Respiratory Distress Syndrome in Neonates

(Hyaline Membrane Disease)

ByArcangela Lattari Balest, MD, University of Pittsburgh, School of Medicine
Reviewed/Revised Jul 2023
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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. Symptoms and signs include grunting respirations, use of accessory muscles, and nasal flaring appearing soon after birth. Diagnosis is clinical; prenatal risk can be assessed with tests of fetal lung maturity. Treatment is surfactant therapy and supportive care.

(See also Overview of Perinatal Respiratory Disorders.)

Extensive physiologic changes accompany the birth process, sometimes unmasking conditions that posed no problem during intrauterine life. For that reason, a person with neonatal resuscitation skills must attend each birth. Gestational age and growth parameters help identify the risk of neonatal pathology.

Etiology of 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. Other risk factors include multifetal pregnancies, maternal diabetes, and being a White male.

Risk decreases with fetal growth restriction, preeclampsia or eclampsia, maternal hypertension, 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.

Pathophysiology of Respiratory Distress Syndrome in Neonates

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, and CO2 retention and respiratory acidosis develop.

Complications of RDS

Complications of RDS include intraventricular hemorrhage, periventricular white matter injury, tension pneumothorax, bronchopulmonary dysplasia, sepsis, and neonatal death. Intracranial complications have been linked to hypoxemia, hypercarbia, hypotension, swings in arterial blood pressure, and low cerebral perfusion (see Intracranial Hemorrhage).

Symptoms and Signs of Respiratory Distress Syndrome in Neonates

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 Respiratory Distress Syndrome in Neonates

  • Clinical evaluation

  • Arterial blood gases (hypoxemia and hypercapnia)

  • Chest x-ray

  • Blood, cerebrospinal fluid, and tracheal aspirate cultures

Diagnosis of RDS is by clinical presentation, including recognition of risk factors; arterial blood gases 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. Cerebrospinal fluid 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). Clinically, group B streptococcal pneumonia is extremely difficult to differentiate from RDS; thus, antibiotics should be started pending culture results.

Screening

Amniotic fluid tests include the

  • Lecithin/sphingomyelin ratio

  • Foam stability index test (the more surfactant in amniotic fluid, the greater the stability of the foam that forms when the fluid is combined with ethanol and shaken)

  • Surfactant/albumin ratio

Risk of RDS is low when lecithin/sphingomyelin ratio is > 2, phosphatidyl glycerol is present, foam stability index 47, or surfactant/albumin ratio is > 55 mg/g.

Diagnosis reference

  1. 1. Srinivasan L, Harris MC, Shah SS: Lumbar puncture in the neonate: Challenges in decision making and interpretation. Semin Perinatol 36(6):445–453, 2012. doi: 10.1053/j.semperi.2012.06.007

Treatment of Respiratory Distress Syndrome in Neonates

  • Intratracheal surfactant if indicated

  • Supplementary oxygen as needed

  • Mechanical ventilation as needed

Specific treatment of RDS is intratracheal surfactant therapy. This therapy requires endotracheal intubation, 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), even in very preterm infants (1). 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). 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).

Surfactant hastens recovery and decreases risk of pneumothorax, interstitial emphysema, intraventricular hemorrhage, bronchopulmonary dysplasia, and neonatal mortality in the hospital and at 1 year. Options for surfactant replacement include

is a lipid bovine lung extract supplemented with proteins B and C, colfosceril palmitate, palmitic acid, and tripalmitin.

is a modified porcine-derived minced lung extract containing phospholipids, neutral lipids, fatty acids, and surfactant-associated proteins B and C.

is a calf lung extract containing phospholipids, neutral lipids, fatty acids, and surfactant-associated proteins B and C.

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.

Treatment references

  1. 1. Blennow M, Bohlin K: Surfactant and noninvasive ventilation. Neonatology 107(4):330–336, 2015. doi: 10.1159/000381122

  2. 2. Bohlin K, Gudmundsdottir T, Katz-Salamon M, et al: Implementation of surfactant treatment during continuous positive airway pressure. J Perinatol 27(7):422–427, 2007. doi: 10.1038/sj.jp.7211754

  3. 3. Aldana-Aguirre JC, Pinto M, Featherstone RM, Kumar M: Less invasive surfactant administration versus intubation for surfactant delivery in preterm infants with respiratory distress syndrome: A systematic review and meta-analysis. Arch Dis Child Fetal Neonatal Ed 102(1):F17–F23, 2017. doi: 10.1136/archdischild-2015-310299

Prognosis for Respiratory Distress Syndrome in Neonates

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.

Prevention of Respiratory Distress Syndrome in Neonates

Preterm Labor.)

Neonates who completed < 30 weeks gestation, especially those who were not exposed to antenatal corticosteroids, are at high risk of developing RDS. Giving prophylactic intratracheal surfactant therapy to these neonates has been shown to decrease risk of neonatal death and certain forms of pulmonary morbidity (eg, pneumothorax).

Key Points

  • Respiratory distress syndrome (RDS) is caused by pulmonary surfactant deficiency, which typically occurs only in neonates born at < 37 weeks gestation; deficiency is worse with increasing prematurity.

  • With surfactant deficiency, alveoli close or fail to open, and the lungs become diffusely atelectatic, triggering inflammation and pulmonary edema.

  • In addition to causing respiratory insufficiency, RDS increases risk of intraventricular hemorrhage, tension pneumothorax, bronchopulmonary dysplasia, sepsis, and death.

  • Diagnose clinically and with chest x-ray; exclude pneumonia and sepsis by appropriate cultures.

  • Give respiratory support as needed and treat with intratracheal surfactant if the infant requires immediate intubation or has worsening respiratory status on nasal continuous positive airway pressure.

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