This article describes the special risk of respiratory syncytial virus (RSV) in late preterm infants. The term "late preterm" was adopted for infants born between 34 and 36 6/7 weeks gestational age (GA) at a 2005 workshop of the National Institute of Child Health and Human Development (Engle, 2006). These infants had been previously referred to as "near-term" or "slightly premature," which did not adequately reflect the fact that they were, indeed, premature infants with special needs. Currently, this group is receiving attention due to the mounting evidence that the number of late preterm infants is increasing, and their outcomes are less than optimal (Engle, Tomashek, & Wallman, 2007; Yoder, Gordon, & Barth, 2008).

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The U.S. preterm birth rate (<==37 weeks GA) is currently 12.7%; the late preterm birth rate, which had climbed more than 25% since 1990, is 9.03% (Hamilton, Martin, & Ventura, 2009). Late preterm infants are physiologically immature, but because their physical appearance is more like term infants than extremely premature infants, parents and nurses may treat these infants as if they are developmentally mature (Hubbard, Stellwagen, & Wolf, 2007). However, late preterm infants are vulnerable to a variety of illnesses and developmental risks, primarily because they are deprived of the last few weeks of development in utero. These infants have higher rates of mortality and morbidity at birth and are more frequently readmitted to the hospital during the neonatal period (Shapiro-Mendoza et al., 2006). Late preterm infants experience more complications after birth than term infants, including temperature instability, hypoglycemia, and respiratory distress (Table 1) (Engle et al., 2007; Hubbard et al.; Raju, Higgins, Start, & Leveno, 2006). They may require hospital readmission for dehydration due to feeding difficulties and for hyperbilirubinemia, and they also receive more medical interventions such as laboratory tests to evaluate sepsis or jaundice and therapies such as intravenous infusions and drugs (Raju et al.). One study found that late preterm infants who are at special risk for complications include those being breastfed at discharge (due to risk of dehydration), firstborn infants, infants whose mothers experienced labor and delivery complications, infants whose mothers are of Asian/Pacific Islander descent, and recipients of public insurance (Shapiro-Mendoza et al.). Additional risk factors in this age group are birth date within 10 weeks of start of RSV season, siblings, sex, and family members with atopy (Simoes et al., 2009).

Table 1. Health Complications Common to Late Preterm Infants

Respiratory Physiology for Late Preterm Infants

Lung development is not completed at the end of pregnancy, but continues through 3 years of age (Martin, Fanaroff, & Walsh, 2006). Beginning with the saccular stage (24—38 weeks GA), the terminal respiratory units of the lung are formed. During the alveolar stage (36 weeks GA to 2 years) capillaries grow into each terminal sac or alveoli, and surfactant levels gradually increase to adult values. The late preterm infant may experience respiratory complications caused by inadequate surfactant, immature pulmonary vascularization leading to fluid retention, and impaired gas exchange, which relate to immature lung structure (Engle et al., 2007). The late preterm infant also suffers from an immature immune system, putting the infant at increased risk for RSV and other infections, for immaturity of natural killer cells and leukocytes has been documented in this group of infants (Martin et al.).

Immunity is further compromised by incomplete transfer of maternal antibodies to the late preterm infant. Because 36 weeks GA is the time when significant transfer of IgG antibodies takes place, infants born before that age have less resistance to disease (Hanson, Korotkova, & Lundin, 2003). If the preterm infant is not breastfed, immunity issues can represent additional risk, for breastfed infants receive benefits in terms of immunity due to transfer of IgA, IgG, and IgM, as well as T and B lymphocytes in the breast milk (Hanson et al.). However, the late preterm infant may have a weak suck and other difficulties in feeding, reducing exposure to breast milk (Hanson et al.).

RSV Infection

RSV accounts for 80% of childhood bronchiolitis and 50% of childhood pneumonia (Pickering, Baker, Long, & McMillan, 2006). This illness has nearly nine times the mortality of influenza and is a leading viral cause of infant death (Thompson et al., 2003). In addition, RSV lower respiratory tract infection has been found to be a risk factor for asthma and wheezing later in childhood (Sorce, 2009).

The pathophysiology of RSV involves the replication of RNA in the respiratory epithelium; viral RNA enters the cytoplasm of infected respiratory epithelial cells, accompanied by enzymes that produce more viral RNA as well as G and F proteins. Attachment (G) proteins promote adherence of the virus within host cells, and fusion (F) proteins promote penetration of the virus from infected cells into adjacent healthy cells. As adjacent cells become infected, membranes between cells merge. This allows for rapid cell-to-cell transmission of the RSV virus, creating large, multinucleated cells called syncytia. Rapid fusion and destruction of ciliated epithelial cells causes the mucus, edema, and bronchoconstriction that are characteristic of RSV infection. Mucus plugs may completely obstruct terminal bronchioles and extend into the alveoli (Welliver, 2004). The spread of infection is compounded by the fact that cell-to-cell transmission allows RSV to spread without contacting antibodies in nasal secretions that are stored within the airways (Pickering et al., 2006).

Entry of the virus is via the eye, nose, or mouth, and the incubation period ranges from 2 to 8 days. RSV infection does not spread beyond the respiratory tract. If epithelial destruction is limited to upper airway cells, then symptoms are those of a severe upper respiratory tract infection. However, in an immunocompromised, previously uninfected individual (such as a late preterm infant) RSV infection often travels to the lower airways, producing typical signs of a lower respiratory tract infection (Black, 2003). RSV disease in infants most often manifests as bronchiolitis, an acute viral infection of the lower respiratory tract.

RSV outbreaks tend to be seasonal, occurring between November and April, but can occur at any time of the year. RSV is transmitted by aerosolized droplets and direct contact with secretions or contaminated surfaces. Touching, kissing, and other personal contact can spread the virus, as well as exposure to droplets after sneezing or coughing. Live viruses can remain on environmental surfaces such as toys, stethoscopes, or counter tops for several hours and on facial tissue or cloth for up to 30 minutes. Touching contaminated surfaces or contaminating clothing with mucus can quickly spread disease (Hall, 2000).

RSV-infected individuals shed the virus within 1 day of being infected, which is often before the onset of major symptoms. The duration of viral shedding is highly variable; adults may shed for only a few days, whereas infants younger than 6 months may shed the virus for up to 6 months. Other variables that prolong viral shedding are severity of infection and immunocompromised status (Hall, 2000).

For most term infants, symptoms of RSV infection are limited to the upper respiratory tract, resembling a common cold. Signs and symptoms of RSV infection typically begin 4 to 6 days after exposure and begin with rhinorrhea, nasal congestion, and cough. By day 5, the infection spreads to the lower respiratory tract causing mild, moderate, or severe respiratory distress. Mild-to-moderate RSV disease begins with low-grade fever, rhinorrhea, coughing, ear infection, and moderate tachypnea. The infant appears irritable and has poor feeding. Severe infection may involve tachypnea, tachycardia, cyanosis, diminished breathing sounds, wheezing, cough, nasal flaring, retraction, and listlessness. Poor gas exchange sets off a downward spiral in the infant's condition, including hypoxia, increased respiratory effort, decreased energy to feed and rest, and dehydration (Peer-Point Medical Education Institute, 2008a).

Physical examination is the most important diagnostic tool, augmented by laboratory evaluation. Using direct fluorescent-antibody (DFA) staining or enzyme immunoassay on loose secretions, test results can be determined quickly, in approximately 1 hour (Pickering et al., 2006). Chest X-ray and pulse oximetry also aid with the diagnosis.

Although most previously healthy full-term infants with an upper airway RSV infection will not require hospitalization, preterm infants are a higher risk group, and often need to be hospitalized (Horn & Smout, 2003; Long, 2008). Low birth weight and prematurity significantly increase the risk of RSV-associated mortality, as found by Leader and Kohlhase (2003), who showed that prematurity and low birth weight, with and without comorbidities, were significant risk factors for death from RSV disease. With comorbidities such as low Apgar score and mechanical ventilation, infants born =35 weeks GA had a mortality of 39 per 100,000 compared with a rate of 6.8 per 100,000 in infants =37 weeks GA. Without comorbidities, the risk of RSV-related death was still significantly higher for infants =35 weeks GA (27.4 per 100,000) compared with infants =37 weeks GA (5.4 per 100,000).

Respiratory Distress and RSV Infection in the Late Preterm Infant

Respiratory distress may be the most dangerous complication experienced by late preterm infants. Engle et al. (2007) summarized research findings showing that the rates of respiratory distress in late preterm infants ranged from 3.6% to 28.9%, whereas rates in term infants were 0.6% to 4.2%. The cause and incidence of respiratory morbidity was further described by Yoder et al. (2008), who showed that more late preterm infants experienced respiratory distress syndrome, transient tachypnea of the newborn, and other respiratory complications than term or postterm infants.

The increased risk of respiratory disease in late preterm infants can be attributed primarily to three factors: (a) underdeveloped lungs, (b) an immature immune system, and (c) incomplete transfer of maternal antibodies (Engle et al., 2007; Hanson et al., 2003; Peer-Point Medical Education Institute, 2008b). Horn and Smout (2003) have shown that late preterm infants are at greater risk from RSV disease than term infants and that they have hospital outcomes as bad or worse than more premature infants born =32 weeks GA.

Chest X-ray may show air trapping and atelectasis or consolidation. Signs of hypoxia and respiratory distress include cyanosis, vomiting, retractions, nasal flaring, and coughing followed by dyspnea. Preterm infants are particularly at risk for apnea, which may precede other RSV symptoms and is associated with immaturity of the respiratory control center (Horn & Smout, 2003).

Treatment depends upon the extent of illness. Most hospitalized infants improve with supportive care, with the average length of stay being less than 5 days (Pickering et al., 2006), although late preterm infants may require longer hospitalization. Extreme hypoxemia can result in respiratory failure, requiring airway intubation early in the course of illness. Likewise, apnea as a presenting sign often necessitates mechanical ventilation and oxygen administration.

In addition to the physical and emotion toll of RSV, severe RSV illness can create an economic burden for families and society. Robinson (2008) noted that for one hospital admission, the total average economic burden was $2135 for full-term infants and $4517 for preterm infants. The annual costs of RSV-associated hospitalizations in the United States have been estimated at $1.1 billion.

The key to treatment of severe RSV infection in the late preterm infant, as for all infants, is supportive nursing care, as outlined in Table 2. When an infant is admitted to the pediatric unit, the nurse monitors the progression of illness carefully. Initially, it is difficult to predict whether an infant's condition will stabilize with treatment, or will progress to respiratory failure. Frequent nasal suctioning is required to prevent airway obstruction by thick mucus. Attention to fluid status is important, for infants in respiratory distress are made NPO and started on intravenous fluids. Temperature must be stabilized and late preterm infants may need environmental support by use of an incubator. Oxygen is administered to infants with oxygen saturations less than 90% or signs of respiratory distress. As infants recover, oxygen is weaned and feedings are gradually resumed (AAP, 2006; Cooper, Banasiak, & Allen, 2003).

Table 2. Supportive Nursing Care for Late Preterm Infants With RSV Infection

When bronchiolitis occurs in the RSV-infected late preterm infant, the treatment should be based on the American Academy of Pediatrics clinical practice guidelines for the management of bronchiolitis (AAP, 2006), including:

1. Ribavirin use is not routinely recommended as an antiviral treatment for RSV bronchiolitis, but has been found to reduce the duration of mechanical ventilation and days of hospitalization in critically ill patients. Ventre and Randolph (2008) concluded that clinical trials of Ribavirin have lacked sufficient power to provide reliable estimates of its effects as a treatment modality. Experts agree that Ribavirin should be used only in infants with life-threatening degrees of bronchiolitis (Ventre & Randolph; Welliver, 2004). The aerosol route of administration presents potential toxic exposure to healthcare professionals, and nurses who are pregnant should not care for patients receiving this drug (Lehne, 2007).

2. Bronchodilators may be considered for children with mild-to-moderate bronchiolitis. Providers should monitor effectiveness closely, and continue only if the infant's condition improves. Because infants' airways are so small, effectiveness may be limited (Black, 2003).

3. Chest physiotherapy is not effective in clearing the airway in bronchiolitis (AAP, 2006).

4. Corticosteroids are not recommended. Steroids have been shown to have little or no benefit in treating infants with RSV bronchiolitis (Black, 2003).

5. Antimicrobial agents are indicated only for infants at special risk for bacterial lung infection. The incidence of bacterial pneumonia is increased 30% to 50% in infants who require mechanical ventilation. Therefore, antibiotics may be indicated in these patients (Pickering et al., 2006).

Nurses can access current treatment guidelines through the resources suggested in the Online Resources for Clinical Practice Guidelines box.

Home Care

When late preterm infants are discharged from the hospital after RSV infection, it will likely be after oxygen has been discontinued. Even after hospital discharge, however, RSV symptoms may persist, for infants shed the virus for a few weeks, and upper airway symptoms such as mucus and cough often continue. Nurses should be aware of the many issues that parents need to be educated about before their infant is discharged: how to use a bulb suction, how to assess respiratory status, and how to perform CPR. Also, due to the late preterm infant's immature lung development, parents may need to limit their infant's time spent in an upright position, including infant seats and swings (Hubbard et al., 2007). They need to make sure that the infant receives adequate nutrition and sleep, and everyone who interacts with the infant should learn appropriate handwashing practices. Because late preterm infants have an immature immune system, they are at greater risk for infection and should not be exposed to sick people. Additionally, parents need to learn when they should call the primary provider versus take the infant to the emergency department. Follow-up with the primary care provider should be emphasized, probably within a few days of discharge.

Prevention of RSV Infection

All high-risk infants hospitalized with RSV should be evaluated to determine if they meet criteria for RSV prophylaxis with palivizumab in the future. Late preterm infants with chronic lung disease or heart disease may meet eligibility criteria (AAP, 2006). Infants who are already on prophylaxis programs should continue monthly injections. Infants who are newly qualified may begin a prophylaxis program in the hospital, by receiving the first injection shortly before discharge. The primary nurse, social worker, or case manager should arrange for follow-up care in the community, in consultation with the primary care provider. Referral to a clinic for prophylaxis often requires a prior authorization and specialized referral, for the cost of palivizumab (Synagis) is significant.

Prevention of severe RSV infection during the winter months is now a practical reality with the development of palivizumab (Synagis), an antibody given by monthly intramuscular injections. This antibody provides passive immunity, and regular injections must be received to maintain adequate antibody titer levels, preventing infection in high-risk infants. Studies have shown that palivizumab is cost-effective for infants born at 32 to 35 weeks gestations with at least a moderate level of risk (Lanctot et al., 2008). The American Academy of Pediatrics Red Book 2006 Guidelines (AAP, 2006) regarding eligibility for palivizumab prophylaxis apply to late preterm infants with the following conditions:

High-risk infants should be referred to community prophylaxis programs by their primary providers or case managers, and tracked throughout the year by outpatient clinic staff (Coffman, Peck, & Rasmussen, 2001). In one clinic's experience, infants and families who needed extra tracking were those whose insurance termed, families relocated, or families had transportation issues (Coffman et al.). Infants who require hospital admission for non-RSV-related problems such as hernia repair may be able to receive a monthly palivizumab injection during the hospitalization, if their condition permits. The goal is to maintain the infant's monthly scheduled injection. Keeping infants on schedule with their monthly injections is critical to maintaining RSV antibody levels that protect them against RSV disease.

Conclusion

Study of the unique characteristics of late preterm infants is becoming more focused, and literature on the care of this special population is expanding (Engle et al., 2007; Hubbard et al., 2007). The vulnerability of these infants challenges nurses to critically assess their needs and to work toward preventing RSV and other illnesses. This article has focused on RSV illness in the late preterm infant, addressing the hospital, home, and clinic care as well as prevention of RSV. The importance of supportive nursing care cannot be overestimated in restoring health to infants with moderate or severe disease. Nurses should also be aware of the current clinical practice guidelines for care of RSV bronchiolitis. Several resources are suggested that can be utilized by nurses to maintain current knowledge of changing guidelines.