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Preeclampsia, a complication of pregnancy characterized by hypertension and proteinuria, has been found to reduce the subsequent risk for breast cancer in female offspring. As this protective effect could be due to exposure to preeclampsia-specific proteins during intrauterine life, the proteomic profiles of umbilical cord blood plasma between preeclamptic and normotensive pregnancies were compared. Umbilical cord plasma samples, depleted of 14 abundant proteins, were subjected to proteomic analysis using the quantitative method of nanoACQUITY ultra performance liquid chromatography–mass spectrometry with elevated energy mode of acquisitionE (NanoUPLC-MSE). Sixty-nine differentially expressed proteins were identified, of which 15 and 6 proteins were only detected in preeclamptic and normotensive pregnancies, respectively. Additionally, expression of 8 proteins (gelsolin, complement C5, keratin type I cytoskeletal 10, pigment epithelium-derived factor, complement factor B, complement component C7, hemoglobin subunit gamma-2 and alpha-fetoprotein) were up-regulated in preeclampsia with a fold change of ⩾2.0 when compared to normotensive pregnancies. The identification of alpha-fetoprotein in preeclamptic umbilical cord blood plasma supported the validity of this screen as alpha-fetoprotein has anti-estrogenic properties and has previously been linked to preeclampsia as well as a reduced breast cancer risk. The findings of this pilot study may provide new insights into the mechanistic link between preeclampsia and potentially reduced breast cancer susceptibility in adult life.

Background: Angiogenic imbalances, characterized by an excess of antiangiogenic factors (soluble fms-like tyrosine kinase 1) and reduced angiogenic factors (vascular endothelial growth factor and placental growth factor), contribute to the mechanisms of disease in preeclampsia. The ratio of soluble fms-like tyrosine kinase 1 to placental growth factor has been used as a biomarker for preeclampsia, but the cutoff values may vary with gestational age and assay platform., Objective: This study aimed to compare multiples of the median of the maternal plasma soluble fms-like tyrosine kinase 1 to placental growth factor ratio, soluble fms-like tyrosine kinase 1, placental growth factor, and conventional clinical and laboratory values in their ability to predict preeclampsia with severe features., Study Design: We conducted a cohort study across 18 United States centers involving hospitalized individuals with hypertension between 23 and 35 weeks' gestation. Receiver operating characteristic curve analyses of maternal plasma biomarkers, highest systolic or diastolic blood pressures, and laboratory values at enrollment were performed for the prediction of preeclampsia with severe features. The areas under the curve were compared, and quasi-Poisson regression models were fitted to estimate relative risks. The primary outcome was preeclampsia with severe features within 2 weeks of enrollment. Secondary outcomes were a composite of severe adverse maternal outcomes (elevated liver enzymes, low platelets count, placental abruption, eclampsia, disseminated intravascular coagulation, and pulmonary edema) and a composite of severe adverse perinatal outcomes (birth weight below the third percentile, very preterm birth [<32 weeks' gestation], and fetal or neonatal death)., Results: Of the 543 individuals included in the study, preeclampsia with severe features within 2 weeks was observed in 33.1% (n=180) of them. A receiver operating characteristic curve-derived cutoff of 11.5 multiples of the median for the soluble fms-like tyrosine kinase 1 to placental growth factor plasma ratio provided good sensitivity (90.6%), specificity (76.9%), positive predictive value (66.0%), negative predictive value (94.3%), positive likelihood ratio (3.91), negative likelihood ratio (0.12), and accuracy (81.4%) for preeclampsia with severe features within 2 weeks. This cutoff was used to compare test positive cases (≥ cutoff) and test negative cases (< cutoff). Preeclampsia with severe features (66.0% vs 5.7%; P<.001) and composites of severe adverse maternal (8.11% vs 2.7%; P=.006) or perinatal (41.3% vs 10.14%; P=.001) outcomes within 2 weeks were more frequent in test positive cases than in test negative cases. A soluble fms-like tyrosine kinase 1 to placental growth factor plasma ratio ≥11.5 multiples of the median was independently associated with preeclampsia with severe features (adjusted incidence rate ratio, 9.08; 95% confidence interval, 6.11-14.06; P<.001) and a composite of severe adverse perinatal outcomes (adjusted incidence rate ratio, 9.42; 95% confidence interval, 6.36-14.53; P<.001) but not with a composite of severe adverse maternal outcomes (adjusted incidence rate ratio, 2.20; 95% confidence interval, 0.95-5.54; P=.08). The area under the curve for the soluble fms-like tyrosine kinase 1 to placental growth factor plasma ratio in multiples of the median (0.91; 95% confidence interval, 0.89-0.94) for preeclampsia with severe features within 2 weeks was significantly higher (P<.001 for all comparisons) than either plasma biomarker alone or any other parameter with the exception of absolute soluble fms-like tyrosine kinase 1 to placental growth factor plasma ratio values., Conclusion: A soluble fms-like tyrosine kinase 1 to placental growth factor plasma ratio ≥11.5 multiples of the mean among hospitalized patients with hypertension between 23 and 35 week's gestation predicts progression to preeclampsia with severe features and severe adverse perinatal outcomes within 2 weeks., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The coronavirus disease 2019 pandemic has significantly disrupted operations in academic departments of obstetrics and gynecology throughout the United States and will continue to affect them in the foreseeable future. It has also created an environment conducive to innovation and the accelerated implementation of new ideas. These departments will need to adapt their operations to accommodate coronavirus disease 2019 and to continue to meet their tripartite mission of clinical excellence, medical education, and women's health research. This "Call to Action" paper from the leaders of American Gynecological and Obstetrical Society and Council of University Chairs of Obstetrics and Gynecology provides a framework to help the leaders of departments of obstetrics and gynecology reimagine and reengineer their operations in light of the current coronavirus disease 2019 crisis and future pandemics., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Study Objective. To compare the clinical outcomes of patients with severe postpartum hemorrhage (PPH) managed with and without the use of Point-of-Care Viscoelastic Testing (PCVT) to direct blood product replacement. Design. A retrospective cohort study of consecutive cases of severe PPH managed at a single tertiary care center between January 1, 2011 and July 31, 2015. Cases included patients managed using PCVT. Controls were patients managed using a standardized massive hemorrhage transfusion protocol, either because PCVT was not yet available or because no PCVT credentialed providers were on site. Setting. Delivery room, postoperative recovery area, intensive care unit. Patients. There were 6,708 cesarean deliveries and 13,641 vaginal births during the study period. Eighty six patients (0.4% of all deliveries) developed severe PPH. Severe PPH occurred in 1% (68/6,708) of cesarean and 0.1% (18/13,641) of vaginal deliveries. Twenty-eight of these 86 patients (32.6%) were managed with PCVT and 58 (67.4%) without PCVT. Interventions. Patients with severe PPH were managed according to a standardized massive transfusion protocol or a PCVT-based protocol to direct blood product replacement. Measurements. PCVT testing was performed using a ROTEM delta device. Results. Patients in the PCVT cohort received significantly fewer transfusions of packed red blood cells, fresh frozen plasma, and platelet concentrates. They also had a significantly lower estimated blood loss, and a significantly lower incidence of cesarean hysterectomy and postoperative ICU admission as compared with patients not managed using PCVT. The length of postpartum hospitalization was also significantly shorter in the PCVT cohort. Among patients who gave birth within 24 hours of admission, the direct cost of hospitalization was 40% lower for patients in the PCVT cohort. Conclusions. PCVT-based goal-directed blood product replacement management was associated with substantial benefits over a standardized massive transfusion protocol both in terms of patient outcomes and cost of care.

Objectives: To compare the characteristics of pregnant women with hyperglycemia according to the severity of glucose intolerance using the 100-g oral glucose tolerance test (OGTT) and to demonstrate the need to manage the condition of women with mild hyperglycemia., Materials and Methods: In this retrospective cohort study, a total of 258 women at high risk of gestational diabetes (GDM) based on a positive 50-g oral glucose challenge test (OGCT) were classified into 0+, 1+, 2+, 3+, and 4+ groups according to the number of abnormal plasma glucose values on the 100-g OGTT. The clinical characteristics of the groups were compared., Results: The rates of advanced maternal age (≥ 35 years), multiparity, prior history of GDM, preterm birth, cesarean delivery, and elevated body mass index were all positively correlated with the number of abnormal plasma glucose values on the OGTT (p < 0.05 for all variables). After adjusting for confounding factors, the fasting plasma glucose levels predicted birth weight in 44.4%, 48.4%, and 58.6% of the women in the positive 50-g OGCT group, the 0+ group, and the 1+ group, respectively. Weight gain during pregnancy predicted birth weight in 42%, 44.6%, and 37.6% of the women in the positive 50-g OGCT group, the 0+ group, and the 2+ group, respectively (p < 0.001 in each case)., Conclusions: These data demonstrate that the detection and management of mild hyperglycemia below the current diagnostic criteria of GDM as well as GDM diagnosed using the 100-g OGTT are necessary for improving pregnancy outcomes., (Copyright © 2015. Published by Elsevier B.V.)

Background: Spontaneous (non-traumatic) rupture of the spleen rarely occurs in the setting of a normal spleen, especially during pregnancy., Objectives: We report a case of spontaneous rupture of a normal spleen at 33.7 weeks gestation and review the literature with the aim of exploring the etiology, diagnosis, and management of this condition during pregnancy., Case Report: A 30-year-old Chinese primigravida presented at 33.7 weeks gestation with acute onset of severe, constant left upper abdominal pain. She developed acute hypotension. Physical examination revealed diffuse abdominal tenderness with rebounding and guarding. An emergent cesarean delivery and abdominal exploration was performed. A non-viable male infant was delivered, and active bleeding was identified at the splenic hilum consistent with splenic rupture. A splenectomy was performed, and a consumptive coagulopathy was identified and treated. The patient had an uncomplicated postoperative course and was discharged home on postoperative day 15., Conclusion: Splenic rupture in pregnancy is a life-threatening complication. Early diagnosis and aggressive surgical intervention will allow for optimal maternal and perinatal outcome., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Pregnancy complications such as pre-eclampsia, placental abruption and growth restriction were once thought to represent end-of-pregnancy issues. Currently, the cause of such complications are being increasingly recognised as defective implantation and placentation. The molecular mechanisms responsible for normal and abnormal implantation are an area of active investigation. Screening tests, such as Doppler ultrasound of the maternal uterine arteries and evaluation of markers in the maternal serum, are being assessed to determine if such tests might allow for better recognition and, perhaps, prevention of many pregnancy complications related to abnormal placentation. Many techniques during pregnancy have been used to prevent pregnancy complications such as pre-eclampsia. Most have been unsuccessful. Ultimately, the solution may reside in pre-pregnancy approaches to improve implantation and placentation. Such approaches are actively being investigated and have promise., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Objective: The aim of this study was to determine whether sonographic fetal pulmonary artery flow velocity waveforms correlate with amniotic fluid biomarkers of fetal lung maturity., Study Design: We studied women with singleton pregnancies undergoing clinically indicated amniocentesis for fetal lung maturity at Yale-New Haven Hospital. Fetal pulmonary artery flow velocity measurements, including systolic/diastolic ratio, pulsatility index, resistance index, and acceleration-time/ejection-time ratio were obtained using spectral Doppler ultrasound. Pearson's correlation coefficient was used to determine the association between fetal pulmonary artery flow velocity parameters and the lecithin/sphingomyelin ratio., Results: Twenty-nine subjects met study criteria. The acceleration-time/ejection-time ratio was inversely correlated with the lecithin/sphingomyelin ratio (r = -0.76; P < or = .001). This relationship was maintained after controlling for potential confounders. Other fetal pulmonary artery flow velocity measurements were not associated with the lecithin/sphingomyelin ratio., Conclusion: There is an inverse correlation between the acceleration-time/ejection-time ratio in the fetal pulmonary artery and the amniotic fluid lecithin/sphingomyelin ratio. This suggests that ultrasound evaluation of fetal pulmonary artery blood flow may be a promising new noninvasive technique to evaluate fetal lung maturity., (Copyright (c) 2010 Mosby, Inc. All rights reserved.)

Objective: We sought to examine changes in the intraamniotic proteomic environment after the administration of antenatal corticosteroids to women with impending preterm delivery., Study Design: Amniotic fluid samples were collected at the time of clinically indicated amniocentesis before and within 7 days of administration of antenatal corticosteroids for impending preterm delivery (n = 12). Proteins differentially expressed before and after corticosteroids were identified by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry. They were isolated, characterized, and quantified by fast protein liquid chromatography, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, in-gel tryptic digestion, immunodepletion assays, enzyme-linked immunosorbent assay, and electrospray ionization tandem mass spectrometry., Results: Five protein peaks of interest were identified and characterized, all of which were significantly decreased after antenatal corticosteroid administration. These included 2 isoforms of transthyretin, albumin, prothrombin fragment 2, and lumican., Conclusion: Four proteins, identified and characterized in amniotic fluid, were differentially expressed with antenatal corticosteroid administration. These data may provide additional insight into the molecular mechanisms by which antenatal corticosteroids prevent neonatal complications., (Copyright 2010 Mosby, Inc. All rights reserved.)

Objective: We implemented a comprehensive strategy to track and reduce adverse events., Study Design: We incrementally introduced multiple patient safety interventions from September 2004 through November 2006 at a university-based obstetrics service. This initiative included outside expert review, protocol standardization, the creation of a patient safety nurse position and patient safety committee, and training in team skills and fetal heart monitoring interpretation. We prospectively tracked 10 obstetrics-specific outcome. The Adverse Outcome Index, an expression of the number of deliveries with at least 1 of the 10 adverse outcomes per total deliveries, was analyzed for trend., Results: Our interventions significantly reduced the Adverse Outcome Index (linear regression, r(2) = 0.50; P = .01) (overall mean, 2.50%). Concurrent with these improvements, we saw clinically significant improvements in safety climate as measured by validated safety attitude surveys., Conclusion: A systematic strategy to decrease obstetric adverse events can have a significant impact on patient safety.

Objective: This study investigates whether 2 cerclage stitches are more effective than 1 stitch in the prevention of preterm birth., Study Design: This is a retrospective cohort study of 150 singleton pregnancies that underwent cervical cerclage. Gestational age at delivery and clinical characteristics were compared., Results: One hundred twelve patients (74.7%) received 1 stitch, and 38 patients (25.3%) received 2 stitches. There were no baseline differences between the groups. Analysis showed no significant difference in gestational age at delivery between the 1 vs 2 cerclage groups overall (median, 38.0 vs 38.3 weeks of gestation, respectively; P = .356) or for a given gestational age cut-off (<37 weeks of gestation: 37.4% vs 34.2% [P = .727]; <34 weeks of gestation: 16.8% vs 18.4% [P = .823]; <28 weeks of gestation: 9.4% vs 2.6% [P = .179])., Conclusion: This study shows no measurable benefit to the placement of 2 stitches over 1 stitch during cervical cerclage in singleton pregnancies; however, further study of preterm birth at <28 weeks of gestation and postcerclage outcomes among a larger cohort is merited.

Objective: Labor is associated with 'decidual activation' with increased proteolysis and extracellular matrix degradation. The balance between plasminogen activator inhibitor-1 (PAI-1) and urokinase (uPA) and tissue-type plasminogen activator (tPA) is an important determinant of proteolytic activity at the maternal-fetal interface. Thrombin released at the time of placental abruption (decidual hemorrhage) is known to promote decidual proteolysis and uterine contractions. This study investigates the separate and interactive effects of steroid hormones and thrombin on PAI-1, uPA, and tPA expression by term decidual cells (DCs)., Study Design: Term DCs were isolated by enzymatic digestion, purified, and depleted of leukocytes. Cells were treated with estradiol (10(-8) mol [E2]), medroxyprogesterone acetate (10(-7) mol [MPA]), both, or vehicle for 7 days. After 24-hour incubation with or without thrombin (0.1-2.5 U/mL), levels of PAI-1, uPA, and tPA in conditioned supernatant were measured by specific ELISA and Western blotting. Levels of PAI-1 and uPA mRNA were measured by quantitative RT-PCR., Results: In the cultured term DCs, ELISA measurements indicated that basal output of PAI-1 was about 2 logs higher than that of either uPA or tPA (2.5 +/- 0.7 ng/mL per microg protein, 13.4 +/- 6.3 pg/mL per microg protein, and 25.4 +/- 10.8 pg/mL per microg protein, respectively). Although E2 alone did not affect PAI-1 output, MPA and E2+MPA significantly enhanced PAI-1 production (2.5 +/- 0.7 vs 8.2 +/- 2.0 ng/mL per microg protein for E2+MPA [3.3-fold]; P < .01). By contrast, uPA output was inhibited by exposure to MPA (13.4 +/- 6.3 vs 2.6 +/- 1.1 pg/mL per microg protein [0.2-fold]; P < .05), whereas tPA production was not affected by MPA. Thrombin did not significantly affect uPA and tPA production by term DCs. In contrast, in E2+MPA-treated term DCs, thrombin, a hemostatic proinflammatory cytokine, selectively increased PAI-1 output in a dose-dependent fashion, which could be blocked by the selective thrombin inhibitor, hirudin. Western blotting confirmed the effects of MPA and thrombin in elevating secreted levels of PAI-1. Unlike the increase in PAI-1 output elicited by thrombin, term DCs were unresponsive to either of the classic proinflammatory cytokines, TNFalpha or IL-1beta. Corresponding effects on PAI-1 mRNA levels were elicited by MPA and thrombin as seen for PAI-1 protein expression, suggesting that these up-regulatory effects are transcriptionally mediated., Conclusion: Progestin enhanced PAI-1 and inhibited uPA expression by term DCs, which may explain in part the pregnancy-prolonging properties of progesterone as a consequence of inhibited proteolytic activity at the maternal-fetal interface. Thrombin augmented PAI-1 expression in the absence of increased uPA or tPA expression by term DCs, suggesting that abruption-associated decidual proteolysis and preterm labor is mediated primarily by thrombin-enhanced matrix metalloproteinase expression rather than an indirect effect on the plasminogen activator/inhibitor system.

Objective: Excess decidual macrophage infiltration has been linked to preeclampsia and a failure of endovascular trophoblast invasion. Severe preeclampsia with shallow placentation has also been linked to acquired and inherited maternal thrombophilias and recurrent decidual hemorrhage, which generates thrombin from decidual cell-expressed tissue factor. Therefore, the current study evaluated whether thrombin affects monocyte chemoattractant protein-1 (MCP-1) expression in stromal cells that are derived from cycling and gestational endometrium., Study Design: Stromal cells that are isolated from cycling endometrium and first trimester and term decidua were grown to confluence, treated for 7 days with 10(-8) mol/L estradiol (E2) + 10(-7) mol/L medroxyprogesterone acetate (MPA), then switched to a serum-free medium that contained the corresponding steroids +/- thrombin. MCP-1 protein release was measured by enzyme-linked immunosorbent assay and Western blot; MCP-1 messenger RNA levels were assessed by real-time quantitative reverse transcription-polymerase chain reaction., Results: Secreted MCP-1 levels were not significantly different in stromal or decidual cell cultures that were incubated with E2 or with E2 + MPA. Thrombin increased immunoreactive MCP-1 expression in a dose-response fashion in first trimester and term decidual cells but not in endometrial stromal cells. Thrombin-induced MCP-1 protein output was unaffected by MPA but was abrogated by incubation with the thrombin inhibitor, hirudin. Unexpectedly, thrombin-enhanced MCP-1 protein expression was unaccompanied by corresponding changes in steady state MCP-1 messenger RNA levels, which suggests its effects were posttranslational., Conclusion: MCP-1 protein expression is up regulated by thrombin in decidual cells across gestation, but not in stromal cells from predecidualized cycling endometrium.

Normal implantation and placentation is critical for pregnancy success. Many pregnancy-related complications that present late in gestation (such as pre-eclampsia and preterm labour) appear to have their origins early in pregnancy with abnormalities in implantation and placental development. Implantation is characterized by invasion of the maternal tissues of the uterus by fetal trophoblast, and the degree to which trophoblast invades these tissues appears to be a major determinant of pregnancy outcome. Excessive invasion can lead to abnormally firm attachment of the placenta to the myometrium (placenta accreta) with increased maternal and perinatal morbidity. Inadequate invasion, specifically restricted endovascular invasion, has been implicated in the pathophysiology of such conditions as pre-eclampsia (gestational proteinuric hypertension), preterm premature rupture of membranes, preterm labour, and intrauterine growth restriction. The molecular and cellular mechanisms responsible for implantation remain enigmatic. This review will include an overview of implantation followed by a discussion of a number of molecular mechanisms implicated in defective implantation and placentation including the role of decidual prostaglandins and haemorrhage in regulating trophoblast invasion. An improved understanding of the molecular mechanisms responsible for abnormal implantation and placentation will likely improve clinicians' abilities to treat disorders that occur along this continuum, including infertility, recurrent pregnancy loss, pre-eclampsia, and preterm birth., (Copyright 2007 Reproductive Healthcare Ltd, Duck End Farm, Dry Drayton, Cambridge CB23 8DB, UK. Published by Elsevier Ltd.. All rights reserved.)

Objective: An association between cesarean delivery and an increased risk of stillbirth in a subsequent pregnancy has been reported in the United Kingdom. This study investigated the association between prior cesarean delivery and unexplained intrauterine fetal demise at term in the United States., Study Design: We conducted a cross-sectional study using the U.S. perinatal mortality data (1995 to 1997). Women aged 15 to 44 years with singleton term (37 weeks or longer) pregnancies were included in the analysis. Study groups were defined as pregnant women with a prior cesarean delivery (prior cesarean delivery) and women with no prior cesarean delivery (no cesarean delivery). Adjustments were made for maternal age, race, underlying medical conditions, and fetal congenital abnormalities. The Cochran-Mantel-Haenszel method was used for relative risk estimation at the 95% confidence interval calculation., Results: A total of 11,061,599 deliveries of singleton pregnancies were recorded in the United States from January 1, 1995, to December 31, 1997. The cesarean delivery rate was 19.6%. The crude term intrauterine fetal demise rate was 1.5 per 1000 births for no cesarean delivery and 1.3 per 1000 births for prior cesarean delivery. After correction for parity greater than 1, congenital anomalies, and underlying maternal medical conditions, term intrauterine fetal demise rates were 0.6 and 0.4 per 1000 births for no cesarean delivery and prior cesarean delivery, respectively. Restriction of the analysis to women with only 1 prior delivery resulted in term intrauterine fetal demise rates of 0.8 and 0.7 per 1000 births for no cesarean delivery and prior cesarean delivery, respectively (relative risk 0.90; 95% confidence interval 0.76-1.06)., Conclusion: A prior cesarean delivery is not associated with an increased risk of stillbirth in a subsequent pregnancy.

Normal implantation and placentation is critical for pregnancy success. Many pregnancy-related complications that present late in gestation (such as pre-eclampsia and preterm labour) appear to have their origins early in pregnancy with abnormalities in implantation and placental development. Implantation is characterized by invasion of the maternal tissues of the uterus by fetal trophoblast, and the degree to which trophoblast invades these tissues appears to be a major determinant of pregnancy outcome. Excessive invasion can lead to abnormally firm attachment of the placenta to the myometrium (placenta accreta) with increased maternal and perinatal morbidity. Inadequate invasion, specifically restricted endovascular invasion, has been implicated in the pathophysiology of such conditions as pre-eclampsia (gestational proteinuric hypertension), preterm premature rupture of membranes, preterm labour, and intrauterine growth restriction. The molecular and cellular mechanisms responsible for implantation remain enigmatic. This review will include an overview of implantation followed by a discussion of a number of molecular mechanisms implicated in defective implantation and placentation including the role of decidual prostaglandins and haemorrhage in regulating trophoblast invasion. An improved understanding of the molecular mechanisms responsible for abnormal implantation and placentation will likely improve clinicians' abilities to treat disorders that occur along this continuum, including infertility, recurrent pregnancy loss, pre-eclampsia, and preterm birth.

Objective: The objective of this study was to examine factors associated with the occurrence of shoulder dystocia and subsequent perinatal outcomes., Study Design: We conducted a retrospective cohort study of 29,612 consecutive term, singleton, vertex vaginal deliveries. The primary outcome was reported shoulder dystocia. Fetal position, ethnicity, and their interaction terms were examined along with maternal characteristics, induction and length of labor, operative vaginal delivery, epidural, and birth weight in both bivariate and multivariate analyses., Results: Among women who met study criteria, 524 (1.8%) experienced a shoulder dystocia. African American women had the highest risk of shoulder dystocia (2.6%), compared with other races/ethnicities (P = .001). Women who delivered in occiput posterior position were noted to have a lower risk for shoulder dystocia (1.1%) as compared with occiput anterior position (1.8%, P = .046). However, in the setting of a shoulder dystocia, a higher risk of brachial plexus injury was observed in neonates delivered in occiput posterior position (adjusted odds ratio 10.4, 95% confidence interval 3.03 to 35.88) by vacuum-assisted vaginal delivery (adjusted odds ratio 3.24, 95% confidence interval 1.37 to 7.67) and neonates weighing 4000 g or more (adjusted odds ratio 2.53, 95% confidence interval 1.09 to 5.85)., Conclusion: Overall African American women have an increased risk of shoulder dystocia, but their neonates are not more likely to experience birth injury. Although occiput posterior position has a protective effect for shoulder dystocia, the risk of brachial plexus injury is increased in the setting of a persistent occiput posterior delivery. These factors should be used to consider a patient's prospective risk for shoulder dystocia and associated outcomes.

Objective: We sought to identify the use of vaginal amniotic fluid (vAF) glucose measurements in predicting infection of the amniotic fluid retrieved by transabdominal amniocentesis (aAF) in women with preterm premature rupture of the membranes (PPROM)., Study Design: Fluid was retrieved by aAF was retreived from 35 consecutive women with PPROM on whom an amniocentesis was clinically indicated to rule out intra-amniotic infection/inflammation and successfully completed. aAF was cultured for aerobic, anaerobic bacteria, Ureaplasma and Mycoplasma species. Clinical laboratory analysis for aAF included glucose concentration, Gram stain, lactate dehydrogenase, and white and red blood cell count. vAF was analyzed only for glucose concentration. Glucose concentration for the paired abdominal-vaginal AF samples (aAF-vAF) was determined by using well-established clinical and research laboratory methods. At the end of enrollment we stratified our patients into 2 groups: (1) positive microbial cultures (+)AFC (n = 17, gestational age [GA]: 27.3 +/- 0.7 weeks) or (2) negative microbial cultures (-)AFC (n = 18, GA: 31.3 +/- 0.5 weeks). Cohen kappa measure of concordance and receiver operating characteristic (ROC) curve analysis were used to test the ability of the vaginal "pool" glucose measurements to discriminate between women with positive or negative AF cultures., Results: Women with (+)AFC ruptured and delivered at an earlier GA compared with the (-)AFC group (p < .001). The latency period was similar (P = .35). There was a significant linear correlation between aAF and vAF glucose concentrations (r = 0.783, P < .001). Women with intra-amniotic infection (IAI) had significantly lower aAF [mean +/- SEM (+)AFC: 11.4 +/- 3.2 vs (-)AFC 23.0 +/- 2.8 mg/dL, P = .01] and vAF glucose levels [(+)AFC: 10.1 +/- 2.8 vs (-)AFC: 19.8 +/- 2.9 mg/dL, P = .02] compared with the noninfected group. Cohen kappa measure of concordance indicated "substantial" agreement between aAF and vAF glucose measurements (kappa = 0.719, 95% CI = 0.491-0.947). The sensitivity of the vAF glucose level to detect IAI ranged from 82% to 47%, whereas specificity ranged from 100% to 56% depending on the threshold we used. A vaginal "pool" (vAF) glucose measurement less than 5 mg/dL had 47.1% sensitivity, 100% specificity, 100% positive predictive value, 66.7% negative predictive value, and 74.2% accuracy in identifying women with (+)AFC., Conclusion: Vaginal glucose determination is a readily available, inexpensive, rapid AF marker that can be measured practically in any clinical laboratory. vAF glucose measurements less than 5 mg/dL have predictive value, but low sensitivity for detection of IAI.

Objective: Preeclampsia is an idiopathic multisystem disorder specific to human pregnancy. This study used proteomic analysis of cerebrospinal fluid (CSF) to identify protein biomarkers characteristic of preeclampsia and related to its severity., Study Design: CSF was collected from women diagnosed clinically with severe preeclampsia (sPE: n = 7), mild preeclampsia (mPE: n = 8), and normotensive controls (CRL: n = 8). Samples were subjected to proteomic analysis using surface-enhanced laser desorption/ionization time-of-flight (SELDI-TOF) mass spectroscopy. A discriminative proteomic biomarker profile was extracted by applying Mass Restricted analysis, and a Preeclampsia Proteomic Biomarker (PPB) score developed based on the presence or absence of four discriminatory protein peaks in individual CSF SELDI tracings. In-gel tryptic digests, Western blot analysis, on-chip immunoassays, ELISA, and spectral analysis were used to identify the biomarkers composing the PPB score., Results: PPB score distinguished patients with a clinical diagnosis of sPE from mPE and CRLs. (PPB median [range]: sPE: 4 [0-4] vs mPE: 1 [0-1] vs CRL: 0 [0-0]; P < 0.001). PPB scores were unaffected by parity, magnesium seizure prophylaxis, CSF leukocyte counts, and total protein content. Proteomic identification techniques matched the discriminatory protein peaks to the alpha- and beta-hemoglobin chains. ELISA confirmed that women diagnosed clinically with sPE had significantly higher CSF hemoglobin concentrations than women with mPE or CRL (median [range]: sPE: 6.6 [0.0-10.3] microg/mL vs mPE: 0 [0-1.3] microg/mL vs CRL: 0 [0-0] microg/mL; P < 0.001)., Conclusion: Proteomic analysis of CSF can accurately distinguish sPE from both mPE and CRL. Patients with sPE have nanomolar amounts of free hemoglobin in their CSF. Further studies are needed to confirm these observations and determine their physiologic implications.

Objective: Term labor is associated with global thinning of the myometrium. We hypothesized that a thickened myometrium at the time of preterm premature rupture of membranes (PPROM) predicts less myometrial wall stress and, consequently, a longer latency interval., Study Design: Myometrial thickness was measured prospectively in 76 pregnant women enrolled in the following groups: PPROM (n=28, mean [range], gestational age [GA]: 29.5 weeks [w] [21.0 w-33.0 w]), preterm nonlabor control group (P-CTR), (n=21, GA: 27.5 w [23.0 w-32.0 w]) and term nonlabor control (T-CTR) (n=27, GA: 38.6 w [37.0 w-41.6 w]). All PPROM women had oligohydramnios (AFI: 1.4 cm [0.0 cm-5.1 cm]). MT was measured ultrasonographically at the midanterior, fundal, posterior, and lower uterine segment wall in cases and controls with an intraoperator variability <10%., Results: Women in the PPROM group displayed uniform thickness of the uterine body (mean +/- SEM, anterior: 10.6 +/- 0.6 mm, fundal: 10.7 +/- 0.7 mm, posterior: 8.9 +/- 0.5 mm, P=.078). At midanterior site the myometrium of the PPROM group was thicker compared to both P-CTR (P < .001) and T-CTR (P=.025) groups. This difference was preserved at the fundus (PPROM vs P-CTR, P < .001; PPROM vs T-CTR, P=.015). There was a positive correlation between fundal MT and latency period (r=0.43, P=0.02) that persisted after adjusting for GA (P=.04). A fundal MT less than 12.1 mm was 93.7% sensitive and 63.6% specific for the identification of women whose latency period was less than 120 hours., Conclusion: Significant thickening of the anterior and fundal walls of the uterus follows PPROM. A thick myometrium in nonlaboring patients with PPROM is associated with longer latency interval. Sonographic evaluation of MT may represent an alternative clinical tool for the prediction of a short latency interval in women with PPROM.

Objective: Serum levels of soluble fms-like tyrosine kinase 1 (sFlt-1), vascular endothelial growth factor (VEGF), and placental growth factor (PlGF) are altered in women with clinical preeclampsia. We sought to identify whether similar alterations in urinary levels of these proteins cluster hypertensive disorders in pregnancy, and identify women with severe preeclampsia (sPE)., Study Design: Free urinary levels of sFlt-1, VEGF, and PlGF were measured by immunoassay in 68 women enrolled prospectively in the following groups: nonpregnant reproductive age (NP-CTR n = 14), healthy pregnant control (P-CTR n = 16), pregnant hypertensive and proteinuric women who did not meet criteria for severe preeclampsia (pHTN n = 21), and women with sPE (n = 17)., Results: There was no difference in gestational age at the time of enrollment among groups (median [range]: sPE: 31 [24-40], pHTN: 34 [16-40], P-CTR: 28 [7-39] wks). Urinary excretion of VEGF was significantly increased in sPE women compared with NP-CTR (P = .023), but did not differ among pregnant groups. Urinary PlGF levels were significantly increased in pregnant compared with nonpregnant women, but were decreased in all hypertensive women compared with healthy P-CTR (P < .001). Urinary sFlt-1 concentrations were significantly increased in women with sPE relative to all other groups (P < .001). pHTN women had higher sFlt-1 urinary output compared with P-CTR group (P = .001). A cutoff >2.1 in the ratio log [sFlt-1/PlGF] had 88.2% sensitivity and 100% specificity in differentiating women with sPE from normotensive controls. We also described that the log[sFlt-1/PlGF] ratio identified women with sPE better than proteinuria alone (P = .03). Our regression model revealed that uric acid correlated best with log[sFlt-1/PlGF] ratio (r = 0.628; P = .005)., Conclusion: sPE is associated with increased urinary output of the antiangiogenic factor sFlt-1 and a decreased output of PlGF at the time of clinical manifestation, providing a rapid noninvasive screening of hypertensive women based on a sFlt/PlGF ratio. This ratio may be used as representation for severity of the disease, and appears to be superior to random urinary protein measurements.

Objective: The purpose of this study was to describe current practice patterns for 7 controversial topics in Maternal-Fetal Medicine., Study Design: An interactive survey of obstetric treatment was performed as part of a postgraduate course at the 2004 Annual Meeting of the Society for Maternal-Fetal Medicine. Seven controversial topics were addressed, which included tocolytic therapy, progesterone supplementation for the prevention of preterm birth, screening for inherited thrombophilia, cervical cerclage for a shortened cervix, treatment of preterm premature rupture of membranes, magnesium sulfate seizure prophylaxis, and dexamethasone therapy for HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome., Results: A total of 298 obstetric care providers attended the postgraduate course. By report, most attendees were maternal-fetal medicine specialists (60.7% of respondents) who were >10 years out from specialty training (56.3% of respondents) and who were practicing in a university-based setting (52.9% of respondents). An average of 233 practitioners (range, 157-298 practitioners) answered each question. An analysis of the responses allowed for the determination of current practice patterns in the 7 controversial areas addressed., Conclusion: Contemporary practice patterns for 7 controversial topics in obstetric medicine are described. Such surveys may be useful in defining standards of care in maternal-fetal medicine.

Objective: This study investigated the association between polymorphism in intron 2 of the interleukin-1 receptor antagonist gene, midtrimester vaginal microflora, vaginal interleukin receptor antagonist and interleukin-1beta levels and subsequent spontaneous preterm birth., Study Design: Vaginal samples from 212 women, collected at 18-22 weeks' gestation, were analyzed for the polymorphism in intron 2 of the interleukin-1 receptor antagonist gene by polymerase chain reaction, qualitative and quantitative vaginal microflora, and interleukin-1beta and interleukin-1ra concentrations by enzyme-linked immunosorbent assay. Pregnancy outcome data were subsequently obtained., Results: Carriage of intron 2 of the interleukin-1 receptor antagonist allele 2 (IL1RN * 2) was associated with an elevated vaginal pH in black ( P < .001) and white ( P = .005) women, a reduced interleukin-1beta response to anaerobic Gram-negative rods and/or Gardnerella vaginalis ( P < .01), and a decreased rate of spontaneous preterm deliveries (6% versus 18%, P = .02). In black women, IL1RN * 2 carriage was associated with increased anaerobic Gram-negative rods, Mycoplasma, and Peptostreptococci and decreased Lactobacilli colonization., Conclusion: IL1RN * 2 carriage was associated with a blunted proinflammatory interleukin-1beta response to abnormal vaginal flora. This property may decrease susceptibility to infection-related preterm birth.

Objective: This purpose of this study was to investigate the association between vaginal microflora, concentrations of interleukin-1beta (IL-1beta), and its natural receptor antagonist (IL-1ra) in the cervicovaginal discharge, and spontaneous preterm birth. Study design Vaginal samples collected at 18 to 22 weeks' gestation from 207 women were analyzed to study qualitative and quantitative microbiologic aspects of vaginal microflora and IL-1beta and IL-1ra concentrations., Results: Among women colonized with anaerobic Gram-negative rods and/or Gardnerella vaginalis, an elevated IL-1beta concentration, or a diminished IL-1ra:IL-1beta ratio were associated with preterm delivery. A cut-off IL-1ra:IL-1beta ratio of <8632:1 optimally discriminated the subjects with subsequent spontaneous preterm deliveries from subjects who delivered at term, with a sensitivity of 78%, specificity of 51%, positive predictive value of 21%, and negative predictive value of 95%., Conclusion: A disproportionate increase in IL-1beta over IL-1ra in response to vaginal colonization with anaerobic Gram-negative rods and/or G. vaginalis at 18 to 22 weeks' gestation is associated with spontaneous preterm delivery.

Objective: The presence of a cervical cerclage at the time of preterm premature rupture of membranes (pPROM) could promote clinically evident infection and adverse pregnancy outcome. This cohort study examines whether the presence of cerclage at the time of pPROM is associated with increased maternal or neonatal inflammatory morbidity., Study Design: All singleton pregnancies with cerclage and pPROM between 24.0 and 33.9 weeks' gestation at our institution (January 1985-December 1997) were reviewed. Controls (pPROM without cerclage) were matched 2.5:1 by year of presentation. Outcome measures suggest clinical evidence of an infectious response and include maternal admission white blood cell count, time to onset of preterm labor, clinical chorioamnionitis, postpartum fever, neonatal white-matter disease (intraventricular hemorrhage or periventricular leukomalacia) at less than 33 weeks, neonatal sepsis, and neonatal death., Results: One hundred fourteen cases of pPROM and cerclage were matched with 288 controls. The study had power (alpha =.05, power = 0.8) to detect a two-fold difference in incidence of adverse neonatal outcome. Among the mothers, the incidence of clinical chorioamnionitis (14.0% vs 18.8%, P =.26), uterine activity at admission (33.3% vs 32.2%, P =.44), maternal postpartum fever (7.9% vs 7.6%, P =.93) in cerclage versus no cerclage were equivalent. Among the neonates, the incidence of neonatal white- matter disease (15.3% vs 13.7%, P =.75), neonatal sepsis (9.1% vs 6.0%, P =.21), and neonatal death were similar., Conclusion: Rates of maternal and neonatal morbidity were similar between both groups. The close overall similarity between the groups strongly suggest clinically insignificant differences between the two groups. These data indicate that a cervical cerclage at the time of pPROM less than 34 weeks does not adversely affect pregnancy outcome.