Pathophysiology, clinical manifestations, and diagnosis of respiratory distress syndrome in the newborn
- Richard Martin, MD
Richard Martin, MD
- Section Editor — Neonatology
- Professor, Pediatrics, Reproductive Biology, and Physiology & Biophysics
- Case Western Reserve University School of Medicine
Respiratory distress syndrome (RDS), formerly known as hyaline membrane disease, is a common problem in preterm infants. This disorder is caused primarily by deficiency of pulmonary surfactant in an immature lung. RDS is a major cause of morbidity and mortality in preterm infants.
The pathophysiology and clinical features of RDS will be presented here. The management of RDS and other disorders of perinatal transition are discussed separately. (See "Prevention and treatment of respiratory distress syndrome in preterm infants" and "Clinical features and diagnosis of meconium aspiration syndrome" and "Persistent pulmonary hypertension of the newborn" and "Transient tachypnea of the newborn".)
Knowledge of the normal fetal lung development is central to understanding the pathophysiology of neonatal RDS, which is due to inadequate surfactant activity resulting from lung immaturity.
Normal fetal alveolar development occurs in the following stages :
●Embryonic period – At approximately 26 days gestation, the embryonic stage begins with the first appearance of the fetal lung, which appears as a protrusion of the foregut. The initial branching of the lung occurs at 33 days gestation forming the prospective main bronchi, which begin to extend into the mesenchyme. Further branching forms the segmental bronchi as the lung enters the next stage of development.To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- Jobe AH. Lung Development and maturation. In: Neonatal-Perinatal Medicine, 9th ed, Martin RJ, Fanaroff AA, Walsh MC (Eds), Elsevier Mosby, St Louis 2010. Vol 2, p.1075.
- Schmitz G, Müller G. Structure and function of lamellar bodies, lipid-protein complexes involved in storage and secretion of cellular lipids. J Lipid Res 1991; 32:1539.
- Frank L, Sosenko IR. Development of lung antioxidant enzyme system in late gestation: possible implications for the prematurely born infant. J Pediatr 1987; 110:9.
- Nogee LM, Garnier G, Dietz HC, et al. A mutation in the surfactant protein B gene responsible for fatal neonatal respiratory disease in multiple kindreds. J Clin Invest 1994; 93:1860.
- Nogee LM, Dunbar AE 3rd, Wert SE, et al. A mutation in the surfactant protein C gene associated with familial interstitial lung disease. N Engl J Med 2001; 344:573.
- Shulenin S, Nogee LM, Annilo T, et al. ABCA3 gene mutations in newborns with fatal surfactant deficiency. N Engl J Med 2004; 350:1296.
- Somaschini M, Nogee LM, Sassi I, et al. Unexplained neonatal respiratory distress due to congenital surfactant deficiency. J Pediatr 2007; 150:649.
- Wert SE, Whitsett JA, Nogee LM. Genetic disorders of surfactant dysfunction. Pediatr Dev Pathol 2009; 12:253.
- Jobe AH, Ikegami M. Biology of surfactant. Clin Perinatol 2001; 28:655.
- Whitsett JA, Weaver TE. Hydrophobic surfactant proteins in lung function and disease. N Engl J Med 2002; 347:2141.
- Whitsett JA, Wert SE, Weaver TE. Alveolar surfactant homeostasis and the pathogenesis of pulmonary disease. Annu Rev Med 2010; 61:105.
- Nkadi PO, Merritt TA, Pillers DA. An overview of pulmonary surfactant in the neonate: genetics, metabolism, and the role of surfactant in health and disease. Mol Genet Metab 2009; 97:95.
- Wu H, Kuzmenko A, Wan S, et al. Surfactant proteins A and D inhibit the growth of Gram-negative bacteria by increasing membrane permeability. J Clin Invest 2003; 111:1589.
- Sato A, Whitsett JA, Scheule RK, Ikegami M. Surfactant protein-d inhibits lung inflammation caused by ventilation in premature newborn lambs. Am J Respir Crit Care Med 2010; 181:1098.
- Verlato G, Cogo PE, Balzani M, et al. Surfactant status in preterm neonates recovering from respiratory distress syndrome. Pediatrics 2008; 122:102.
- Hallman M, Kulovich M, Kirkpatrick E, et al. Phosphatidylinositol and phosphatidylglycerol in amniotic fluid: indices of lung maturity. Am J Obstet Gynecol 1976; 125:613.
- Carlton DP, Albertine KH, Cho SC, et al. Role of neutrophils in lung vascular injury and edema after premature birth in lambs. J Appl Physiol (1985) 1997; 83:1307.
- Clark RH, Gerstmann DR, Jobe AH, et al. Lung injury in neonates: causes, strategies for prevention, and long-term consequences. J Pediatr 2001; 139:478.
- Naik AS, Kallapur SG, Bachurski CJ, et al. Effects of ventilation with different positive end-expiratory pressures on cytokine expression in the preterm lamb lung. Am J Respir Crit Care Med 2001; 164:494.
- Brus F, van Oeveren W, Okken A, Oetomo SB. Number and activation of circulating polymorphonuclear leukocytes and platelets are associated with neonatal respiratory distress syndrome severity. Pediatrics 1997; 99:672.
- Turunen R, Nupponen I, Siitonen S, et al. Onset of mechanical ventilation is associated with rapid activation of circulating phagocytes in preterm infants. Pediatrics 2006; 117:448.
- Buss IH, Senthilmohan R, Darlow BA, et al. 3-Chlorotyrosine as a marker of protein damage by myeloperoxidase in tracheal aspirates from preterm infants: association with adverse respiratory outcome. Pediatr Res 2003; 53:455.
- Cheah FC, Winterbourn CC, Darlow BA, et al. Nuclear factor kappaB activation in pulmonary leukocytes from infants with hyaline membrane disease: associations with chorioamnionitis and Ureaplasma urealyticum colonization. Pediatr Res 2005; 57:616.
- Nitta K, Kobayashi T. Impairment of surfactant activity and ventilation by proteins in lung edema fluid. Respir Physiol 1994; 95:43.
- Smith DE, Otulakowski G, Yeger H, et al. Epithelial Na(+) channel (ENaC) expression in the developing normal and abnormal human perinatal lung. Am J Respir Crit Care Med 2000; 161:1322.
- Helve O, Pitkänen OM, Andersson S, et al. Low expression of human epithelial sodium channel in airway epithelium of preterm infants with respiratory distress. Pediatrics 2004; 113:1267.
- Jobe AH, Hillman N, Polglase G, et al. Injury and inflammation from resuscitation of the preterm infant. Neonatology 2008; 94:190.
- Edberg KE, Sandberg K, Silberberg A, et al. Lung volume, gas mixing, and mechanics of breathing in mechanically ventilated very low birth weight infants with idiopathic respiratory distress syndrome. Pediatr Res 1991; 30:496.
- Macklem PT, Proctor DF, Hogg JC. The stability of peripheral airways. Respir Physiol 1970; 8:191.
- NELSON NM, PROD'HOM LS, CHERRY RB, et al. Pulmonary function in the newborn infant. II. Perfusion--estimation by analysis of the arterial-alveolar carbon dioxide difference. Pediatrics 1962; 30:975.
- Goldsmith J, Karotkin E. Assisted Ventilation of the Neonate, 4th ed, WB Saunders, Philadelphia 2003.
- Stoll BJ, Hansen NI, Bell EF, et al. Neonatal outcomes of extremely preterm infants from the NICHD Neonatal Research Network. Pediatrics 2010; 126:443.
- Consortium on Safe Labor, Hibbard JU, Wilkins I, et al. Respiratory morbidity in late preterm births. JAMA 2010; 304:419.
- Anadkat JS, Kuzniewicz MW, Chaudhari BP, et al. Increased risk for respiratory distress among white, male, late preterm and term infants. J Perinatol 2012; 32:780.
- LUNG DEVELOPMENT
- Pulmonary surfactant
- - Synthesis, secretion, and absorption
- - Prematurity
- Surfactant deficiency
- Inflammation and lung injury
- Pulmonary edema
- Surfactant inactivation
- Pulmonary function and gas exchange
- - Hypoxemia
- CLINICAL MANIFESTATIONS
- Clinical course
- Laboratory findings
- Differential diagnosis
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS