Antenatal steroids for fetal lung maturity [Classics Series]

1. Respiratory distress syndrome (RDS) and perinatal mortality were significantly less common among preterm infants whose mothers received betamethasone prior to delivery.

Original Date of Publication: Oct 1972

Study Rundown: Respiratory complications of preterm birth are an important and common cause of preterm morbidity and mortality. Prior to 34 weeks estimated gestational age, fetal lungs are considered immature due to the lack of surfactant present in pulmonary alveoli. As the fetal lungs develop, they begin to produce greater quantities of surfactant and specifically increase the amount of lecithin production, thus increasing the lecithin to sphingomyelin ratio (L/S ratio), which is a marker of fetal lung maturity. An L/S ratio >2 in fetal amniotic fluid has been shown to be associated with fetal lung maturity and decreased risk of respiratory distress syndrome (RDS) while an L/S ratio <1.5 is associated with an increased risk of RDS.

As of the late 1969s, there were no interventions to reduce the respiratory morbidity associated with preterm birth. In the late 1960s, animal studies in lambs and rabbits demonstrated that fetal lung maturity was accelerated in animal fetuses whose mothers received glucocorticoids prior to preterm delivery. These studies stimulated obstetricians and scientists to test whether fetal lung maturity might be similarly improved in humans. Unlike some other animals (e.g. cows), the human placenta is relatively permeable to glucocorticoids, suggesting that maternal administration of steroids would allow transfer of these medicines to the preterm fetus. In the present work, authors randomized women at risk of preterm delivery to receive antenatal steroids or placebo and compared the incidence of RDS between groups.

This landmark study demonstrated a decreased incidence of RDS among fetuses born to women who received antenatal steroids. Strengths included randomized, double-blinded design and standardization of the primary outcome of RDS via the Silverman score (respiratory rate, grunting, chest retractions). Limitations included a small sample size of women who delivered at the same institution in New Zealand.

Click to read the study in Pediatrics

Dr. Alan Peaceman, MD, talks to 2 Minute Medicine: Northwestern University School of Medicine; Chief, Division of Obstetrics and Gynecology-Maternal Fetal Medicine.

“This classic trial from the 1970s assessed the impact of antenatal steroids on neonatal morbidity and mortality in women at risk for preterm delivery. Findings demonstrate that antenatal steroids confer a significant reduction in risk of perinatal death and respiratory distress syndrome. Subsequent investigations would go on to support these findings and establish additional fetal benefits of steroid administration, including decreased risk for intraventricular hemorrhage.” 

In-Depth [randomized controlled trial]: A total of 213 women with threatened preterm labor were randomized to receive betamethasone (n = 117) or placebo (n = 96) and received tocolysis with ethanol or salbutamol in attempts to delay delivery for 48-72 hours after the first betamethasone injection. Pharmacists randomized patients to allow healthcare providers to remain blinded to group assignments. Primary outcome assessed was perinatal death; secondary outcomes included respiratory distress syndrome.

RDS was one-third as common among infants in the betamethasone treatment group compared to controls (9 vs 26%, p < 0.01). Perinatal death was less common in the treatment group compared to placebo (6 vs 18%, p = 0.02). No infants in the treatment group experienced hyaline membrane disease or intraventricular hemorrhage compared to incidence sof 7% and 5%, respectfully, in the control group.

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