Cervical Length Changes During Preterm Cervical Ripening: Effect of 17-α- Hydroxyprogesterone Caproate
Abstract & Commentary
By John C. Hobbins, MD, Professor of Obstetrics and Gynecology, University of Colorado Health Sciences Center, Denver, is Associate Editor for OB/GYN Clinical Alert.
Dr. Hobbins reports no financial relationship to this field of study.
Synopsis: The purpose of this study was to evaluate whether 17-alpha-hydroxyprogesterone caproate (17P) treatment affect changes in cervical length.
Source: Facchinetti F, et al. Am J Obstet Gynecol. 2007 May;196(5):453.e1-4; discussion 421.
In previous Clinical Alerts, much attention has been given to preterm labor (PTL), perhaps to a point where the readers might prefer that another subject be covered this month. For those, I have an addendum to follow.
In the May issue of the American Journal of Obstetrics and Gynecology, there was a report of a small randomized trial that might generate some cautious optimism regarding the treatment of PTL. The Italian authors studied 60 patients who were admitted in PTL, defined as having contractions 6 or more times in 30 minutes, and demonstrating cervical change by digital examination. Thirty patients were randomized to treatment with 17-α-hydroxyprogesterone caproate (17P) and the remaining 30 controls were not given the medication. All 60 patients received "standard tocolysis." Two of the authors, blinded to which group the patients were in, performed cervical length (CL) examinations by transvaginal ultrasound on admission, and then at 1 and 3 weeks later.
Frankly, the results were surprising. Fifty-seven percent (57%) of controls delivered prior to the 37 weeks vs 16% treated with 17P. The average birth weight in the control group was 2809 gm vs 3193 gm in the 17P patients. There was a statistically insignificant difference between groups with regard to delivery prior to 35 weeks, but the same trend persisted (23% in the placebo group vs 10% in the 17P group). What was intriguing were the changes in the CL over time between groups. At 7 days, the average decrease in CL between controls and treated patients, respectively, was 2.37 mm vs 0.83 mm; and at 21 days was 4.60 mm vs 2.40 mm.
Commentary
After years of evidence that tocolytics do not seem to work in preventing preterm birth, along came two studies to show that we should not give up in patients who are truly in PTL. These authors used progesterone as a last ditch effort in those patients already demonstrating strong evidence of labor, rather than as a prophylactic tactic, as first published by Meis et al (using IM 17P) or da Fronseca et al, using daily progesterone suppositories. Also, in the January issue of the same journal an article appeared suggesting that transdermal nitroglycerine patches prolong pregnancy by 10 days, on average, and can decrease neonatal morbidity significantly. They were particularly effective in those pregnancies below 28 weeks.
For a variety of reasons, I have been very skeptical about the efficacy of weekly IM progesterone in the prevention of PTL. However, it is clear from in vitro animal and human investigation, the role that progesterone plays to quiet smooth muscle, and here now is evidence to suggest that, even once the hormonal cascade of labor has been triggered, progesterone may work when given every 4 hours in patients presumably in preterm labor by the most stringent criteria.
Maybe there is light at the end of the tunnel?
On another note, the very next study in the above issue of the American Journal caught my eye. For years it has been common practice to administer antibiotics during cesarean sections after the cord has been clamped. The idea is that one would circumvent the fetus/infant from getting an unneeded, and potentially problematic, dose of antibiotics. Sullivan et al randomized 357 patients to be given one dose of cefazolin 15 to 60 minutes before skin incision or, alternatively, to have this given at the time of cord clamping (controls). The "early" group had less endometritis (1% vs 5%), fewer wound infections (2% vs 5%), and less "total infectious morbidity" (4.5% vs 11.5%). Yet, there were no differences in any types of neonatal morbidity between groups. Interestingly, there were fewer days in the nursery for infants born to the "early" mothers.
Like voting in Chicago, "early" may make sense, but not "often"—only once is recommended.
References
- Facchinetti F, et al. Am J Obstet Gynecol. 2007;196: 453.e1-453.e4.
- Meis P, et al. N Engl J Med. 2003;348:2379- 2385.
- da Fonseca EB, et al. Am J Obstet Gynecol. 2003;183:419-424.
- Smith GN, et al. Am J Obstet Gynecol. 2007;196: 37.e1-37.e-8.
- Sullivan SA, et al. Am J Obstet Gynecol. 2007;196:455.e1-455.e5.
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