The Amazing Premature Lung

The lung is often the weak link (organ) that limits survival of the extremely premature infant because the lung must function for gas exchange immediately after birth and then for many months of neonatal care until maturity. The infant with 24-week gestation has developed for only 22 weeks or 58% of a 38-week-term gestation, with subtraction of the 2 weeks from last menstrual period to conception used to calculate a normal 40-week-term gestation. Survival of infants with 24-week gestation is now common, and infants as early as 22 weeks of gestation are now at the margins of viability (20 weeks of a 38-week gestation = 53% of gestation). As normal lung maturation defined as normal gas exchange at birth occurs at approximately 36 weeks (34 weeks from conception), these very preterm lungs can support survival 3 to 4 months prior to normal lung maturation with help from the modern tools of neonatology. Multiple elements of lung development, injury, and repair contribute to this quite remarkable survival potential for the very preterm infant.

• References

• 1 Frank DB, Penkala IJ, Zepp JA. , et al. Early lineage specification defines alveolar epithelial ontogeny in the murine lung. Proc Natl Acad Sci U S A 2019
• 2 Whitsett JA, Kalin TV, Xu Y, Kalinichenko VV. Building and regenerating the lung cell by cell. Physiol Rev 2019; 99 (01) 513-554
• 3 Roberts D, Brown J, Medley N, Dalziel SR. Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database Syst Rev 2017; 3: CD004454
• 4 American College of Obstetricians and Gynecologists; Society for Maternal-Fetal Medicine. Obstetric care consensus no. 6: periviable birth. Obstet Gynecol 2017; 130 (04) e187-e199
• 5 Kallapur SG, Presicce P, Rueda CM, Jobe AH, Chougnet CA. Fetal immune response to chorioamnionitis. Semin Reprod Med 2014; 32 (01) 56-67
• 6 Hillman NH, Kallapur SG, Jobe AH. Physiology of transition from intrauterine to extrauterine life. Clin Perinatol 2012; 39 (04) 769-783
• 7 Guo M, Du Y, Gokey JJ. , et al. Single cell RNA analysis identifies cellular heterogeneity and adaptive responses of the lung at birth. Nat Commun 2019; 10 (01) 37
• 8 Tingay DG, Pereira-Fantini PM, Oakley R. , et al. Gradual aeration at birth is more lung protective than a sustained inflation in preterm lambs. Am J Respir Crit Care Med 2019
• 9 Fawke J, Lum S, Kirkby J. , et al. Lung function and respiratory symptoms at 11 years in children born extremely preterm: the EPICure study. Am J Respir Crit Care Med 2010; 182 (02) 237-245
• 10 Narayanan M, Beardsmore CS, Owers-Bradley J. , et al. Catch-up alveolarization in ex-preterm children: evidence from (3)He magnetic resonance. Am J Respir Crit Care Med 2013; 187 (10) 1104-1109
• 11 Doyle LW, Halliday HL, Ehrenkranz RA, Davis PG, Sinclair JC. An update on the impact of postnatal systemic corticosteroids on mortality and cerebral palsy in preterm infants: effect modification by risk of bronchopulmonary dysplasia. J Pediatr 2014; 165 (06) 1258-1260
• 12 Ardini-Poleske ME, Clark RF, Ansong C. , et al; LungMAP Consortium. LungMAP: the molecular atlas of lung development program. Am J Physiol Lung Cell Mol Physiol 2017; 313 (05) L733-L740