Liver enzymes and other plasma proteins are produced by the fetus, and these levels do not correlate with maternal levels (Weiner, 1992). Concentrations of plasma proteins, which include albumin, lactic dehydrogenase, aspartate aminotransferase, 1-glutamyl transpeptidase, and alanine transferase, all rise. Conversely, prealbumin levels decline with gestational age (Fryer, 1993). At birth, mean total plasma protein and albumin concentrations in fetal blood are similar to maternal levels. This is important because albumin binds unconjugated bilirubin to prevent kernicterus in the newborn (Chap. 33, p. 626).
Lung maturation and biochemical indices of functional fetal lung maturity are important predictors of early neonatal outcome. Morphological or functional immaturity at birth leads to the development of the respiratoy distress syndrome (Chap. 34, p. 636). A suicient amount of surface-active materialscollectively referred to as suactant-in the amnionic fluid is evidence of fetal lung maturity. As Liggins (1994) emphasized, however, the structural and morphological maturation of fetal lung also is extraordinarily important to proper lung function.
The limits of viability appear to be determined by the usual process of pulmonary growth. Like the branching of a tree, lung development proceeds along an established timetable that apparently cannot be hastened by antenatal or neonatal therapy. Within this framework, four essential lung development stages are described by Moore (2000). First, the pseudoglandular stage entails growth of the intrasegmental bronchial tree between the 5th and 17th weeks. During this period, the lung looks microscopically like a gland. Second, during the canalicular stage, from 16 to 25 weeks, the bronchial cartilage plates extend peripherally. Each terminal bronchiole gives rise to several respiratory bronchioles, and each of these in turn divides into multiple saccular ducts. Third, the terminal sac stage begins after 25 weeks. During this stage, alveoli give rise to primitive pulmonary alveoli, that is, the terminal sacs. Simultaneously, an extracellular matrix develops from proximal to distal lung segments until term. Finally, the alveolar stage begins during the late fetal period and continues well into childhood. An extensive capillary network is built, the lymph system forms, and type II pneumocytes begin to produce surfactant. At birth, only approximately 15 percent of the adult number of alveoli is present. hus, the lung continues to grow, adding more alveoli for up to 8 years.
Various insults can upset this process, and their timing determines the sequelae. One example is fetal renal agenesis, in which amnionic luid is absent at the beginning oflung growth, and major defects occur in all four developmental stages. In another instance, the fetus with membrane rupture and subsequent oligohydramnios before 20 weeks usually exhibits nearly normal bronchial branching and cartilage development but has immature alveoli. In contrast, membrane rupture after 24 weeks may have minimal long-term efect on pulmonary structure. In another example, various growth factors are expressed abnormally in the fetus with a diaphragmatic hernia (Candilira, 2015). Finally, vitamin D is thought to be important for several aspects oflung development (Hart, 2015; Lykkedegn, 2015).