Factors that affect the state of lung development at birth include prematurity, maternal diabetes, and genetic factors (white race, history of RDS in siblings, male sex). Thoracic malformations that cause lung hypoplasia, such as diaphragmatic hernia, may also increase the risk of surfactant deficiency. Genetic disorders of surfactant production and metabolism include surfactant protein B and surfactant protein C gene mutations, and mutations of the ABCA3 gene, whose product is an adenosine triphosphate (ATP)-binding cassette transporter localized to the lamellar bodies of alveolar type II cells. These rare disorders cause a severe RDS-like picture, often in term infants, and are usually fatal without lung transplantation.

Factors that may acutely impair surfactant production, release, or function include perinatal asphyxia in premature infants and cesarean section without labor. Infants delivered before labor starts do not benefit from the adrenergic and steroid hormones released during labor, which increase surfactant production and release. As a result, RDS may be seen in late preterm or early term infants delivered by elective cesarean section.

Assessment of fetal lung maturity (FLM). Prenatal prediction of lung maturity can be made by testing amniotic fluid obtained by amniocentesis.

Antenatal corticosteroid therapy should be given to pregnant women 24 to 34 weeks’ gestation with intact membranes or with preterm rupture of the membranes (ROM) without chorioamnionitis who are at high risk for preterm delivery within the next 7 days. The efficacy of treatment at gestational ages earlier than 24 weeks is uncertain; however, administration below this age may be reasonable depending upon clinical circumstances. This strategy induces surfactant production and accelerates maturation of the lungs and other fetal tissues, resulting in a substantial reduction of RDS, intraventricular hemorrhage (IVH), necrotizing enterocolitis (NEC), and perinatal mortality. A full course consists of two doses of betamethasone (12 mg IM) separated by a 24-hour interval, or four doses of dexamethasone (6 mg IM) at 12-hour intervals, although incomplete courses may improve outcome. Contraindications to treatment include chorioamnionitis or other indications for immediate delivery. Most studies suggest that betamethasone may be preferable because of potential neurotoxicity of dexamethasone. However, the only randomized trial (Betacode trial) comparing both drugs found no difference in most outcomes, except that the rate of IVH and brain lesions was higher in infants exposed to betamethasone.

Delivery of oxygen should be sufficient to meet target saturation values, although the range of optimal oxygenation is uncertain. For infants who require supplemental oxygen, one approach is to target SpO₂ in the 88% to 92% range for infants less than 30 weeks’ gestation or 1,250 g (set monitor alarm limits 85%—95%). For infants 30 weeks’ gestation or more, or when infants reach 30 weeks’ postmenstrual age, target SpO₂ from 88% to 95% (set alarm limits 85%—97%). If these targets are maintained, arterial PO₂ rarely will exceed 90 mm Hg. (see Chap. 30, Section II.D.1.c. Targeted saturation values). Higher than necessary fractional concentration of inspired oxygen (FiO₂) levels should be avoided because of the danger of potentiating the development of lung injury and retinopathy of prematurity. The oxygen is warmed, humidified, and delivered through an air-oxygen blender that allows precise control over the oxygen concentration. For infants with acute RDS, oxygen is ordered by concentration to be delivered to the infant’s airway, not by flow, and oxygen concentration is checked at least hourly. It should be titrated to the targeted oxygen saturation, which should be monitored continuously. When hand ventilation is required during suctioning of the airway, during insertion of an endotracheal tube, or during an apneic spell, the oxygen concentration should be similar to that before bagging to avoid hyperoxia and should be adjusted in response to continuous monitoring.

Blood gas monitoring (see Chap. 30). During the acute stages of illness, frequent sampling may be required to maintain arterial blood gases within appropriate ranges. Arterial blood gases (arterial oxygen tension [PaO₂], arterial carbon dioxide tension [PaCO₂], and pH) should be measured 30 minutes after changes in respiratory therapy, such as alteration in the FiO₂ or ventilator settings. We use indwelling arterial catheters for this purpose. To monitor trends in oxygenation continuously, we use pulse oximeters. In more stable infants, capillary blood from warmed heels may be adequate for monitoring PaCO₂ and pH.

Indications. We begin continuous positive airway pressure (CPAP) therapy as soon as possible after birth in infants with RDS, including those at extremely low gestational age (see Chap. 29). Although both the CPAP or Intubation at Birth (COIN) and Surfactant, Positive Pressure, and Oxygenation Randomized Trial (SUPPORT) trials found that the rate of death or bronchopulmonary dysplasia (BPD) was not different between groups that received early CPAP or surfactant treatment, infants in the nasal CPAP group required less mechanical ventilation. The rate of pneumothorax was higher in the CPAP infants in the COIN trial, but not in SUPPORT trial. In infants with RDS, CPAP appears to help prevent atelectasis, thereby minimizing lung injury and preserving the functional properties of surfactant, and allowing reduction of oxygen concentration as the
PaO₂ rises. Infants who fail early nasal CPAP and require intubation are typically extremely immature or those with severe respiratory distress, who require FiO₂ higher than 0.4 or 0.5 to maintain the targeted oxygen saturation, and have PaCO₂ greater than 55 to 60 mm Hg. Infants with RDS who require intubation and mechanical ventilation should be treated with surfactant.

If CPAP enables the infant to inspire on a more compliant portion of the pressure—volume curve, PaCO₂ may fall. However, minute ventilation may decrease on CPAP, particularly if the distending pressure is too great. We obtain a chest radiograph before or soon after starting CPAP to confirm the diagnosis of RDS and to exclude disorders in which this type of therapy should be approached with caution, such as air leak.

Methods of administering CPAP. We usually begin CPAP through nasal prongs using a continuous-flow ventilator. We generally start at a pressure of 5 to 7 cm H₂O, using a flow high enough to avoid rebreathing (5—10 L/minute), then adjust the pressure in increments of 1 to 2 cm H₂O to a maximum of 8 cm H₂O, observing the baby’s respiratory rate and effort and monitoring oxygen saturation. An orogastric tube is placed to decompress swallowed air. Simpler CPAP delivery devices utilizing tubing submerged in sterile water to deliver the desired distending pressure (“bubble” CPAP) can also be used and may have some benefits over a continuous-flow ventilator. Variable flow CPAP devices that reduce the work of breathing, especially during expiration, are available, although significant longterm clinical benefits have not been observed with their use.

Weaning. As the infant improves, we reduce the FiO₂ in decrements of 0.05 to maintain the targeted oxygen saturation. Generally, when FiO₂ is <0.30, CPAP can be reduced to 5 cm H₂O, monitoring oxygen saturation. Physical examination will provide evidence of respiratory effort during weaning, and chest radiographs may help estimate lung volume. Lowering of the distending pressure should be attempted with caution if lung volume appears low and alveolar atelectasis persists. We generally discontinue CPAP if there is no distress and if the FiO₂ remains <0.3.