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Prostaglandin inhibitors deemed optimal tocolytic agent

Reuters Health • The Doctor's Channel Daily Newscast

NEW YORK (Reuters Health) – For first-line tocolytic therapy before 32 weeks’ gestation, prostaglandin inhibitors appear to be the most effective and tolerable agents for delaying delivery for 7 days, according to a meta-analysis published in the March issue of Obstetrics and Gynecology.

Among very low birthweight infants, delaying delivery by as little as 1 week “decreases neonatal mortality by 30% and allows opportunity to transfer the mother to a tertiary care facility with a neonatal intensive care unit and to administer antenatal corticosteroids,” which the authors say is “pivotal to improving neonatal outcomes.”

Led by Dr. David M. Haas at Indiana University School of Medicine in Indianapolis, the research team identified 58 randomized controlled trials comparing different medications, or medications with placebo treatments or usual care, in women with preterm labor. Tocolytic agents were grouped into categories of betamimetics, calcium-channel blockers, magnesium sulfate, nitrates, oxytocin receptor antagonists, and prostaglandin inhibitors.

Pooled analyses showed that all agents were superior to control groups at delaying delivery for at least 48 hours (75%-93% vs 53%) and for at least 7 days (61%-78% vs 39%). On the other hand, the agents did not differ significantly in their ability to prevent neonatal death or respiratory distress syndrome.

In a cohort of 1000 women at risk, the authors estimate that “only 80…treated initially with prostaglandin inhibitors would deliver within 48 hours, as compared with 182 to 416 for other treatments.” Prostaglandin inhibitors included indomethacin, sulindac, nimesulide, ketorolac, rofecoxib, celecoxib, and mefenamic acid.

In a decision analysis, calcium-channel blockers (nifedipine and nicardipine) were superior to prostaglandin inhibitors for delaying delivery until 37 weeks of gestation.

“These agents have the best combination of tolerability and efficacy and should be considered the best choices for first-line tocolysis, taking into account maternal and fetal factors that might influence the choice of tocolytic agents,” Dr. Haas and his associates conclude.

Obstet Gynecol 2009;113:585-594.