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Risks, Benefits of Prenatal Steroids Questioned.

SAN FRANCISCO -- Current knowledge about the risks and benefits of giving multiple courses of prenatal corticosteroids to women at risk for preterm delivery can be summed up in one word: confusion.

Clinicians must rely on conflicting data and conflicting recommendations until the results of four randomized controlled trials become available 3-5 years from now. Three of those four trials, however, are investigating protocols based on the faulty assumption that a single course of corticosteroids remains effective for 1 week despite fair evidence that the benefits last for at least 2 weeks, Dr. Julian T. Parer said at a meeting on antepartum and intrapartum management sponsored by the University of California, San Francisco (UCSF).

A National Institutes of Health consensus conference held last year concluded that prenatal corticosteroids to enhance lung maturation in preterm infants should be limited to one course of treatment because of the potential harmful effects of additional courses, including fetal growth restriction, impaired brain development, adrenal suppression, neonatal sepsis, chronic lung disease, and death.

Other investigators analyzed the same data considered by the consensus conference and came to a different conclusion: that one course be recommended unless there's an urgent reason to give additional corticosteroids, which may reduce the incidence and severity of respiratory distress syndrome, noted Dr. Parer, professor and director of perinatal medicine and genetics at the university.

UCSF's own guidelines come closer to the latter strategy, which echoes a 1998 Committee Opinion by the American College of Obstetricians and Gynecologists stating that repeated courses of corticosteroids given in a "rescue approach," rather than routinely, seem reasonable.

Repeat courses of antenatal corticosteroids should be given only when the threat of preterm delivery persists, the UCSF guidelines state. Preterm delivery remains a risk in mothers with preterm premature rupture of membranes, preterm labor with advanced cervical dilatation, persistent bleeding, or preeclampsia at less than 28 weeks' gestation.

Women sent home after a bout of preterm labor who are no longer threatening to deliver should not be sent home with corticosteroids, Dr. Parer emphasized.

The UCSF recommendations rest on "fair evidence" in the literature that the benefits of corticosteroids last at least 2 weeks and that the potential risks increase significantly when corticosteroids are administered earlier in gestation (less than 28 weeks). The latter is "unfortunate, because that's when we would expect to see the greatest benefit to the fetus" from corticosteroid treatment, Dr. Parer commented.

Under the university's recommendations, repeat courses are spaced 2 weeks apart with no repeat course at 32 weeks' gestation or later. At most, three courses are allowed with no third course at 30 weeks' gestation or later. (See box.)

Preliminary data from a decision analysis being conducted by Dr. Parer and his associates suggest that no more than two courses would be best, "but it's too soon to recommend that so we're sticking with this protocol," he said.

The 2-week interval between courses, a relatively new strategy, is being compared with a single course of antenatal corticosteroids in a Canadian randomized controlled trial. The three other randomized controlled trials in progress use weekly schedules, comparing a single course of corticosteroids with weekly repeat courses or a single course plus weekly placebos with weekly courses of corticosteroids.

All mothers at UCSF at risk for preterm delivery at 24-34 weeks' gestation get at least one course of antenatal corticosteroids even if delivery is expected within 6 hours. "In view of the unpredictability about when a baby is going to deliver, we just think that they should get [corticosteroids] when they walk in the door even if they're highly advanced in cervical dilatation."

Mothers at risk for preterm delivery at greater than 34 weeks also would get a course of corticosteroids if tests fail to show fetal lung maturity.
UCSF Draft Protocol:
Timing of Prenatal Corticosteroid Administration *
 First Course Subsequent Course(s)
(gestational week) (gestational week)
 24 26, 28
 25 27, 29
 26 28
 27 29
 28 30
 29 31
 30-34 weeks no additional courses
(*)Applies to patients with persisting risk of
preterm delivery.
Source: Dr. Julian T. Parer
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Publication:OB GYN News
Date:Aug 15, 2001
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