asthma. Incomplete passage of maternal immunity and a high degree of genetic variability within the virus contribute to morbidity and have also prevented successful neonatal vaccine development. Monoclonal antibodies reduce the risk of hospitalization from severe RSV disease, with palivizumab protecting high-risk newborns with comorbidities including chronic lung disease and congenital heart disease. Unfortunately, palivizumab is costly and requires monthly administration of up to five doses during the RSV season for optimal protection.Rapid advances in the past two decades have facilitated the identification of antibodies with broad neutralizing activity and allowed manipulation of their genetic code to extend half-life. These advances have culminated with nirsevimab, a monoclonal antibody targeting the Ø antigenic site on the RSV prefusion protein and protecting infants from severe disease for an entire 5-month season with a single dose. Four landmark randomized controlled trials, the first published in July 2020, have documented the efficacy and safety of nirsevimab in healthy late-preterm and term infants, healthy preterm infants, and high-risk preterm infants and those with congenital heart disease. Nirsevimab reduces the risk of RSV disease requiring medical attention (number needed to treat [NNT] 14–24) and hospitalization (NNT 33–63) with rare mild rash and injection site reactions. Consequently, the Centers for Disease Control and Prevention has recently recommended nirsevimab for all infants younger than 8 months of age entering or born during the RSV season and high-risk infants 8–19 months of age entering their second season. Implementing this novel therapy in this large population will require close multidisciplinary collaboration. Equitable distribution through minimizing barriers and maximizing uptake must be prioritized.

Hepatitis B viral infection is a significant source of morbidity and mortality worldwide. The United States has experienced a precipitous drop in acute hepatitis B infection after the introduction and widespread adoption of recombinant vaccines. Neonates experience significant risk from both vertical and horizontal hepatitis B exposure during a period of immaturity of the innate and adaptive immune systems. Acquisition of hepatitis B virus at or near birth confers the highest lifetime risk of chronic infection and subsequent complications including liver cirrhosis and hepatocellular carcinoma. Pregnant women should be screened for the presence of hepatitis B surface antigen, indicating acute or chronic infection, and, if positive, hepatitis B viral deoxyribonucleic acid, allowing for quantification of viral load. The development of highly effective and safe recombinant vaccines allows partial protection of late preterm and term neonates immediately after birth. Additionally, administration of hepatitis B immune globulin in the setting of suspected or confirmed exposure supplements the immune response and decreases the risk of chronic infection. The optimal timing of vaccination is later in low-birth-weight neonates due to the aforementioned immune system immaturity. Health care providers serving neonates must familiarize themselves with national guidelines regarding hepatitis B vaccination and hepatitis B immune globulin therapy. Understanding the risks of infection and the evidence basis supporting vaccination and immunotherapy will allow providers to educate families and support decision-making, with the potential to eradicate this vaccine-preventable illness in our lifetime.

Bronchopulmonary dysplasia (BPD) is a morbidity of prematurity with implications for respiratory and neurologic health into adulthood. Multiple risk factors contribute to the development of BPD leading to examination of various prevention strategies. The roles of systemic corticosteroids and caffeine have been addressed by the American Academy of Pediatrics. The place in therapy of other agents commonly utilized in clinical practice remains unclear. Inhaled nitric oxide has been the subject of numerous large, randomized controlled trials in preterm infants. Despite sound rationale, these trials have largely failed to document benefit, suggesting a limited role for inhaled nitric oxide therapy in the preterm population. In contrast, intramuscular vitamin A has been documented to reduce the incidence of BPD in randomized trials. However, the invasiveness and the sporadic availability of this therapy have led to decreased utilization. All macrolide antibiotics do not appear to have a similar impact on the incidence of BPD; however, azithromycin administered to infants colonized withUreaplasmamay have impact. Questions remain about the optimal dosing approach and long-term safety of this intervention. Finally, diuretic therapy is widely used in clinical practice despite significant toxicities and limited data supporting a role in BPD prevention. Taken together, available data suggest that caffeine and selective use of corticosteroids remain the mainstays of pharmacologic BPD prevention.

Respiratory distress syndrome (RDS) impacts a high proportion of preterm neonates, resulting in significant morbidity and mortality. Advances in pharmacotherapy, specifically antenatal corticosteroids and postnatal surfactant therapy, have significantly reduced the incidence and impact of neonatal RDS. Antenatal corticosteroids accelerate fetal lung maturation by increasing the activity of enzymes responsible for surfactant biosynthesis, resulting in improved lung compliance. Maternal antenatal corticosteroid treatment has improved survival of preterm neonates and lowered the incidence of brain injury. After birth, exogenous surfactant administration improves lung compliance and oxygenation, resulting in reductions in the incidence of pneumothorax and of death. Future research will identify the optimal surfactant product, timing of the initial dose, and mode of delivery.

In response to the growing epidemic of antibiotic-resistant bacterial infections, antimicrobial stewardship programs (ASP) have been rapidly implemented in the United States (US). This study examines the prevalence of the Centers for Disease Control and Prevention’s (CDC) seven core elements of a successful ASP within a large subset of US Children’s Hospitals. In 2016, a survey was conducted of 52 pediatric hospitals assessing the presence of the seven core elements: leadership commitment, accountability, drug expertise, action, tracking, reporting, and education. Forty-nine hospitals (94%) had established ASPs and 41 hospitals (79%) included all seven core elements. Physician accountability (87%) and a dedicated ASP pharmacist or drug expert (88%) were present in the vast majority of hospitals. However, substantial variability existed in the financial support allotted to these positions. This variability did not predict program actions, tracking, reporting, and education. When compared with previous surveys, these results document a dramatic increase in the prevalence and resources of pediatric stewardship programs, although continued expansion is warranted. Further research is required to understand the feasibility of various core stewardship activities and the impact on patient outcomes in the setting of finite resources.

Gastroesophageal reflux is a normal physiologic occurrence that is common throughout infancy and usually resolves on its own. Infrequently, reflux causes complications and turns into gastroesophageal reflux disease (GERD), which may warrant intervention. Available interventions vary in invasiveness and supporting data may be lacking for efficacy and safety. Nonpharmacologic interventions are first-line therapy for GERD in infants, whereas pharmacologic and surgical approaches are controversial. Efficacy data are limited for pharmacologic strategies for infantile GERD and safety data have demonstrated serious risks, especially in younger infants. Utilization of these medications should be approached cautiously in this population, if appropriate diagnostic techniques determine acid suppression could be beneficial. A robust monitoring plan with frequent reassessment of need for therapy may optimize benefit and minimize risk.

Neonatal abstinence syndrome (NAS) from in utero opioid exposure has reached epidemic levels in the United States. Although nonpharmacologic therapies form the foundation of care, many neonates require pharmacotherapy. Morphine represents the most widely used first-line agent and effectively treats the symptoms of withdrawal. However, methadone or buprenorphine may facilitate earlier discharge. Although phenobarbital is traditionally used when opioids fail, clonidine may be a more appropriate adjunctive agent to minimize negative neurodevelopmental impact. Consideration of the available data allows hospitals to generate effective pharmacologic strategies to manage NAS while further research continues.