Distal pulmonary epithelial maturation in preterm infants: does the lung of the preterm infant continue its functional pulmonary development postnatally?

Abstract

Disruption of pulmonary development caused by premature birth before the achievement of functional pulmonary maturation culminates in respiratory distress syndrome, primarily due to surfactant deficiency. Furthermore, the severity of this syndrome intensifies, particularly in the case of extremely premature neonates. This investigation aimed to evaluate the presence of postnatal pulmonary functional maturation in premature neonates. In pursuit of this objective, we conducted immunohistochemical assays for surfactant and Napsin A within the pulmonary tissue of 67 preterm neonates, with gestational ages ranging from 23 to 35 weeks, whose lifespans varied between one day and 149 days. The two immunohistochemical markers were evaluated within the pulmonary distal epithelium, and their expression was interpreted in relation to various pre- and postnatal factors. The examination was performed on tissue microarrays, sectioned at 5 micrometers, and the assessment of the immunohistochemical markers was interpreted from photographs captured under the optical microscope. Our investigation revealed that all neonates, regardless of their gestational age or lifespan, demonstrated the presence of surfactant within the pulmonary tissue. The intensity of Napsin A expression exhibited a positive correlation with gestational age, duration of oxygen therapy/mechanical ventilation, administration of antenatal corticosteroids, and maternal infections during pregnancy. In summary, our research demonstrated that mechanical ventilation, through the dynamic process of alveolar distension, promotes surfactant production within the distal lung epithelium. Antenatal treatment with corticosteroids and maternal antenatal infections enhances pulmonary function, facilitating surfactant production.

Keywords: Napsin A; functional pulmonary maturation; premature birth; surfactant; surfactant deficiency.

Figure 1

Microscopic images captured at a magnification of 400x, illustrating the immunolabeling for surfactant. A, lung tissue from a 24-week gestation neonate whose mother received antenatal corticosteroid therapy. The membranes ruptured 72 hours before delivery, and the infant required mechanical ventilation for three days, during which exogenous surfactant was administered; survival was three days. B, tissue from a 25-week gestation twin neonate born after an amniotic rupture occurring less than 1 hour before birth. The mother did not receive corticosteroids, and the infant was ventilated for 1.5 days without surfactant therapy; survival was 1.5 days. C, a 25-week gestation infant with intrauterine growth restriction and maternal hypertension. The mother received corticosteroids; mechanical ventilation lasted 3 days, surfactant was given; survival was 3 days. D, tissue from a 26-week gestation infant born to a mother with preeclampsia who did not receive antenatal steroids. The neonate required prolonged ventilation (45 days) and received surfactant therapy; survival was 45 days. E, a 26-week gestation infant whose mother experienced infection during pregnancy and received corticosteroids. Mechanical ventilation continued for 54 days, surfactant was administered, and survival was 54 days. F, lung from a 26-week gestation infant of an infected mother who did not receive steroids; ventilation lasted 93 days, surfactant was given, and survival was 93 days. G, tissue from a 27-week gestation infant delivered after 696 hours of membrane rupture in a mother treated with corticosteroids. The neonate underwent mechanical ventilation for 39 days without surfactant therapy; survival was 39 days. H, a 29-week gestation infant of a mother with gestational hypertension who received antenatal steroids. The infant required 9 days of mechanical ventilation without surfactant administration; survival was 9 days.

Figure 2

Microscopic images illustrating the immunolabeling for Napsin A (400× magnification). A, Lung tissue was obtained from a 23-week-old neonate who survived for 16 days (score 0). B, Lung tissue was obtained from a 25-week-old neonate who survived for 1.5 days (score 1). C, Lung tissue was obtained from a 29-week-old neonate who survived for 76 days (score 2). D, Lung tissue was obtained from a 27-week-old neonate who survived for 6 days (score 3).