Acquired and Idiopathic Disorders in Neonates and Young Children

Introduction

Disorders presenting in neonates and young children comprise a heterogeneous group of conditions that can be divided into two broad categories, entities with a known etiology and those of unknown or poorly understood etiology. The well-characterized disorders include those that reflect altered lung growth and development or a poor transition from intrauterine to extrauterine life, including pulmonary hypoplasia, hyaline membrane disease (HMD), chronic lung disease of prematurity (eg, bronchopulmonary dysplasia [BPD]), persistent pulmonary hypertension of the newborn (PPHN), and pulmonary interstitial emphysema (PIE). Those classified as poorly understood include two idiopathic lung diseases unique to infants and very young children: pulmonary interstitial glycogenosis (PIG) and neuroendocrine cell hyperplasia of infancy (NEHI).

Growth Abnormalities

Abnormalities of lung growth, specifically pulmonary hypoplasia and pulmonary hyperplasia, largely reflect the influence of a developmental process or malformation that alters lung maturation. Distension of the lung with liquid and fetal respiratory movements is required for normal fetal lung growth, so any mechanism that interferes with these processes can result in a prenatal growth disorder. Prenatal-onset pulmonary hypoplasia ranges from mild to severe, depending on the mechanism of hypoplasia and timing of the insult in relation to the stage of lung development. Early insults that take place before 16 weeks’ gestation (renal anomalies, congenital diaphragmatic hernia) may interfere with airway branching, as well as acinar development, whereas later events (premature rupture of membranes) will exclusively affect acinar development. Because lung maturation continues well into the postnatal period, with most alveolarization occurring within the first year of a term birth, postnatal events can affect lung growth as well. Postnatal-onset growth abnormalities are commonly associated with premature birth (see “Complications of Prematurity and Its Therapy” ) and Down syndrome and, not infrequently, are seen in patients with congenital heart disease.

Like pulmonary hypoplasia, pulmonary hyperplasia, or excessive growth of the parenchyma, is a secondary phenomenon. During development it appears to be a response to airway obstruction, which blocks the outflow of fetal fluid leading to increased alveolar growth. Pulmonary hyperplasia has been also referred to as polyalveolar lobe and type 3 cystic adenomatoid malformation. The pathogenesis and clinical characteristics of this entity are related to congenital lobar overinflation/emphysema.

Radiologic Features

Radiographic identification of late-onset pulmonary hypoplasia is often difficult. Secondary findings include spontaneous pneumothorax and pneumomediastinum. Pulmonary hypoplasia in Down syndrome may appear as peripheral cystic disease.

In pulmonary hyperplasia chest radiographs demonstrate progressive hyperinflation or hyperlucency of a lobe. Marked overinflation may lead to compression of the adjacent lung and mediastinum ( Fig. 5.1 ).

Pathologic Features

Gross Findings

Grossly, the hypoplastic lung is small and the ratio of lung weight to body weight is lower than expected. Normal mean ratios are 0.018 for term infants (37–41 weeks), 0.025 for infants 28 to 36 weeks’ gestation, and 0.030 for infants 16 to 27 weeks’ gestation. In pulmonary hyperplasia, lungs are large, bulky, and often pale with normal lobation. It may affect all or some lobes.

Microscopic Findings

To define pulmonary hypoplasia, specific criteria have been devised that are based on reduced lung weight, lung volume, DNA content, and radial alveolar count. Although limited to the later stages of lung development (late saccular to alveolar) and well-inflated lung, the simplest method is the radial alveolar count, which measures complexity of the acinus. Radial alveolar count is the number of alveoli transected by a perpendicular line drawn from the center of a respiratory bronchiole to the nearest septal division or pleural margin. At least ten fields should be counted to offset bias due to differences between counts made from first-order and from third-order respiratory bronchioles. The radial count in a full-term infant should average five alveolar spaces and increases to approximately eight to ten alveolar spaces by 1 year of age. In pulmonary hypoplasia there is a reduction of alveolar spaces for gestational age, which is often accompanied by prominence of the bronchovascular structures and thickened interlobular septa. Widened alveolar ducts, enlarged airspaces, and dilatation of the subpleural alveoli that may resemble cysts characterize deficient alveolarization of postnatal onset ( Fig. 5.2 ).

Pulmonary hyperplasia, diffuse or focal, is characterized by a striking increase in alveoli in relation to airways, which can be confirmed by the radial alveolar count. Alveoli are often abnormally enlarged and simplified, and there may be a decrease or absence of interlobular septa ( Fig. 5.3 ).

Differential Diagnosis

Due to the presence of alveolar enlargement, pulmonary hypoplasia is often misinterpreted as emphysematous change or remodeling after lung injury. However, unlike these conditions, in a growth abnormality there is no evidence of a destructive or reparative process, including inflammation, type II cell hyperplasia, and significant fibrosis.

Pulmonary hyperplasia should be distinguished from congenital lobar overinflation. In the latter condition, the volume increase is due to alveolar enlargement as opposed to an absolute increase in alveoli. Radial alveolar counts can be helpful for distinguishing between these two abnormalities.

Pulmonary Interstitial Glycogenosis

PIG, previously referred to as cellular interstitial pneumonitis, is a poorly understood entity seen exclusively in infants less than 1 year of age. The hallmark histologic feature of PIG is a variable proliferation of glycogen-laden mesenchymal cells within the alveolar septa. PIG may be an isolated disorder or a component of another preexisting congenital or neonatal condition. The disorder commonly occurs in the setting of a lung growth abnormality, such as chronic neonatal lung disease of prematurity and pulmonary hypoplasia, but may also be seen in the setting of pulmonary hypertension, meconium aspiration, PIE, and congenital lung malformations (eg, congenital pulmonary airway malformation). There is debate concerning the underlying etiology of this condition. Some authors propose that accumulation of immature mesenchymal cells within the interstitium may represent a selective delay or aberration in the maturation of pulmonary mesenchymal cells, whereas others suggest that this accumulation is a nonspecific feature of several conditions that transiently alter lung growth and development in the neonatal period.