External validity of first-trimester algorithms in the prediction of pre-eclampsia disease severity.

OBJECTIVE: To compare disease features in women with pre-eclampsia between those who are correctly identified (true positive) and those who are missed (false negative) when applying first-trimester prediction algorithms for pre-eclampsia to a prospectively enrolled population. METHOD: Six first-trimester early (requiring delivery < 34 weeks' gestation) pre-eclampsia algorithms were applied to a prospective cohort of singleton pregnancies enrolled at first-trimester screening. Maternal outcomes, neonatal outcomes and severity parameters for pre-eclampsia were compared between true-positive and false-negative predictions. RESULTS: Twenty of 2446 (0.8%) women developed early pre-eclampsia, with 65% of these developing severe features and 20% HELLP syndrome. At enrollment, true-positive cases were more likely to be African-American and chronically hypertensive, while false-negative cases were more likely to be Caucasian. At delivery, true-positive cases were more likely to have pre-eclampsia superimposed on hypertension, severely elevated blood pressure and creatinine level > 1.1 mg/dL. False-negative cases were more likely to have HELLP syndrome (all P < 0.05). CONCLUSION: In an urban population with a high prevalence of chronic hypertension, patients who are correctly identified by first-trimester screening models are more likely to develop pre-eclampsia superimposed on chronic hypertension with severely elevated blood pressure and evidence of renal failure. In contrast, patients who are missed by these algorithms are more likely to have HELLP syndrome. Further research is needed to confirm these findings and the algorithm adjustments that may be necessary to better predict pre-eclampsia phenotypes.

Preinduction cervical ripening. A randomized trial of intravaginal misoprostol alone vs. a combination of transcervical Foley balloon and intravaginal misoprostol.

OBJECTIVE: To determine if the addition of a mechanical ripening agent (transcervical Foley balloon) to a pharmacologic agent (intravaginal misoprostol) improves the efficiency of preinduction cervical ripening. STUDY DESIGN: Singleton patients with an indication for delivery, unfavorable cervix (Bishop score < or = 5) and no contraindication to labor were randomly assigned to two groups: misoprostol alone (25 micrograms intravaginally every 3 hours for no more than 12 hr) or combination therapy (25-French transcervical Foley balloon inflated to 50 mL of sterile water with identical intravaginal misoprostol dosing). All patients received a history and physical examination (including Bishop score), preripening ultrasound, electronic fetal heart rate and contraction monitoring (to rule out spontaneous labor and document fetal well-being). Multiple variables of perinatal outcome were analyzed, including the main outcome variables of ripening-to-delivery time and cesarean section rate. RESULTS: During August 1998 to August 1999, 81 patients were randomized, 40 to misoprostol alone and 41 to combination therapy. There were no differences between the groups with respect to maternal demographics, preripening Bishop score, maternal complications, intrapartum intervention or neonatal outcome. The misoprostol group spent longer periods of time in active labor, and there was a trend for the combination group to require oxytocin for longer intervals. These findings did not significantly affect the total ripening-to-delivery time or cesarean section rate which were similar for both groups. CONCLUSION: The addition of mechanical ripening with a transcervical Foley balloon to intravaginal misoprostol did not improve the efficiency of preinduction cervical ripening. Mechanical and pharmacologic cervical ripening agents appear to act independently rather than synergistically.

Revisiting the short cervix detected by transvaginal ultrasound in the second trimester: why cerclage therapy may not help.

OBJECTIVE: The purpose of this study was to identify the risk factors that are associated with increased neonatal morbidity in patients who were treated for sonographic evidence of internal os dilation and distal cervical shortening during the second trimester. STUDY DESIGN: From May 1998 to June 2000 patients between 16 and 24 weeks of gestation with the following sonographic criteria were randomly assigned to McDonald cerclage or no cerclage: internal os dilation and either membrane prolapse into the endocervical canal at least 25% of the total cervical length but not beyond the external os or a shortened distal cervix <2.5 cm. Before randomization, all patients were treated identically with an amniocentesis, multiple urogenital cultures, and therapy with indomethacin and clindamycin for 48 to 72 hours. Except for the cerclage, all patients were treated identically after randomization. Multiple variables of perinatal outcome were analyzed. A regression model with gestational age at delivery as the dependent variable was constructed and repeated with neonatal morbidity as the dependent variable. This model was applied to 3 populations: the cerclage group, the no cerclage group, and both groups combined. RESULTS: Of the 135 patients, 20 patients declined randomization, and 2 patients were diagnosed with acute chorioamnionitis. Of the 113 patients remaining, 55 patients were randomly assigned to the cerclage group, and 58 patients were randomly assigned to the no cerclage group. There were 8 rescue cerclage procedures (4 in each group). Regression analysis showed that readmission for preterm labor, chorioamnionitis, and abruption were consistently associated with early gestational age at delivery and increased morbidity. Cerclage did not affect perinatal outcome. CONCLUSION: The sonographic findings of second trimester internal os dilation, membrane prolapse, and distal cervical shortening likely represent a common pathway of several pathophysiologic processes. Use of cerclage does not alter any perinatal outcome variables. Increased neonatal morbidity in these patients appears to be associated with subclinical infection, preterm labor, and abruption.

Preinduction cervical ripening techniques compared.

OBJECTIVE: To assess the clinical efficacy of pharmacologic, mechanical and combination techniques of cervical ripening. STUDY DESIGN: From March 1997 to August 1998, all cervical-ripening patients at Lehigh Valley Hospital were randomly assigned to three groups: intravaginal misoprostol, intracervical Foley catheter, or combination prostaglandin E2 (PGE2) gel and Foley catheter. Inclusion criteria included Bishop score < or = 5 and no contraindication to labor. The remaining delivery process was actively managed according to established guidelines. Multiple variables in perinatal outcome were analyzed, with the cesarean section rate and time from ripening to delivery as the main outcome variables. RESULTS: Of the 205 patients, 65 were randomized to the misoprostol group, 71 to the Foley group and 69 to the catheter-and-gel group. There were no differences between groups in delivery indications, maternal demographics, ultrasound findings, labor interventions, intrapartum times, mode of delivery, postpartum complications or neonatal outcomes. The misoprostol group demonstrated a higher rate of uterine tachysystole and required oxytocin less when compared to the two catheter groups. CONCLUSION: The higher rate of uterine tachysystole with misoprostol did not increase the cesarean section rate. The higher rate of oxytocin required by the two catheter groups did not increase the delivery time intervals. There appears to be no benefit to adding intracervical or intravaginal PGE2 gel to the intracervical Foley balloon. The misoprostol and catheter ripening techniques have similar safety and efficacy.

A randomized trial of cerclage versus no cerclage among patients with ultrasonographically detected second-trimester preterm dilatation of the internal os.

OBJECTIVE: The aim of this study was to compare perinatal outcomes of patients with second-trimester ultrasonographic evidence of preterm dilatation of the internal os treated with cerclage versus those of patients not treated with cerclage. STUDY DESIGN: From May 1998 through June 1999 patients with ultrasonographic evidence of preterm dilatation of the internal os between 16 and 24 weeks' gestation were randomly assigned to receive a McDonald cerclage or no cerclage. Before random assignment all patients underwent amniocentesis and urogenital cultures and then received 48 hours of therapy with indomethacin and antibiotics. After treatment each patient was followed up as an outpatient with bed rest and weekly ultrasonographic evaluation. RESULTS: Of the 61 patients 31 were randomly assigned to cerclage and 30 were randomly assigned to no cerclage. There were no differences between groups with respect to maternal demographic characteristics, risk factors for preterm birth, cervical measurements, rescue procedures, readmission, chorioamnionitis, and abruptio placentae. The mean gestational age at delivery (33.5 +/- 6.3 weeks) and the perinatal death rate (12. 9%) in the cerclage group were similar to the mean gestational age at delivery (34.7 +/- 4.7 weeks; P =.4) and the perinatal death rate (10.0%; P =.9) in the no-cerclage group. CONCLUSION: Treatment with McDonald cerclage of preterm dilatation of the cervix detected ultrasonographically during the second trimester did not improve perinatal outcomes.

Second trimester abortion using prostaglandin E2 suppositories with or without intracervical Laminaria japonica: a randomized study.

OBJECTIVE: To compare the abortifacient efficacy of vaginal prostaglandin (PG) E2 suppositories with and without pretreatment with intracervical PGE2 gel and Laminaria japonica. METHODS: One hundred seventy-five women between 16 and 20 weeks' gestation requesting abortion were divided randomly into three groups. Forty-one received PGE2 vaginal suppositories alone to induce abortion, 72 had Laminaria placed 24 hours before vaginal PGE2, and 62 were given intracervical 0.5 mg PGE2 gel plus Laminaria 24 hours before vaginal PGE2. Maternal demographic characteristics, induction to delivery time, number of suppositories required, and complications were analyzed. RESULTS: The mean maternal age, gravidity, parity, race, and gestational age were similar among groups. Ninety-five percent of all women delivered within 24 hours. The induction to delivery time was significantly longer in the PGE2-only women (mean +/- standard deviation 689+/-319 minutes) compared with that of those receiving PGE2 plus Laminaria (487+/-321 minutes) and PGE2 plus Laminaria plus gel (547 +/-374 minutes, P = .01). There was a statistically significant difference in the number of suppositories needed to complete the abortion process. The PGE2-only group required more suppositories (median three, range 1-8) compared with PGE2 plus Laminaria (median 3, range 1-3) and PGE2 plus Laminaria plus gel (median 2.5, range 1-9; P = .001). Patients in the PGE2 plus Laminaria plus gel group reported more pain associated with placement (median pain score 4, range 0-10) compared with PGE2 plus Laminaria (median 2, range 0-9; P = .003). There was a lower incidence of febrile episodes in the PGE2-only group (29%) compared with PGE2 plus Laminaria (68%) and PGE2 plus Laminaria plus gel (54%, P = .002). CONCLUSION: Placement of Laminaria japonica 24 hours before PGE2 vaginal suppository-induced abortion resulted in a significantly shorter induction-to-delivery time, and pretreatment with Laminaria japonica decreased the number of suppositories required to complete abortion. Pretreatment with intracervical PGE2 gel increased pain associated with Laminaria placement and did not improve the efficacy of the procedure.

Preeclampsia: immunologic alteration of Nitabuch's membrane? Clinical sequelae.

OBJECTIVE: To determine if preeclampsia is an immunologic disease process consistent with a host-vs.-graft reaction by examining differences in immunoglobulin deposition at the maternal fetal interface (Nitabuch's layer) in preeclamptic patients. STUDY DESIGN: A prospective study of patients at Lehigh Valley Hospital was conducted between July 1993 and April 1994. Group 1 (study) consisted of 11 primigravid women meeting the criteria for the diagnosis of preeclampsia. Group 2 (control) consisted of 11 primigravid women who had an uncomplicated pregnancy. At delivery, basal plate placental specimens were obtained, fixed, and processed for study by a blinded observer utilizing IgG, IgA, IgM, IgE immunofluorescence techniques. The placenta was then sent to a gynecologic pathologist for blinded evaluation and measurement of Nitabuch's membrane by light microscopy. RESULTS: Taking the average width of 3 measurements of Nitabuch's membrane by light microscopy revealed no significant difference (group 1, .1839 mm vs. group 2, .1555 mm). Immunofluorescence techniques revealed that the thickness of immunofluorescence of Nitabuch's membrane was significantly greater in the study group vs. the control group (157.48 pixels vs. 63.80 pixels, P = .006, respectively). CONCLUSION: Evaluation of the maternal-fetal interface reveals the deposition of increased immunoglobulins, the physiology of which may be similar to nephropathies as seen in systemic disease processes. The deposition of immunoglobulins may be associated with a common antigen which may point to an immunologic etiology for preeclampsia in some women.