Fetal Lung Maturity Profile

The ability of the fetus to survive outside of the uterus is greatly dependent on proper pulmonary function. Pulmonary surfactant is needed to reduce the surface tension of the air-liquid interface of the alveolar lining, so that alveoli don’t collapse upon expiration.  Infants born with a deficiency of pulmonary surfactant are at increased risk of developing respiratory distress syndrome (RDS). The incidence of RDS is dependent on gestational age, with more RDS occurring in younger fetuses. For instance, the risk of RDS is 0% at 40 weeks, 2% at 36 weeks, and 8 to 23% at 34 weeks, depending on birth weight.  RDS can occur at term, especially with Rh isoimmunization and maternal diabetes. 

Surfactant is a complex mixture of lipids, proteins, and carbohydrates.  Most of the lipids are phospholipids including lecithin (L), sphingomyelin (S), disaturated lecithin, phophatidyl inositol (PI), and phosphatidyl glycerol (PG). All of these phospholipids are manufactured by the fetal lung, possess surface tension activity, and are secreted into the amniotic fluid.  Lecithin is present in the lung in the highest concentration, but must be stabilized by PI and/or PG to have maximal surface tension reducing activity. The relative concentrations of these phospholipids determine the degree of fetal lung maturity. The fetal risk of RDS can be estimated by measuring amniotic fluid phospholipid concentrations.  

 In early pregnancy, the concentration of lecithin is very small, while that of sphingomyelin is much greater. Lecithin begins to be secreted into amniotic fluid by the developing fetal lung between 24 and 26 weeks of gestation. At 30 to 32 weeks, lecithin concentration remains relatively low, less than or equal to sphingomyelin. PI concentration is also low at this time and PG is nonexistent.  Subsequently, sphingomyelin concentration levels off and lecithin begins to increase, with an abrupt rise at 35 weeks.  I increases in parallel with lecithin until 35 weeks and subsequently declines. PG becomes detectable at 36 weeks. Fetal lung maturity is established during the 2 to 3 week interval when the L/S ratio increases to 2.2 or more, PI decreases, and PG becomes detectable.  Because PG appears later in gestation, it is a good indicator of maturity (positive predictive value >95%). 

Generally, fetal lung maturity testing was not necessary when the gestational age is >39 weeks because fetal lungs are usually mature. Unfortunately, complications such as diabetes and Rh isoimmunization retard fetal lung development. Women with these complications may require testing. Testing was also not usually necessary when the gestational age was <30 weeks, because most fetuses are expected to have immature lungs. However, a number of disorders accelerate pulmonary maturity including maternal hypertension, preeclampsia, HELLP syndrome, premature rupture of the membranes, intrauterine growth restriction, maternal smoking and drug use, and maternal hemoglobinopathies. Women with one of these complications and preterm labor or premature rupture of the membranes may require testing.  

In the past, FLM testing was used to determine whether the fetus' lungs were developed enough to allow for safe preterm or early-term delivery. No, studies have demonstrated that FLM testing alone is sufficient to confirm adequate maturity of all organ systems to justify a preterm delivery. There are no other laboratory tests currently recommended to assess for fetal maturity. In recent years, guidelines have shifted to state that there are other factors that should be used to determine whether to deliver a fetus, and FLM test results demonstrating mature lungs are not a rationale to proceed with delivery. FLM testing is no longer indicated to guide timing of preterm or early-term delivery. This test should not be ordered for any clinical scenarios involving pregnant women.

References

Mackenna J, Hodson CA, Brame RG. Clinical utility of fetal lung maturity profile. Obstet Gynecol. 1981 Apr;57(4):493-5.

ACOG Committee Opinion No. 765: Avoidance of Nonmedically Indicated Early-Term Deliveries and Associated Neonatal Morbidities. Obstetrics and Gynecology 133(2) (2019) e156-e163.

ACOG Committee Opinion No. 764: Medically Indicated Late-Preterm and Early-Term Deliveries. Obstetrics and Gynecology 133(2) (2019) e151-e155.