Merck Manual

Please confirm that you are a health care professional

honeypot link

Respiratory Distress Syndrome in Neonates

(Hyaline Membrane Disease)

By

Arcangela Lattari Balest

, MD, University of Pittsburgh, School of Medicine

Reviewed/Revised Jul 2023
View PATIENT EDUCATION

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.

Etiology of Respiratory Distress Syndrome in Neonates

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 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 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 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.

Complications of RDS

Complications of RDS include 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 Intraventricular hemorrhage and/or intraparenchymal hemorrhage , periventricular white matter injury, tension pneumothorax Pneumothorax (Tension) Tension pneumothorax is accumulation of air in the pleural space under pressure, compressing the lungs and decreasing venous return to the heart. (See also Overview of Thoracic Trauma.) Tension... read more Pneumothorax (Tension) , 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 degree of prematurity and extent of supplemental... read more Bronchopulmonary Dysplasia (BPD) , sepsis Neonatal Sepsis Neonatal sepsis is invasive infection, usually bacterial, occurring during the neonatal period. Signs are multiple, nonspecific, and include diminished spontaneous activity, less vigorous sucking... read more , and neonatal death. Intracranial complications have been linked to hypoxemia, hypercarbia, hypotension, swings in arterial blood pressure, and low cerebral perfusion (see Intracranial Hemorrhage Intracranial 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 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 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.

Screening

RDS can be anticipated prenatally using tests of fetal lung maturity, which are done on amniotic fluid obtained by amniocentesis or collected from the vagina (if membranes have ruptured) and which can help determine the optimal timing of delivery. These are indicated for elective deliveries before 39 weeks when fetal heart tones, human chorionic gonadotropin levels, and ultrasound measurements cannot confirm gestational age and for nonelective deliveries between 34 weeks and 36 weeks.

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. 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

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 preterm 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 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 , 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 ).

  • Beractant

  • Poractant alfa

  • Calfactant

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

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

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

  • 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. 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

When a fetus must be delivered between 24 weeks and 34 weeks, giving the mother betamethasone or dexamethasone 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 .)

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 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 ).

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.

  • If preterm delivery is anticipated, assess lung maturity by testing amniotic fluid for lecithin/sphingomyelin ratio, foam stability, or the surfactant/albumin ratio.

  • Give the mother several doses of a parenteral corticosteroid (betamethasone, dexamethasone) if time allows and she must deliver between 24 weeks and 34 weeks gestation; corticosteroids induce fetal surfactant production and reduce the risk and/or severity of RDS.

  • 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.

Drugs Mentioned In This Article

Drug Name Select Trade
Novarel, Ovidrel, Pregnyl
Survanta
Curosurf
Infasurf
Adbeon, Alphatrex, Beta 1 Kit, Beta Derm , Betanate , Betatrex, Beta-Val, BSP 0820, Celestone, Del-Beta , Diprolene, Diprolene AF, Diprosone, Luxiq Foam, Maxivate, ReadySharp Betamethasone, Sernivo, Valisone
AK-Dex, Baycadron, Dalalone, Dalalone D.P, Dalalone L.A, Decadron, Decadron-LA, Dexabliss, Dexacort PH Turbinaire, Dexacort Respihaler, DexPak Jr TaperPak, DexPak TaperPak, Dextenza, DEXYCU, DoubleDex, Dxevo, Hemady, HiDex, Maxidex, Ocu-Dex , Ozurdex, ReadySharp Dexamethasone, Simplist Dexamethasone, Solurex, TaperDex, ZCORT, Zema-Pak, ZoDex, ZonaCort 11 Day, ZonaCort 7 Day
No brand name available
Albuked , Albumarc, Albuminar, Albuminex, AlbuRx , Albutein, Buminate, Flexbumin, Kedbumin, Macrotec, Plasbumin, Plasbumin-20
View PATIENT EDUCATION
NOTE: This is the Professional Version. CONSUMERS: View Consumer Version
quiz link

Test your knowledge

Take a Quiz! 
iOS ANDROID
iOS ANDROID
iOS ANDROID
TOP