SAN DIEGO — Babies born before 34 weeks' gestation to mothers who received one rescue course of antenatal corticosteroids had a 31% reduction in composite neonatal morbidity, compared with their counterparts whose mothers did not receive the drugs, results of a 5-year multicenter study showed.
They also had a significant decrease in respiratory distress syndrome, ventilator support, and surfactant use, yet no decrease in head circumference or birth weight, Dr. James T. Kurtzman reported at the annual meeting of the Society for Maternal-Fetal Medicine.
“This is very exciting because it allows [you] more freedom to give that first course without feeling you've used the only card in your hand. … If the patient remains pregnant, it appears safe from both the fetal and maternal standpoint in the short term to proceed with that second rescue course when delivery is soon anticipated,” Dr. Kurtzman said.
“Everyone is in agreement that if you are anticipating a preterm delivery (generally before 32 or 33 weeks), … giving two doses of 12 mg betamethasone or four doses of 6 mg dexamethasone is going to decrease the rate of respiratory distress syndrome and intraventricular hemorrhage,” Dr. Kurtzman said in an interview prior to the meeting. “The data [on that are] very clear. But the problem is, the duration of the optimal benefit of that course may be limited, and most would consider that window to be 7–10 days from administration.”
In the late 1990s, it was routine practice to administer weekly courses of antenatal corticosteroids to patients who were seemingly about to deliver but who remained pregnant, said Dr. Kurtzman of the department of ob.gyn. at the University of California, Irvine, who is also a maternal-fetal medicine attending physician at Saddleback Women's Hospital, Laguna Hills, Calif. For example, if a mother presented with preterm labor at 25 weeks of gestational age, she might get multiple courses of steroids before she finally gave birth.
However, studies began to emerge which demonstrated that repeat courses of antenatal corticosteroids were associated with a decrease in the head circumference of the babies born to the mothers who received them. “So this raised a major concern,” he said. “The risk of giving multiple courses was called into question. But when you look at [those data], there was a clear relationship between the number of courses and the potentially harmful effects. Generally, those biometric differences were seen in babies that had received three or more courses.”
One question remained, he said: What if the mothers received just one rescue course of corticosteroids shortly before delivery? This question inspired the current study, which is the first of its kind to evaluate the impact of a single rescue course of antenatal corticosteroids on neonatal outcomes. Dr. Kurtzman and Dr. Thomas Garite, professor emeritus and former chairman of the department of ob.gyn. at the University of California, Irvine, were the two principal investigators.
Eligible patients for the 5-year randomized trial included 437 mothers with singletons or twins of less than 33 weeks' gestational age; all of these patients had completed a single course of betamethasone before 30 weeks and at least 14 days prior to delivery, and were judged to have a recurring threat of preterm delivery in the coming week. Researchers at 18 medical centers allocated 223 patients to receive a single rescue course of antenatal corticosteroids and 214 to receive placebo.
Patients with premature ruptured membranes, dilation that exceeded 5 cm, chorioamnionitis, and other steroid use were excluded from the study.
The primary outcome was composite neonatal morbidity prior to 34 weeks, although the investigators also planned to analyze the outcomes of all neonates delivered.
The mean age of patients was 29 years. The two groups were similar in terms of mean gestational age at randomization (29 weeks) and at delivery (33 weeks); proportion of twins; delivery route; delivery indications; Apgar scores; cord pH; birth weight; and head circumference.
The treatment group had a significant reduction in composite neonatal morbidity prior to 34 weeks, compared with the placebo group (44% vs. 64%, respectively), as well as significantly decreased rates of respiratory distress syndrome, need for ventilator support, and surfactant use.
Dr. Kurtzman further reported that 47% of mothers in the treatment group delivered within 7 days of the rescue course, whereas 68% delivered within 7–14 days. “That shows that the timing of this is very important,” he said. “We were able to do a reasonably good job of predicting the timing of delivery using the discretionary rescue protocol.”
When the researchers included all neonates in the analysis, regardless of gestational age at delivery, there was still a 25% reduction in composite neonatal morbidity in the treatment group, compared with the placebo group (32% vs. 43%, respectively). The odds ratio for composite neonatal morbidity in babies born before 34 weeks was 0.45, which was reflective of the significant reduction of neonatal respiratory morbidity in the treatment group. When all neonates were included, the odds ratio of 0.66 was still indicative of a significant reduction in morbidity.
As an example of how to apply the rescue course, Dr. Kurtzman offered the scenario of a mother who presents with signs of preterm labor at 25 weeks' gestational age and a cervix that is 2 cm dilated. “Let's say you give her the first course of corticosteroids in anticipation of delivery, and a week goes by and she doesn't deliver,” he said. “Instead of giving her weekly steroids, you wait until something has changed that makes it look like delivery is more imminent. At that point, the rescue course is given. This repeat course is done at the discretion of the physician. The idea is that you wait until the clinical circumstances evolve such that delivery within a week and before 34 weeks has become extremely likely, but you try not to wait until the last second on the way to the delivery room.”
Dr. Kurtzman now advocates this rescue course approach in his practice, and he believes that the data from the current study are strong enough to support offering it in everyday clinical practice when the patient's circumstances are applicable. The study was funded by Pediatrix Medical Group based in Sunrise, Fla.
A full report of the study findings is scheduled to appear in the March 2009 issue of the American Journal of Obstetrics and Gynecology.
Dr. Kurtzman had no conflicts to disclose.
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