Skip to main content Accessibility help
×
Hostname: page-component-76fb5796d-x4r87 Total loading time: 0 Render date: 2024-04-26T16:43:28.235Z Has data issue: false hasContentIssue false

15.1 - Fetal lung growth, development, and lung fluid

Physiology and pathophysiology

from Section 2 - Fetal disease

Published online by Cambridge University Press:  05 February 2013

Mark D. Kilby
Affiliation:
Department of Fetal Medicine, University of Birmingham
Anthony Johnson
Affiliation:
Baylor College of Medicine, Texas
Dick Oepkes
Affiliation:
Department of Obstetrics, Leiden University Medical Center
Get access

Summary

Introduction

The lung develops in utero as a secretory, gland-like organ, and for normal growth and development to occur the lung must be maintained in an expanded state during at least the latter half of gestation. A considerable amount of research in recent years has gone into understanding how lung development is regulated at the molecular level, and also how the lung’s physicochemical environment affects its development. In this chapter we focus on how normal lung development is regulated before birth, and how it is affected by the intrauterine environment. Indeed, there is now a large body of evidence indicating that alterations in lung development that occur during fetal and early postnatal life can persist throughout life, and can impair adult lung function and accelerate the age-related decline in lung function. Lung development is completed during early postnatal life; therefore, after infancy there is limited scope for repairing abnormal lung development. Thus, it is important to be able to detect alterations in lung development early in life, and to understand the processes involved in normal lung development in order to be able to devise therapies to normalize any major alterations. We begin by presenting a brief overview of fetal lung development.

Normal lung development

In order to understand how the lung can be affected by intrauterine conditions, it is important to appreciate how the lung develops. The lung develops as an essentially tubular structure of increasing complexity due to complex interactions between cells of endodermal and mesenchymal origin. At least four or five distinct stages of lung development are recognized, based on microscopic appearance: these are the embryonic, pseudoglandular, canalicular, and saccular-alveolar stages [1]. A final stage of microvascular maturation can also be recognized [2]. These stages of lung development overlap and are conserved between species, although the timing of each stage differs [3].

Type
Chapter
Information
Fetal Therapy
Scientific Basis and Critical Appraisal of Clinical Benefits
, pp. 271 - 281
Publisher: Cambridge University Press
Print publication year: 2012

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Hooper, S. Respiratory system. In: Harding, R, Bocking, AD, eds. Fetal Growth and Development. Cambridge, Cambridge University Press. 2001; 114–36.
Burri, PH. Structural aspects of postnatal lung development – alveolar formation and growth. Biol Neonate 2006;89(4):313–22.Google Scholar
Pinkerton, KE, Joad, JP. The mammalian respiratory system and critical windows of exposure for children’s health. Environ Health Perspect 2000;108 Suppl 3:457–62.Google Scholar
Cardoso, W. Lung morphogenesis, role of growth factors and transcription factors. In: Harding, R, Pinkerton, K, Plopper, CG, eds. The Lung: Development, Aging and the Environment. London, Elsevier Academic Press. 2004; 3–11.
Morrisey, EE, Hogan, BL. Preparing for the first breath: genetic and cellular mechanisms in lung development. Develop Cell 2010;18(1):8–23.Google Scholar
Harding, R, Hooper, SB, Wallace, MJ. Lung development: overview. In: Laurent, G, Shapiro, D, eds. Encyclopedia of Respiratory Medicine. Oxford, Elsevier. 2006; 613–18.
Groenman, F, Unger, S, Post, M. The molecular basis for abnormal human lung development. Biol Neonate 2005;87(3):164–77.Google Scholar
Warburton, D, El-Hashash, A, Carraro, G, et al. Lung organogenesis. Curr Top Dev Biol 2010;90:73–158.Google Scholar
Flecknoe, SJ, Wallace, MJ, Cock, ML, Harding, R, Hooper, SB. Changes in alveolar epithelial cell proportions during fetal and postnatal development in sheep. Am J Physiol 2003;285(3):L664–70.Google Scholar
Flecknoe, SJ, Wallace, MJ, Harding, R, Hooper, SB. Determination of alveolar epithelial cell phenotypes in fetal sheep: evidence for the involvement of basal lung expansion. J Physiol 2002;542 (Pt 1):245–53.Google Scholar
Gonzalez, RF, Allen, L, Dobbs, LG. Rat alveolar type I cells proliferate, express OCT-4, and exhibit phenotypic plasticity in vitro. Am J PhysiolAm J Physiol 2009;297(6):L1045–55.Google Scholar
Adamson, TM, Boyd, RD, Platt, HS, Strang, LB. Composition of alveolar liquid in the foetal lamb. J Physiol 1969;204(1):159–68.Google Scholar
Hooper, SB, Harding, R. Fetal lung liquid: a major determinant of the growth and functional development of the fetal lung. Clin Exp Pharm Physiol 1995;22(4):235–47.Google Scholar
Harding, R, Hooper, SB. Regulation of lung expansion and lung growth before birth. J Appl Physiol 1996;81(1):209–24.Google Scholar
Alcorn, D, Adamson, TM, Lambert, TF, et al. Morphological effects of chronic tracheal ligation and drainage in the fetal lamb lung. J Anat 1977;123(3):649–60.Google Scholar
Moessinger, AC, Harding, R, Adamson, TM, Singh, M, Kiu, GT. Role of lung fluid volume in growth and maturation of the fetal sheep lung. J Clin Invest 1990;86(4):1270–7.Google Scholar
Boland, RE, Nardo, L, Hooper, SB. Cortisol pretreatment enhances the lung growth response to tracheal obstruction in fetal sheep. Am J Physiol 1997;273(6 Pt 1):L1126–31.Google Scholar
Nardo, L, Hooper, SB, Harding, R. Stimulation of lung growth by tracheal obstruction in fetal sheep: relation to luminal pressure and lung liquid volume. Pediatr Res 1998; 43(2):184–90.Google Scholar
Sozo, F, Wallace, MJ, Zahra, VA, Filby, CE, Hooper, SB. Gene expression profiling during increased fetal lung expansion identifies genes likely to regulate development of the distal airways. Physiol Genomics 2006;24(2):105–13.Google Scholar
Mesas-Burgos, C, Nord, M, Didon, L, Eklof, AC, Frenckner, B. Gene expression analysis after prenatal tracheal ligation in fetal rat as a model of stimulated lung growth. J Pediatr Surg 2009;44(4):720–8.Google Scholar
Boucherat, O, Franco-Montoya, ML, Thibault, C, et al. Gene expression profiling in lung fibroblasts reveals new players in alveolarization. Physiol Genomics 2007;32(1):128–41.Google Scholar
Gillett, AM, Wallace, MJ, Gillespie, MT, Hooper, SB. Increased expansion of the lung stimulates calmodulin 2 expression in fetal sheep. Am J Physiol 2002;282(3):L440–7.Google Scholar
Liu, M, Xu, J, Tanswell, AK, Post, M. Inhibition of mechanical strain-induced fetal rat lung cell proliferation by gadolinium, a stretch-activated channel blocker. J Cell Physiol 1994;161(3):501–7.Google Scholar
Bolt, RJ, van Weissenbruch, MM, Lafeber, HN, Delemarre-van de Waal, HA. Glucocorticoids and lung development in the fetus and preterm infant. Pediatr Pulmonol 2001;32(1):76–91.Google Scholar
Boland, R, Joyce, BJ, Wallace, MJ, et al. Cortisol enhances structural maturation of the hypoplastic fetal lung in sheep. J Physiol 2004;554(Pt 2):505–17.Google Scholar
Dickson, KA, Harding, R. Restoration of lung liquid volume following its acute alteration in fetal sheep. J Physiol 1987;385:531–43.Google Scholar
Harding, R, Sigger, JN, Wickham, PJ, Bocking, AD. The regulation of flow of pulmonary fluid in fetal sheep. Respir Physiol 1984;57(1):47–59.Google Scholar
Harding, R, Bocking, AD, Sigger, JN. Influence of upper respiratory tract on liquid flow to and from fetal lungs. J Appl Physiol 1986;61(1):68–74.Google Scholar
Miller, AA, Hooper, SB, Harding, R. Role of fetal breathing movements in control of fetal lung distension. J Appl Physiol 1993;75(6):2711–17.Google Scholar
Albuquerque, CA, Smith, KR, Saywers, TE, et al. Relation between oligohydramnios and spinal flexion in the human fetus. Early Hum Development 2002;68(2):119–26.Google Scholar
Harding, R, Hooper, SB, Dickson, KA. A mechanism leading to reduced lung expansion and lung hypoplasia in fetal sheep during oligohydramnios. Am J Obstet Gynecol 1990;163(6 Pt 1):1904–13.Google Scholar
Lines, A, Nardo, L, Phillips, ID, Possmayer, F, Hooper, SB. Alterations in lung expansion affect surfactant protein A, B, and C mRNA levels in fetal sheep. Am J Physiol 1999;276(2 Pt 1):L239–45.Google Scholar
Morin, FC 3rd, Stenmark, KR. Persistent pulmonary hypertension of the newborn. Am J Respir Crit Care Med 1995;151(6):2010–32.Google Scholar
Suzuki, K, Hooper, SB, Cock, ML, Harding, R. Effect of lung hypoplasia on birth-related changes in the pulmonary circulation in sheep. Pediatr Res 2005;57(4):530–6.Google Scholar
Suzuki, K, Hooper, SB, Wallace, MJ, Probyn, ME, Harding, R. Effects of antenatal corticosteroid treatment on pulmonary ventilation and circulation in neonatal lambs with hypoplastic lungs. Pediatr Pulmonol 2006;41(9):844–54.Google Scholar
Langer, R, Kaufmann, HJ. Primary (isolated) bilateral pulmonary hypoplasia: a comparative study of radiologic findings and autopsy results. Pediatr Radiol 1986;16(3):175–9.Google Scholar
Gould, S. Pulmonary hypoplasia: hyaline membrane disease and chronic lung disease. In: Hanson, MA, Spencer, JAD, Rodeck, CH, eds. Fetus and Neonate: Breathing. Cambridge, Cambridge University Press. 1994; 214–36.
Sherer, DM, Davis, JM, Woods, JR Jr. Pulmonary hypoplasia: a review. Obstet Gynecol Surv 1990;45(11):792–803.Google Scholar
Thibeault, DW, Beatty, EC Jr, Hall, RT, Bowen, SK, O’Neill, DH. Neonatal pulmonary hypoplasia with premature rupture of fetal membranes and oligohydramnios. J Pediatr 1985;107(2):273–7.Google Scholar
Logan, JW, Rice, HE, Goldberg, RN, Cotten, CM. Congenital diaphragmatic hernia: a systematic review and summary of best-evidence practice strategies. J Perinatol 2007;27(9):535–49.Google Scholar
Lund, DP, Mitchell, J, Kharasch, V, et al. Congenital diaphragmatic hernia: the hidden morbidity. J Pediatric Surg 1994;29(2):258–62; discussion 262–4.Google Scholar
Wung, JT, Sahni, R, Moffitt, ST, Lipsitz, E, Stolar, CJ. Congenital diaphragmatic hernia: survival treated with very delayed surgery, spontaneous respiration, and no chest tube. J Pediatric Surg 1995;30(3):406–9.Google Scholar
Reiss, I, Schaible, T, van den Hout, L, et al. Standardized postnatal management of infants with congenital diaphragmatic hernia in Europe: the CDH EURO Consortium consensus. Neonatology 98(4):354–64.
Soll, RF. Inhaled nitric oxide in the neonate. J Perinatol 2009;29 Suppl 2:S63–7.Google Scholar
De Luca, D, Zecca, E, Vento, G, De Carolis, MP, Romagnoli, C. Transient effect of epoprostenol and sildenafil combined with iNO for pulmonary hypertension in congenital diaphragmatic hernia. Paediatr Anaesth 2006;16(5):597–8.Google Scholar
Inamura, N, Kubota, A, Nakajima, T, et al. A proposal of new therapeutic strategy for antenatally diagnosed congenital diaphragmatic hernia. J Pediatr Surg 2005;40(8):1315–19.Google Scholar
Harrison, MR, Adzick, NS, Flake, AW, et al. Correction of congenital diaphragmatic hernia in utero VIII: Response of the hypoplastic lung to tracheal occlusion. J Pediatr Surg 1996;31(10):1339–48.Google Scholar
Hashim, E, Laberge, JM, Chen, MF, Quillen, EW Jr. Reversible tracheal obstruction in the fetal sheep: effects on tracheal fluid pressure and lung growth. J Pediatr Surg 1995;30(8):1172–7.Google Scholar
Bratu, I, Flageole, H, Laberge, JM, Chen, MF, Piedboeuf, B. Pulmonary structural maturation and pulmonary artery remodeling after reversible fetal ovine tracheal occlusion in diaphragmatic hernia. J Pediatr Surg 2001;36(5):739–44.Google Scholar
Baird, R, Khan, N, Flageole, H, et al. The effect of tracheal occlusion on lung branching in the rat nitrofen CDH model. J Surg Res 2008;148(2):224–9.Google Scholar
Probyn, ME, Wallace, MJ, Hooper, SB. Effect of increased lung expansion on lung growth and development near midgestation in fetal sheep. Pediatr Res 2000;47(6):806–12.Google Scholar
Piedboeuf, B, Laberge, JM, Ghitulescu, G, et al. Deleterious effect of tracheal obstruction on type II pneumocytes in fetal sheep. Pediatr Res 1997;41(4 Pt 1):473–9.Google Scholar
Deprest, J, Gratacos, E, Nicolaides, KH. Fetoscopic tracheal occlusion (FETO) for severe congenital diaphragmatic hernia: evolution of a technique and preliminary results. Ultrasound Obstet Gynecol 2004;24(2):121–6.Google Scholar
Saura, L, Castanon, M, Prat, J, et al. Impact of fetal intervention on postnatal management of congenital diaphragmatic hernia. Eur J Pediatr Surg 2007;17(6):404–7.Google Scholar
Stocker, JT, Madewell, JE, Drake, RM. Congenital cystic adenomatoid malformation of the lung. Classification and morphologic spectrum. Hum Pathol 1977;8(2):155–71.Google Scholar
Harrison, MR, Adzick, NS, Jennings, RW, et al. Antenatal intervention for congenital cystic adenomatoid malformation. Lancet 1990;336(8721):965–7.Google Scholar
Crombleholme, TM, Coleman, B, Hedrick, H, et al. Cystic adenomatoid malformation volume ratio predicts outcome in prenatally diagnosed cystic adenomatoid malformation of the lung. J Pediatr Surg 2002;37(3):331–8.Google Scholar
Wilson, RD, Hedrick, HL, Liechty, KW, et al. Cystic adenomatoid malformation of the lung: review of genetics, prenatal diagnosis, and in utero treatment. Am J Med Genet 2006;140(2):151–5.Google Scholar
Curran, PF, Jelin, EB, Rand, L, et al. Prenatal steroids for microcystic congenital cystic adenomatoid malformations. J Pediatr Surg 2010;45(1):145–50.Google Scholar
Adzick, NS. Management of fetal lung lesions. Clin Perinatol 2003;30(3):481–92.Google Scholar
Bianchi, S, Lista, G, Castoldi, F, Rustico, M. Congenital primary hydrothorax: effect of thoracoamniotic shunting on neonatal clinical outcome. J Matern Fetal Neonatal Med 2010;23(10):1225–9.Google Scholar
Waller, K, Chaithongwongwatthana, S, Yamasmit, W, Donnenfeld AE. Chromosomal abnormalities among 246 fetuses with pleural effusions detected on prenatal ultrasound examination: factors associated with an increased risk of aneuploidy. Genet Med 2005;7(6):417–21.Google Scholar
Patton, MA, Baraitser, M, Nickolaides, K, Rodeck, CH, Gamsu, H. Prenatal treatment of fetal hydrops associated with the hypertelorism-dysphagia syndrome (Opitz-G syndrome). Prenat Diag 1986;6(2):109–15.Google Scholar
Nakamura, Y, Harada, K, Yamamoto, I, et al. Human pulmonary hypoplasia. Statistical, morphological, morphometric, and biochemical study. Arch Path Lab Med 1992;116(6):635–42.Google Scholar
Fukushima, K, Morokuma, S, Fujita, Y, et al. Short-term and long-term outcomes of 214 cases of non-immune hydrops fetalis. Early Hum Dev 87(8):571–5.
Blott, M, Greenough, A. Neonatal outcome after prolonged rupture of the membranes starting in the second trimester. Arch Dis Child 1988;63(10 Spec No):1146–50.Google Scholar
Roberts, AB, Mitchell, JM. Direct ultrasonographic measurement of fetal lung length in normal pregnancies and pregnancies complicated by prolonged rupture of membranes. Am J Obstet Gynecol 1990;163(5 Pt 1):1560–6.Google Scholar
Harding, R, Liggins, GC. The influence of oligohydramnios on thoracic dimensions of fetal sheep. J Dev Physiol 1991;16(6):355–61.Google Scholar
Singla, A, Yadav, P, Vaid, NB, Suneja, A, Faridi, MM. Transabdominal amnioinfusion in preterm premature rupture of membranes. Int J Gynaecol Obstet 2010;108(3):199–202.Google Scholar
Locatelli, A, Ghidini, A, Verderio, M, et al. Predictors of perinatal survival in a cohort of pregnancies with severe oligohydramnios due to premature rupture of membranes at <26 weeks managed with serial amnioinfusions. EurJ Obstet Gynecol Reprod Biol 2006;128(1–2):97–102.Google Scholar
Tchirikov, M, Steetskamp, J, Hohmann, M, Koelbl, H. Long-term amnioinfusion through a subcutaneously implanted amniotic fluid replacement port system for treatment of PPROM in humans. Eur J Obstet Gynecol Reprod Biol 2010;152(1):30–3.Google Scholar
Klaassen, I, Neuhaus, TJ, Mueller-Wiefel, DE, Kemper, MJ. Antenatal oligohydramnios of renal origin: long-term outcome. Nephrol Dial Transplant 2007;22(2):432–9.Google Scholar
Vilos, GA, McLeod, WJ, Carmichael, L, Probert, C, Harding, PG. Absence or impaired response of fetal breathing to intravenous glucose is associated with pulmonary hypoplasia in congenital myotonic dystrophy. Am J Obstet Gynecol 1984;148(5):558–62.Google Scholar
Pena, SD, Shokeir, MH. Syndrome of camptodactyly, multiple ankyloses, facial anomalies, and pulmonary hypoplasia: a lethal condition. J Pediatr 1974;85(3):373–5.Google Scholar
Moessinger, AC. Fetal akinesia deformation sequence: an animal model. Pediatrics 1983;72(6):857–63.Google Scholar
Solopova, A, Wisser, J, Huisman, TA. Osteogenesis imperfecta type II: fetal magnetic resonance imaging findings. Fetal Diagn Ther 2008;24(4):361–7.Google Scholar
Scurry, JP, Adamson, TM, Cussen, LJ. Fetal lung growth in laryngeal atresia and tracheal agenesis. Aust Paediatr J 1989;25(1):47–51.Google Scholar
McDougall, AR, Hooper, SB, Zahra, VA, et al. The oncogene Trop2 regulates fetal lung cell proliferation. Am J Physiol 301(4):L478–89.
Jelin, EB, Etemadi, M, Encinas, J, et al. Dynamic tracheal occlusion improves lung morphometrics and function in the fetal lamb model of congenital diaphragmatic hernia. J Pediatr Surg 2011;46(6):1150–7.Google Scholar
Khan, PA, Cloutier, M, Piedboeuf, B. Tracheal occlusion: a review of obstructing fetal lungs to make them grow and mature. Am J Med Genet C Semin Med Genet 2007;145C(2):125–38.Google Scholar

Save book to Kindle

To save this book to your Kindle, first ensure coreplatform@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×