The use of prostaglandin E2 in pregnant patients with asthma

Objective

Prostaglandin E₂ is a pharmacologic agent that is used commonly in obstetrics; however, its usage in patients with asthma is unclear. The study objective was to examine pregnant patients with asthma who received prostaglandin E₂.

Study design

All pregnancies that were given prostaglandin E₂ suppositories and/or gel were recorded prospectively from January 1989 through December 2000. Those cases with a history of asthma or active asthma were analyzed for any clinical evidence of disease exacerbation after the administration of the agent. Clinical exacerbation was defined as any respiratory complaint that followed drug usage, the initiation of bronchodilator medications by patients currently not on therapy, or an increase in bronchodilator usage by patients with active disease.

Results

During the study period, 2513 patients received treatment with the cervical ripening gel, of whom 158 patients had a history of asthma or active asthma. Additionally, 536 patients were administered the 20-mg suppositories, of whom 31 patients had a history of asthma or active asthma. Thus, a total of 189 patients with a history of asthma or active asthma were exposed to prostaglandin E₂, and none of the patients had any evidence of a clinical exacerbation of the disease (0/189 cases; 95% CI, 0- 2%).

Conclusion

Based on the 95% CI of these data, the maximum risk for the development of a clinical exacerbation of asthma, if exposed to the obstetric forms of prostaglandin E₂, is ≤2%. Although all drug usage in patients with asthma should be monitored carefully, this information would support the usage of prostaglandin E₂, if obstetrically indicated, in pregnant patients with asthma.     

Factors predicting labour onset in patients treated with prostaglandin E2 for cervical ripening

The aim of this study is the evaluation of predictive factors in the onset of labour after pre-induction cervical ripening with prostaglandins. We enrolled 112 consecutive singleton term pregnancies (37–42.3 weeks) with unfavourable cervix and intact membranes, requiring induction of labour because prolonged pregnancy (59%) or maternal/fetal complications (41%). Treatment consisted of the cervical application (once or twice, 12 h apart) of prostaglandin E₂ gel (Upjohn, Italy). Uterine activity was monitored by external cardio-tocography before and during the next 2 h. Two patients showed uterine hyperstimulation and acute fetal distress requiring caesarean section. Sixty percent of patients went to labour and delivered without further stimulations. In this group the rate of caesarean section (9.1%) was lower than in patients failing to onset labour (68.2%). According to the logistic regression three factors positively predicted the onset of labour: first-hour uterine contractility, basal uterine activity and gestational age. The first-hour contractility in particular, represents the myometrial sensitivity to prostaglandin E₂ and may become a practical marker of spontaneous onset of labour in patients undergoing cervical ripening.     

A comparison of misoprostol and prostaglandin E2 gel for preinduction cervical ripening and labor induction

Objective: Our purpose was to compare the safety ad efficacy of intravaginal misoprostal versus intracervical prostaglandin E₂ (dinoprostone) gel for preinduction cervical ripening and induction of labor.Study design: One hundred thirty-five patients with indications for induction of labor and unfavorable cercices were randomly assigned to receive either intravaginal misoprostol or intracervical dinoprostate. Fifty microgram tablets of misoprostol were placed in the posterior vaginal fornix every 3 hours for a maximum of six doses. Prostaglandin E₂ in gel form, 0.5 mg, was placed into the endocervix every 6 hours for a maximum of three doses. Medication was not given after either spontaneous rupture of membranes or beginning of active labor.Results: Among 135 patients enrolled, 68 received misprostol and 67 dinoprostone. The average interval from start of induction to vaginal delivery was shorter in the misoprostol group (903.3 ± 482.1 minutes) than in the dinoprostone group (1410.9 ± 869.1 minutes) (p < 0.001). Oxytocin augmentation of labor occurred more often in the dinoprostone group (65.7%) than in the misoprostal group (33.8%) p < 0.001). There were no significant differences between routes of delivery. Ten of the misoprostol-treated patients (14.7%) and 13 of the dinoprostone-treated patients (19.4%) had cesarean deliveries. There was a higher prevalence of tachysystole (six or more uterine contractions in a 10-minute window for two consecutive 10-minute periods) in the misoprostol group (36.7%) than in the dinoprostone group (11.9%) (p < 0.001). However, there were no significant differences in frequency of uterine hyperstimulation or hypertonus. There was a higher prevalence of meconium passage in the misoprostol group (27.9%) than in the dinoprostone group (10.5%) (p < 0.05). Thee was no significant difference in frequency of abnormal fetal heart rate tracings, 1- or 5-minute Apgar scores <7, neonatal resuscitations, or admissions to the neonatal intensive care unit between the two groups.Conclusions: Vaginally administered misoprostol is an effective agent for cervical ripening and induction of labor; however when given at this dosage, it is associated with a higher prevalence of tachysystole and meconium passage than is dinoprostone. Further studies to compare the safety of misoprostol to that of dinoprostone and to delineate an optimal dosing regimen for misoprostol are needed.     

Efficacy of outpatient induction with low-dose intravaginal prostaglandin E2: A randomized, double-blind, placebo-controlled trial

OBJECTIVE: Our purpose was to determine whether a protocol for outpatient induction is safe and effective for initiating labor.STUDY DESIGN: A randomized, double-blind, a placebo-controlled trial was performed with 100 low-risk patients having well-dated pregnancies. Women with a Bishop score ≤6 at 38 to 40 weeks' gestation were administered either 2 mg of intravaginal prostaglandin E₂ gel or placebo for 5 consecutive days as outpatients while undergoing fetal monitoring.RESULTS: The median interval from randomization to delivery was 4 days in the prostaglandin E₂ group (range 0 to 28 days) and versus 10 days in the placebo group (range 0 to 26 days, p = 0.002). Twenty-seven of 50 patients (54%) in the prostaglandin E₂ group were admitted for labor during the dosing interval compared with 10 placebo-treated patients (20%, p = 0.001). The mean gestational age at delivery was significantly reduced in the treatment group (39.9 ± 1.0 weeks vs 40.5 ± 0.99 weeks, p = 0.003) as was the incidence of postdates pregnancy (40% vs 66%, p = 0.016). Hyperstimulation was observed in one prostaglandin E₂-treated patient, but no intervention was required.CONCLUSIONS: Outpatient low-dose prostaglandin E₂ gel administration is effective for initiating labor in patients with an unfavorable cervix and appears safe if performed with adequate monitoring.     

Preinduction cervical ripening: A randomized prospective comparison of the efficacy and safety of intravaginal and intracervical prostaglandin E2 gel

OBJECTIVE: The purpose of this study was to compare the effectiveness and safety of vaginally administered 5 mg prostaglandin E₂ gel prepared in our hospital pharmacy with a commercially available 0.5 mg intracervical prostaglandin E₂ gel.STUDY DESIGN: Eighty-three patients undergoing labor induction were randomly assigned to one of two groups for cervical ripening. Either a preparation of 5 mg of prostaglandin E₂ was placed vaginally or a commercially available 0.5 mg of prostaglandin E₂ was placed intracervically. A maximum of three doses at 6-hour intervals was administered before oxytocin was begun.RESULTS: Among the 83 patients evaluated, 44 were given vaginal gel and 39 were given intracervical gel. No statistically significant differences were observed between the two treatment groups with respect to the incidence of spontaneous versus induced labor, need for oxytocin augmentation, gel-to-induction interval, Bishop score change, maximum oxytocin dose, maximum dilatation rate, length of labor, cesarean section rate, fetal Apgar scores, fetal umbilical vein pH, or fetal umbilical artery pH.CONCLUSIONS: The two prostaglandin E₂ formulations appear equivalent in efficacy and safety. Constraints placed on intracervical prostaglandin E₂ gel make the vaginal preparation a desirable choice. (Am J Obstet Gynecol 1997;176:1305-12.)     

Induction of labour with prostaglandin E2 vaginal tablets

A new tablet formulation of PGE₂ for intravaginal administration to induce labour has been developed. The clinical results in a pilot study of 47 patients, together with an assessment of the absorption rate by serial plasma 15-keto-PGE₂ equivalents, in 10 patients are presented.     

Induction of labor with a stable-based prostaglandin E2 vaginal tablet

Vaginal tablets containing 3 mg prostaglandin E₂ in a stable base were administered to 163 patients with features favorable for induction of labor. Delivery was achieved after the insertion of a single tablet in 87 cases; 76 patients required a second tablet. Additional augmentation with oxytocin was necessary in 25 cases. Only 5 patients were delivered by cesarean section.The vaginal tablet was found to be a highly acceptable, safe and simple preparation for the induction of labor at term.     

Comparison of the safety and efficacy of intravaginal misoprostol (prostaglandin E1 ) with those of dinoprostone (prostaglandin E2 ) for cervical ripening and induction of labor in a community hospital

Objective: This clinical trial evaluated the efficacy of intravaginal misoprostol (prostaglandin E₁ ) and compared it with that of dinoprostone (prostaglandin E₂ ) for cervical ripening and induction of labor in a community hospital. Study Design: This study involved a retrospective analysis of 81 patients undergoing cervical ripening and induction of labor with prostaglandin E₂ from May 1, 1996, to May 1, 1997. A comparison prospective analysis of 145 patients undergoing the same procedure with prostaglandin E₁ from May 1, 1997 to May 1, 1998, was performed. Results: The mean time to delivery was significantly shorter with misoprostol (19.8 ± 10.4 hours) than with prostaglandin E₂ (31.3 ± 13.0 hours, P < .001). Delivery within 24 hours of induction was significantly more frequent with misoprostol (71.9% of subjects vs 31.3%, P < .001). There was no difference in the cesarean delivery rate with misoprostol (25.6% vs 22.2%, P < .67). The incidence of uterine hyperstimulation was higher with prostaglandin E₂ (7.4% vs 0.7%, P < .007). There were no uterine ruptures with prostaglandin E₂ . There were 2 uterine ruptures and 1 dehiscence with prostaglandin E₁ in 3 patients with previous cesarean deliveries and 1 rupture in a patient without a history of uterine scarring. There was no difference in neonatal outcome, with the exception of a fetal death related to uterine rupture in the misoprostol group. Conclusions: Compared with prostaglandin E₂ , misoprostol is more effective in cervical ripening and induction of labor, is as safe for patients who do not have a history of cesarean birth, may carry a higher incidence of uterine rupture, and should not be used for patients attempting vaginal birth after previous cesarean delivery. (Am J Obstet Gynecol 1999;180:1551-9.)     

Vaginal prostaglandin E2 gel and breech presentation

Intravaginal prostaglandin (PG) E₂ has been shown to ripen the cervix before induction and to shorten labor when the fetal presentation is cephalic. This study reports the influence of PGE₂ gel on induction and labor in 13 primigravid patients with unfavorable cervixes and breech presentation. The results were compared with 25 similarly treated primigravidae with cephalic presentations. Comparable cervical ripening was achieved in the breech and cephalic groups; labors were of similar duration and the incidence of cesarean section was not significantly different in the breech patients. There were no unwanted fetal or maternal effects associated with the gel.PGE₂ gel is an effective aid to induction of labor when the cervix is unfavorable and the breech presents in otherwise uncomplicated pregnancies.     

Induction of labor with oral prostaglandin E2 tablets in high-parity patients

Labor was induced with two low-dose regimens of prostaglandin E₂ (PGE₂) tablets in 46 high-parity women at term who had singleton pregnancies with a success rate of 97.8%. Of the successfully induced patients, 42 had vaginal delivery and three were dilivered by cesarean section for cephalopelvic disproportion. There was one failure of induction. Both dose regimens (0.5 mg and 0.75 mg hourly) were equally effective in inducing labor. The pattern of labor and mean induction-delivery interval of 5.8 h was similar to a comparable group of high-parity patients with spontaneous labor. It appears from this study that induction of labor with PGE₂ tablets is safe in high-parity patients.     

Randomized comparison of the effects of endocervical and vaginal prostaglandin E2 gel in women with various degrees of cervical ripeness

OBJECTIVE: The trial was conducted to obtain an unbiased comparison of the relative merits of endocervical and vaginal prostaglandin E₂ gel in a weighted case mix of parous and nulliparous women with favorable and unfavorable cervical features.STUDY DESIGN: Multicenter ranodmized trial with 285 participants, (three exclusions) was performed with sealed envelopes stratified for parity and Bishop score.RESULTS: Outcomes of labor and delivery were clearly related to the cervical score at trial entry, especially in nulliparous women. Endocervical prostaglandin E₂ had a more marked effect on cervical ripeness than did vaginal prostaglandin E₂, but this did not result in any differences in more substantive outcomes. Frequencies of delivery within 12 (50%) and 24 hours (77.7%), cesarean section (7.3%), instrumental vaginal delivery (11.7%), and poor infant outcomes were similar with both preparations.CONCLUSION: Because differences in effectiveness between endocervical and vaginal prostaglandin E₂ in triacetin gel are marginal, preferences of women and clinicians can determine the choice between them.     

A comparison of prostaglandin E2 pessaries and laminaria tents for ripening the cervix before termination of pregnancy

Summary. Forty primigravid womcn aged 15–45 years were randomly allocated to receive either an intravaginal pessary of 3 mg prostaglandin E, (PGE₂) or an intracervical 5-mm laminaria tent (LT) 12–16 h before termination of pregnancy at 6–14 weeks gestation. The degree of dilatation of the cervix a t operation and its resistance t o further dilatation during the procedure were assessed by a 'blind' operator. Laminaria tents were more effective in achieving dilatation and softening of the cervix than were PGE₂ pessaries and in 40% of women no further dilatation was necessary. There were no associated side-effects or complications. A cervical tear occurred in two of 20 patients treated with PGE₂ pessaries and all 20 required further dilatation of the cervix. Laminaria tents provide a simple. safe, acceptable and effective means of 'ripening' the cervix prior to termination of early pregnancy.     

Randomized, double-blind trial of prostaglandin E2 intravaginal gel versus low-dose oxytocin for cervical ripening before induction of labor

OBJECTIVE: Our purpose was to compare two methods of preinduction cervical ripening in a randomized, double-blind clinical trial. STUDY DESIGN: Two intravaginal, 4 mg prostaglandin E₂ gel applications administered 4 hours apart were compared with 10 hours of low-dose oxytocin (2 mU/min) in 200 patients undergoing preinduction cervical ripening. RESULTS: There were no differences in parity, initial Bishop scores, estimated gestational ages, indications for induction, or birth weights. Prostaglandin E₂ gel was significantly better (p < 0.0001) at achieving a change in the Bishop score of 3 or more. The number of successful inductions was significantly greater (p < 0.0003) and the mean time to active labor was significantly shorter (p < 0.0002) in the prostaglandin E₂ group than in the oxytocin group. More multiple-day inductions (p < 001) occurred in the oxytocin group, and fewer discharged patients who did not deliver infants (p < 003) were seen in the prostaglandin E₂ gel group. There were no differences between patient groups in the cesarean section rate, meconium staining, hyperstimulation, and Apgar scores. CONCLUSION: Two 4 mg doses of prostaglandin E₂ intravaginal gel applied 4 hours apart are superior to low-dose oxytocin in producing cervical ripening and preparing for successful induction. (Am J Obstet Gynecol 1996;174:1910-6.)     

Lipogranuloma of the cervix in a postmenopausal patient with a uterine prolapse

Objective Lipogranuloma is a rare inflammatory reactive process related to exogenous or endogenous lipids with an admission to the dermis and subcutis. It is described most frequently in the penis and scrotum of young adults. Lipogranuloma of the female genitalia is a rather uncommon condition. The lesion is histopathologically characterized by fat vacuoles with foreign body type giant cells and scattered lymphocytes. Case We described an incidental lipogranuloma of the cervix in a 60-year-old woman who presented with total uterine prolapse. Conclusion Although lipogranuloma mostly occurs in young male patients, especially in the genital tract, clinicians should be aware of this entity in the cervix of a postmenopausal woman with uterine prolapse, which may challenge the differential clinical diagnosis.     

Two dosing regimens for preinduction cervical priming with intravaginal dinoprostone pessary: a randomised clinical trial.

OBJECTIVE: To compare the efficacy within 24 hours of a three-times-a-day intensive dosing regimen with a standard once daily dosing regimen using dinoprostone vaginal pessary in preinduction cervical priming. DESIGN: Randomised controlled trial. SETTING: Department of Obstetrics and Gynaecology, Singapore General Hospital. PARTICIPANTS: One hundred singleton term primigravidae with cephalic presentation with unfavourable cervical scores (Bishop score < or = 5) requiring induction of labour. METHODS: Eligible women were randomly assigned the standard regimen (3000 microg dinoprostone [Prostin, Upjohn, Crawley, UK] once daily) or an intensive regimen (3000 microg dinoprostone given sequentially three times daily four hours apart) for cervical priming until successful priming (Bishop score of > or = 6) or the onset of active labour occurred. MAIN OUTCOME MEASURES: Number of women whose cervices were ripened successfully or who entered active labour within 24 hours of starting cervical priming, priming to induction interval, and priming to delivery interval. RESULTS: Forty-nine women were assigned to the standard regimen and 51 to the intensive regimen. The median number (range) of dinoprostone pessaries used was two (one to seven) in the standard regimen and three (one to nine) in the intensive regimen. Forty-two women (82.4%) who underwent the intensive regimen achieved successful cervical ripening or active labour within 24 hours, compared with 21 assigned to standard regimen (OR 6.2, 95% CI 2.3-17.4). This difference was statistically significant. The median intervals from priming to induction, and from priming to delivery, were also statistically significantly shorter in women treated with the intensive regimen. Thirty-five women (68.63%) assigned the intensive regimen experienced pain, compared with 21 (42.86%) in the standard regimen (OR 2.92, 95% CI 1.19-7.21), with two and one women in the respective regimens requiring opiate analgesics. Five women with oligohydramnios had transient cardiotocographic abnormalities during priming with the intensive regimen, none of which required immediate intervention, and the babies were born in good condition. There were no cases of uterine hypertonus and the outcomes of labour were similar for women from both regimens. CONCLUSIONS: Preinduction cervical priming with the intensive dosing regimen improves the chances of successful ripening within 24 hours for primigravidae with unfavourable cervical scores at full term singleton pregnancies, and shortens the interval from priming to induction, and priming to delivery. This regimen may be more cost effective by shortening the period of hospital stay. The overall incidence of adverse reactions to the mother and fetus during priming was low. However, close fetal surveillance must be maintained, particularly in pregnancies complicated with oligohydramnios.     

An appraisal of oral prostaglandin E2 and intravenous oxytocin in the induction of labor

Oral prostaglandin E₂ (PGE₂) was used to induce labor in 39 patients. These were matched closely with a similar number of patients induced with intravenous oxytocin. The induction-full dilatation interval was significantly shorter in the oxytocin group than in the group on oral PGE₂. Possible explanations for the difference are offered. The rest of the results showed no significant difference.     

Effect of prostaglandin E2 and its metabolites on lower segment myometrium in vitro

The spontaneous activity of pregnant human lower segment myometrium has been studied in vitro using strips removed at cesarean section. Contractions were measured isometrically. During the 4-h experiments there was an increase in amplitude and decrease in frequency of contractions in control preparations. Prostaglandin F_2α (PGF_2α), its metabolites and prostaglandin E₂ (PGE₂) have been shown to be oxytocic in vivo, but there are no published data on the oxytocic effect of PGE₂ metabolites. The effect on contractile activity of adding either PGE₂ or one of its initial metabolites (15-keto-PGE₂, 13,14-dihydro-15-keto-PGE₂ or 13,14-dihydro-PGE₂) or prostaglandin A₂ (PGA₂) to the tissue baths has been tested.No significant or consistent change in contractility was observed after the addition of any of the compounds tested. This probably indicates an inherent difference in the response of different portions of the uterine muscle, and cannot be taken to exclude activity in the intact uterus, particularly since PGE₂ is a well-known oxytocic agent in vivo. The difficulty of working with this type of preparation is stressed, since there is wide variation in contractility as well as a constantly changing pattern.