Optimal timing of delivery is a critical determinant of perinatal outcome. When faced with a pregnancy complication and possibility of a premature birth, knowledge of the lung maturity status of the fetus may assist the obstetric care provider in deciding about timing of delivery. Amniocentesis and use of one or more biochemical tests to measure the surface-active properties of surfactant phospholipids secreted by the fetal lungs into the amniotic fluid remains the only reliable technique for predicting risk for neonatal RDS. Since its development in the early 1970s,7,8
the L/S ratio has become one of the best validated and most commonly used biochemical tests to predict fetal lung maturity. It remains the test of choice in many institutions throughout the United States. A cutoff of 2.0 or 2.5 is generally regarded as being predictive of pulmonary maturity without regard to gestational age. Gestational age is an important determinant of RDS2–6
; as such, having a single L/S value cutoff for all gestational ages may not be reasonable. Gestational age-specific cutoffs for the prediction of RDS have previously been described for many other fetal lung maturity assays,11–16
but no such analysis has previously been done for the L/S ratio.
By modeling the odds of neonatal RDS using multivariate logistic regression based on our study population, we have confirmed that both L/S ratio and gestational age are independent predictors of RDS. The data demonstrate that lower L/S ratio cutoff values can be used at increasing gestational ages to predict the same risk of RDS. For example, a probability of RDS of 3% or less was noted at an L/S ratio cutoff of ≥3.4 at 34 weeks, ≥2.6 at 36 weeks, ≥1.6 at 38 weeks, and ≥1.2 at term. Stated differently, the L/S value cutoff conferring the same probability of RDS within the clinically important gestational age window of 32 to 37 weeks ranges from 3.4 to 1.2. Above 38 weeks, RDS is so unusual that an L/S ratio as low as 1.2 would still confer a less than 3% probability of RDS. Similarly, at a gestational age of < 34 weeks, the risk of RDS is so high that a probability of RDS as low as 3% is not yielded by our algorithm. At 31 weeks, an L/S ratio of 3.6 in our model yields a probability of RDS of ~25%, highlighting the potential risk of proceeding with delivery at lower gestational ages, even when the L/S ratio is greater than 2.0. The lowest gestational age at which we have data (26 weeks) yields a probability of RDS of 97 to 99% irrespective of the L/S ratio. summarizes the gestational age-specific risks of RDS by L/S ratio results that may be relevant when counseling patients about the risk of RDS. These data further suggest that there may be little clinical utility to amniocentesis and measurement of amniotic fluid L/S ratio prior to 31 weeks’ gestation.
This study is limited by sample size. Even though we included consecutive patients over a 7-year period undergoing amniocentesis for fetal lung maturity at a major tertiary care center that uses L/S ratio as a primary test, the requirement that delivery occur within 72 hours of the test result limited the number of subjects and cases of RDS. If the L/S ratio was suggestive of pulmonary immaturity, delivery was often delayed and amniocentesis repeated at a later date. This naturally limits the potential to correlate RDS temporally with L/S ratios. With only eight cases of RDS in our study sample, the confidence intervals surrounding our predictions for probability of RDS in are wide. Our decision to include only women who delivered within 72 hours of amniocentesis resulted in most of the exclusions (n
= 158) and significantly impacted the number of subjects in our study, but was necessary to accurately correlate L/S ratio values with probability of RDS. The small number of RDS cases also explains why we were unable to confirm previous reported associations between risk of neonatal RDS and, among others, African-American ethnicity,17
male gender, antenatal tobacco use,18
and diabetes mellitus.20
Interestingly, prior mathematical modeling has shown that these factors, although likely associated with neonatal RDS, have a very minor effect when compared with gestational age and fetal lung maturity tests.21
Likewise, the small number of cases precluded subgroup analysis by conditions such as preterm premature rupture of membranes and preterm labor.
Administration of antenatal corticosteroids is known to protect against the development of RDS in infants delivered prior to 34 weeks of gestation,9,10
but there are no consistent data showing benefit to routine administration of antenatal steroids in preventing RDS after 34 weeks. Moreover, the usual response to an “immature” L/S ratio test after 34 weeks is not to administer steroids, but to delay delivery and repeat the L/S ratio measurement a week later. Because the mean gestational ages of the two groups were different, the observation that more women in the RDS group received antenatal steroids than in the non-RDS group is likely a marker of earlier gestational age and not an independent predictor of neonatal RDS.
In conclusion, this study shows for the first time that gestational age-specific cutoffs for the amniotic fluid L/S ratio may be important in predicting risk of neonatal RDS. These data confirm that antenatal prediction of RDS is not a dichotomous endeavor, but represents a continuum of risk depending on gestational age, biochemical assays (such as the L/S ratio), and clinical factors. A better understanding of the risk of neonatal RDS based on these criteria will aid clinical decision making and lead to improvements in neonatal outcome.