Surfactant

The human fetus continues to develop lung maturity up until a term gestation, but the lungs generally are sufficiently mature to maintain extrauterine respiration by 36 weeks' gestation. Infants delivered prior to this time have variable degrees of pulmonary maturity as surfactant composition, synthesis, and storage change with advancing fetal development. Tests for determining fetal lung maturation depend on amniotic fluid analysis for surfactant presence and composition because fetal surfactant leaves the lung as an effluent that ebbs and flows with fetal breathing movement and is balanced by fetal swallowing.

In general, in the healthy fetus, growth, size, and maturation typically are linked with gestational age. Fetal lung maturity has been assessed using the lecithin-to-sphingomyelin ratio (L:S) for more than 30 years. This test is time-consuming and requires thin-layer chromatography. It depends on fetal lung fluid flowing into the amniotic fluid and altering the amniotic fluid phospholipid composition, with the results expressed as the ratio of a lecithin (phosphatidylcholine) to sphingomyelin per milliliter of amniotic fluid. The sphingomyelin content of amniotic fluid decreases after 32 weeks' gestational age, while the lecithin content, including that portion that is disaturated, increases. The L:S ratio is designed to account for varying amniotic fluid volumes that generally cannot be measured precisely. An L:S ratio of 2.0 typically is achieved by 35 weeks' gestation. Clinically, respiratory distress syndrome (RDS) due to surfactant deficiency is very unlikely if the L:S ratio is 2.0 or greater, it is indeterminate if the L:S ratio is 1.5 to 2.0, and the incidence of RDS is high if the L:S ratio is less than 1.0. Of note, the L:S ratio can increase over a period of several days or can be induced by the administration of glucocorticoids to the mother.

Phosphatidylinositol (PI) is a pulmonary phospholipid that increases throughout gestation, as does disaturated lecithin. PI concentrations decrease after 35 weeks' gestation. The mere presence of PI or disaturated lecithin, therefore, does not indicate lung maturity. Phosphatidylglycerol (PG) generally can be detected in the amniotic fluid at 36 weeks' gestation. Due to its appearance relatively late in gestation, it has been used as an indicator of pulmonary surfactant maturity.

In pregnancies complicated by maternal diabetes, a mature L:S ratio (>2.0) or the presence of PG may not indicate pulmonary surfactant maturity. In this setting, fetal lung maturity is determined best using a quantitative analysis of total surfactant activity. This rapidly determined, automated fluorescence polarization assay measures all surfactant phospholipids in amniotic fluid referenced as milligrams of surfactant per gram of albumin present. Recent data suggest that a total surfactant activity of greater than 45 mg surfactant phospholipids per gram of albumin is as good as, or better than, an L:S ratio of 2.0 in predicting fetal lung maturity, especially in the presence of maternal diabetes