Effect of Implementing a Standardized Shoulder Dystocia Documentation Form on Quality of Delivery Notes.

OBJECTIVES: Complete and accurate documentation by the delivering provider in cases of shoulder dystocia is critical for providing clinical information and care to the patient and protecting providers from litigation risks. Standardized forms improve inclusion of certain data elements in the medical record, but the impact on subsequent narrative notes is unknown. We aimed to determine if implementation of a standardized shoulder dystocia documentation form improves obstetric provider written narrative delivery notes. METHODS: In February 2005, our institution introduced a mandatory, standardized shoulder dystocia form containing 29 discrete data points relevant to shoulder dystocia documentation. We identified all deliveries complicated by shoulder dystocia from 1 year before and 4 years after implementation of this form and analyzed medical records for inclusion of delivery information in both the required form and the narrative delivery notes. RESULTS: We identified 52 cases before and 100 cases after implementation of the standardized form. Inclusion of elements from the form in narrative delivery notes increased significantly after implementation (P = 0.01). Elements present at higher rates included prepregnancy maternal weight (13% before vs 28% after, P = 0.043), total maternal weight gain (19% vs 36%, P = 0.03), estimated fetal weight (60% vs 77%, P = 0.03), duration of active labor (40% vs 65%, P < 0.01), duration of second stage (27% vs 52%, P < 0.01), and time of delivery from head to body (4% vs 30%, P < 0.01). CONCLUSIONS: Use of a mandatory shoulder dystocia documentation form is associated with significant improvement in the comprehensiveness of delivering provider narrative notes and may encourage more complete and accurate charting. Such improvements can allow for more complete and accurate explanation of events to patients and better demonstrate adherence to standards of care in the management of shoulder dystocia and may improve litigation defensibility.

Protein misfolding, congophilia, oligomerization, and defective amyloid processing in preeclampsia.

Preeclampsia is a pregnancy-specific disorder of unknown etiology and a leading contributor to maternal and perinatal morbidity and mortality worldwide. Because there is no cure other than delivery, preeclampsia is the leading cause of iatrogenic preterm birth. We show that preeclampsia shares pathophysiologic features with recognized protein misfolding disorders. These features include urine congophilia (affinity for the amyloidophilic dye Congo red), affinity for conformational state-dependent antibodies, and dysregulation of prototype proteolytic enzymes involved in amyloid precursor protein (APP) processing. Assessment of global protein misfolding load in pregnancy based on urine congophilia (Congo red dot test) carries diagnostic and prognostic potential for preeclampsia. We used conformational state-dependent antibodies to demonstrate the presence of generic supramolecular assemblies (prefibrillar oligomers and annular protofibrils), which vary in quantitative and qualitative representation with preeclampsia severity. In the first attempt to characterize the preeclampsia misfoldome, we report that the urine congophilic material includes proteoforms of ceruloplasmin, immunoglobulin free light chains, SERPINA1, albumin, interferon-inducible protein 6-16, and Alzheimer's ß-amyloid. The human placenta abundantly expresses APP along with prototype APP-processing enzymes, of which the α-secretase ADAM10, the ß-secretases BACE1 and BACE2, and the γ-secretase presenilin-1 were all up-regulated in preeclampsia. The presence of ß-amyloid aggregates in placentas of women with preeclampsia and fetal growth restriction further supports the notion that this condition should join the growing list of protein conformational disorders. If these aggregates play a pathophysiologic role, our findings may lead to treatment for preeclampsia.

A comprehensive obstetric patient safety program reduces liability claims and payments.

Begun in 2003, the Yale-New Haven Hospital comprehensive obstetric safety program consisted of measures to standardize care, improve teamwork and communication, and optimize oversight and quality review. Prior publications have demonstrated improvements in adverse outcomes and safety culture associated with this program. In this analysis, we aimed to assess the impact of this program on liability claims and payments at a single institution. We reviewed liability claims at a single, tertiary-care, teaching hospital for two 5-year periods (1998-2002 and 2003-2007), before and after implementing the safety program. Connecticut statute of limitations for professional malpractice is 36 months from injury. Claims/events were classified by event-year and payments were adjusted for inflation. We analyzed data for trends as well as differences between periods before and after implementation. Forty-four claims were filed during the 10-year study period. Annual cases per 1000 deliveries decreased significantly over the study period (P < .01). Claims (30 vs 14) and payments ($50.7 million vs $2.9 million) decreased in the 5-years after program inception. Compared with before program inception, median annual claims dropped from 1.31 to 0.64 (P = .02), and median annual payments per 1000 deliveries decreased from $1,141,638 to $63,470 (P < .01). Even estimating the monetary awards for the 2 remaining open cases using the median payments for the surrounding 5 years, a reduction in the median monetary amount per case resulting in payment to the claimant was also statistically significant ($632,262 vs $216,815, P = .046). In contrast, the Connecticut insurance market experienced a stable number of claims and markedly increased cost per claim during the same period. We conclude that an obstetric safety initiative can improve liability claims exposure and reduce liability payments.

Antenatal corticosteroids impact the inflammatory rather than the antiangiogenic profile of women with preeclampsia.

Circulating antiangiogenic factors and proinflammatory cytokines are implicated in the pathogenesis of preeclampsia. This study was performed to test the hypothesis that steroids modify the balance of inflammatory and proangiogenic and antiangiogenic factors that potentially contribute to the patient's evolving clinical state. Seventy singleton women, admitted for antenatal corticosteroid treatment, were enrolled prospectively. The study group consisted of 45 hypertensive women: chronic hypertension (n=6), severe preeclampsia (n=32), and superimposed preeclampsia (n=7). Normotensive women with shortened cervix (<2.5 cm) served as controls (n=25). Maternal blood samples of preeclampsia cases were obtained before steroids and then serially up until delivery. A clinical severity score was designed to clinically monitor disease progression. Serum levels of angiogenic factors (soluble fms-like tyrosine kinase-1 [sFlt-1], placental growth factor [PlGF], soluble endoglin [sEng]), endothelin-1 (ET-1), and proinflammatory markers (IL-6, C-reactive protein [CRP]) were assessed before and after steroids. Soluble IL-2 receptor (sIL-2R) and total immunoglobulins (IgG) were measured as markers of T- and B-cell activation, respectively. Steroid treatment coincided with a transient improvement in clinical manifestations of preeclampsia. A significant decrease in IL-6 and CRP was observed although levels of sIL-2R and IgG remained unchanged. Antenatal corticosteroids did not influence the levels of angiogenic factors but ET-1 levels registered a short-lived increase poststeroids. Although a reduction in specific inflammatory mediators in response to antenatal steroids may account for the transient improvement in clinical signs of preeclampsia, inflammation is unlikely to be the major contributor to severe preeclampsia or useful for therapeutic targeting.

Improving maternal health and safety through adherence to postpartum hemorrhage protocol in Latin America.

OBJECTIVE: To determine provider compliance with protocols for the prevention of postpartum hemorrhage and provider characteristics associated with adherence and non-adherence. METHODS: A multicenter descriptive study was conducted involving 78 direct observations of provider-implemented protocols and 52 interviews with Peruvian maternal healthcare providers at 4 Peruvian clinical sites representing the local, regional, and national levels of care. Parturient participants planning a normal vaginal delivery were 17-49 years of age and 34-42 weeks pregnant. Primary outcomes were compared using χ2 testing, while quantitative survey data were evaluated using means, standard deviations, and Student t test or analysis of variance for statistical significance. RESULTS: There were 3 significant differences between the national, regional, and local levels of care: adherence to all 3 interventions (P<0.001); professional experience (P<0.04); and retention of healthcare providers (P<0.001). There were no differences in provider training (P<0.097), and the retention of experienced healthcare providers was not associated with greater adherence to protocols. There were no significant differences in parturient characteristics. CONCLUSION: Individual characteristics and institutional beliefs may have more influence than experience or training on adherence to protocols for prevention of postpartum hemorrhage; addressing these biases may improve patient safety in Peru and throughout Latin America.

Engaging the health care team through Operations Councils: strategies to improve population health from within.

PURPOSE: Clinical front-line staff are best positioned within the organizations to identify patient safety problems and craft solutions. However, in traditional models, safety committees are led by senior executives who are not clinically responsible for patients. This top-down approach can result in missed opportunities to address patient-centered challenges and better manage the health of the defined populations served by these organizations. DESIGN/METHODOLOGY/APPROACH: To foster teamwork, enhance empowerment, and improve the patient care environment, Operations Councils led by trained front-line staff were deployed in 15 clinical areas at the Ohio State University Wexner Medical Center (OSUWMC) as a performance improvement tool. FINDINGS: Standardized training of Council facilitators was designed and implemented to guide the performance improvement process. Balanced scorecards were developed in each Council based on the risks and concerns of that particular clinical area. After initial implementation of the Operations Councils, patient safety events declined and team engagement improved by over 34% across the medical center; the highest changes were seen in areas where Operations Councils had been deployed. Additionally, outcome metrics including area-specific and system-wide mortality and readmissions improved after implementation. ORIGINALITY/VALUE: We suggest that this type of approach may be an appropriate strategy to consider in other health care organizations as such institutions are challenged to better manage the health of their defined patient populations.

Antenatal lamivudine to reduce perinatal hepatitis B transmission: a cost-effectiveness analysis.

OBJECTIVES: This study aimed to determine whether administration of lamivudine to pregnant women with chronic hepatitis B in the third trimester is a cost-effective strategy in preventing perinatal transmission. STUDY DESIGN: We developed a decision analysis model to compare the cost-effectiveness of 2 management strategies for chronic hepatitis B in pregnancy: (1) expectant management or (2) lamivudine administration in the third trimester. We assumed that lamivudine reduced perinatal transmission by 62%. RESULTS: Our Markov model demonstrated that lamivudine administration is the dominant strategy. For every 1000 infected pregnant women treated with lamivudine, $337,000 is saved and 314 quality-adjusted life-years are gained. For every 1000 pregnancies with maternal hepatitis B, lamivudine prevents 21 cases of hepatocellular carcinoma and 5 liver transplants in the offspring. The model remained robust in sensitivity analysis. CONCLUSION: Antenatal lamivudine administration to pregnant patients with hepatitis B is cost-effective, and frequently cost-saving, under a wide range of circumstances.

Mode of delivery and neonatal outcomes in preterm, small-for-gestational-age newborns.

OBJECTIVE: To compare neonatal outcomes by method of delivery in preterm (34 weeks of gestation or prior), small-for-gestational-age (SGA) newborns in a large diverse cohort. METHODS: Birth data for 1995-2003 from New York City were linked to hospital discharge data. Data were limited to singleton, liveborn, vertex neonates delivered between 25 and 34 weeks of gestation. Births complicated by known congenital anomalies and birth weight less than 500 g were excluded. Small for gestational age was used as a surrogate for intrauterine growth restriction. Associations between method of delivery and neonatal morbidities were estimated using logistic regression. RESULTS: Two thousand eight hundred eighty-five SGA neonates meeting study criteria were identified; 42.1% were delivered vaginally, and 57.9% were delivered by cesarean. There was no significant difference in intraventricular hemorrhage, subdural hemorrhage, seizure, or sepsis between the cesarean delivery and vaginal delivery groups. Cesarean delivery compared with vaginal delivery was associated with increased odds of respiratory distress syndrome. The increased odds persisted after controlling for maternal age, parity, ethnicity, education, primary payer, prepregnancy weight, gestational age at delivery, diabetes, and hypertension. CONCLUSION: Cesarean delivery was not associated with improved neonatal outcomes in preterm SGA newborns and was associated with an increased risk of respiratory distress syndrome.

Comparative analysis of 2-D versus 3-D ultrasound estimation of the fetal adrenal gland volume and prediction of preterm birth.

OBJECTIVE: We aim to test the hypothesis that two-dimensional (2-D) fetal adrenal gland volume (AGV) measurements offer similar volume estimates as volume calculations based on 3-D technique. METHODS: Fetal AGV was estimated by three-dimensional (3-D) ultrasound (VOCAL) in 93 women with signs/symptoms of preterm labor and 73 controls. Fetal AGV was calculated using an ellipsoid formula derived from 2-D measurements of the same blocks (0.523 × length × width × depth). Comparisons were performed by intraclass correlation coefficient (ICC), coefficient of repeatability, and Bland-Altman method. The corrected AGV (cAGV; AGV/fetal weight) was calculated for both methods and compared for prediction of preterm birth (PTB) within 7 days. RESULTS: Among 168 volumes, there was a significant correlation between 3-D and 2-D methods (ICC = 0.979; 95% confidence interval [CI]: 0.971 to 0.984). The coefficient of repeatability for the 3-D was superior to the 2-D method (intraobserver 3-D: 30.8, 2-D:57.6; interobserver 3-D:12.2, 2-D: 15.6). Based on 2-D calculations, cAGV ≥ 433 mm3/kg was best for prediction of PTB (sensitivity: 75%, 95% CI = 59 to 87; specificity: 89%, 95% CI = 82 to 94). Sensitivity and specificity for the 3-D cAGV (cutoff ≥ 420 mm3/kg) was 85% (95% CI = 70 to 94) and 95% (95% CI = 90 to 98), respectively. In receiver-operating-curve curve analysis, 3-D cAGV was superior to 2-D cAGV for prediction of PTB (z = 1.99, p = 0.047). CONCLUSION: 2-D volume estimation of fetal adrenal gland using ellipsoid formula cannot replace 3-D AGV calculations for prediction of PTB.

Prenatal hazardous substance use and adverse birth outcomes.

OBJECTIVE: Assess the relative effects of a variety of illicit and licit drugs on risk for adverse birth outcomes. METHODS: We used data from two large prospective investigations, and a novel analytic method, recursive partitioning class analysis to identify risk factors associated with preterm birth and delivering a small for gestational age infant. RESULTS: Compared to cocaine and opiate non-users, cocaine users were 3.53 times as likely (95% CI: 1.65-7.56; p = 0.001) and opiate users 2.86 times as likely (95% CI: 1.11-7.36; p = 0.03) to deliver preterm. The odds of delivering a small for gestational age infant for women who smoked more than two cigarettes daily was 3.74, (95% CI: 2.47-5.65; p<0.0001) compared to women who smoked two or less cigarettes daily and had one previous child. Similarly, less educated, nulliparous women who smoked two or fewer cigarettes daily were 4.12 times as likely (95% CI: 2.04-8.34; p < 0.0001) to have a small for gestational age infant. CONCLUSIONS: Among our covariates, prenatal cocaine and opiate use are the predominant risk factors for preterm birth; while tobacco use was the primary risk factor predicting small for gestational age at delivery. Multi-substance use did not substantially increase risk of adverse birth outcomes over these risk factors.

Screening for gestational diabetes mellitus: are the criteria proposed by the international association of the Diabetes and Pregnancy Study Groups cost-effective?

OBJECTIVE: The International Association of the Diabetes and Pregnancy Study Groups (IADPSG) recently recommended new criteria for diagnosing gestational diabetes mellitus (GDM). This study was undertaken to determine whether adopting the IADPSG criteria would be cost-effective, compared with the current standard of care. RESEARCH DESIGN AND METHODS: We developed a decision analysis model comparing the cost-utility of three strategies to identify GDM: 1) no screening, 2) current screening practice (1-h 50-g glucose challenge test between 24 and 28 weeks followed by 3-h 100-g glucose tolerance test when indicated), or 3) screening practice proposed by the IADPSG. Assumptions included that 1) women diagnosed with GDM received additional prenatal monitoring, mitigating the risks of preeclampsia, shoulder dystocia, and birth injury; and 2) GDM women had opportunity for intensive postdelivery counseling and behavior modification to reduce future diabetes risks. The primary outcome measure was the incremental cost-effectiveness ratio (ICER). RESULTS: Our model demonstrates that the IADPSG recommendations are cost-effective only when postdelivery care reduces diabetes incidence. For every 100,000 women screened, 6,178 quality-adjusted life-years (QALYs) are gained, at a cost of $125,633,826. The ICER for the IADPSG strategy compared with the current standard was $20,336 per QALY gained. When postdelivery care was not accomplished, the IADPSG strategy was no longer cost-effective. These results were robust in sensitivity analyses. CONCLUSIONS: The IADPSG recommendation for glucose screening in pregnancy is cost-effective. The model is most sensitive to the likelihood of preventing future diabetes in patients identified with GDM using postdelivery counseling and intervention.

Mode of delivery in nulliparous women and neonatal intracranial injury.

OBJECTIVE: To compare neonatal neurologic complication rates of cesarean deliveries, forceps-assisted vaginal deliveries, and vacuum-assisted vaginal deliveries. METHODS: Data on singleton live births at 34 weeks or greater gestation born to nulliparous women from 1995 to 2003 in New York City were linked to hospital discharge data. Any diagnosis of neonatal subdural hemorrhage, intraventricular hemorrhage, seizures, scalp laceration or cephalohematoma, fracture, facial nerve palsy, brachial plexus injury, or 5-minute Apgar score of less than 7 was considered significant. Multivariable logistic regression was used to estimate associations between delivery mode and these neonatal morbidities. RESULTS: Forceps-assisted vaginal deliveries were associated with significantly fewer seizures and 5-minute Apgar scores less than 7 compared with vacuum-assisted vaginal deliveries and cesarean deliveries. Cesarean deliveries were linked to less subdural hemorrhages compared with forceps-assisted vaginal deliveries or vacuum-assisted vaginal deliveries. When seizure, intraventricular hemorrhage, and subdural hemorrhage were examined collectively to best predict neurologic outcome, forceps-assisted vaginal deliveries had an overall reduced risk compared with both vacuum-assisted vaginal deliveries (odds ratio [OR] 0.60, 95% confidence interval [CI] 0.40-0.90) and cesarean deliveries (OR 0.68, 95% CI 0.48-0.97). The number needed to treat to prevent one case of severe neurologic morbidity is 509 for forceps-assisted vaginal deliveries compared with vacuum-assisted vaginal deliveries and 559 for forceps-assisted vaginal deliveries compared with cesarean deliveries. CONCLUSION: Compared with vacuum-assisted vaginal delivery or cesarean delivery, a forceps-assisted vaginal delivery is associated with a reduced risk of adverse neonatal neurologic outcomes. LEVEL OF EVIDENCE: II.

Ultrasonographic evaluation of myometrial thickness and prediction of a successful external cephalic version.

OBJECTIVE: To test the hypothesis that myometrial thickness predicts the success of external cephalic version. METHODS: Abdominal ultrasonographic scans were performed in 114 consecutive pregnant women with breech singletons before an external cephalic version maneuver. Myometrial thickness was measured by a standardized protocol at three sites: the lower segment, midanterior wall, and the fundal uterine wall. Independent variables analyzed in conjunction with myometrial thickness were: maternal age, parity, body mass index, abdominal wall thickness, estimated fetal weight, amniotic fluid index, placental thickness and location, fetal spine position, breech type, and delivery outcomes such as final mode of delivery and birth weight. RESULTS: Successful version was associated with a thicker ultrasonographic fundal myometrium (unsuccessful: 6.7 [5.5-8.4] compared with successful: 7.4 [6.6-9.7] mm, P=.037). Multivariate regression analysis showed that increased fundal myometrial thickness, high amniotic fluid index, and nonfrank breech presentation were the strongest independent predictors of external cephalic version success (P<.001). A fundal myometrial thickness greater than 6.75 mm and an amniotic fluid index greater than 12 cm were each associated with successful external cephalic versions (fundal myometrial thickness: odds ratio [OR] 2.4, 95% confidence interval [CI] 1.1-5.2, P=.029; amniotic fluid index: OR 2.8, 95% CI 1.3-6.0, P=.008). Combining the two variables resulted in an absolute risk reduction for a failed version of 27.6% (95% CI 7.1-48.1) and a number needed to treat of four (95% CI 2.1-14.2). CONCLUSION: Fundal myometrial thickness and amniotic fluid index contribute to success of external cephalic version and their evaluation can be easily incorporated in algorithms before the procedure. LEVEL OF EVIDENCE: III.

Indications contributing to the increasing cesarean delivery rate.

OBJECTIVE: To examine physician-documented indications for cesarean delivery in order to investigate the specific factors contributing to the increasing cesarean delivery rate. METHODS: We analyzed rates of primary and repeat cesarean delivery, including indications for the procedure, among 32,443 live births at a major academic hospital between 2003 and 2009. Time trends for each indication were modeled to estimate the absolute and cumulative annualized relative risk of cesarean by indication over time and the relative contribution of each indication to the overall increase in primary cesarean delivery rate. RESULTS: The cesarean delivery rate increased from 26% to 36.5% between 2003 and 2009; 50.0% of the increase was attributable to an increase in primary cesarean delivery. Among the documented indications, nonreassuring fetal status, arrest of dilation, multiple gestation, preeclampsia, suspected macrosomia, and maternal request increased over time, whereas arrest of descent, malpresentation, maternal-fetal indications, and other obstetric indications (eg, cord prolapse, placenta previa) did not increase. The relative contributions of each indication to the total increase in primary cesarean rate were: nonreassuring fetal status (32%), labor arrest disorders (18%), multiple gestation (16%), suspected macrosomia (10%), preeclampsia (10%), maternal request (8%), maternal-fetal conditions (5%), and other obstetric conditions (1%). CONCLUSION: Primary cesarean births accounted for 50% of the increasing cesarean rate. Among primary cesarean deliveries, more subjective indications (nonreassuring fetal status and arrest of dilation) contributed larger proportions than more objective indications (malpresentation, maternal-fetal, and obstetric conditions).

A comprehensive obstetrics patient safety program improves safety climate and culture.

OBJECTIVE: The purpose of this study was to determine the effect of an obstetrics patient safety program on staff safety culture. STUDY DESIGN: We implemented (1) obstetrics patient safety nurse, (2) protocol-based standardization of practice, (3) crew resource management training, (4) oversight by a patient safety committee, (5) 24-hour obstetrics hospitalist, and (6) an anonymous event reporting system. We administered the Safety Attitude Questionnaire on 4 occasions over 5 years (2004-2009) to all staff members that assessed teamwork and safety cultures, job satisfaction, working conditions, stress recognition, and perceptions of management. RESULTS: We observed significant improvements in the proportion of staff members with favorable perceptions of teamwork culture (39% in 2004 to 63% in 2009), safety culture (33% to 63%), job satisfaction (39% to 53%), and management (10% to 37%). Individual roles (obstetrics providers, residents, and nurses) also experienced improvements in safety and teamwork, with significantly better congruence between doctors and nurses. CONCLUSION: Safety programs can improve workforce perceptions of safety and an improved safety climate.

Accreta complicating complete placenta previa is characterized by reduced systemic levels of vascular endothelial growth factor and by epithelial-to-mesenchymal transition of the invasive trophoblast.

OBJECTIVE: We sought to characterize serum angiogenic factor profile of women with complete placenta previa and determine if invasive trophoblast differentiation characteristic of accreta, increta, or percreta shares features of epithelial-to-mesenchymal transition. STUDY DESIGN: We analyzed gestational age-matched serum samples from 90 pregnant women with either complete placenta previa (n = 45) or uncomplicated pregnancies (n = 45). Vascular endothelial growth factor (VEGF), placental growth factor, and soluble form of fms-like-tyrosine-kinase-1 were immunoassayed. VEGF and phosphotyrosine immunoreactivity was surveyed in histological specimens relative to expression of vimentin and cytokeratin-7. RESULTS: Women with previa and invasive placentation (accreta, n = 5; increta, n = 6; percreta, n = 2) had lower systemic VEGF (invasive previa: median 0.8 [0.02-3.4] vs control 6.5 [2.7-10.5] pg/mL, P = .02). VEGF and phosphotyrosine immunostaining predominated in the invasive extravillous trophoblasts that coexpressed vimentin and cytokeratin-7, an epithelial-to-mesenchymal transition feature and tumorlike cell phenotype. CONCLUSION: Lower systemic free VEGF and a switch of the interstitial extravillous trophoblasts to a metastable cell phenotype characterize placenta previa with excessive myometrial invasion.

Ultrasound measurement of fetal adrenal gland enlargement: an accurate predictor of preterm birth.

OBJECTIVE: The objective of the study was to test whether ultrasound-measured fetal adrenal gland volume (AGV) and fetal zone enlargement (FZE) predicts preterm birth (PTB) better than cervical length (CL). STUDY DESIGN: Three-dimensional and 2-dimensional ultrasound were used prospectively to measure fetal AGV, FZE, and CL in women with preterm labor symptoms. We corrected AGV for fetal weight (cAGV). The ratio between whole gland depth (D) and central fetal zone depth (d) (d/D) was used to measure FZE. Ability of cAGV, d/D, and CL to predict PTB 7 days or less was compared. RESULTS: Twenty-seven of 74 women (36.5%) presenting between 21 and 34 weeks had PTB of 7 days or less. FZE greater than 49.5% was the single best predictor for PTB (sensitivity/specificity 100%/89%) compared with cAGV (81%/87%) and CL (56%/60%; P < .05). Prediction was independent of obstetrics history and tocolytic use. CONCLUSION: The 2-dimensional measurement of the adrenal gland FZE is highly effective performing superior to CL in identifying women at risk for PTB within 7 days.

IL-6 trans-signaling system in intra-amniotic inflammation, preterm birth, and preterm premature rupture of the membranes.

Classic IL-6 signaling is conditioned by the transmembrane receptor (IL-6R) and homodimerization of gp130. During trans-signaling, IL-6 binds to soluble IL-6R (sIL-6R), enabling activation of cells expressing solely gp130. Soluble gp130 (sgp130) selectively inhibits IL-6 trans-signaling. To characterize amniotic fluid (AF) IL-6 trans-signaling molecules (IL-6, sIL-6R, sgp130) in normal gestations and pregnancies complicated by intra-amniotic inflammation (IAI), we studied 301 women during second trimester (n = 39), third trimester (n = 40), and preterm labor with intact (n = 131, 85 negative IAI and 46 positive IAI) or preterm premature rupture of membranes (PPROM; n = 91, 61 negative IAI and 30 positive IAI). ELISA, Western blotting, and real-time RT-PCR were used to investigate AF, placenta, and amniochorion for protein and mRNA expression of sIL-6R, sgp130, IL-6R, and gp130. Tissues were immunostained for IL-6R, gp130, CD15(+) (polymorphonuclear), and CD3(+) (T cell) inflammatory cells. The ability of sIL-6R and sgp130 to modulate basal and LPS-stimulated release of amniochorion matrix metalloprotease-9 was tested ex vivo. We showed that in physiologic gestations, AF sgp130 decreases toward term. AF IL-6 and sIL-6R were increased in IAI, whereas sgp130 was decreased in PPROM. Our results suggested that fetal membranes are the probable source of AF sIL-6R and sgp130. Immunohistochemistry and RT-PCR revealed increased IL-6R and decreased gp130 expression in amniochorion of women with IAI. Ex vivo, sIL-6R and LPS augmented amniochorion matrix metalloprotease-9 release, whereas sgp130 opposed this effect. We conclude that IL-6 trans-signaling molecules are physiologic constituents of the AF regulated by gestational age and inflammation. PPROM likely involves functional loss of sgp130.