The invasive phenotype of placenta accreta extravillous trophoblasts associates with loss of E-cadherin.

INTRODUCTION: Epithelial-to-mesenchymal transition (EMT) is a process of molecular and phenotypic epithelial cell alteration promoting invasiveness. Loss of E-cadherin (E-CAD), a transmembrane protein involved in cell adhesion, is a marker of EMT. Proteolysis into N- and C-terminus fragments by ADAM10 and presenilin-1 (PSEN-1) generates soluble (sE-CAD) and transcriptionally active forms. We studied the protein expression patterns of E-CAD in the serum and placenta of women with histologically-confirmed over-invasive placentation. METHODS: The patterns of expression and levels of sE-CAD were analyzed by Western blot, immunoassay, and immunoprecipitation. Tissue immunostaining for E-CAD, cytokeratin-7 (epithelial marker), vimentin (mesenchymal marker), ADAM10, PSEN-1 and ß-catenin expression were investigated in parallel. RESULTS: N-terminus cleaved 80 kDa sE-CAD fragments were present in serum of pregnant women with gestational age regulation of the circulatory levels. Women with advanced trophoblast invasion did not display circulatory levels of sE-CAD different from those of women with normal placentation. Histologically, extravillous trophoblasts (EVT) closer to the placental-myometrial interface demonstrated less E-CAD staining than those found deeper in the myometrium. These cells expressed both vimentin and cytokeratin, an additional feature of EMT. EVT of placentas with advanced invasion displayed intracellular E-CAD C-terminus immunoreactivity predominating over that of the extracellular N-terminus, a pattern consistent with preferential PSEN-1 processing. DISCUSSION: Local processing of E-CAD may be an important molecular mechanism controlling the invasive phenotype of accreta EVT.

Universal cervical-length screening to prevent preterm birth: a cost-effectiveness analysis.

OBJECTIVE: To determine whether routine measurement of second-trimester transvaginal cervical length by ultrasound in low-risk singleton pregnancies is a cost-effective strategy. METHODS: We developed a decision analysis model to compare the cost-effectiveness of two strategies for identifying pregnancies at risk for preterm birth: (1) no routine cervical length screening and (2) a single routine transvaginal cervical length measurement at 18-24 weeks' gestation. In our model, women identified as being at increased risk (cervical length < 1.5 cm) for preterm birth would be offered daily vaginal progesterone supplementation. We assumed that vaginal progesterone reduces preterm birth at < 34 weeks' gestation by 45%. We also assumed that a decreased cervical length could result in additional costs (ultrasound scans, inpatient admission) without significantly improved neonatal outcomes. The main outcome measure was incremental cost-effectiveness ratio. RESULTS: Our model predicts that routine cervical-length screening is a dominant strategy when compared to routine care. For every 100,000 women screened, $12,119,947 can be potentially saved (in 2010 US dollars) and 423.9 quality-adjusted life-years could be gained. Additionally, we estimate that 22 cases of neonatal death or long-term neurologic deficits could be prevented per 100,000 women screened. Screening remained cost-effective but was no longer the dominant strategy when cervical-length ultrasound measurement costs exceeded $187 or when vaginal progesterone reduced delivery risk at < 34 weeks by less than 20%. CONCLUSION: In low-risk pregnancies, universal transvaginal cervical length ultrasound screening appears to be a cost-effective strategy under a wide range of clinical circumstances (varied preterm birth rates, predictive values of a shortened cervix and costs).

Human labor is associated with reduced decidual cell expression of progesterone, but not glucocorticoid, receptors.

CONTEXT: Unchanging plasma progesterone (P4) levels suggest that human labor is initiated by reduced P4 receptor (PR) expression, which elicits functional P4 withdrawal. The glucocorticoid receptor (GR) is also implicated in this process. OBJECTIVE: Our objective was to compare PR and GR staining in human decidual cells (DCs) and interstitial trophoblasts (ITs) of gestational age-matched pre- and postcontraction specimens and to evaluate steroid effects on PR and GR expression in human DC cultures. INTERVENTIONS AND MAIN OUTCOME MEASURES: Decidua basalis and parietalis sections were immunostained for PR or GR and then for the cytoplasmic DC and IT markers vimentin and cytokeratin. Western blotting measured PR and GR levels in nuclear extracts of cultured leukocyte-free term DCs after incubation with estradiol-17beta (E2) with or without medroxyprogesterone acetate (MPA). RESULTS: PR histological scores (HSCOREs) were significantly higher in DC nuclei from pre- vs. post-uterine-contraction decidua basalis and parietalis sections with PR immunostaining absent from ITs. In contrast, immunoreactive GR was localized in IT and DC nuclei. GR HSCORES were significantly higher in ITs than DCs but similar in pre- vs. post-uterine-contraction specimens. In term DC monolayers, PR-A and PR-B were enhanced by E2 and inhibited by MPA, whereas E2 plus MPA produced intermediate PR expression. The GR was constitutively expressed. CONCLUSIONS: In post- vs. pre-uterine-contraction specimens, significantly lower HSCOREs in DC nuclei, but not IT, and unchanging GR levels in DCs and ITs suggest that functional P4 withdrawal may occur in DCs and is unlikely to involve the GR. Nuclear extracts from DC monolayer cultures express steroid-regulated PR-A and PR-B and constitutive GR.

The role of urinary soluble endoglin in the diagnosis of pre-eclampsia: comparison with soluble fms-like tyrosine kinase 1 to placental growth factor ratio.

OBJECTIVE: Endoglin, an anti-angiogenic glycoprotein expressed on endothelial cells, has been proposed recently as a biomarker of pre-eclampsia (PE). Given that PE is characterised by an imbalance of angiogenic factors, we sought to determine the clinical utility of urinary soluble endoglin, relative to the soluble fms-like tyrosine kinase 1 to placental growth factor (PlGF) ratio, in the diagnosis of PE during gestation. DESIGN: Prospective observational cohort. SETTING: Tertiary referral university hospital. POPULATION: Two hundred and thirty-four pregnant women were enrolled prospectively in the following groups: healthy controls, n = 63; gestational age (GA), median (interquartile range), 33 weeks (27-39 weeks); chronic hypertension, n = 27; GA, 33 weeks (30-36 weeks); mild PE, n = 38; GA, 37 weeks (34-40 weeks); severe PE, n = 106; GA, 32 weeks (29-37 weeks). METHODS: Free urinary levels of soluble endoglin, soluble fms-like tyrosine kinase 1 and PlGF were measured by sensitive and specific immunoassay. Levels for all urinary analytes were normalised to creatinine. MAIN OUTCOME MEASURES: Urinary soluble endoglin, and the soluble fms-like tyrosine kinase 1 to PlGF ratio. RESULTS: In healthy controls, urinary soluble endoglin levels were increased significantly at term relative to those earlier in gestation. Severe PE was characterised by an increased urinary level of soluble endoglin, soluble fms-like tyrosine kinase 1, protein to creatinine ratio and soluble fms-like tyrosine kinase 1 to PlGF ratio compared with all other groups. There was a direct correlation between urinary soluble endoglin and proteinuria that remained after GA correction (R = 0.382, P < 0.001). Urinary soluble endoglin could not differentiate mild PE from severe preterm PE. Overall, soluble endoglin had the ability to discriminate PE from chronic hypertension and healthy controls only in women who were evaluated at <37 weeks of GA. The sensitivity, specificity and accuracy of urinary soluble endoglin alone in the diagnosis of PE or in the identification of women with PE requiring a mandated delivery before 37 weeks of gestation were 70%, 86% and 76%, respectively. These values were inferior to those of the soluble fms-like tyrosine kinase 1 to PlGF ratio (P < 0.001). The addition of urinary soluble endoglin did not improve the diagnostic accuracy of the soluble fms-like tyrosine kinase 1 to PlGF ratio alone. CONCLUSIONS: We have provided evidence that soluble endoglin is present and elevated in the urine of women who develop preterm PE. Urinary soluble endoglin has only limited ability to determine the severity of PE and to distinguish between PE and chronic hypertension both preterm and at term. Compared with urinary soluble endoglin, the soluble fms-like tyrosine kinase 1 to PlGF ratio remains a better marker of disease presence, severity and outcome.

Progestin and thrombin regulate tissue factor expression in human term decidual cells.

CONTEXT: Perivascular cell membrane-bound tissue factor (TF) initiates hemostasis via thrombin generation. The identity and potential regulation of TF-expressing cells at the human maternal-fetal interface that confers hemostatic protection during normal and preterm delivery is unclear. OBJECTIVES: The objective of the study were to identify TF-expressing cells at the maternal-fetal interface in term and preterm decidual sections by immunohistochemistry and evaluate progestin, thrombin, TNF-alpha, and IL-1beta effects on TF expression by cultured human term decidual cells (DCs). INTERVENTIONS AND MAIN OUTCOME MEASURES: Serial placental sections were immunostained for TF. Leukocyte-free term DC monolayers were incubated with 10(-8) M estradiol (E2) or E2 plus 10(-7) M medroxyprogestrone acetate (MPA) +/- thrombin or TNF-alpha or IL-1beta. ELISA and Western blotting assessed TF in cell lysates. Quantitative real-time RT-PCR measured TF mRNA levels. RESULTS: Immunolocalized TF in DC membranes in preterm and term placental sections displayed higher Histologic Scores than villous mesenchymal cells (P < 0.05). TF was undetected in interstitial or extravillous trophoblasts. Compared with DCs incubated with E2, MPA and 2.5 U/ml thrombin each doubled TF levels (P < 0.05) and E2 + MPA + thrombin further doubled TF levels (P < 0.05), whereas TNF-alpha and IL-1beta were ineffective. Western blotting confirmed the ELISA results. Quantitative RT-PCR revealed corresponding changes in TF mRNA levels. CONCLUSIONS: In human term placental sections, DC-expressed TF exceeds that of other cell types at the maternal-fetal interface and is localized at the cell membranes in which it can bind to factor VII and meet the hemostatic demands of labor and delivery via thrombin formation. Unlike the general concept that TF is constitutive in cells that highly express it, MPA and thrombin significantly enhanced TF expression in term DC monolayers.

Maternal anxiety and ultrasound markers for aneuploidy in a multiethnic population.

OBJECTIVE: Discussion of isolated ultrasound (US) markers for fetal aneuploidy can provoke significant patient anxiety. The objective of this study is to quantify maternal anxiety associated with the detection of these markers. METHODS: All patients undergoing routine second-trimester US examination for fetal anatomical survey over a one-year period were administered the State-Trait Anxiety Inventory (STAI) for Adults before and after the procedure. Women with isolated fetal markers for aneuploidy were notified of the findings but discouraged from pursuing amniocentesis. Rates of normal US examination, aneuploidy markers, anomalies, amniocentesis, and pregnancy outcomes were assessed across the ethnic groups. Pre- and post-ultrasound STAI surveys were scored and standardized with previously established norms. Student t-tests, Chi-square, and analysis of variance (ANOVA) were used where appropriate. RESULTS: Among the 798 patients tested, 57% were Hispanic, 30% were Asian, 6% were Black, and 7% were White. Maternal anxiety level was decreased in women after a normal US. The anxiety level increased with aneuploidy markers and was the highest with anomalies. Aneuploidy markers were more common among Hispanic and Asian fetuses, without any associated aneuploidy. Women with isolated aneuploidy markers underwent amniocentesis as often as women with advanced maternal age. CONCLUSION: The detection and communication of isolated aneuploidy markers is associated with increased maternal anxiety and unnecessary amniocentesis.

Risk factors for pre-eclampsia in nulliparous and parous women: the Jerusalem perinatal study.

Pre-eclampsia has been described as a 'disease of first pregnancies' and many believe that its occurrence in a later pregnancy signals a fundamentally different entity. We sought to compare risk factors in first and subsequent pregnancies. We studied 1319 cases of pre-eclampsia recorded in a historical cohort of 82,436 deliveries in Jerusalem in 1964-76. Logistic regression was used to control for covariates. The adjusted odds ratio (OR) for pre-eclampsia in first births was 2.58 (95% confidence interval[CI] 2.23, 2.97), compared with all later birth order groups, between which there were no detectable differences in risk. Other risk factors included increasing maternal age, diabetes (OR 5.64, 95% CI 4.33, 7.35), multiple gestations (OR 3.38, 95% CI 2.54, 4.49), fetal haemolytic disease (OR 2.24, 95% CI 1.43, 3.50) and lower maternal education. The risk of pre-eclampsia was not associated with the mother's employment outside the home and did not differ between immigrants vs. Israeli-born mothers or between groups of women whose fathers had been born in Western Asia, North Africa or Europe. Effects of each risk factor were similar within first and subsequent births. These results lend no support to the hypothesis that there is a fundamental difference between pre-eclampsia in a first pregnancy compared with that occurring in a later pregnancy; conclusions may be moderated, however, by the knowledge that the incidence of pre-eclampsia was low in this historical cohort.

Pregnancy-related thrombosis in a woman with congenital afibrinogenemia: a report of two successful pregnancies.

We managed two pregnancies in a woman with congenital afibrinogenemia with increasing amounts of cryoprecipitate to achieve a pre-infusion fibrinogen level of 60 mg/dL. The first pregnancy resulted in placental abruption at 36 weeks, in spite of recent cryoprecipitate infusion. Both placentas showed infarction. Post-partum ovarian and renal vein thromboses complicated the second pregnancy. Mean FVIII (344%) and vWF Antigen (323%) were elevated prior to cryoprecipitate infusion, with mean post-infusion levels of 367% and 363%. The clearance of fibrinogen after cryoprecipitate infusion increased during the course of pregnancy. A paradoxical prothrombotic state with embolization may play a role in the observed complications of pregnancy.

Fetal and maternal plasma leptin levels during the second half of normal pregnancies and those with Down syndrome.

OBJECTIVE: To assess the correlation of fetal and maternal plasma leptin concentrations during the second half of uncomplicated, euploid pregnancies and to compare these values with those obtained from pregnancies with Down syndrome. METHODS: Paired maternal venous and fetal umbilical blood samples were obtained during cordocentesis in 36 uncomplicated, euploid pregnancies and nine pregnancies with Down syndrome fetuses. Concentrations of leptin were measured by sensitive radioimmunoassay. RESULTS: Among pregnancies with euploid fetuses, there was significant correlation between both fetal and maternal leptin levels and gestational age (r = 0.464, p = 0.005 and r = 0.629, p < 0.001, respectively). Fetal plasma leptin concentrations also correlated with maternal levels (r = 0.485, p = 0.003), but fetal levels were significantly lower than maternal values (mean 2.12 +/- 0.44 ng/ml vs. 17.79 +/- 5.48 ng/ml, respectively; p < 0.001). Down syndrome fetuses had significantly lower fetal plasma leptin levels than gestational age-matched control euploid fetuses (0.72 + 0.54 ng/ml vs. 2.12 + 0.44 ng/ml; p < 0.002). However, there was no difference in maternal leptin concentrations between euploid and Down syndrome pregnancies. CONCLUSION: In euploid pregnancies, fetal leptin levels were significantly lower than the corresponding maternal values but increased across gestation. Down syndrome was associated with significantly lower fetal leptin levels.

Intrauterine transfusion for rhesus alloimmunization elevates fetal beta2-microglobulin levels.

BACKGROUND: Intrauterine transfusions for rhesus alloimmunization leads to alterations in circulating T-cell populations. Given that elevations in circulating beta2-microglobulin are a marker of T-cell-mediated organ transplant rejection, we evaluated the effect of intrauterine transfusion on fetal beta2-microglobulin levels. METHODS: Umbilical venous samples were obtained immediately prior to initial transfusion in ten anemic fetuses and in 12 fetuses with prior transfusions. Samples were also obtained from 18 gestational age-matched non-anemic fetuses and eight healthy neonates. RESULTS: The median concentration of beta2-microglobulin was significantly higher in fetuses with prior transfusions compared with non-anemic controls. In non-anemic controls, and in transfused fetuses, beta2-microglobulin levels decreased throughout gestation (r = -0.69, p = 0.01; and r = -0.80, p = 0.01, respectively). Among anemic and transfused fetuses, beta2-microglobulin levels displayed a negative correlation with fetal hematocrit (r = -0.62, p < 0.05; and r = -0.58, p = 0.04, respectively). CONCLUSIONS: We conclude that intrauterine transfusion for fetal anemia is associated with increased beta2-microglobulin levels, suggesting immunomodulatory effects of intrauterine transfusion on host immune responses to donor leukocyte antigens.

Compliance with prenatal care visits in substance abusers.

OBJECTIVE: We sought to determine whether pregnant, inner-city substance abusers, cared for in a multidisciplinary setting, had comparable numbers of missed appointments and similar outcomes in comparison with a low-risk patient population. METHODS: A retrospective review was conducted on a sample of 97 patients with uncomplicated prenatal care over a 7-year period (1994-2001). They were compared to a sample of 88 substance abusers cared for and delivered at Bellevue Hospital over the same period. Demographic information was recorded, as well as frequency of prenatal visits, number of missed appointments, birth weight, and gestational age at delivery. RESULTS: In our population, substance abusers were found to be significantly older (28.9 vs. 25.6 years, p < 0.0001), had had more pregnancies (4.3 vs. 2.4, p < 0.0001) and had had more children (2.0 vs. 0.7, p < 0.0001) than controls. Both substance abusers and control patients had a similar number of scheduled appointments (11.4 in each group, p = 0.99), but substance abusers missed more appointments (1.6 vs. 0.7, p < 0.0005). CONCLUSIONS: When cared for in a multidisciplinary setting, substance abusers will attend an adequate number of prenatal visits. However, they are still more likely than non-substance abusers to miss visits, although the difference may not be clinically significant.

Glutathione peroxidase levels throughout normal pregnancy and in pre-eclampsia.

OBJECTIVE: Evidence suggests that hemoglobin, in addition to its function as a carrier of oxygen, also serves to transport nitric oxide, as S-nitroso cysteine, from the lungs to the peripheral circulation, where it can be released. Glutathione peroxidase, besides being an important antioxidant, is known to catalyze the release of nitric oxide from smaller carrier molecules, and may play a role in the distribution of nitric oxide throughout the body. In light of these findings, we sought to determine whether glutathione peroxidase levels differed throughout gestation, and specifically between pre-eclamptic and normal women. METHODS: A nested case-control study of women receiving routine prenatal care was conducted. Pre-eclampsia was defined by a blood pressure of at least 140 mmHg systolic and/or 90 mmHg diastolic as well as proteinuria > 300 mg/24 h or > 2+ by dipstick, both occurring on two occasions at least 6 h apart. Blood was collected in heparinized tubes and was then centrifuged in a clinical centrifuge for 10 min. Plasma was frozen promptly at -80 degrees C for later enzyme-linked immunosorbent assay (ELISA), with which plasma glutathione peroxidase was determined. RESULTS: The maternal demographics of the pre-eclamptic and non-pre-eclamptic study groups did not significantly vary with respect to mean maternal age, gravidity, parity and gestational age at the time of delivery. The median maternal ages were 33 and 34 years, and the median gestational ages at the time of birth were 37.5 and 38.1 weeks, respectively. In evaluating the glutathione peroxidase levels of all patients across the three trimesters, we found that there was essentially no difference in mean levels (83.7, 81.0 and 89.5 ng/ml, respectively). There was no difference between the pre-eclamptic and non-pre-eclamptic patients, again stratified by trimester. A linear regression analysis indicated that the plasma glutathione peroxidase concentration did not correlate with gestational age or the presence of pre-eclampsia. CONCLUSIONS: Plasma glutathione peroxidase expression is similar across all trimesters. There is no change in the glutathione peroxidase levels in pre-eclamptic patients.

Plasma levels of thrombin-antithrombin complexes predict preterm premature rupture of the fetal membranes.

OBJECTIVE: Decidual hemorrhage (abruption) is strongly associated with preterm premature rupture of fetal membranes (PPROM). Moreover, thrombin enhances decidual matrix metalloproteinase (MMP) expression, and MMP has been strongly linked to PPROM. The current study sought to determine whether increased thrombin activation, as assessed by circulating maternal plasma thrombin-antithrombin (TAT) complexes, predicted subsequent PPROM. STUDY DESIGN: We conducted a nested, case-control study of plasma TAT levels, measured by sensitive immunoassay, among 27 women with a singleton preterm birth preceded by PPROM and 54 matched, term controls. Receiver operating characteristic curve analysis was performed to identify the optimal TAT cut-off level predicting PPROM. RESULTS: Mean gestational age at delivery in cases was 33.3 weeks, compared to 39.7 weeks in controls (p < 0.001). Compared with controls, women with PPROM had increased median plasma TAT levels in both the second trimester (5.1 microg/l (range 2.2-26.3 microg/l) vs. 3.2 microg/l (range 1.3-7.3 microg/l); p = 0.001) and third trimester (7.0 microg/l (range 2.6-85.8 microg/dl) vs. 4.8 microg/l (range 1.7-15.4 microg/dl); p = 0.01). In the PPROM group, 16.0% of the women exhibited bleeding during the pregnancy, while the corresponding value among controls was 3.6% (p = 0.07). In the second trimester, the odds ratio for PPROM with a TAT level of > 3.9 microg/l was 6.0 (95% CI 1.67-21.1). This value predicted PPROM with a sensitivity of 88%, specificity of 68% and positive and negative predictive values of 82% and 97%, respectively. CONCLUSION: Second-trimester elevated plasma TAT concentrations are predictive of subsequent PPROM. These data provide further evidence that PPROM is associated with decidual thrombin activation.

Central hemodynamic monitoring in a woman with acute respiratory insufficiency after evacuation of a complete molar pregnancy. A case report.

BACKGROUND: The incidence of hydatiform moles in the United States is approximately 1 in 1,200 pregnancies. Acute respiratory insufficiency is a known complication of molar pregnancies, occurring in 8-11%. While there have been numerous case reports and retrospective studies describing respiratory complications following evacuation of hydatiform moles, only a limited number of reports provide data from central hemodynamic monitoring in patients with this complication. CASE: A 16-year-old, Hispanic woman, gravida 1, para 0, presented to the emergency room at 13 weeks' gestational age by menstrual dating with complaints of vaginal bleeding for two days. The serum quantitative beta-hCG level was 1 x 10(6) mIU/mL, and a bedside sonogram was consistent with hydatiform mole. After informed consent was obtained, the patient underwent dilation and suction curettage. Approximately five minutes after evacuation of the uterus was begun, the patient developed pulmonary edema in the setting of oliguria. A pulmonary artery catheter was inserted to determine the etiology of the edema. The initial pulmonary capillary wedge pressure was > 18 mm Hg, consistent with hydrostatic pulmonary edema. Volume overload in association with a reduced colloid osmotic pressure to wedge pressure gradient was primarily responsible for the pulmonary edema in this patient. CONCLUSION: The majority of case reports of pulmonary complications after evacuation of a hydatidiform mole were either presumed or documented to be due to trophoblastic pulmonary embolism. Thyrotoxicosis, fluid overload with dilutional anemia, preeclampsia, sepsis, hypoalbuminemia or a combination of these factors may be more common than trophoblastic embolization.

Labor and vaginal delivery with maternal aortic aneurysm.

BACKGROUND: Maternal aortic aneurysm can be an unsettling finding for the practicing obstetrician. However, thoracic surgeons generally do not treat asymptomatic aortic aneurysms that are less than 6 cm in diameter in otherwise healthy adults. CASE: A young nullipara was incidentally found to have a 4.5-cm thoracic aortic aneurysm during prenatal care. After extensive counseling and discussions with thoracic surgeons, anesthesiologists, and perinatologists, the patient requested a trial of labor and underwent an uncomplicated assisted vaginal delivery of a healthy female infant. CONCLUSION: A vaginal delivery occurred safely in a woman with an asymptomatic aortic aneurysm that was less than 6 cm in diameter and not associated with Marfan's syndrome.

Cervical length after multifetal pregnancy reduction in remaining twin gestations.

OBJECTIVE: Multifetal pregnancy reduction is associated with an increased risk of prematurity. Because cervical length correlates with preterm delivery risk, we sought to determine whether multifetal pregnancy reduction twin gestations are associated with shorter cervical lengths compared with non-multifetal pregnancy reduction twins. STUDY DESIGN: We compared an historic cohort of patients who underwent multifetal pregnancy reduction to twins (n = 35) to a control group of twin gestations without multifetal pregnancy reduction (n = 83) from July 1996 to January 2000. Both groups of patients were treated with identical protocols. Cervical lengths across gestation and pregnancy outcomes were compared. RESULTS: Study and control groups did not differ significantly in mean maternal age (37.8 +/- 4.9 years vs 35.5 +/- 6.2 years; P =.06), median parity (0 [range, 0-1] vs 0 [range, 0-2]; P =.56), or mean gestational age at delivery (36.2 +/- 2.6 weeks vs 35.8 +/- 3.8 weeks; P =.50). The proportion delivering before 35 weeks of gestation was not significantly different (14.3% vs 30.1%; P =.10) nor was delivery before 32 weeks of gestation (8.6% vs 8.4%; P =.98). Cervical length did not differ significantly between the 2 groups. At 14 to 19 weeks the median was 3.9 cm (range, 2.4-6.0 cm) in the multifetal pregnancy reduction group versus 3.7 cm (range, 3.1-4.7 cm) in the control subjects (P =.15); at 20 to 25 weeks, the medians were 3.2 cm (range, 2.2-5.4 cm) and 3.7 cm (range, 1.5-5.7 cm), respectively (P =.43); and at 26 to 31 weeks the medians were 3.5 cm (range, 1.2-5.9 cm) versus 3.8 cm (range, 1.2-5.3 cm), respectively (P =.56). CONCLUSION: Cervical length across gestation in twin pregnancies is not affected by multifetal pregnancy reduction, despite the likely inflammatory response expected to accompany this procedure.

Residency selection: should interviewers be given applicants' board scores?

OBJECTIVE: The aim of this study was to determine the influence of advance knowledge of board scores on interviewers' assessments of residency applicants. STUDY DESIGN: During a 2-year period we prospectively evaluated our residency selection process. In year 1 interviewers were provided with each candidate's entire application, whereas in year 2 the United States Medical Licensing Examination scores were not included. In each year interviewers were asked to provide numerical assessments of the applicants solely on the basis of their own impressions of the interviews. Analysis was performed only for evaluations by interviewers who participated during both study periods under review. Interview scores were compared with United States Medical Licensing Examination part I scores within each year by means of a scatter plot and correlation coefficients. RESULTS: Applicant demographic characteristics were similar during years 1 and 2. Interview scores did not differ between year 1 (4.2 +/- 0.1) and year 2 (4.3 +/- 0.1; P > .05). During year 1 interview and board scores were significantly correlated (correlation coefficient, 0.64; slope of best-fit line, 13.9), whereas there was a negative correlation in year 2 (correlation coefficient, -0.06; slope, -1.3). CONCLUSION: When they are available to interviewers, markers of academic achievement such as United States Medical Licensing Examination scores may bias the interview evaluation. The interview process when conducted in this manner may simply be a validation process for candidates already judged on the basis of the application alone. Knowledge of United States Medical Licensing Examination scores by the interviewers may therefore negate the interview as an independent means of evaluating candidates.

Distribution of study designs in four major US journals of obstetrics and gynecology.

OBJECTIVE: To classify and compare articles, based on the study design, in four leading US obstetrics and gynecology journals. METHODS: One year of each journal, American Journal of Obstetrics and Gynecology (AJOG), Obstetrics and Gynecology (O&G), Gynecologic Oncology (GO), and Fertility and Sterility (F&S), beginning May 1997, was reviewed. Supplementary issues were excluded from review. The percentage of articles devoted to observational versus experimental study design was determined, and the quality of evidence was assessed including how heavily randomized controlled trials were represented versus other study designs. RESULTS: 1,517 articles were reviewed. The average percentage of clinical research articles was 90.4. The percentage of animal studies were 10.7 (AJOG), 1.1 (O&G), 1.1 (GO) and 4.2 (F&S) (chi(2) p < 0.001). There were 5.3, 1.9, 6.5, and 7.5% basic science articles, respectively (chi(2) p = 0.007). The average percentage of observational articles was 68.2 and that of experimental articles was 14.1. The percentages of total articles classified as controlled experimental were 10.9 (AJOG), 14.6 (O&G), 5.1 (GO), and 15.2 (F&S) (chi(2) p = 0.01). There were 8.7, 11.1, 3.3 and 9.5% randomized controlled trials, respectively (chi(2) p = 0.008). CONCLUSIONS: The majority of research reviewed was clinical, and more than half of the articles were observational. Under the US Preventative Services Task Force rating system, the randomized control trial is given the highest rating - class I evidence. The drive toward evidence-based clinical practice may not be fully supported by researchers in obstetrics and gynecology, as reflected by submissions to and publications in the major obstetrics and gynecology journals.

A corticotropin releasing hormone receptor antagonist does not delay parturition in rats.

OBJECTIVE: To determine the effects of CP-154, 526, a corticotropin releasing hormone (CRH) receptor antagonist, on the length of normal rat gestation. STUDY DESIGN: Twenty-four timed-pregnant Sprague-Dawley rats were purchased for this study. The drug and placebo were administered to the animals using an osmotic pump surgically inserted in the dorsal subcutaneous space. Six animals received 6 mg/kg/day of the drug, six animals received 12 mg/kg/day of the drug and twelve animals received the placebo. The gestational period, weight of each pup and number of pups in each litter were recorded and compared in the drug group versus placebo group. RESULTS: No difference was noted in the gestational period of the drug and placebo rats. The mean weight of pups in both the drug and placebo groups was 6.18 g. The number of pups per litter were similar in the drug and placebo groups. CONCLUSION: Antagonism of CRH receptors in rats has no effect on the length of gestational period, pup weight or number of pups per litter. Further studies are needed to define the role of CRH and its antagonism in primate pregnancy, as has been done in sheep.

Change in cervical length after cerclage as a predictor of preterm delivery.

OBJECTIVE: To determine whether the degree of cervical lengthening after cerclage and whether serial follow-up measurements of cervical length after cerclage are predictive of pregnancy outcome. METHODS: Eighty women whose primary physician determined that a prophylactic (n = 50) or urgent cerclage (n = 30) was indicated had transvaginal ultrasonographic evaluation before and after cerclage. Thereafter, most women had three additional transvaginal ultrasound examinations until 32 weeks' gestation. At each examination, the mean of three measurements was calculated. Statistical analyses were done by t test, analysis of variance, and logistic regression, with significance set at P <.05. RESULTS: The mean +/- standard deviation precerclage cervical length was 27.2 +/- 10.3 mm and after cerclage was 34.1 +/- 9.9 mm (n = 80, P <.001, paired t test). No significant association was found (r = -0.26) between the difference in cervical length (postcerclage - precerclage lengths) and pregnancy outcome. Patients with a prophylactic cerclage had a mean cervical length that was consistently longer in patients delivering at term compared with those who delivered preterm at 20 to 32 weeks' gestation. In the urgent cerclage group a significant difference in cervical length between those who delivered at term compared with preterm was evident only at 28 to 32 weeks. CONCLUSION: The increase in cervical length after cerclage is not predictive of term delivery. Serial cervical length measurements in the late second or early third trimester predict preterm birth but could provide earlier warning in patients with a prophylactic cerclage than in patients with urgent cerclage.