A shift in progesterone-to-estradiol balance to estradiol dominance is assumed to be a prerequisite for regular uterine contractions. To antagonize this effect in premature labor 24 consecutive women were treated with intravenous cortisol for 3 days and with weekly intramuscular injections of 17 alpha-hydroxyprogesterone caproate (17 OHP-C). Twenty-four similar patients treated with ritodrine served as a reference group. The delivery was postponed by at least 1 week in 21 patients (87.5%) in the steroid treatment group and in 18 patients (75%) in the ritodrine group. The premature labor lasted for 5.1 +/- 0.4 hours (mean +/- SEM) with steroid therapy and for 2.2 +/- 0.3 hours with ritodrine. In singleton pregnancies the gestational length and birth weight of the newborn infants were greater in the steroid treatment group (N = 23, 39.1 +/- 0.3 weeks, 3,460 +/- 119 gm) than in the ritodrine group (N = 24, 37.7 +/- 0.4 weeks, 3,106 +/- 118 gm). Steroid treatment suppressed serum estradiol concentrations (maximally by 60%) and, to a lesser extent, testosterone, estriol, and progresterone levels (maximally by 30%).
PMID 7424996 7424996 DOI 10.1016/0002-9378(80)90137-4 10.1016/0002-9378(80)90137-4
Cite this article
Kauppila, A., Hartikainen-Sorri, A. L., Jänne, O., Tuimala, R., & Järvinen, P. A. (1980). Suppression of threatened premature labor by administration of cortisol and 17 alpha-hydroxyprogesterone caproate: a comparison with ritodrine. American journal of obstetrics and gynecology, 138(4), 404-408. https://doi.org/10.1016/0002-9378(80)90137-4
Kauppila A, Hartikainen-Sorri AL, Jänne O, Tuimala R, Järvinen PA. Suppression of threatened premature labor by administration of cortisol and 17 alpha-hydroxyprogesterone caproate: a comparison with ritodrine. Am J Obstet Gynecol. 1980;138(4):404-408. doi:10.1016/0002-9378(80)90137-4
Kauppila, A., et al. "Suppression of threatened premature labor by administration of cortisol and 17 alpha-hydroxyprogesterone caproate: a comparison with ritodrine." American journal of obstetrics and gynecology, vol. 138, no. 4, 1980, pp. 404-408.
Our aim was to determine the efficacy and safety of tocolytic agents currently used to treat premature labor. We carried out a comprehensive review of tocolytic agents in the treatment of premature labor. Three hundred twenty-eight studies published between 1933 and 1992 were analyzed. An analysis of randomized, placebo-controlled, clinical trials showed that magnesium sulfate is not better than placebo in the treatment of premature labor. beta-Adrenergic receptor agonists effectively stop premature labor for only 24 to 48 hours. Calcium channel blockers and oxytocin antagonists inhibit uterine contractions, but their role in stopping labor is undefined. Prostaglandin inhibitors appear to be effective in treating premature labor and have few adverse side effects. The only tocolytic drugs that might be effective are the prostaglandin inhibitors. Tocolytic agents should be used only between 24 and 32 completed weeks of gestation. Magnesium sulfate should not be used to treat premature labor. Oxytocin antagonists should be used only in experimental clinical trials. Calcium channel blockers and beta-adrenergic receptor agonists inhibit uterine contractions but do not prolong gestation for longer than 48 hours.
The null hypothesis of this study is that maternal administration of indomethacin or terbutaline will not affect fetal breathing and body movements. Thirty patients with a low-risk pregnancy, gestational age 26 to 32 weeks, and no signs of preterm labor were randomly assigned to receive either terbutaline (5 mg), indomethacin (50 mg), or a placebo. Ultrasonographic evaluation of fetal breathing and body movements was performed for 1 hour before and 1 hour after treatment. The total amount of time of fetal breathing and body movements in each group was subject to statistical analysis that included analysis of variance and covariance and a multiple comparison procedure. Indomethacin increased fetal breathing from 20.8 +/- 13.1 minutes to 42.2 +/- 14.8 minutes (p < 0.01), whereas terbutaline increased fetal breathing movements from 19.8 +/- 9.0 minutes to 35.2 +/- 12.4 minutes (p < 0.01). No significant treatment effect was detected on fetal body movements. Between 26 and 32 weeks' gestation, a single dosage of indomethacin or terbutaline increases fetal breathing movements by 103% and 78%, respectively.
Home uterine activity monitoring has been described as an effective means of detecting uterine contractions, but controversy exists whether it is home uterine activity monitoring or increased nursing support in conjunction with it that contributes to earlier detection of preterm labor. In this study 377 women at risk for preterm labor from three centers were prospectively, randomly assigned to high-risk prenatal care alone (not monitored) or to the same care with twice-daily home uterine activity monitoring without increased nursing support (monitored). The two groups were medically and demographically similar at entry into the study. Routine visits, nonroutine visits, and gestational age at diagnosis of preterm labor were similar in both groups. Preterm labor occurred in 41 of 198 monitored and 39 of 179 not monitored patients. Mean cervical dilatation was 1.4 cm in 41 monitored compared with 2.5 cm for 37 not monitored (p = 0.0006); 73.1% of monitored and 27.5% of not monitored had preterm labor detected before 2 cm dilatation (p = 0.00009). Neonatal outcome of singleton pregnancies showed greater birth weight, fewer days in the neonatal intensive care unit, and fewer babies requiring oxygen therapy and mechanical ventilation in the monitored group. The better outcomes are probably due to the increased likelihood of diagnosis of preterm labor before advanced cervical dilatation with home uterine activity monitoring, thus providing the clinician with a better chance to initiate tocolytic therapy directed at improving pregnancy outcome.
A randomized prospective trial was performed to compare the efficacy and safety of ritodrine and indomethacin in the long-term treatment of preterm labor. Forty patients with intact membranes in preterm labor at 23 to 34 weeks' gestation were randomized to receive either intravenous ritodrine or oral indomethacin as the first-line tocolytic agent. Successful intravenous ritodrine therapy was followed by oral terbutaline therapy, and indomethacin-treated patients continued to receive oral indomethacin. Treatment failures were defined as progressive preterm labor or patient intolerance, and these patients were treated with intravenous magnesium sulfate. Ritodrine and indomethacin were equally successful in delaying preterm birth as defined by interval to delivery, gestational age at delivery, delivery delayed greater than 7 days, attainment of 35 weeks of gestation, percentage of patients who required magnesium sulfate therapy, percentage of patients who were readmitted with premature rupture of membranes, absence of recurrent preterm labor, and infant birth weight. More than 80% of mothers who received ritodrine voiced complaints of beta-sympathomimetic side effects, and one patient discontinued treatment as the result of intolerance. There were minimal patient complaints with indomethacin use. No statistically significant differences were noted in neonatal outcome as defined by Apgar scores, umbilical cord pH, intensive care days, ventilator days, or neonatal deaths. However, three cases of primary pulmonary hypertension were observed in the indomethacin group. We had not previously observed this problem with short-term (24 to 48 hours) indomethacin therapy.