Antenatal thyrotropin-releasing hormone to prevent lung disease in preterm infants. North American Thyrotropin-Releasing Hormone Study Group.

BACKGROUND: Pulmonary disease is common in preterm infants, despite antenatal glucocorticoid therapy. The addition of antenatal thyrotropin-releasing hormone therapy has been reported to decrease pulmonary morbidity in these infants. METHODS: We enrolled 996 women at 13 North American centers who were in preterm labor at <30 weeks' gestation in a double-blind, placebo-controlled, randomized trial of antenatal thyrotropin-releasing hormone, given intravenously in four doses of 400 microg each at eight-hour intervals. The primary outcome was chronic lung disease or death of the infant on or before the 28th day after delivery, and secondary outcomes were respiratory distress syndrome and chronic lung disease or death at 36 weeks' postmenstrual age. Complete data were available for 981 women and their 1134 live-born infants. The 769 infants born at < or = 32 weeks' gestation were defined as the group at risk. RESULTS: There were no significant differences between the at-risk treatment and placebo groups in mean (+/-SD) birth weight (1109+/-354 vs. 1097+/-355 g), gestational age (27.9+/-2.1 vs. 27.9+/-2.1 weeks), sex, or race. The frequencies of respiratory distress syndrome (66 percent vs. 65 percent), death at 28 days (11 percent vs. 11 percent), chronic lung disease or death at 28 days (45 percent vs. 42 percent) and at 36 weeks (32 percent vs. 34 percent), and other neonatal complications as well as the severity of lung disease were not significantly different in the at-risk treatment and placebo groups. Similarly, there were no differences in outcome between the treatment and placebo groups for the infants born at >32 weeks' gestation. CONCLUSIONS: In preterm infants at risk for lung disease, antenatal administration of thyrotropin-releasing hormone and glucocorticoid is no more beneficial than glucocorticoid alone.

Outpatient cervical ripening.

A limited number of studies have provided preliminary data on the efficacy and safety of PGE2 used as an outpatient cervical ripening agent. Multiple inpatient studies have confirmed the effect of PGE2 in favorably changing the cervical score, reducing the incidence of failed inductions and instrumental deliveries, shortening the induction-to-delivery interval, and reducing oxytocin use with few maternal side effects and no known adverse effects on neonatal outcome. These studies, however, are difficult to compare because of differences in study design, PGE2 formulation, patient selection (including differences in cervical scoring criteria), indications for labor induction, placement of the PGE2 agent, and outcome variables, and they certainly cannot be extrapolated to outpatient use. Intracervically applied Prepidil is the only form of PGE2 approved by the Food and Drug Administration available for cervical ripening. The commercial production of an intravaginal form of PGE2, which would require less effort and expertise in administration and greater patient comfort, may warrant exploration. In an environment of increasing pressures for cost containment, the convenience and cost-effectiveness of outpatient cervical ripening provides a stimulus for further controlled studies in this area to delineate an effective and safe dose and vehicle for widespread application.

Pre-induction cervical ripening: a randomized comparison of two methods.

OBJECTIVES: To compare two methods of pre-induction cervical ripening in a randomized clinical trial. METHODS: A single intracervical prostaglandin E2 (PGE2) gel application was compared with a single insertion of hygroscopic dilators in 441 women at term with unfavorable cervical scores. Induction success was defined as entry into active labor within 6 hours of oxytocin infusion. RESULTS: There was no statistical difference in pre- or post-ripening cervical scores. In the group receiving hygroscopic dilators, only 28% entered the active phase of labor within 6 hours of oxytocin infusion compared with 45% (P < .001) in the PGE2 group. Thus, in this study, a change in cervical score did not directly predict induction success. There was a higher rate of postpartum endometritis (24 versus 14%; P = .007) and suspected neonatal infection (10 versus 5%; P = .03) in the dilator group. CONCLUSIONS: Pre-induction ripening by hygroscopic dilators and intracervical PGE2 was equivalent as measured by changes in the cervical score. The change in cervical score, however, was not predictive of successful induction, and PGE2 was more frequently associated with induction success. Hygroscopic dilators were associated with a higher incidence of postpartum maternal and neonatal infection because of a longer duration of labor. Hospital charges for intracervical PGE2 gel totaled $522 compared with $91 for the insertion of three dilators.

Patient-administered outpatient intravaginal prostaglandin E2 suppositories in post-date pregnancies: a double-blind, randomized, placebo-controlled study.

OBJECTIVE: To shorten post-date pregnancies in a safe, effective manner by outpatient acceleration of cervical ripening. METHODS: Eighty patients with uncomplicated pregnancies at or beyond 41 weeks' gestation and a cervical Bishop score less than 9 were randomized to daily self-administered, 2-mg intravaginal prostaglandin E2 (PGE2) or placebo suppositories. Each followed a standard post-date antepartum surveillance protocol. Patients were admitted for spontaneous labor or for induction if the Bishop score reached 9, antepartum testing was nonreassuring, exclusion criteria were fulfilled, or if the gestational age reached 44 weeks. RESULTS: Fewer suppositories were used in the PGE2 group (four versus seven; P = .006), resulting in earlier gestational age on admission (295 versus 297 days; P = .021) and lower antepartum testing charges ($476.97 versus $647.29; P = .001). Labor and delivery time was significantly decreased in nulliparas (10.7 +/- 5.1 versus 15.3 +/- 7.6 hours; P = .035). CONCLUSIONS: Daily low-dose, patient-administered PGE2 vaginal suppositories can decrease the gestational length and cost of uncomplicated post-date pregnancies by reducing the time to achieve a favorable cervix, the need for antepartum testing, and, potentially, post-date-related complications.

Sequential outpatient application of intravaginal prostaglandin E2 gel in the management of postdates pregnancies.

A randomized blinded investigation was undertaken to determine the efficacy and safety of sequentially applied intravaginal prostaglandin E2 (PGE2) gel for accelerating cervical ripening in an outpatient setting in low-risk prolonged pregnancies. Fifty women with uncomplicated pregnancies at or beyond 41 weeks' gestation and Bishop scores below 9 received twice-weekly outpatient administration of gel containing 2.0 mg of PGE2 or placebo. Thirty nulliparas and 20 multiparas were enrolled. The PGE2 gel failed to improve cervical ripening over placebo, as judged by Bishop scores. There was no difference between the groups in gestational age on admission to the labor and delivery suite, number of gel applications, requirement for oxytocin, incidence of cesarean delivery, or neonatal outcome. Only two patients (4%) experienced regular uterine contractions after gel insertion; these subsided spontaneously in both. None of the subjects experienced labor, tetanic contractions, evidence of fetal distress, or any other side effects related to gel insertion. We conclude that PGE2 gel in this dosage may be used safely in an outpatient setting, but more frequent application or earlier initiation may be required to produce a clinical effect.

The effect of magnesium sulfate infusion on systemic and renal prostacyclin production.

Recent in vitro studies have suggested that magnesium sulfate (MgSO4) infusions may increase prostacyclin production. We studied the effect of MgSO4 infusion on prostacyclin (PGI2) metabolite excretion in women with either pregnancy induced hypertension or preterm labor. Excretion of renal and systemic metabolites of PGI2 was measured prior to and following the start of MgSO4 infusion in the two groups. An increased in renal PGI2 metabolite preterm labor excretion was noted in the hypertension group but no change was noted in systemic PGI2 excretion in either group. These data fail to support a generalized, short term increase in endothelial cell PGI2 production as the basis for the beneficial effect of MgSO4.

Late diagnosis of nonconjoined monoamniotic twins using computed tomographic imaging: a case report.

Monoamniotic twin gestations, although rare, are associated with a high perinatal mortality rate. Early antenatal diagnosis is important to ensure optimal perinatal care. However, the diagnosis can be difficult to confirm, especially in late gestation when a dividing membrane may be difficult to visualize. Intra-amniotic injection of Renografin followed by a single-slice computed tomographic scan at the level of the umbilicus is described. This imaging method assisted in the confirmation of monoamniotic twinning.