Respiratory morbidity and lung function in preterm infants of 32 to 36 weeks' gestational age

Abstract

Normal lung development follows a series of orchestrated events. Premature birth interrupts normal in utero lung development, which results in significant alterations in lung function and physiology. Increasingly, there are reports documenting the broad range of complications experienced by infants aged 34 to 36 weeks' gestational age (GA). Our objective was to summarize the evidence demonstrating respiratory system vulnerability in infants aged 34 to 36 weeks' GA and to review the developmental and physiologic principles that underlie this vulnerability. A comprehensive search for studies that reported epidemiologic data and respiratory morbidity was conducted on the PubMed, Medline, Ovid Biosis, and Embase databases from 2000 to 2009 by using medical subject headings "morbidity in late preterm infants," "preterm infants and lung development," "prematurity and morbidity," and "prematurity and lung development." Because the number of studies exclusive to infants aged 34 to 36 weeks' GA was limited, selected studies also included infants aged 32 to 36 weeks' GA. Of the 24 studies identified, 16 were retrospective population-based cohort studies; 8 studies were observational. These studies consistently revealed that infants born at 32 to 36 weeks' GA, including infants of 34 to 36 weeks' GA, experience substantial respiratory morbidity compared with term infants. Levels of morbidity were, at times, comparable to those observed in very preterm infants. The developmental and physiologic mechanisms that underlie the increased morbidity rate and alterations in respiratory function are discussed. We also present evidence to demonstrate that the immaturity of the respiratory system of infants 34 to 36 weeks' GA at birth results in increased morbidity in infancy and leads to deficits in lung function that may persist into adulthood.

FIGURE 1

Proportion of infants with neonatal morbidity as a function of GA. Newborn morbidity was assessed by using a combination of indicators on infants' hospital discharge record and mortality data available from death certificates. Infants born at 34 to 35 weeks' GA were 7 times more likely to have neonatal morbidity than term infants. Infants born at 34 weeks' GA had 20 times the risk of morbidity compared with infants born at 40 weeks' GA. Term (37- to 41-week-GA) infants: n = 377 638; preterm (34- to 36-week-GA) infants: n = 26 170. (Adapted with permission from Shapiro-Mendoza CK, Tomashek KM, Kotelchuck M, et al. Pediatrics. 2008;121[2]:e227. Available at: www.pediatrics.org/cgi/content/full/121/2/e223.)

FIGURE 2

A, Correlation between GA and chest-wall compliance. (Reproduced with permission by Blackwell Publishing, Ltd, from Gerhardt T, Bancalari E. Acta Paediatr Scand. 1980;69[3]:361.) B, Correlation between age and chest-wall compliance. (Reproduced with permission from Papastamelos C, Panitch HB, England SE, Allen JL. J Appl Physiol. 1995;78[1]:182, copyright © 1995 American Physiologic Society.)

FIGURE 3

Airway-tethering. Tension is transmitted to the airway through the surrounding alveolar septal walls. Airway diameter, and therefore expiratory flows, are increased at higher lung volumes. (Reprinted with permission from Leff A, Schumacker PT. Respiratory Physiology: Basics and Applications. Philadelphia, PA: W.B. Saunders Company; 1993:43.)

FIGURE 4

Growth rate of lung function in healthy preterm infants born at <35 weeks' GA (no significant respiratory disease; patients were excluded if they required any mechanical ventilation, supplemental oxygen for >48 hours, or treatment with surfactant). Shown are flow-volume curves in preterm infants (solid line) versus control term group (dotted line), quantified by the FVC and forced expiratory flow at 75% of FVC (forced expiratory flow [FEF₇₅]) (P < .05 between groups). Despite normal lung volume, preterm infants had persistently reduced airflow through the age of 16 months. (Reprinted with permission from Friedrich L, Pitrez PM, Stein RT, Goldani M, Tepper R, Jones MH. Am J Respir Crit Care Med. 2007;176[12]:1272, copyright © 2007 American Thoracic Society.)