Safety and pharmacokinetics of nelfinavir during the second and third trimesters of pregnancy and postpartum.

PURPOSE: Evaluate the safety, tolerability, and pharmacokinetics (PK) of nelfinavir during pregnancy and postpartum in HIV-infected women. METHODS: Phase IV, non-randomized, open-label study of nelfinavir 625 mg tablets (1250 mg) in combination with lamivudine/zidovudine twice daily. Primary endpoint was treatment-related or possibly treatment-related gastrointestinal or hepatic adverse events (AEs). Selected maternal and infant outcomes were recorded. Frequent plasma samples were collected for PK studies during the 2nd and 3rd trimesters, and 6 weeks postpartum, to analyze total and free nelfinavir and M8 concentrations. RESULTS: Sixteen HIV+ pregnant women were enrolled. Six mild treatment-related AEs and 3 serious AEs occurred; 1 serious AE (elevated AST) met the primary endpoint. Compared with 6 weeks postpartum, levels of total nelfinavir were reduced by 44% and 46%, total M8 by 82% and 83%, free nelfinavir by 48% and 39%, and free M8 by 83% and 79% in the 2nd and 3rd trimesters, respectively. At 6 weeks postpartum, 75% and 50% of subjects maintained HIV-1 RNA levels <400 and <50 copies/mL, respectively. All pregnancies resulted in live births without transmission in 15 infants. CONCLUSIONS: Nelfinavir in combination with lamivudine/zidovudine was generally well tolerated. Total and free nelfinavir and M8 exposure were reduced in late pregnancy.

Systemic inflammatory response syndrome, organ failure, and outcome in critically ill obstetric patients treated in an ICU.

STUDY OBJECTIVES: To determine the incidence of systemic inflammatory response syndrome (SIRS) and organ failure and to describe the outcomes in critically ill obstetric patients who have been treated in medical ICUs. DESIGN: Retrospective review. SETTING: A multidisciplinary ICU at a tertiary-care institution. METHODS: We collected data on 74 obstetric patients who were admitted consecutively to the ICU from January 1991 through December 1998. Acute physiology and chronic health evaluation (APACHE) II scores were calculated. A p value < 0.05 was considered to be significant. MEASUREMENTS AND RESULTS: Fifty-eight percent of patients were admitted to the ICU postpartum. Their mean (+/- SD) age was 25.9 +/- 7.0 years, and 64% were African American and 34% were white. Fifty percent had preexisting medical conditions. Their mean APACHE II score was 14.0 +/- 5.9, and their predicted mortality rate was 17.6%. The most common reason for admission was respiratory insufficiency. Preeclampsia was present in 38% of patients, and hemolytic anemia, elevated liver enzymes, and low platelet count syndrome were present in 7% of patients. SIRS developed in 59% of patients. Patients with SIRS had longer ICU stays (p = 0.0008). Organ failure developed in 65% of patients, and ARDS developed in 15% of patients. Invasive mechanical ventilation was required in 45% of patients, and pulmonary artery catheterization was required in 35% of patients. The in-hospital mortality rate was 2.7%. There were five spontaneous abortions and eight perinatal deaths. CONCLUSIONS: The most common reason for admission to the ICU of critically ill obstetric patients was respiratory failure. Despite the severity of illness and the development of SIRS and organ failure in most patients, the mortality rate was low.

Accuracy of colposcopically directed biopsy in patients with cervical neoplasia.

The histologic diagnoses of premalignant and malignant lesions of the cervix obtained by examining the colposcopically directed biopsy material from 643 patients were compared with those of the surgical material subsequently obtained. The procedures during which samples were acquired included hysterectomy (370), cervical conization (263), cervical amputation (2), and removal of a retained cervical stump (8). The diagnostic accuracy of colposcopically directed biopsy was 93.0% in those patients with satisfactory colposcopy, ie, the final diagnosis did not differ by more than 1 grade from that of the directed biopsy diagnosis. Two patients with widespread stage III cervical intraepithelial neoplasia on directed biopsy had microinvasive carcinoma in the therapeutic cone specimen. All invasive carcinomas (stage IB, occult) were diagnosed by directed biopsy and confirmed by subsequent examination of the surgical specimen.

Abdominal pregnancy: review of current management and addition of 10 cases.

Ten cases of abdominal pregnancy managed at the Brookdale Hospital Medical Center over a 17-year period are presented. An incidence of 1 abdominal pregnancy in 7095 deliveries occurred in this series; another institution reported 1 in 7931. A perinatal mortality rate of 80% and no maternal mortality in the study are contrasted to rates of 75 to 95% and 2 to 18%, respectively, from the world literature. Recurrent abdominal pain in the gravid patient with a prior history of infertility, tubal pregnancy, and/or surgery may signal abdominal pregnancy. Similarly, the management of fetal death should include consideration of the presence of abdominal pregnancy. The role of ultrasonography in diagnosis and the importance of immediate surgical intervention with minimal disturbance of the placenta are stressed.

Vaginally administered cocaine overdose in a pregnant woman.

The deleterious effects of cocaine have been described in the adult population and in the neonate. Documentation of adverse effects in pregnant patients has been limited. We report the first known fatal vaginal administration of cocaine.

Reproductive performance of DES-exposed female progeny.

The reproductive performance of 106 patients exposed in utero to diethylstilbestrol by maternal ingestion is described. Fetal wastage is high, apparently because of spontaneous abortion during the first and second trimesters. Recommendations are made for preconception counseling of exposed progeny to increase fetal salvage.

Diagnosis of intracranial hemorrhage in utero after a maternal seizure.

Reported is a patient who noted decreased fetal movements after a seizure at 32 weeks' gestation. Sonography revealed fetal death and findings consistent with an intraventricular hemorrhage. The possible explanations for and the significance of an association between a maternal seizure and fetal intraventricular hemorrhage are discussed.

Cervical ripening and labor induction with a controlled-release dinoprostone vaginal insert: a meta-analysis.

OBJECTIVE: To systematically review published randomized trials that compared efficacy of a 10-mg, controlled-release dinoprostone vaginal insert with other prostaglandins for cervical ripening and labor induction. DATA SOURCES: We supplemented a search of entries in electronic databases with references cited in original studies and review articles to identify randomized clinical trials of dinoprostone vaginal inserts for cervical ripening and labor induction. METHODS OF STUDY SELECTION: We evaluated, abstracted data, and assessed the quality of randomized clinical trials on the efficacy of dinoprostone vaginal inserts as cervical ripening and labor induction agents. Only published randomized trials were included in this meta-analysis. TABULATION, INTEGRATION, AND RESULTS: Seventeen studies were identified, eight of which met our criteria for metaanalysis. Those eight trials included 964 subjects, 490 of whom were allocated to dinoprostone vaginal inserts and 474 to other prostaglandin (PG) preparations. We calculated an estimate of the odds ratio (OR) and risk difference for dichotomous outcomes, using a random- and fixed-effects model. Continuous outcomes were pooled using a variance-weighted average of within-study difference in means. Compared with women who received other PG preparations, those who received dinoprostone vaginal inserts had lower incidence of vaginal delivery within 12 hours of PG application (OR 0.55, 95% confidence interval 0.39, 0.79). Vaginal inserts were associated with longer intervals to vaginal delivery and lower rates of active labor. There were no differences in cesarean delivery rates, incidence of hyperstimulation, or need for oxytocin augmentation between dinoprostone and other PGs. CONCLUSION: Dinoprostone vaginal insert was less effective than other prostaglandins for cervical ripening and labor induction.

Labor induction with intravaginal misoprostol in term premature rupture of membranes: a randomized study.

OBJECTIVE: To evaluate the safety and clinical effectiveness of intravaginal misoprostol, a synthetic prostaglandin E1 analogue, for labor induction in gravidas with premature rupture of membranes (PROM) at term. METHODS: One hundred forty-one pregnant women with term PROM were assigned randomly to one of two induction groups: 1) intravaginal misoprostol or 2) intravenous oxytocin by continuous infusion. RESULTS: Seventy subjects were allocated to the misoprostol group and 71 to the oxytocin group. The mean (+/- standard deviation) interval from induction to delivery was significantly shorter in the misoprostol group (416 +/- 276 compared with 539 +/- 372 minutes; P = .04). In 85.7% of patients in the misoprostol group, only one dose was required. Intrapartum complication rates, mode of delivery, and neonatal or maternal adverse event rates were similar in the two treatment groups. Uterine tachysystole occurred more frequently with misoprostol than with oxytocin (28.6% compared with 14.0%; P < .04). CONCLUSION: Intravaginal administration of misoprostol induces labor safely and effectively in patients with PROM at term.

Misoprostol for cervical ripening and labor induction: a meta-analysis.

OBJECTIVE: To analyze published randomized trials assessing the safety and efficacy of misoprostol for cervical ripening and labor induction. DATA SOURCES: We supplemented a search of entries in electronic data bases with references cited in original studies and review articles to identify randomized trials of misoprostol for cervical ripening and labor induction. METHODS OF STUDY SELECTION: Two blinded investigators performed independent trial quality evaluation and data abstraction of randomized clinical trials assessing the efficacy of misoprostol as a cervical ripening and labor-inducing agent. TABULATION, INTEGRATION, AND RESULTS: We calculated an estimate of the odds ratio (OR) and risk difference for dichotomous outcomes, using both a random- and fixed-effects model. Continuous outcomes were pooled using a variance-weighted average of the within-study difference in means. Of 16 studies identified, eight met our criteria for meta-analysis. These eight trials included 966 patients (488 received misoprostol and 478 were controls). Women who received misoprostol for cervical ripening and labor induction had a significantly lower overall cesarean rate (OR 0.67, 95% confidence interval [CI] 0.48, 0.93) and a higher incidence of vaginal delivery within 24 hours of misoprostol application (OR 2.64, 95% CI 1.87, 3.71). Use of misoprostol was associated with a higher incidence of tachysystole (OR 2.70, 95% CI 1.80, 4.04) but not hyperstimulation (OR 1.91, 95% CI 0.98, 3.73). The incidences of abnormal 5-minute Apgar scores and admissions to the neonatal intensive care unit were similar in the misoprostol and control groups. The pooled estimate of the mean interval from start of induction to delivery was 4.6 hours fewer (95% CI -3.5, -5.7) in the misoprostol group. CONCLUSION: Published data confirm the safety and efficacy of intravaginal misoprostol as an agent for cervical ripening and labor induction.

Labor induction with prostaglandin E1 misoprostol compared with dinoprostone vaginal insert: a randomized trial.

OBJECTIVE: To compare the safety, efficacy, and costs of intravaginal misoprostol versus dinoprostone vaginal inserts for cervical ripening and labor induction. METHODS: Two hundred twenty-three labor induction patients were assigned randomly to one of two treatment groups: 1) intravaginal misoprostol or 2) dinoprostone vaginal inserts. Fifty micrograms of misoprostol were placed in the posterior vaginal fornix every 3 hours for a maximum period of 24 hours. Ten milligrams of dinoprostone was administered in a single application as a vaginal insert for 12 hours. RESULTS: Among 223 patients evaluated, 108 were allocated to the misoprostol group and 115 to the dinoprostone group. The median interval from induction to vaginal delivery was significantly shorter in the misoprostol group: 698 (range 395-1053) versus 1041 (range 792-1531) minutes (P < .001). Vaginal delivery within 12 hours of ripening occurred in 40.7% of patients who received misoprostol compared with 19.1% for those receiving dinoprostone (P < .001); no significant difference between the groups was noted for vaginal delivery within 24 hours. Uterine tachysystole occurred more frequently in patients in the misoprostol group (21.3%) than in the dinoprostone group (7.0%) (P = .004). Nevertheless, no statistically significant differences were noted between the groups with respect to intrapartum complications, including uterine hyperstimulation, mode of delivery, and neonatal or maternal adverse outcomes. The average cost per patient for misoprostol treatment was $85 compared with $606 for treatment with the vaginal insert. CONCLUSION: Intravaginal misoprostol and the dinoprostone vaginal insert appear to be safe agents for cervical ripening and labor induction. However, misoprostol is less expensive and more effective than the dinoprostone vaginal insert.

Delayed onset of clear cell adenocarcinoma of the vagina in DES-exposed progeny.

Clear cell adenocarcinoma of the vagina occurred in a diethylstilbestrol (DES)-exposed patient in the fourth year of continuous observation for adenosis. Diagnosis was suspected by digital and colposcopic examination and confirmed by target biopsy. Cytology was negative. The development of malignancy in a patient who has been known to have adenosis has been previously described but is very rare. The necessity for careful regular follow-up using cytology, digital palpation, and colposcopy at 6-month intervals is emphasized.

Sweet syndrome with involvement of the female genital tract.

Acute febrile neutrophilic dermatosis, otherwise known as Sweet syndrome, usually occurs in women after prior respiratory infections. The first case of Sweet syndrome with involvement of the female genital tract is reported here. The woman recovered completely, and no evidence of other underlying disease has appeared.

Abnormal cervical cytology in pregnancy: a 17-year experience.

OBJECTIVE: To evaluate the safety and accuracy of colposcopy and colposcopically directed biopsy in pregnant women with abnormal cervical cytology. METHODS: A retrospective analysis of 612 gravidas with abnormal cervical cytology was conducted. Colposcopy and directed biopsy were performed using standard techniques. Two patients underwent diagnostic conization during the second trimester. One hundred twelve patients had procedures that provided a final specimen. Endocervical curettage was omitted. The transformation zone was fully visualized in all patients by the 20th week of gestation. Directed cervical biopsy was performed on the following patients: 1) with colposcopic evidence of invasion or cervical intraepithelial neoplasia (CIN) III, 2) with discordancy between colposcopy and cytology, 3) electing termination of pregnancy, and 4) whose anticipated reliability was even remotely questioned. RESULTS: A colposcopically directed biopsy was performed in 449 patients (73%). Ninety-one patients (15%) did not have biopsies because of normal colposcopic findings, and the remaining 72 patients (12%) had either CIN I or II. Thirty-nine of these patients (6%) were lost to follow-up. Colposcopically directed biopsy and colposcopic impression had a 95% concordancy within one degree of severity; however, 14% of CIN I colposcopic impressions and 54% of normal colposcopic findings turned out to be CIN III and CIN I or II, respectively. Ninety-five percent of the biopsy diagnoses correlated with the final pathology to within one degree of severity. CONCLUSION: The data confirm previous findings that colposcopically directed biopsy is a safe and reliable method of evaluating pregnant patients with abnormal cervical cytology.

Labor induction with the prostaglandin E1 methyl analogue misoprostol versus oxytocin: a randomized trial.

OBJECTIVE: To compare the safety and efficacy of intravaginal misoprostol versus intravenous (IV) oxytocin infusion for labor induction. METHODS: One hundred thirty patients were randomly assigned to one of two induction groups: 1) intravaginal misoprostol or 2) IV oxytocin by continuous infusion, with prior cervical ripening using prostaglandin (PG) E2 gel if necessary. RESULTS: Among 129 patients evaluated, 64 were allocated to the misoprostol group and 65 to the oxytocin group. Prostaglandin E2 gel was administered to 29 patients (45%) in the oxytocin group with unripe cervices. Uterine tachysystole occurred more frequently in patients in the misoprostol group (34.4%) than in the oxytocin group (13.8%) (P < .05). Nevertheless, no statistically significant differences were noted between the groups in intrapartum complications including uterine hyperstimulation syndrome, mode of delivery, and neonatal or maternal adverse outcomes. The interval from induction to vaginal delivery was significantly shorter in the misoprostol group (11 versus 18 hours; P = .004). In 74% of patients in the misoprostol group, only one intravaginal dose was required for successful labor induction. CONCLUSIONS: Intravaginal administration of misoprostol safely and effectively induces labor while minimizing the expense associated with IV oxytocin infusion. The higher frequency of uterine tachysystole associated with the use of misoprostol did not increase the risk of adverse intrapartum or perinatal outcomes. The use of PGE2 gel for cervical ripening contributed to the longer induction-to-vaginal delivery interval noted in the oxytocin group. Clinical trials appear warranted to detail misoprostol's optimal route, dose, and schedule for labor induction and its safety.

Calcium supplementation in mild preeclampsia remote from term: a randomized double-blind clinical trial.

OBJECTIVE: To determine whether calcium supplementation prevents progression to severe disease in preterm nulliparous women with mild preeclampsia. METHODS: Seventy-five women hospitalized at 24-36 weeks' gestation because of mild preeclampsia were randomized to receive either 2 g/day of elemental calcium (36 women) or placebo (39). Both groups had similar demographic characteristics, initial blood pressure measurements, and amount of proteinuria. Diagnostic criteria and clinical management for severe preeclampsia were applied consistently. RESULTS: Eighteen of 36 calcium-treated subjects (50%, 95% confidence interval [CI] 33-67) developed severe preeclampsia, compared with 19 of 39 (48.7%, 95% CI 32-65) in the placebo group (relative risk 1.03, 95% CI 0.64-1.03; P = 1.00). Blood pressure values, gestational age at delivery, newborn weights, incidence of low Apgar scores, and umbilical arterial blood gases were similar for the two groups. CONCLUSION: Calcium supplementation does not prevent severe preeclampsia in preterm patients with mild disease.

Human chorionic gonadotropin in cervicovaginal secretions as a predictor of preterm delivery.

OBJECTIVES: To determine whether human chorionic gonadotropin (hCG) detected in cervicovaginal secretions of patients with symptoms suggestive of preterm labor is a predictor of preterm birth. METHODS: Women presenting to labor and delivery with symptoms of preterm labor were invited to participate. After collecting secretions with a cotton-tipped applicator from the posterior fornix and endocervical canal, we placed the swab in a test tube containing 1 ml of normal saline. From this solution, we performed qualitative and quantitative hCG measurements. Qualitative and quantitative hCG results from women who delivered at term were compared with those delivering prior to 37 weeks' gestation. RESULTS: Samples were obtained and analyzed from 86 women at a mean (+/- standard deviation) gestational age of 30.7+/-2.9 weeks. Of the 86 subjects enrolled, 28 (32.6%) delivered preterm. A positive rapid qualitative assay from cervicovaginal secretions between 24 and 34 weeks' gestation was associated with a significant increase in the incidence of preterm delivery (relative risk 2.62, 95% confidence interval (CI) 1.38, 4.98). The likelihood ratios for a positive and negative test were 2.19 (95% CI 1.35, 3.56) and 0.51 (95% CI 0.30, 0.85) respectively. Using a cut-off of 19 mIU/ml, similar diagnostic accuracy for predicting preterm birth was obtained with the quantitative test 1.93 (95% CI 1.14, 3.26) and 0.62 (95% CI 0.40, 0.98). CONCLUSIONS: Qualitative and quantitative hCG measurements from cervicovaginal secretions may be useful predictors of preterm birth in symptomatic patients. The qualitative hCG test can be used at the bedside with results obtained in minutes.

Cervical ripening in women with previous cesarean deliveries.

OBJECTIVE: To evaluate the safety and efficacy of preinduction cervical ripening in women with previous cesarean deliveries undergoing induction of labor. METHODS: Retrospective study of women with previous low transverse cesarean deliveries who underwent ripening of an unfavorable cervix prior to induction of labor (n = 89). Multiparas without previous cesarean deliveries undergoing ripening and induction of labor during the same time period were used for comparison (n = 61). Ripening was performed with prostaglandin E2 (PGE2) gel, or an osmotic dilator, or both. Induction of labor with oxytocin followed the American College of Obstetricians and Gynecologists' guidelines. Outcome data were analyzed using the unpaired Student's t-test or chi 2-test as appropriate. Significance was established at P < 0.05. RESULTS: The mean gestational age was 39.6 +/- 2.6 and 38.2 +/- 2.9 weeks for the study and comparison groups, respectively. There were no differences between the groups in Bishop score, duration of the first stage of labor, maximum dose of oxytocin, indications for cesarean delivery, puerperal morbidity, birthweight, Apgar scores or NICU admissions. Sixty-four percent (57 of 89) of study women delivered vaginally compared with 82% (50 of 61) of women in the comparison group (P < 0.03). The data were analyzed separately for those women undergoing cervical ripening with PGE2 gel only. No differences were observed between the groups in any of the categories mentioned above. CONCLUSION: Cervical ripening appears to be safe and effective in women with previous low transverse cesarean deliveries undergoing induction of labor with an unfavorable cervix.

Percutaneous drainage of fluid collections in the bladder flap of febrile post-cesarean-section patients. A report of seven cases.

Post-cesarean-section infections are a common cause of fevers on obstetric wards. Patients whose fevers are refractory to antibiotics often have pelvic collections. The contents of these collections and course of patients with collections have not been reported on before in detail. The development of sophisticated imaging techniques has led to the frequent use of percutaneous drainage in the management of abdominal collections. We used percutaneous drainage of collections in febrile post-cesarean-section patients. Hematomas were the most common collections associated with post-cesarean-section infection, and percutaneous drainage was a useful technique for obtaining material for culture and for distinguishing hematomas from abscesses. Most patients defervesced shortly after percutaneous drainage.

Abnormal cervical cytology in adolescents. A 15-year experience.

The onset of sexual activity at a young age (< 17 years) has been identified in several studies as the most important epidemiologic risk factor in the development of cervical intraepithelial neoplasia (CIN). In characterizing the natural history of CIN, investigators have indicated that a percentage of such lesions progress to invasive carcinoma if left untreated. CIN in adolescents was first reported in 1961. The subsequently reported CIN prevalence rates in sexually active, medically indigent teenage populations have increased over time, temporally paralleling increasing early sexual activity among teenagers. In our 15-year experience with abnormal cervical cytology in adolescents, all grades of CIN were observed. Fully 13% of patients had histologically proven CIN 3, a preinvasive lesion. Given reports of an increase in cervical cancer in young women (< 35 years old), the findings of this and similar studies mandate routine cervical cytologic screening in all sexually active teenage girls.