Respiratory Distress Syndrome in Neonates

Surfactant is not produced in adequate amounts until relatively late in gestation (34 to 36 weeks); thus, risk of respiratory distress syndrome (RDS) increases with decreasing gestational age. Although typically a disease of premature infants, even early term (37 weeks to 38 weeks 6 days) infants have a higher risk of RDS than infants born at 39 weeks gestational age or later (1).

More mature infants can also have surfactant deficiency because of mutations in genes encoding for surfactant proteins or proteins necessary for surfactant binding and transport (surfactant protein [SP-B and SP-C] and ATP-binding cassette transporter A3 [ABCA3] genes) or maternal disease such as diabetes (type 1, type 2, or gestational) (1, 2).

Other risk factors that have been reported for RDS include advanced maternal age, intrauterine distress, cesarean delivery, and male sex (3, 4).

Pulmonary surfactant is a mixture of phospholipids and lipoproteins secreted by type II pneumocytes (see Neonatal Pulmonary Function). It diminishes the surface tension of the water film that lines alveoli, thereby decreasing the tendency of alveoli to collapse and the work required to inflate them.

With surfactant deficiency, a greater pressure is needed to open the alveoli. Without adequate airway pressure, the lungs become diffusely atelectatic, triggering inflammation and pulmonary edema. Because blood passing through the atelectatic portions of lung is not oxygenated (forming a right-to-left intrapulmonary shunt), the infant becomes hypoxemic. Lung compliance is decreased, thereby increasing the work of breathing. In severe cases, the diaphragm and intercostal muscles fatigue, leading to hypoventilation, carbon dioxide retention, and respiratory acidosis.

Symptoms and signs of RDS include rapid, labored, grunting respirations appearing immediately or within a few hours after delivery, with suprasternal and substernal retractions and flaring of the nasal alae. As atelectasis and respiratory failure progress, symptoms worsen, with cyanosis, lethargy, irregular breathing, and apnea, and may ultimately lead to cardiac failure if adequate lung expansion, ventilation, and oxygenation are not established.

Neonates weighing < 1000 g may have lungs so noncompliant they are unable to initiate or sustain respirations in the delivery room.

On examination, breath sounds are decreased, and crackles may be heard.

• Arterial blood gases (hypoxemia and hypercapnia)

• Chest radiograph

• Blood, cerebrospinal fluid, and tracheal aspirate cultures

Diagnosis of RDS is by clinical presentation, including recognition of risk factors; arterial or capillary blood gases showing hypoxemia and hypercapnia; and chest radiograph. Chest radiograph shows diffuse atelectasis classically described as having a ground-glass appearance with visible air bronchograms and low lung expansion; appearance correlates loosely with clinical severity.

Respiratory Distress Syndrome in a Premature Neonate

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Steven Needell/SCIENCE SOURCE/SCIENCE PHOTO LIBRARY

Differential diagnosis includes:

• Bacterial pneumonia and sepsis

• Transient tachypnea of the newborn

• Persistent pulmonary hypertension of the newborn

• Aspiration

• Pulmonary edema

• Congenital cardiopulmonary anomalies

Neonates typically require blood cultures. Cerebrospinal fluid cultures are not routinely performed after birth because there is low incidence of meningitis associated with early-onset sepsis, but they may be performed in certain cases (eg, blood cultures are positive for gram-negative bacilli, concern of late-onset sepsis) (1). Clinically, group B streptococcal pneumonia is extremely difficult to differentiate from RDS; thus, antibiotics should be started empirically pending culture results.

• Surfactant if indicated

• Supplementary oxygen as needed

• Ventilatory support as needed, with a preference for noninvasive strategies

Specific treatment of RDS is surfactant therapy. This therapy may be delivered intratracheally with an endotracheal tube, but less-invasive surfactant administration (LISA) via a small catheter inserted into the trachea is also acceptable. Surfactant may also be administered via supraglottic or laryngeal mask airway (1–3).

Surfactant hastens recovery and decreases risk of pneumothorax, pulmonary interstitial emphysema, intraventricular hemorrhage, bronchopulmonary dysplasia, and neonatal mortality in the hospital and at age 1 year (4). Options for surfactant replacement include bovine- and porcine-derived as well as synthetic products.

Surfactant may be administered prophylactically (eg, given to all infants below a certain gestational age) or selectively (eg, given only to infants who require intubation). Criteria for administration are highly center-specific.

Less-invasive ventilation techniques, such as nasal continuous positive airway pressure (CPAP) or noninvasive or nasal intermittent positive pressure ventilation (NIPPV), are preferred because of the decreased risk of death and development of bronchopulmonary dysplasia, even in very preterm infants (1, 2, 5–7). However, mechanical ventilation is still required in some for adequate ventilation and/or oxygenation.

Lung compliance can improve rapidly after therapy. If the neonate is mechanically ventilated, the ventilator peak inspiratory pressure may need to be lowered rapidly to reduce risk of a pulmonary air leak. Other ventilator parameters (eg, fraction of inspired oxygen [FIO2], rate) also may need to be reduced.

Prognosis with treatment is good; mortality in the United States was approximately 6% in 2014 (1). With adequate ventilatory support alone, surfactant production eventually begins, and once production begins, RDS resolves within 4 or 5 days. However, in the meantime, severe hypoxemia can result in multiple organ failure and death.

A greater degree of prematurity is associated with higher risk of bronchopulmonary dysplasia (chronic lung disease of prematurity) (2).

When a fetus must be delivered before 34 weeks gestation, giving the pregnant patient betamethasone or dexamethasone before delivery induces fetal surfactant production and reduces the risk of RDS or decreases its severity (When a fetus must be delivered before 34 weeks gestation, giving the pregnant patient betamethasone or dexamethasone before delivery induces fetal surfactant production and reduces the risk of RDS or decreases its severity (1). (See Preterm Labor.)

Neonates born at < 30 weeks gestation, especially those who were not exposed to antenatal glucocorticoids, are at high risk of developing RDS. Along with noninvasive ventilatory strategies, including CPAP, early selective surfactant therapy (provided within 1 to 2 hours after birth to infants showing signs of RDS) seems superior from an efficacy and adverse effect perspective to universal prophylactic surfactant administration based on gestational age alone (2–6).