Lamellar Body Counts

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. 

Initially, the fetal risk of RDS was estimated by measuring amniotic fluid phospholipid concentrations. The ratio of lecithin to sphingomyelin was measured by extraction of phospholipids from amniotic fluid and separation by chromatography. The percent of each phospholipid was determined by scanning the chromatography plate and measuring the area under each phospholipid peak. A lecithin to sphingomyelin (L/S) ratio of 2.2 or higher indicated fetal lung maturity. 

Because PG appeared later in gestation, it was a good indicator of maturity. PG was detected using the AmnioStat-FLM test. The positive predictive value  was greater than 95%.

Because the L/S ratio procedure was so labor intensive, many laboratories adopted the FLM II assay from Abbott Laboratories to assess fetal lung maturity. However, Abbott ended production of FLM II on Dec 31, 2011 due to the retirement of their TDx and FLx instruments.

In response, some hospital laboratories validated Lamellar Body Counts (LBC) as a replacement for FLM II. Type II pneumocytes package surfactant into intracellular storage granules called lamellar bodies, which are excreted into the alveolar space. Lamellar bodies appear in the amniotic fluid at 28 to 32 weeks and increase exponentially as gestation continues. Thus,LBC was a direct measurement of surfactant production. Due to the similar size of lamellar bodies and platelets, automated hematology analyzers can accurately count amniotic fluid lamellar bodies using the platelet channel. 

Outcome-based studies have demonstrated that LBC performs at least as well as the TDx FLM II test. A meta-analysis calculated receiver-operating characteristic curves based upon data from six studies and showed the lamellar body count performed slightly better than the lecithin/sphingomyelin ratio in predicting respiratory distress. 

Interpretive guidelines were developed by a consensus panel. 

Amniotic fluid is a heterogeneous mixture of fluid, sloughed cells, hair and other fetal debris that can have varying effects on LBC measurement. Blood contamination can lead to false elevation of the lamellar body count because platelets are counted as lamellar bodies. Meconium has been shown to lower LBC. Mucus artificially increases LBC. Vaginal pool samples can be counted if they are free of mucus. Amniotic fluid specimens contaminated with meconium or mucus cannot be run through the hematology analyzer. If amniotic fluid appears bloody, a red cell count is performed. LBC can be reported if the RBC count is <30,000/uL.

Due to improvements in gestational age dating, maternal administration of corticosteroids that accelerate fetal lung maturity in at-risk pregnancies, and exogenous surfactant replacement therapies, the number of newborn deaths due to respiratory distress syndrome has declined considerably over the last 25 years. Most clinical laboratories in the United States have noted a steady decline in the number of fetal lung maturity tests that they perform each year. 

Many obstetricians in the United States have indicated that laboratory tests for fetal lung maturity are no longer needed for patient care. Furthermore, European physicians rarely, if ever, order these tests and yet the rates of infant death due to respiratory distress are no worse than they are in the US. Therefore, 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.