The clinical utility of fetal lung maturity testing revisited 20 years later

There is a saying in science that every 10 or 20 years scientists "reinvent" things. This refers to observations someone made and published, but the findings were largely ignored for 10-20 years until a new scientist comes along and makes the same or similar observation and suddenly everyone takes notice.  It seems to me that is what is happening with fetal lung maturity testing.

As early as 1993 Wigton et al made the observation that in spite of documented fetal lung maturity (by L/S ratio or PG) major neonatal morbidity was observed in a population of 213 patients <37 weeks gestational age.  In 1997, Ghidini et al made a similar observation that the incidence of major neonatal complications among 153 preterm infants was high even in the presence of mature fetal lung tests.  I guess we didn't really pay attention to those papers since the Wigton paper has only been cited 16 times in 20 years and the Ghidini paper was cited 13 times in 16 years.

In March of 2011 David discussed a study by Bates et al, that had been published in 2010 (17 years after Wigton's paper)  which showed the very same thing in a larger population. They demonstrated that even after documented fetal lung maturity (L/S ratio or PG), infants born 36 to 39 weeks (n=459) were at higher risk of adverse outcomes than infants born at 39 to 40 weeks (n=13,339). Infants born before 39 weeks were, overall, at 1.6-fold greater risk of having something bad happen to them.  Things like elevated serum bilirubin, ventilator support, low blood glucose, admission to a neonatal intensive care unit, or even RDS. People are beginning to take notice because this paper has already been cited 20 times in just 2 years!

The Bates paper was followed in 2011 by a paper by Kamath et al Their study was not as large as Bates, but it broke down deliveries into late preterm (34 to 36 6/7 weeks; n=76) and early term (37 to 39 6/7 weeks; n=76) with documented fetal lung maturity as compared to infants greater than or equal to 39 weeks of gestation (n=262). These authors measured fetal lung maturity by TDx-FLM II, LBC, or PG. They again concluded that fetal lung maturity is insufficient to determine an infant's readiness for postnatal life.

So here we are in 2013, twenty years after Wigton's paper, and the largest study of preterm infants with mature lung indices has just been published by Fang et al. This study was very similar to the Bates study and compares infants born 36 to 38 6/7 weeks gestation with mature fetal lungs (as determined by LBC, L/S, or PG; n=1011) to infants 39-41 weeks of gestation (n=11,701).  They found that delivery prior to 39 weeks with documented fetal lung maturity was associated with an 8.4% composite neonatal morbidity rate as compared to 3.3% for deliveries at 39 weeks or greater. This is compared to 6.1% and 2.5% respectively for the Bates study. Fang observed that a large proportion (49%) of women in their study who were undergoing an amniocentesis to determine fetal lung maturity, between 36 and 38 weeks of gestation, had pregestational or gestational diabetes. Because this could be a confounding factor in their results, they excluded all diabetics and reanalyzed their data. They found that even in non-diabetic patients, significantly higher rates of neonatal morbidity persisted in the group that was delivered <39 weeks.

So what can we take away from these three "reinvented" papers? Certainly some pregnancy conditions require premature delivery. In these cases fetal lung maturity testing is irrelevant because the condition requires delivery regardless of lung maturity. In cases where premature delivery is not imminent, these studies show that gestational age itself has the strongest inverse correlation with morbidity.  Although fetal lung maturity testing may help to predict the absence of RDS, it does not mean that the infant will not have other complications due to immaturity. Essentially, delivery <39 weeks should be avoided regardless of fetal lung maturity testing. If lung maturity testing is performed, women should be counseled regarding the risk of neonatal morbidity even in the presence of a test results that indicates fetal lung maturity.

As David concluded in 2011, "perhaps it is time to send these tests away once and for all".

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