Deborah A. Wing

Multicenter randomized trial of cerclage for preterm birth prevention in high-risk women with shortened midtrimester cervical length

OBJECTIVE The objective of the study was to assess cerclage to prevent recurrent preterm birth in women with short cervix. STUDY DESIGN Women with prior spontaneous preterm birth less than 34 weeks were screened for short cervix and randomly assigned to cerclage if cervical length was less than 25 mm. RESULTS Of 1014 women screened, 302 were randomized; 42% of women not assigned and 32% of those assigned to cerclage delivered less than 35 weeks (P = .09). In planned analyses, birth less than 24 weeks (P = .03) and perinatal mortality (P = .046) were less frequent in the cerclage group. There was a significant interaction between cervical length and cerclage. Birth less than 35 weeks (P = .006) was reduced in the less than 15 mm stratum with a null effect in the 15-24 mm stratum. CONCLUSION In women with a prior spontaneous preterm birth less than 34 weeks and cervical length less than 25 mm, cerclage reduced previable birth and perinatal mortality but did not prevent birth less than 35 weeks, unless cervical length was less than 15 mm.

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

OBJECTIVE Our purpose was to compare the safety and efficacy of intravaginal misoprostol 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 cervices were randomly assigned to receive either intravaginal misoprostol or intracervical dinoprostone. 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 misoprostol and 67 received 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 misoprostol 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). There 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.

A comparison of propylthiouracil versus methimazole in the treatment of hyperthyroidism in pregnancy

OBJECTIVE Our purpose was to demonstrate that propylthiouracil and methimazole are equally effective and safe in the treatment of hyperthyroidism during pregnancy. STUDY DESIGN Between 1974 and 1990 records were available on 185 pregnant patients with a history or diagnosis of hyperthyroidism. Ninety-nine patients were treated with propylthiouracil and 36 with methimazole. The response to therapy was compared with respect to the time to normalization of the free thyroxine index and the incidences of congenital anomalies and hypothyroidism. RESULTS The time to normalization of the free thyroxine index was compared in the two groups by means of survival analysis. The median time to normalization of the free thyroxine index on propylthiouracil and methimazole was 7 and 8 weeks, respectively (p = 0.34, log-rank test). The incidence of major congenital malformations in mothers treated with propylthiouracil and methimazole was 3.0% and 2.7%, respectively. No neonatal scalp defects were seen. One infant was overtly hypothyroid at delivery. CONCLUSION Propylthiouracil and methimazole are equally effective and safe in the treatment of hyperthyroidism in pregnancy.

Disruption of Prior Uterine Incision following Misoprostol for Labor Induction in Women with Previous Cesarean Delivery

Background Although induction of labor in women with prior cesareans is controversial, we compared misoprostol to oxytocin in such women in a randomized trial. The investigation was terminated prematurely because of safety concerns. Cases Disruption of the prior uterine incision was found in two of 17 misoprostol-treated women. The first woman underwent repeat cesarean delivery at 42 weeks because of fetal tachycardia and repetitive late decelerations. A 10-cm vertical rent in the anterior myometrium was discovered. The second woman underwent induction for fetal growth restriction. Loss of fetal heart tones and abnormal abdominal contour prompted emergent cesarean for suspected uterine rupture. An 8-cm longitudinal uterine defect was found. Conclusion When misoprostol is used in women with previous cesareans, there is a high frequency of disruption of prior uterine incisions.

A comparison of intermittent vaginal administration of misoprostol with continuous dinoprostone for cervical ripening and labor induction

OBJECTIVE Our purpose was to compare the effect of vaginal administration of misoprostol (Cytotec) with that of dinoprostone (Cervidil) on cervical ripening and labor induction. STUDY DESIGN Two hundred patients with indications for induction of labor and unfavorable cervical examinations were randomly assigned to receive vaginally administered misoprostol (prostaglandin E1) or the dinoprostone (prostaglandin E2) vaginal insert. Twenty-five microgram tablets of misoprostol were placed in the posterior vaginal fornix every 4 hours for a maximum of six doses. Additional misoprostol was not given after either spontaneous rupture of membranes, adequate cervical ripening (Bishop score of > or = 8 or cervical dilatation of > or = 3 cm), or beginning of active labor. The vaginal insert, Cervidil, containing 10 mg of dinoprostone in a timed-release preparation was placed in the posterior vaginal formix for a maximum period of 24 hours. The vaginal insert was removed for spontaneous rupture of membranes, entry into active labor, adequate cervical ripening, or abnormality of uterine contractile pattern or fetal cardiac activity. RESULTS Of the 200 patients enrolled, 99 were randomized to misoprostol and 101 to dinoprostone. The average interval from start of induction to vaginal delivery was 1 hour shorter in the misoprostol group (1296.7 +/- 722.1 minutes) than in the dinoprostone group (1360.0 +/- 792.0 minutes), but this difference was not statistically significant (p = 0.97). Oxytocin augmentation of labor was used in 50 (50.5%) misoprostol-treated patients and 43 (43.5%) dinoprostone-treated patients (relative risk 1.14, 95% confidence interval 0.86 to 1.51, p = 0.35). There were no significant differences between routes of delivery with misoprostol or dinoprostone. Overall, 38 patients (19.3%) had cesarean deliveries. There was a significantly lower prevalence of tachysystole (six or more uterine contractions in a 10-minute window for two consecutive 10-minute periods) in the misoprostol group (7.1%) than in the dinoprostone group (18.4%) (relative risk 0.52, 95% confidence interval 0.31 to 0.89, p = 0.02). There were no significant differences in frequency of uterine hyperstimulation or hypertonus. Abnormal fetal heart rate tracings were found in 23 (23.2%) of misoprostol-treated patients and 35 (35.7%) of dinoprostone-treated patients (relative risk 0.73, 95% confidence interval 0.52 to 1.01, p = 0.0546). No significant differences were found in meconium passage, 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 as effective as dinoprostone for cervical ripening and the induction of labor. Mean time intervals to delivery, need for oxytocin augmentation, and routes of delivery were similar between the two groups. Incidence of uterine tachysystole with misoprostol every 4 hours was significantly less than with dinoprostone.

A comparison of differing dosing regimens of vaginally administered misoprostol for preinduction cervical ripening and labor induction

OBJECTIVE Our purpose was to compare two dosing regimens of vaginally administered misoprostol for preinduction cervical ripening and induction of labor. STUDY DESIGN Five hundred twenty-two patients with indications for induction of labor and unfavorable cervices were randomly assigned to one of two dosing regimens of vaginally administered misoprostol. Twenty-five microgram tablets of misoprostol were placed in the posterior vaginal fornix either every 3 hours to a maximum of eight doses or every 6 hours to a maximum of four doses. The maximal period of cervical ripening was 24 hours regardless of the number of misoprostol doses administered. Medication was not given after either spontaneous rupture of membranes or the beginning of active labor. RESULTS Among 522 patients enrolled, 261 were randomized to receive misoprostol every 3 hours and 261 to receive misoprostol every 6 hours. The average interval from start of induction to vaginal delivery was shorter in the 3-hour dosing group (1311.74 +/- 785.14 minutes) than in the 6-hour dosing group (1476.96 +/- 805.30 minutes) (p < 0.05). Oxytocin augmentation of labor occurred more commonly in the 6-hour dosing group (51.4%) than in the 3-hour dosing group (41.8%) (p < 0.05) [corrected]. There were no significant differences between routes of delivery. Overall, 108 patients (20.8%) were delivered by cesarean section. There was a slightly higher prevalence of tachysystole (six or more uterine contractions in a 10-minute window for two consecutive 10-minute periods) in the 3-hour group (14.6%) than in the 6-hour group (11.2%), but this difference was not statistically different. There were no significant differences in the frequency of uterine hyperstimulation or hypertonus. There was no significant difference between groups in the frequency of abnormal fetal heart rate tracings, meconium passage, 1- or 5-minute Apgar scores < 7, neonatal resuscitations, or admissions to the neonatal intensive care unit. CONCLUSIONS Vaginally administered misoprostol is an effective agent for cervical ripening and induction of labor. Patients with the 6-hour dosing schedule had longer intervals to delivery, more frequently required oxytocin augmentation, and had more failed inductions than did patients with 3-hour dosing. Further investigation to characterize the safety of misoprostol is needed.

Effects of Maternal Obesity on Duration and Outcomes of Prostaglandin Cervical Ripening and Labor Induction

OBJECTIVE: To estimate the effect of maternal body mass index (BMI) on progress and outcomes of prostaglandin labor induction. METHODS: This study was a secondary analysis of data collected during the Misoprostol Vaginal Insert Trial, a multisite, double-blind, randomized trial of women requiring cervical ripening before induction of labor. The duration, characteristics, and outcomes of labor were analyzed after stratification by BMI categories. Multivariable regression analysis was performed on all outcomes of interest, adjusting for race, parity, and treatment group allocation. RESULTS: One thousand two hundred seventy-three patients were stratified according to BMI categories, with 418 study participants classified as lean (BMI less than 30), 644 as obese (BMI 30–39.9), and 211 as extremely obese (BMI 40 or higher). The incidence of cesarean delivery increased from 21.3% in the BMI less than 30 group to 29.8% in the BMI 30–39.9 group (odds ratio [OR] 1.57, 95% confidence interval [CI] 1.18–2.1, P=.002) and 36.5% in the BMI 40 or higher group (OR 2.12, 95% CI 1.47–3.06, P<.001). Median dose and duration of predelivery oxytocin in the lean group (2.6 units and 6.5 hours) was significantly lower than for women in either the obese (3.5 units and 7.7 hours) or the extremely obese (5.0 units and 8.5 hours) group. Median time to delivery was significantly longer in the BMI 40 or higher (27.0 hours) and BMI 30–39.9 (24.9 hours) groups compared with the BMI less than 30 (22.7 hours) group (P<.001). The relationship between maternal obesity and adverse labor and delivery outcomes persisted in a multivariable analysis that adjusted for race, parity, and treatment group allocation. CONCLUSION: Duration of labor, oxytocin requirements, and cesarean delivery rates are significantly higher with increasing maternal obesity in prostaglandin-induced women. LEVEL OF EVIDENCE: II

Labor induction with misoprostol

Misoprostol, a prostaglandin E(1 ) analog, is widely used in the United States for cervical ripening and labor induction. Its use for these indications is not approved by the US Food and Drug Administration. The only Food and Drug Administration-approved indication in the product labeling is the treatment and prevention of intestinal ulcer disease resulting from nonsteroidal anti-inflammatory use. Multiple trials have proved that misoprostol is an effective agent for cervical ripening and labor induction in term pregnancy; however, investigations continue regarding the optimal dose, dosing regimen, and route of administration. Uterine contraction abnormalities are often found in association with higher misoprostol doses. Some trials also indicate increased frequencies of meconium passage, neonatal acidemia, and cesarean delivery for fetal distress in women receiving higher doses of misoprostol. Overall, most trials fail to demonstrate a significant change in the cesarean delivery rate with the use of this agent. Misoprostol is an effective agent for cervical ripening and labor induction when used in a judicious and cautious fashion.

Fetal Programming of Body Composition, Obesity, and Metabolic Function: The Role of Intrauterine Stress and Stress Biology

Epidemiological, clinical, physiological, cellular, and molecular evidence suggests that the origins of obesity and metabolic dysfunction can be traced back to intrauterine life and supports an important role for maternal nutrition prior to and during gestation in fetal programming. The elucidation of underlying mechanisms is an area of interest and intense investigation. In this perspectives paper we propose that in addition to maternal nutrition-related processes it may be important to concurrently consider the potential role of intrauterine stress and stress biology. We frame our arguments in the larger context of an evolutionary-developmental perspective that supports roles for both nutrition and stress as key environmental conditions driving natural selection and developmental plasticity. We suggest that intrauterine stress exposure may interact with the nutritional milieu, and that stress biology may represent an underlying mechanism mediating the effects of diverse intrauterine perturbations, including but not limited to maternal nutritional insults (undernutrition and overnutrition), on brain and peripheral targets of programming of body composition, energy balance homeostasis, and metabolic function. We discuss putative maternal-placental-fetal endocrine and immune/inflammatory candidate mechanisms that may underlie the long-term effects of intrauterine stress. We conclude with a commentary of the implications for future research and clinical practice.

A comparison of orally administered misoprostol with vaginally administered misoprostol for cervical ripening and labor induction

OBJECTIVE Our purpose was to compare orally administered with vaginally administered misoprostol for cervical ripening and labor induction. MATERIAL AND METHODS Two hundred twenty subjects with medical or obstetric indications for labor induction and undilated, uneffaced cervices were randomly assigned to receive orally administered or vaginally administered misoprostol. Fifty micrograms of oral misoprostol or 25 microgram of vaginal misoprostol was given every 4 hours. If cervical ripening (Bishop score of >/=8 or cervical dilatation of >/=3) or active labor did not occur, repeated doses were given to a maximum of 6 doses or 24 hours. Thereafter, oxytocin was administered intravenously by a standardized incremental infusion protocol to a maximum of 22 mU/min. RESULTS Of the 220 subjects evaluated, 110 received orally administered misoprostol and 110 received vaginally administered misoprostol. Fewer subjects who received the oral preparation (34/110, 30.9%) were delivered vaginally within 24 hours of initiation of induction, in comparison with those who received the vaginal preparation (52/110, 47.3%) (P =.01). The average interval from start of induction to vaginal delivery was nearly 6 hours longer in the oral treatment group (mean and SD 1737.9 +/- 845.7 minutes) than in the vaginal treatment group (mean and SD 1393.2 +/- 767.9) (P =.005, log-transformed data). Orally treated patients required significantly more doses than vaginally treated patients (orally administered doses: mean and SD 3.3 +/- 1.7; vaginally administered doses: mean and SD 2.3 +/- 1.2) (P <.0001). Oxytocin administration was necessary in 83 (75.4%) of 110 orally treated subjects and in 65 (59.1%) of 110 vaginally treated subjects (P =.01, relative risk 1. 28, 95% confidence interval 1.06-1.54). Vaginal delivery occurred in 95 (86.4%) orally treated subjects and in 85 (77.3%) vaginally treated subjects (P =.08, relative risk 1.12, 95% confidence interval 0.99-1.27), with the remainder undergoing cesarean delivery. There was no difference in the incidence of uterine contractile abnormalities (tachysystole, hypertonus, or hyperstimulation), intrapartum complications, or neonatal outcomes between the 2 groups. CONCLUSIONS Oral administration of 50-microgram doses of misoprostol appears less effective than vaginal administration of 25-microgram doses of misoprostol for cervical ripening and labor induction. Further investigation is needed to determine whether orally administered misoprostol should be used for cervical ripening and labor induction.