Does the combined antenatal use of corticosteroids and antibiotics increase late-onset neonatal sepsis in the very low birth weight infant?

OBJECTIVE: The purpose of this study was to determine whether the combined use of maternal antenatal corticosteroids and antibiotic therapy is associated with an increased risk of late-onset neonatal sepsis among very low birth weight infants. STUDY DESIGN: The outcomes of infants admitted to the 3 Cincinnati neonatal intensive care units between May 1991 and May 2000 were retrospectively evaluated. Late-onset neonatal sepsis was defined either as the occurrence of a positive blood culture obtained after 72 hours of life with clinical signs of sepsis or as the need for >5 consecutive days of antibiotic therapy for presumed sepsis that initiated after 72 hours of life. Wilcoxon rank sum, chi-square test, and multiple logistic regression were used for analysis. RESULTS: Among the parturients delivering the study infants, 434 women (24%) received corticosteroids only, 175 women (9%) received antibiotics only, 819 women (46%) received both corticosteroids and antibiotics, and 370 women (20%) received neither corticosteroids nor antibiotics. Among 1978 study infants, there were 732 infants (41%) with late-onset neonatal sepsis. By univariate analysis, the odds ratio for late-onset neonatal sepsis caused by combined corticosteroid and antibiotic use was 0.96 (95% CI, 0.89%, 1.04%). Multiple logistic regression analysis was used to evaluate the risk of combined corticosteroids and antibiotic use after controlling for potential covariates and confounders. After controlling for outborn birth (odds ratio, 1.3; 95% CI, 1.0%-1.8%), increasing gestational age at delivery (odds ratio, 0.63; 95% CI, 0.60%-0.66%), interaction between white race and male gender (P =.01) and interaction between antibiotics and prolonged rupture of membranes (P =.02), the use of corticosteroids and antibiotics was not associated with an increased risk of late-onset neonatal sepsis (P =.9). CONCLUSION: The combined use of maternal corticosteroids and antibiotic therapy is not associated with an increased risk for late-onset neonatal sepsis.

A comparison of various routes and dosages of misoprostol for cervical ripening and the induction of labor.

OBJECTIVE: The purpose of this study was to compare the efficacy of different routes of misoprostol administration for cervical ripening and the induction of labor. STUDY DESIGN: Three hundred thirty women at > or = 32 weeks gestation with a Bishop score < or = 6 and an indication for induction were randomized to 1 of 3 double-blinded groups: (1) 25 microg orally administered misoprostol plus 25 microg vaginally administered misoprostol, (2) orally administered placebo plus 25 microg vaginally administered misoprostol, or (3) 25 microg orally administered misoprostol plus vaginally administered placebo. Doses were repeated every 4 hours until onset of labor or a maximum of 12 doses were given. The primary outcome of the trial was vaginal delivery within 24 hours of the initiation of induction. Secondary outcomes were the time from induction to delivery, need for oxytocin augmentation, mode of delivery, frequency of side effects, and neonatal and maternal outcome. Analysis of variance, chi-square test, and logistic regression were used for analysis. RESULTS: There were no significant differences in maternal characteristics or indications for induction. The percentage of women who achieved vaginal delivery within 24 hours was highest in the vaginally administered misoprostol group: 67% compared with 53% in the oral-plus-vaginal group (P < .05) and 36% in the oral group (P < .05). The median time to vaginal delivery was shorter in the vaginal and oral-plus-vaginal misoprostol groups, 13.5 hours and 14.3 hours, respectively, when compared with 23.9 hours in the oral group (P < .05). The rate of cesarean delivery was lowest in the vaginal misoprostol group (17% compared with 30% in the oral-plus-vaginal group and 32% in the oral group; P < .05). Uterine tachysystole occurred least frequently in the oral misoprostol group (10% compared with 32% in the vaginal group and 34% in the oral-plus-vaginal group; P < .05). Uterine hyperstimulation also occurred least frequently in the oral misopro-stol group (4% compared with 15% in the vaginal group and 22% in the oral-plus-vaginal group; P < .05). CONCLUSION: At the doses studied, induction of labor with vaginally administered misoprostol is more efficacious than either oral-plus-vaginal or oral-only route of administration.

Maturity testing with preterm premature rupture of the membranes.

The presence or absence of fetal pulmonary maturity as assessed by amniotic fluid analysis and the role of fetal maturity tests in the management of premature rupture of the membranes are addressed. The hazards of the high falsely immature test are carefully explored. A management scheme based on the results of amniotic fluid analysis is also described.

Antibiotic prophylaxis at Cesarean delivery.

OBJECTIVE: Our aim was to compare the efficacy of ampicillin, cefotetan, and ampicillin/sulbactam in the prevention of post-Cesarean endomyometritis. METHODS: Consenting patients undergoing Cesarean delivery at the University of Louisville Hospital were enrolled in a prospective, double-blinded randomization to receive either ampicillin/sulbactam (Group 1), cefotetan (Group 2), or ampicillin (Group 3) single dose antibiotic prophylaxis following umbilical cord clamping. The primary outcome variable was the frequency of endomyometritis in the respective groups. RESULTS: Among 301 randomized patients, outcome data was available for 298 patients. Fourteen patients (4.7%), all of whom underwent non-elective Cesarean delivery, developed endomyometritis. The frequency of endomyometritis was not different among groups: Group 1, 4/101 (4%); Group 2, 4/96 (4.2%); and Group 3, 6/101 (5.9%). Wound infections were infrequently observed 4/298 (1.3%) without significant differences among groups. Stepwise discriminative analysis identified only last cervical dilatation as a significant predictor of endomyometritis (P = 0.006). CONCLUSION: Post-Cesarean endomyometritis occurs infrequently following single dose antibiotic prophylaxis after umbilical cord clamping. An advantage of broader spectrum antibiotics over ampicillin was not demonstrated.

Maintenance oral nifedipine for preterm labor: a randomized clinical trial.

OBJECTIVE: This study was undertaken to evaluate the efficacy of maintenance oral nifedipine in patients initially treated with intravenous magnesium sulfate for preterm labor. STUDY DESIGN: Patients with a diagnosis of preterm labor between 24 and 33.9 weeks' gestation were randomly assigned to receive either maintenance tocolytic therapy with oral nifedipine (20 mg every 4-6 hours) or no treatment (control) after discontinuation of magnesium tocolysis. Pregnancy and neonatal outcomes were evaluated. A sample size of 50 patients was required to detect a 10-day difference in mean time gained (beta =.2, alpha =.05). Statistical analyses were based on intent to treat. The t, chi(2), and Fisher exact tests were performed. RESULTS: Seventy-four patients were randomly assigned to receive either oral nifedipine (n = 37) or no treatment (n = 37). There were no statistically significant differences in age, race, parity, preterm delivery risk factors, enrollment gestational age, results of cervical examination, delivery gestational age, time gained, or neonatal complications between the groups. Delivery gestational age (mean +/- SD) was 35.4 +/- 3.2 weeks for patients randomly assigned to receive nifedipine and 35.3 +/- 3.2 weeks for patients who received no treatment (P =.9). Time gained during pregnancy was 37 +/- 23.9 days in the nifedipine group and 32.8 +/- 20.4 days in the control group (P =.4). CONCLUSION: Maintenance therapy with oral nifedipine does not significantly prolong pregnancy in patients initially treated with intravenous magnesium sulfate for preterm labor.

Human chorionic gonadotropin exhibits potent inhibition of preterm delivery in a small animal model.

OBJECTIVE: The purpose of this study was to test the capability of human chorionic gonadotropin to inhibit prostaglandin-induced preterm delivery in a murine model. STUDY DESIGN: A preterm delivery model was developed by using intraperitoneal injection of 20 microgram of prostaglandin F(2)(alpha) to induce preterm labor in C3H/HeN inbred mice. Mice were then pretreated with human chorionic gonadotropin 4 hours before administration of prostaglandin F(2)(alpha), and time to delivery of the first pup was recorded. After initial promising results, mice were then given increasing intraperitoneal doses of human chorionic gonadotropin (100 IU, 250 IU, or 1000 IU or sodium chloride solution vehicle) 4 hours after administration of prostaglandin F(2)(alpha). The specificity of the human chorionic gonadotropin effect was assessed by treating mice with whole human chorionic gonadotropin, an equal mass dose of the beta-subunit or the alpha-subunit of human chorionic gonadotropin, or an equal mass dose of luteinizing hormone 4 hours after administration of prostaglandin F(2)(alpha). Delivery times between groups were compared by using the Mann-Whitney U test and the log-rank test. Survival estimates were computed by using the Kaplan-Meier method. RESULTS: Pilot studies in 52 mice confirmed that a single intraperitoneal injection of 20 microgram of prostaglandin F(2)(alpha) on day 16 (80% gestation) consistently induced preterm delivery compared with the effect of sodium chloride solution on control mice (prostaglandin F(2)(alpha), 19.3 +/- 2.9 hours; sodium chloride solution, 53.5 +/- 13.6 hours; P <.0001). Mice pretreated with human chorionic gonadotropin (1000 IU) demonstrated significant delays in delivery times compared with the prostaglandin-only group (prostaglandin F(2)(alpha) only, 21.9 +/- 2. 0 hours; human chorionic gonadotropin pretreatment plus prostaglandin F(2)(alpha), 48.5 +/- 20 hours; P <.0001; n = 17). Mice treated with human chorionic gonadotropin (100 IU, 250 IU, 1000 IU) 4 hours after administration of prostaglandin F(2)(alpha) demonstrated significant dose-dependent inhibition of preterm delivery compared with the prostaglandin-only group (P <.00005; n = 34). Mice treated with the alpha-subunit or the beta-subunit of human chorionic gonadotropin after prostaglandin administration did not demonstrate delays in delivery times (P =.46; n = 27). Administration of luteinizing hormone delayed delivery compared with the effect of prostaglandin F(2)(alpha) on control animals (P <.05; n = 17); however, the effect was less pronounced than that seen with a mass equivalent of human chorionic gonadotropin. CONCLUSIONS: Human chorionic gonadotropin exhibits potent inhibition of prostaglandin-induced preterm delivery in mice. The effect is dose-dependent, and whole human chorionic gonadotropin is required to elicit inhibition. Further studies are needed to determine the safety and efficacy of human chorionic gonadotropin as a potential therapy for preterm labor inhibition in human pregnancy.

Pregnancy complicated by the antiphospholipid syndrome: outcomes with intravenous immunoglobulin therapy.

OBJECTIVE: To assess maternal and fetal outcomes in 15 patients with antiphospholipid syndrome (19 pregnancies) treated with intravenous immunoglobulin (IV Ig) during pregnancy. METHODS: Monthly IV Ig therapy was initiated in the first or early second trimester of all pregnancies except two. Additional therapy consisted of low-dose aspirin and subcutaneous heparin. Six patients also received steroid therapy. Serial anticardiolipin IgG levels were measured in eight pregnancies. RESULTS: The live-birth rate was 84% (16 of 19 live births), and there were three pregnancy losses. There were no cases of fetal growth restriction (FGR). Preeclampsia and nonreassuring fetal status were each diagnosed in 25% of the pregnancies. Seventy-five percent of the infants were delivered at 34 weeks' gestation or later. Anticardiolipin IgG decreased throughout the course of therapy in seven pregnancies. Placental pathology was minimal. CONCLUSION: Pregnancy complications appear to be minimized with the use of IV Ig. Definitive recommendations regarding the use of IV Ig in pregnancy await the conclusion of randomized trials. If the combination of IV Ig, aspirin, and heparin significantly decreases the incidences of FGR and prematurity, it may be a cost-effective primary therapy for pregnancies complicated by the antiphospholipid syndrome.

Predictive value of fetal ultrasonography in the diagnosis of a lethal skeletal dysplasia.

BACKGROUND: Certain ultrasonographic findings identified in a fetus suspected of having a skeletal dysplasia may be predictive of a lethal outcome. METHODS: We evaluated 27 fetuses suspected of having a skeletal dysplasia using targeted ultrasonography between 16 and 31 weeks' gestation. Clinical examination and skeletal radiography were done after delivery. RESULTS: A skeletal dysplasia was confirmed and a diagnosis established in all but one case. The skeletal dysplasia was lethal in 23 cases and, in each case, the outcome was accurately predicted prenatally; however, three of the infants survived several months. In 11 of the 23 cases (48%), the specific diagnosis was correctly determined before birth. Ultrasonographic findings not considered to reflect a lethal outcome, were accurately predicted in two other cases. In an additional two, sonographic examination suggested a lethal osteochondrodysplasia, though both survived. Findings consistent with a lethal skeletal dysplasia included a femur length < 1st centile, combined with either a bell-shaped thorax, decreased bone echogenicity, or both. Using these criteria provided a positive-predictive value for neonatal deaths of 80% (20/25), and 92% (23/25) if the three that died in infancy were included. CONCLUSIONS: In the fetus suspected of having a skeletal dysplasia, certain findings on targeted ultrasonography frequently are predictive of a lethal outcome; the ability to predict this appears greatest when more than one of these abnormalities is present.

Informed consent and the redefining of conception: a decision ill-conceived?

The purposes of this study are to assess the use of the American College of Obstetricians and Gynecologists' (ACOG) definitions of conception (a synonym for implantation) and the beginning of pregnancy (at implantation) in the clinical practice of its members and to explore the implications of differing definitions of conception and pregnancy onset for the process of informed consent. A survey was mailed to 112 members of the Louisville Ob/Gyn Society asking what definition of conception they used in their clinical practice and when they judged pregnancy began. A second mailing was sent to nonresponding members. Using logistic regression analysis, the responses to these questions were evaluated with respect to practice type, number of years in practice, and the ACOG membership. Responses were received from 86% (96 of 112) of the members. A total of 73% (70 of 96) (95% CI 69-77%) of the members indicated that conception was a synonym for fertilization, and 24% (23 of 96) (95% CI 21-28%) indicated that conception was a synonym for implantation (P < .001). Of the members, 50% (48 of 96) indicated that pregnancy began at fertilization, and 48% (46 of 96) indicated that pregnancy began with implantation (NS). Regression analysis failed to demonstrate a significant relationship to type of practice, years in practice, or the ACOG membership for these responses. Neither ACOG definition has been consistently adopted by its members whose definitions are more consistent with lay and embryologist definitions. Potentially, the process of informed consent is jeopardized by these ambiguities. The ACOG is urged to reconsider its definitions.

Chorioamnionitis: is continuation of antibiotic therapy necessary after cesarean section?

OBJECTIVE: Our purpose was to determine whether the continuation of antibiotics postoperatively after cesarean section in patients whose labors were complicated by chorioamnionitis would reduce the incidence of endometritis. STUDY DESIGN: Patients with a clinical diagnosis of chorioamnionitis treated with ampicillin during labor and who required cesarean delivery for obstetric indications received preoperative intravenous clindamycin and gentamicin and were randomized into 2 groups. Group 1 received no scheduled postoperative antibiotics and group 2 continued to receive clindamycin 900 mg every 8 hours and gentamicin 1.5 mg/kg every 8 hours until afebrile for a minimum of 24 hours (temperature

Transvaginal versus transperineal ultrasonography: a blinded comparison in the assessment of cervical length at midgestation.

OBJECTIVE: The study's objective was to determine the correlation and agreement between transperineal ultrasonography and transvaginal ultrasonography in the assessment of cervical length in gravid patients. STUDY DESIGN: After a pilot, unblinded series of transperineal and transvaginal cervical length measurements in 200 gravid patients, 206 study patients between 14 and 34 weeks' gestation with intact membranes and cervical dilatation of < or = 2 cm underwent transperineal and transvaginal cervical length assessment under a blinded, 2-sonographer protocol. The Pearson correlation coefficient, Lin concordance coefficient, and Bland-Altman plot were used. Acceptable concordance was defined as > 0.82, with an acceptable correlation of > 0.9 and an acceptable difference between the means of < 3 mm. The power of the study to detect this degree of concordance was estimated to be 95% at this sample size. RESULTS: Paired ultrasonographic measurements were obtained for all 206 study patients. Transperineal mean cervical length was 35 +/- 8.6 mm. Transvaginal mean cervical length was 35.9 +/- 8.8 mm. The Pearson correlation coefficient was 0.959, and the Lin concordance coefficient was 0.955, with a 95% confidence lower bound of 0.949. Close agreement between transperineal and transvaginal measurements was observed across the full range of cervical lengths (1-5 cm). The estimated difference between the paired means was 1 mm. The 95% tolerance interval for any given paired observation (Transperineal length - Transvaginal length) was -5.7 to +4 mm. CONCLUSIONS: Cervical length measured by transperineal ultrasonography demonstrates close correlation and agreement with transvaginal measurements. With sonographer experience and optimal technique, approximately 95% of transperineal cervical length observations can be expected to be within 5 mm of a given paired transvaginal measurement. Transperineal ultrasonography may be a preferred method of cervical length assessment for situations in which vaginal placement of instruments should be minimized.

Immune recognition of endometrial tumor antigens induced by multiparity.

OBJECTIVE: The risk of developing endometrial cancer is reduced with increasing parity. The purpose of this study was to investigate the possibility that maternal immunization against fetal antigens might be elicited during pregnancy and, if so, to characterize antigens reactive with this immune response. METHODS: Sera were obtained from nulliparous (n = 9) and multiparous women (n = 14). Cellular proteins were isolated from normal endometrium and cultured cells from early (HEC-1A) and late (KLE and RL95-2) stage endometrial cancers. These were separated by SDS-PAGE and those proteins reactive with each individual's serum were assessed by Western immunoblot. Reactive proteins were isolated from KLE tumor cells by immunoaffinity columns. Three commonly recognized proteins were identified, separated, and processed for internal microsequencing. RESULTS: Sera from multiparous women, used as primary antibodies, recognized multiple bands on endometrial tumors, ranging from 10 to 120 kDa. Several antigens were commonly recognized by the sera of multiparous women. The three commonly recognized proteins, normally expressed by fetal tissues, were identified as cystatin A (10 kDa), epidermal fatty acid binding protein (18 kDa), and keratin 10 (54 kDa). Nulliparous women failed to recognize these antigens. CONCLUSION: These findings suggest that certain antigens expressed by the fetus and/or the placenta immunize women during pregnancy. This immune response may protect these women from developing endometrial cancer and explain epidemiologic findings. Future studies will explore the utility of these reexpressed fetal antigens as possible targets for active immunotherapy.

Hemolytic disease of the fetus: a comparison of the Queenan and extended Liley methods.

OBJECTIVE: To compare the clinical utility of the Liley and Queenan methods to monitor the severity of fetal hemolytic disease. METHODS: Amniotic fluid bilirubin was measured in specimens from 73 women sensitized to red blood cell antigens. Chloroform-extracted amniotic fluid was evaluated spectrophotometrically for bilirubin content by using the change-from-expected value of the optical density at 450 nm. Values in the four Queenan zones were compared with those of the four zones of the Liley graph (middle zone subdivided). Clinical utility and accuracy of the two methods were compared. RESULTS: Treatment was based on interpretation of bilirubin values plotted on the Liley graph. Hydrops fetalis was not observed. The highest value for each patient was significantly more likely to be plotted in the highest zone using the Queenan method (23 of 73 compared with eight of 73 patients; P < .001). Overestimation of risk occurred with greater frequency when using the Queenan method (13 of 67 compared with seven of 67 patients; P = .031). Overestimation of risk by the Queenan method also was more likely at or before 28 weeks' gestation (10 of 49 compared with four of 49 patients; P = .031). In nine cases (13%), the Queenan graph and method would have prompted unnecessary or premature umbilical vein sampling that was withheld using the Liley graph. CONCLUSION: The performance of the linearly extended Liley graph was superior to that of the Queenan graph, because the Queenan method frequently overestimated risk.

Preterm premature rupture of membranes: aggressive tocolysis versus expectant management.

The objective of our study is to determine whether aggressive tocolysis in patients with preterm premature rupture of membranes between 24 and 34 weeks gestation improves neonatal outcome. Patients with documented preterm premature rupture of membranes between 24 and 34 weeks gestation were prospectively randomized to group I, aggressive tocolysis with intravenous magnesium sulfate, or to group II, no tocolysis. The lecithin/sphingomyelin ratio was determined upon hospital admission and every 48-96 hours until delivery. Both groups received weekly steroids and antibiotics pending culture results and were promptly delivered when chorioamnionitis, fetal stress, or an Lecithin/sphingomyelin ratio of > or = 2.0 occurred. The study group involved 145 patients. No statistically significant differences between groups I (n = 78) and II (n = 67) were observed regarding demographic characteristics, gestational age at enrollment or at delivery, latency, development of clinical chorioamnionitis, birth weight, number of days in neonatal intensive care unit, days on oxygen or ventilatory support, frequency of hyaline membrane disease, necrotizing enterocolitis, intraventricular hemorrhage, neonatal sepsis, or neonatal mortality. Our data suggest that tocolysis in patients with preterm premature rupture of membranes does not significantly improve perinatal outcome.

Induction of immune responses to ovarian tumor antigens by multiparity.

OBJECTIVE: Because epidemiologic data indicate a reduction in ovarian cancer risk with increased parity, the occurrence of maternal immunization against ovarian tumor-associated antigens during pregnancy was investigated. METHODS: Sera were obtained from nulligravid and multiparous women and from men. Cellular proteins were isolated from four ovarian tumor cell lines as well as from normal ovaries. These proteins were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and the presence of cellular proteins reactive with each individual's serum was assessed by Western immunoblot. Tumor-reactive antibodies from two multiparous women were used to prepare immunoaffinity columns for the isolation of reactive proteins from ovarian tumor cells. These immunoaffinity-purified antigens were transferred electrophoretically to nitrocellulose membranes, stained with Ponceau S, and identified by amino acid sequencing. RESULTS: Western immunoblot analysis of the cellular proteins from four established ovarian tumor cell lines using sera from multiparous women as the primary antibody indicated that these samples recognized multiple bands on ovarian tumors, ranging from 30 to 150 kD. Two commonly recognized proteins were isolated and subjected to microsequencing, which identified the 56-kD band protein as elongation factor-1 alpha and the 38-kD protein as nucleophosmin/B23 protein. Both of these proteins play integral roles in cell growth. CONCLUSION: These findings suggest that certain antigens expressed by the fetus immunize women during pregnancy. This immune response may protect these women from the subsequent development of cancer.

Mechanism of action of intrauterine contraceptive devices and its relation to informed consent.

The purposes of this review are to evaluate the available evidence for the mechanisms of action of copper-impregnated intrauterine contraceptive devices and to describe the informed consent consequences of those mechanisms. The medical literature was reviewed with the use of the Bioethics and Medline databases (1966 to present). Reports that supported or refuted the two major postulated mechanisms (interference with implantation of the fertilized ovum or spermicidal inhibition of fertilization) were assessed for their relative strength and support for the exclusivity of one or the other mechanism. The analysis of the evidence strongly suggests that the contraceptive effectiveness of intrauterine contraceptive devices is achieved by both a prefertilization spermicidal action and a postfertilization inhibition of uterine implantation. Patient informed consent for intrauterine contraceptive device insertion should include a discussion of these mechanisms of actions so as to avoid their use in patients with moral objections to postfertilization contraception.

Perforation rate using a single pair of orthopedic gloves vs. a double pair of gloves in obstetric cases.

Our purpose was to determine the perforation rate for a single pair of orthopedic gloves vs. a double pair of regular gloves in obstetric cases. Faculty, residents, medical students, and surgical technicians were assigned randomly to use either double gloves or single orthopedic gloves. After each procedure, the gloves were examined by filling with water, occluding the cuff, and observing for streams of water. The perforation rate for the double gloves (both inner and outer glove at the same location) was 7% (12/169), similar to the 7% (12/172) for single orthopedic gloves (P < 0.9). After adjusting for procedure type there was no association between the type of gloves and perforation rate. Fifty-four percent of all perforations were not recognized intraoperatively. Of those individuals with glove perforations, 4/24 (17%) observed blood on the hand at the end of the procedure. Double-gloved users complained more frequently than single-gloved users of loss of dexterity (77/169, 46%, 95% CI 38-53%) vs. (6/172, 3.5%, 95% CI 0.7-6%) (P < 0.001) and numbness (12/169, 7%, 95% CI 3.2-11%) vs (1/172 0.6%, 95% CI 0.55-1.7%) (P < 0.005). Although the use of a single pair of orthopedic gloves is more costly than a double pair of regular gloves ($78 vs. $15 per box), it is as safe and as effective as a double pair of gloves in maintaining a sterile barrier. The primary advantage of a single pair of orthopedic gloves is that surgical dexterity is minimally compromised when compared to double gloves.

Effect of three concentrations of intracervical prostaglandin E2 gel for cervical ripening.

To evaluate the efficacy and safety of three concentrations of prostaglandin E2 (PGE2) gel for preinduction cervical ripening. Two hundred ninety-one patients with an unfavorable cervix scheduled for induction of labor were eligible to participate in a prospective, randomized, double-blind study of one or two doses of intracervical PGE2 gel. Group 1 received a dose of 0.125 mg/2 ml; group 2 received 0.25 mg/2 ml; and group 3 received 0.5 mg/2 ml. Outcome variables included change in Bishop score, uterine tachysystole, oxytocin use, route of delivery, and maternal and neonatal complications. Two hundred twenty-nine patients were included in the study, 79 in group 1, 70 in group 2, and 80 in group 3. Among the three groups, no statistically significant differences were noted for change in Bishop score, uterine tachysystole, oxytocin use, route of delivery, or incidence of maternal or neonatal complications, Subsequent labors were frequently complicated by fetal heart rate abnormalities (24.3%) and uterine tachysystole (9.6%); 84 (38.9%) patients were delivered by cesarean section. A dose-dependent influence on outcome variables was not identified. Complications from PGE2-ripening within 4 hours of gel application were not dose dependent and occurred infrequently. This study demonstrates that there is no dose in the range tested that assures an absences of tachysystole, limiting the role of outpatient cervical ripening without some period of observation.