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 greater prematurity Preterm Infants An infant born before 37 weeks gestation is considered preterm. Prematurity is defined by the gestational age at which infants are born. Previously, any infant weighing < 2.5 kg was termed... read more . Other risk factors include multifetal pregnancies Multifetal Pregnancy Multifetal pregnancy is presence of > 1 fetus in the uterus. Multifetal (multiple) pregnancy occurs in up to 1 of 30 deliveries. Risk factors for multiple pregnancy include Ovarian stimulation... read more , maternal diabetes Diabetes Mellitus in Pregnancy Pregnancy aggravates preexisting type 1 (insulin-dependent) and type 2 (non–insulin-dependent) diabetes but does not appear to exacerbate diabetic retinopathy, nephropathy, or neuropathy ( 1)... read more , and being a white male.

Risk decreases with fetal growth restriction, preeclampsia or eclampsia Preeclampsia and Eclampsia Preeclampsia is new-onset or worsening of existing hypertension with proteinuria after 20 weeks gestation. Eclampsia is unexplained generalized seizures in patients with preeclampsia. Diagnosis... read more , maternal hypertension Hypertension in Pregnancy Recommendations regarding classification, diagnosis, and management of hypertensive disorders (including preeclampsia) are available from the American College of Obstetricians and Gynecologists... read more , prolonged rupture of membranes, and maternal corticosteroid use.

Rare cases are hereditary, caused by mutations in surfactant protein (SP-B and SP-C) and ATP-binding cassette transporter A3 (ABCA3) genes.

Pulmonary surfactant is a mixture of phospholipids and lipoproteins secreted by type II pneumocytes (see Neonatal pulmonary function Neonatal Pulmonary Function The transition from life in utero to life outside the womb involves multiple changes in physiology and function. See also Perinatal Problems. (See also Liver Structure and Function and Neonatal... read more ). 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 Pulmonary Edema Pulmonary edema is acute, severe left ventricular failure with pulmonary venous hypertension and alveolar flooding. Findings are severe dyspnea, diaphoresis, wheezing, and sometimes blood-tinged... read more . 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, and CO2 retention and respiratory acidosis Respiratory Acidosis Respiratory acidosis is primary increase in carbon dioxide partial pressure (Pco2) with or without compensatory increase in bicarbonate (HCO3⁻); pH is usually low but may be near... read more develop.

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 stiff that they are unable to initiate or sustain respirations in the delivery room.

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

Diagnosis of RDS is by clinical presentation, including recognition of risk factors; ABGs showing hypoxemia and hypercapnia; and chest x-ray. Chest x-ray 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.

Differential diagnosis includes

Neonates typically require cultures of blood. CSF cultures are not routinely done after birth because there is low incidence of meningitis associated with early-onset sepsis, but they may be done in certain cases (eg, blood cultures are positive for gram-negative bacilli, concern of late-onset sepsis) (1 Diagnosis reference Respiratory distress syndrome is caused by pulmonary surfactant deficiency in the lungs of neonates, most commonly in those born at < 37 weeks gestation. Risk increases with degree of prematurity... read more ). Clinically, group B streptococcal pneumonia is extremely difficult to differentiate from RDS; thus, antibiotics should be started pending culture results.

Prognosis with treatment is excellent; mortality is < 10%. 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. Greater prematurity is associated with higher risk of chronic lung disease, bronchopulmonary dysplasia, or both.

Specific treatment of RDS is intratracheal surfactant therapy. This therapy requires endotracheal intubation Mechanical Ventilation Initial stabilization maneuvers include mild tactile stimulation, head positioning, and suctioning of the mouth and nose followed as needed by Supplemental oxygen Continuous positive airway... read more , which also may be necessary to achieve adequate ventilation and oxygenation.

There is increasing evidence supporting use of less invasive ventilation techniques, such as nasal continuous positive airway pressure (CPAP Continuous Positive Airway Pressure (CPAP) Initial stabilization maneuvers include mild tactile stimulation, head positioning, and suctioning of the mouth and nose followed as needed by Supplemental oxygen Continuous positive airway... read more ), even in very premature infants (1 Treatment references Respiratory distress syndrome is caused by pulmonary surfactant deficiency in the lungs of neonates, most commonly in those born at < 37 weeks gestation. Risk increases with degree of prematurity... read more ). Infants with RDS who are receiving nasal CPAP and who need an increasing fraction of inspired oxygen (FIO2) have been shown to benefit from brief intubation to deliver surfactant followed by immediate extubation (1 Treatment references Respiratory distress syndrome is caused by pulmonary surfactant deficiency in the lungs of neonates, most commonly in those born at < 37 weeks gestation. Risk increases with degree of prematurity... read more ). Administration of intratracheal surfactant via a thin catheter is a newer technique that has also been shown to be beneficial in reducing the risk of BPD. Both of these techniques show a trend toward fewer cases of BPD but not fewer days of mechanical ventilation (2, 3 Treatment references Respiratory distress syndrome is caused by pulmonary surfactant deficiency in the lungs of neonates, most commonly in those born at < 37 weeks gestation. Risk increases with degree of prematurity... read more ).

Surfactant hastens recovery and decreases risk of pneumothorax Pneumothorax Pulmonary air-leak syndromes involve dissection of air out of the normal pulmonary airspaces. (See also Overview of Perinatal Respiratory Disorders.) Extensive physiologic changes accompany... read more , interstitial emphysema Pulmonary interstitial emphysema (PIE) Pulmonary air-leak syndromes involve dissection of air out of the normal pulmonary airspaces. (See also Overview of Perinatal Respiratory Disorders.) Extensive physiologic changes accompany... read more , intraventricular hemorrhage Intraventricular hemorrhage and/or intraparenchymal hemorrhage The forces of labor and delivery occasionally cause physical injury to the infant. The incidence of neonatal injury resulting from difficult or traumatic deliveries is decreasing due to increasing... read more , bronchopulmonary dysplasia Bronchopulmonary Dysplasia (BPD) Bronchopulmonary dysplasia is chronic lung disease of the neonate that typically is caused by prolonged ventilation and is further defined by age of prematurity and extent of supplemental oxygen... read more , and neonatal mortality in the hospital and at 1 year. Options for surfactant replacement include

Beractant is a lipid bovine lung extract supplemented with proteins B and C, colfosceril palmitate, palmitic acid, and tripalmitin; dose is 100 mg/kg every 6 hours as needed up to 4 doses.

Poractant alfa is a modified porcine-derived minced lung extract containing phospholipids, neutral lipids, fatty acids, and surfactant-associated proteins B and C; dose is 200 mg/kg followed by up to 2 doses of 100 mg/kg 12 hours apart as needed.

Calfactant is a calf lung extract containing phospholipids, neutral lipids, fatty acids, and surfactant-associated proteins B and C; dose is 105 mg/kg every 12 hours up to 3 doses as needed.

Lucinactant is a synthetic surfactant with a pulmonary surfactant protein B analog, sinapultide (KL4) peptide, phospholipids, and fatty acids; dose is 175 mg/kg every 6 hours up to 4 doses.

Animal-derived surfactants are generally considered superior to synthetic ones.

Lung compliance can improve rapidly after therapy. The ventilator peak inspiratory pressure may need to be lowered rapidly to reduce risk of a pulmonary air leak. Other ventilator parameters (eg, FIO2, rate) also may need to be reduced.

When a fetus must be delivered between 24 weeks and 34 weeks, giving the mother 2 doses of betamethasone 12 mg IM 24 hours apart or 4 doses of dexamethasone 6 mg IV or IM every 12 hours at least 48 hours before delivery induces fetal surfactant production and reduces the risk of RDS or decreases its severity. ( See Preterm Labor Preterm Labor Labor (contractions resulting in cervical change) that begins before 37 weeks gestation is considered preterm. Risk factors include prelabor rupture of membranes, uterine abnormalities, infection... read more .)

Prophylactic intratracheal surfactant therapy given to neonates who are at high risk of developing RDS (infants < 30 weeks completed gestation especially in absence of antenatal corticosteroid exposure) has been shown to decrease risk of neonatal death and certain forms of pulmonary morbidity (eg, pneumothorax Pneumothorax Pulmonary air-leak syndromes involve dissection of air out of the normal pulmonary airspaces. (See also Overview of Perinatal Respiratory Disorders.) Extensive physiologic changes accompany... read more ).