Prevention of Preterm Birth

Jeffrey M. Denney; Jennifer F. Culhane; Robert L. Goldenberg


Women's Health. 2008;4(6):625-638. 

In This Article


Both animal and human studies provide evidence that maternal progesterone concentrations decline before labor.[74,75,76,77,78] Hence, many randomized studies have evaluated the effect of exogenous progestin supplementation, including weekly injections of 17 α-hydroxyprogesterone caproate, in women considered at risk of preterm birth. In clinical trials, progesterone has been administered as vaginal suppositories as well as intramuscular injections.[79,80] In women with a history of preterm birth, risk of preterm delivery was reduced by approximately a third in two trials of progesterone supplementation, administered as weekly intramuscular injections of 17 α-hydroxprogesterone caproate 250 mg or as daily vaginal progesterone.[79,80] In meta-analyses of these studies with data from earlier trials, the risk of recurrent preterm birth was reduced by 40-55% (relative risk [RR]: 0.58; 95% CI: 0.48-40.70).[81]

Progesterone was also found to be of benefit when used for threatened preterm labor; this trial found a reduction in delivery prior to 37 weeks gestation (RR: 0.29; 95% CI: 0.12-10.69), but not at 34 weeks gestation.[82] However, Rouse et al. reported that 17 α-hydroxyprogesterone caproate had no effect on the rate of preterm birth in women with twins in a randomized, placebo-controlled trial.[83] Another study reported similar results.[84]

The exact mechanism of action of progestins on reducing preterm birth is speculative at this point. The absence of effect in twin pregnancy together with the positive results in women with historical risk, short cervix and the recent cerclage data, suggests that progesterone's effect on preterm birth rates may be related to reducing inflammation rather than acting as a tocolytic agent.[76] More information is needed not only regarding the mechanism of action, but also in regard to maternal outcomes following antenatal therapy, preference by patient in terms of mode of delivery, satisfaction of care, optimal dose, optimal route of administration and optimal gestational age at which to begin therapy. The ACOG has echoed this need.[85]


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