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Vaginal progesterone cuts preterm birth neonatal morbidity and mortality

Reuters Health • The Doctor's Channel Daily Newscast

NEW YORK (Reuters Health) – Vaginal progesterone given to pregnant women with mid-trimester sonographic evidence of short cervix reduces the risk of preterm birth and neonatal complications and death, according to a report online December 14 in the American Journal of Obstetrics and Gynecology (AJOG).

A systematic review and meta-analysis of relevant studies found that vaginal progesterone decreased the rate of preterm birth by 42%, and significantly reduced the rate of respiratory distress syndrome and the need for mechanical ventilation, as well as several other neonatal morbidities.

The evidence for benefit is compelling, Dr. Roberto Romero, of the National Institute of Child Health & Human Development in Rockville, Maryland, and colleagues say.

They note that treatment reduced early preterm birth (those occurring before 33 or 28 weeks of gestation) and it also decreased a fraction of late preterm births — the most common preterm deliveries.

Importantly, they write, there was no evidence of demonstrable risk. The profile of adverse events was similar to placebo and follow-up studies of babies exposed to progesterone in utero out to age of 18 or 24 months showed no evidence of any behavioral or physical problems.

Based on their analysis, Dr. Romero and colleagues recommend that transvaginal sonographic measurement of cervical length be performed in pregnant women between 19 and 24 weeks of gestation.

They say vaginal progesterone at a dose of 90 milligrams per day should be considered for women with a short cervix, mainly those with a cervical length between 10 and 20 millimeters, from 20 to 36 6/7 weeks of gestation.

Preterm birth is the leading cause of perinatal illness and death worldwide; it’s also the main cause of infant mortality. It’s estimated that about 12.9 million births worldwide are preterm, with most (92%) occurring in Africa, Asia, Latin America, and the Caribbean. In the United States and Europe, there are about 1 million preterm births per year.

Progesterone is essential to maintain a pregnancy and a decline in progesterone action is implicated in the onset of labor. If this happens in the mid-trimester, cervical shortening may occur, predisposing a woman to preterm delivery. Vaginal progesterone is thought to help maintain a high concentration of the hormone in the uterine cervix.

Dr. Romero and colleagues pooled data from five high-quality trials evaluating vaginal progesterone versus placebo in a total of 775 women (723 [93%] with singleton pregnancies and 52 [7%] with twin pregnancies) and 827 infants.

They report that treatment with vaginal progesterone in asymptomatic women with mid-trimester short cervix was associated with a significant 42% reduction in the rate of preterm birth at < 33 weeks (12.4% vs 22.0%). The number needed to treat (NNT) to prevent one case of preterm birth before 33 weeks was 11. Treatment with vaginal progesterone also cut the rate of preterm birth at 35 weeks (31%) and < 28 weeks (50%). [pg13/abs]

The reduction in the rates of preterm birth (< 33 weeks) and composite neonatal morbidity and mortality was evident in both women with no previous spontaneous preterm birth and women with a history of spontaneous preterm birth.

This has practical implications, the investigators say, because vaginal progesterone is a less expensive and less invasive alternative than placing a stitch in the uterine cervix (cerclage) in patients with previous preterm birth and short cervix.

Infants whose mothers received vaginal progesterone had 52% lower risk of respiratory distress syndrome (6.1% vs 12.5%; NNT for benefit, 15) and 43% lower risk of composite neonatal morbidity/ mortality (9.7% vs 17.3%; NNT for benefit 13). They were also less apt to be of low birth weight and require admission to the neonatal ICU or mechanical ventilation.

There was no difference in efficacy when a dose of either 90 to 100 milligrams per day or 200 milligrams per day of vaginal progesterone was used.

For twin gestation, the reduction in preterm birth did not reach significance (30% at < 33 weeks), most likely due to the small number of twins in the studies. However, there was a significant reduction in the risk of composite neonatal morbidity and mortality (48%). The authors say a study of vaginal progesterone in twin pregnancies with short cervix is needed. [disc/pr/pg17]

In a statement, AJOG co-editor-in-chief, Dr. Thomas J. Garite said: The results of this analysis of five large randomized trials have the potential to result in a sea change in obstetrical practice in the U.S. and Europe and eventually in the rest of the world.

Reference:

Vaginal Progesterone In Women With An Asymptomatic Sonographic Short Cervix In The Midtrimester Decreases Preterm Delivery And Neonatal Morbidity: A Systematic Review And Meta-Analysis Of Individual Patient Data

Am J Obstet Gynecol 2011. Published online December 14, 2011.