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The pathophysiologic origins of obstetrical emergencies are complicated and may well be influenced by events prior to conception. Such problems are not likely to be resolved soon, and in the meantime, high resource countries simply cannot afford to divert more and more money to litigation and the costs of preventable morbidities for either mother or child. It is long past time we tackled these acute care problems where most first occur-the Maternity unit. It is reasonable to ask whether hospitals (and society at large) are getting what they believe they are buying? Training to satisfy a regulation without improving patient outcome functionally erects one more barrier to the pursuit of optimal patient outcomes. And if current hospital training is not improving outcomes, why continue squandering limited resources and precious lives? In this monograph, I focus on training programs for the management of obstetrical emergencies.

Objective Preterm birth (PTB) at or before 32 weeks complicates up to 2 ​% of United States (US) births and accounts for 80 ​% of perinatal expenditures in the first year of life. Existing screening tests for PTB performed from 12 weeks to 19 weeks 5 days have receiver operated area under the curve (AUC) indices of Methods Using the US rates for EOP (0.5 ​%) and sPTB ​≦ ​32 weeks (1.8 ​%) and adjusting the US pregnancy/neonatal medical costs to US dollars (2017 value), we calculated the cost per 100,000 singletons with or without universal FutureBIRTH™ testing before 19 weeks and 6 days using three detection rates and assuming screen-positive women would be treated with and respond to aspirin (assumed 80 ​% efficacy for EOP) and vaginal progesterone (assumed 38 ​% efficacy for sPTB). We also assessed test performance at disease incidence rates below that of the US (down to 0.46 ​%). For considering screening costs, we assumed test costs of $750, and treatment costs of $1000 for patients over 20 weeks gestational age. Results The identification and treatment of ‘at-risk’ pregnancies by FutureBIRTH™ with existing therapies would reduce direct healthcare costs by up to $95 million per 100,000 births. The projected savings were robust and achievable at each FutureBIRTH™ price despite the conservative costs, efficacy, and detection rate assumptions. The incidence of PTB ≦ 32 weeks would decline by 40 %–50 ​% with a test cost of $750 and an 80 ​% detection rate. Conclusion The accurate risk assessment provided by universal FutureBIRTH™ screening coupled with existing preventative treatments could lead to a 40 %–50 ​% decrease in PTB ≦ 32 weeks due to sPTB and EOP among ‘at-risk’ pregnancies, covering the cost of screening and treatment while still saving $450-$950 per pregnancy.

Rationale: Human umbilical cord blood (hUCB) contains diverse populations of stem/progenitor cells. Whether hUCB-derived nonhematopoietic cells would induce cardiac repair remains unknown. Objective: To examine whether intramyocardial transplantation of hUCB-derived CD45 − Lin − nonhematopoietic cellular fraction after a reperfused myocardial infarction in nonimmunosuppressed rats would improve cardiac function and ameliorate ventricular remodeling. Methods and Results: Nonhematopoietic CD45 − Lin − cells were isolated from hUCB. Flow cytometry and quantitative polymerase chain reaction were used to characterize this subpopulation. Age-matched male Fischer 344 rats underwent a 30-minute coronary occlusion followed by reperfusion and 48 hours later received intramyocardial injection of vehicle or hUCB CD45 − Lin − cells. After 35 days, compared with vehicle-treated rats, CD45 − Lin − cell–treated rats exhibited improved left ventricular function, blunted left ventricular hypertrophy, greater preservation of viable myocardium in the infarct zone, and superior left ventricular remodeling. Mechanistically, hUCB CD45 − Lin − cell injection favorably modulated molecular pathways regulating myocardial fibrosis, cardiomyocyte apoptosis, angiogenesis, and inflammation in postinfarct ventricular myocardium. Rare persistent transplanted human cells could be detected at both 4 and 35 days after myocardial infarction. Conclusions: Transplantation of hUCB-derived CD45 − Lin − nonhematopoietic cellular subfraction after a reperfused myocardial infarction in nonimmunosuppressed rats ameliorates left ventricular dysfunction and improves remodeling via favorable paracrine modulation of molecular pathways. These findings with human cells in a clinically relevant model of myocardial ischemia/reperfusion in immunocompetent animals may have significant translational implications.Visual Overview: An online visual overview is available for this article.

Background Several meta analyses have concluded n-3 fatty acids, including docosahexaenoic acid (DHA), reduce early preterm birth (EPB, 0.90). Interpretation Clinicians could consider prescribing 1000 mg DHA daily during pregnancy to reduce EPB in women with low DHA status if they are able to screen for DHA. Funding The National Institutes of Health Child Health and Human Development (NICHD) funded the study. Life's DHA™-S oil, DSM Nutritional Products LLC, Switzerland provided all capsules.

Background: Several meta analyses have concluded n-3 fatty acids, including docosahexaenoic acid (DHA), reduce early preterm birth (0.90). Interpretation: Physicians should consider prescribing 1000 mg DHA daily during pregnancy to reduce early preterm birth, particularly in women entering pregnancy with low DHA status. Trial Registration: The study is registered with ClinicalTrials.gov (NCT02626299) and closed to enrollment. Funding Statement: National Institutes of Health Child Health and Human Development (NICHD) R01HD083292. Declaration of Interests: SEC has received honorariums for presentations about DHA in infancy and pregnancy. CJV is an employee of RB Nutrition, which produces infant formulas and supplements, however, RB had no involvement in the study execution or analysis. She conducted this study through her role as an Adjunct Professor at The University of Cincinnati. The other authors have no competing interests. Ethics Approval Statement: The University of Kansas Medical Center granted approval under a central IRB with reliance by the other institutions (STUDY00003455). All participants gave written consent.

ObjectiveTo compare the rapid bedside test for placental α microglobulin-1 with the instrumented fetal fibronectin test for prediction of imminent spontaneous preterm delivery among women with symptoms of preterm labor.MethodsWe conducted a prospective observational study on pregnant women with signs or symptoms suggestive of preterm labor between 24 and 35 weeks of gestation with intact membranes and cervical dilatation less than 3 cm. Participants were prospectively enrolled at 15 U.S. academic and community centers. Placental α microglobulin-1 samples did not require a speculum examination. Health care providers were blinded to placental α microglobulin-1 results. Fetal fibronectin samples were collected through speculum examination per manufacturer requirements and sent to a certified laboratory for testing using a cutoff of 50 ng/mL. The coprimary endpoints were positive predictive value (PPV) superiority and negative predictive value (NPV) noninferiority of placental α microglobulin-1 compared with fetal fibronectin for the prediction of spontaneous preterm birth within 7 days and within 14 days.ResultsOf 796 women included in the study cohort, 711 (89.3%) had both placental α microglobulin-1 and fetal fibronectin results and valid delivery outcomes available for analysis. The overall rate of preterm birth was 2.4% (17/711) within 7 days of testing and 4.2% (30/711) within 14 days of testing with respective rates of spontaneous preterm birth of 1.3% (9/703) and 2.9% (20/701). Fetal fibronectin was detected in 15.5% (110/711), and placental α microglobulin-1 was detected in 2.4% (17/711). The PPVs for spontaneous preterm delivery within 7 days or less among singleton gestations (n=13) for placental α microglobulin-1 and fetal fibronectin were 23.1% (3/13) and 4.3% (4/94), respectively (P

Purpose To investigate the impact of chronic hypoxia on neonatal brains, and follow developmental alterations and adaptations noninvasively in a guinea pig model. Chronic hypoxemia is the prime cause of fetal brain injury and long-term sequelae such as neurodevelopmental compromise, seizures, and cerebral palsy. Materials and Methods Thirty guinea pigs underwent either normoxic and hypoxemic conditions during the critical stage of brain development (0.7 gestation) and studied prenatally (n = 16) or perinatally (n = 14). Fourteen newborns (7 hypoxia and 7 normoxia group) were scanned longitudinally to characterize physiological and morphological alterations, and axonal myelination and injury using in vivo diffusion tensor imaging (DTI), T2 mapping, and T2-weighted magnetic resonance imaging (MRI). Sixteen fetuses (8 hypoxia and 8 normoxia) were studied ex vivo to assess hypoxia-induced neuronal injury/loss using Nissl staining and quantitative reverse transcriptase polymerase chain reaction methods. Results Developmental brains in the hypoxia group showed lower fractional anisotropy in the corpus callosum (−12%, P = 0.02) and lower T2 values in the hippocampus (−16%, P = 0.003) compared with the normoxia group with no differences in the cortex (P > 0.07), indicating vulnerability of the hippocampus and cerebral white matter during early development. Fetal guinea pig brains with chronic hypoxia demonstrated an over 10-fold increase in expression levels of hypoxia index genes such as erythropoietin and HIF-1α, and an over 40% reduction in neuronal density, confirming prenatal brain damage. Conclusion In vivo MRI measurement, such as DTI and T2 mapping, provides quantitative parameters to characterize neurodevelopmental abnormalities and to monitor the impact of prenatal insult on the postnatal brain maturation of guinea pigs. J. Magn. Reson. Imaging 2015;42:658–665.

Objectives The purpose of this study was to identify the predictors of left ventricular (LV) recovery in patients with peripartum cardiomyopathy (PPCM) and to record rates of implantable cardioverter-defibrillator (ICD) use. Background PPCM is a rare, life-threatening disease. The use of ICDs has not been clearly understood in this patient group. Identification of the predictors of persistent LV dysfunction can help select patients at risk for sudden cardiac death. Methods A retrospective study was conducted at 2 academic centers between January 1, 1999, and December 31, 2012. Clinical and demographic variables and delivery records of patients with a diagnosis of PPCM (International Classification of Diseases, 9th Revision code 674.5) were reviewed. Improvement in LV function was noted from echocardiography reports. Results The total sample comprised 100 patients, of whom 55% were African Americans, 39% were Caucasians, and 6% were Hispanic, with a mean age of 30 ± 6 years. Mean left ventricular ejection fraction (LVEF) at diagnosis was 28 ± 9%. Forty-two percent of patients showed improvement in LVEF over a mean duration of 33 ± 21 months. Postpartum diagnosis (hazard ratio: 3.0; p = 0.01) and Caucasian/Hispanic race (hazard ratio: 2.2; p = 0.01) were predictors of improvement in LVEF. Only 7 of the 58 patients (12%) who did not have improvement in their LVEF had an ICD implanted. There were 11 deaths, with a trend toward higher mortality in those who did not display improved LV function (15% vs. 5%; p = 0.1). Conclusions More than one-third of women with PPCM improve LV function with delayed recovery noted in the majority of these patients. Caucasians and those diagnosed in the postpartum period appear to be the most likely to recover. The rate of ICD implantation for primary prevention of sudden cardiac death in this patient group is low.

Background: Ovarian cancer is the most lethal gynecological malignancy and the fifth most common cancer in women in the U.S. Patients diagnosed in advanced-stage ovarian cancer have 70-95 % chance of relapse. Additional non-invasive approaches to monitor response to treatment and to predict recurrent disease are urgently needed. Aberrant expression levels of circulating microRNAs are diagnostic, prognostic, and predictive biomarkers in ovarian cancer. We recently published that microRNA-205 (miR-205) expression is elevated in ovarian cancer and correlates with advanced-stage disease. Here, we investigate circulating microRNA-205 as a potential biomarker for monitoring disease in patients diagnosed with advanced-stage ovarian cancer. Methods: Plasma samples from normal controls (n=12) and recurrent stage III/IV ovarian cancer patients (n=5) in our biorepository were used. Samples were collected 1 day before surgery operation and at 1 month, 2 months and 6 months after the primary surgery. All samples were from serous ovarian carcinomas. All the patients went through the standard chemotherapy and CA-125 levels were decreased to the normal range ( Results: Our results confirmed that the expression of circulating miR-205 was significantly elevated in stage III/IV ovarian cancer plasma samples compared with normal controls (5.91 fold; p Conclusion: Dynamic changes of the circulating miR-205 expression in pre- and post-operative plasma samples of recurrent stage III/IV ovarian cancer patients demonstrated that circulating miR-205 levels could be used as non-invasive biomarkers for monitoring disease in patients diagnosed with advanced stage ovarian cancer. Further investigation is warranted in larger cohorts of patients. Citation Format: Meghan W. Kusch, Julia A. Chapman, Carl P. Weiner, Katherine F. Roby, Dineo Khabele, Helen H. Zhou. Circulating microRNA-205 as a potential prognostic biomarker for recurrent ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2235.

Twin-twin transfusion syndrome is a complication of monochorionic-diamniotic placentation. Should one twin die, ≈30% of co-twins will also die, and if they survive, ≈30% experience severe morbidity rates, each believed secondary to hemorrhage of the co-twin into the deceased twin. We report apparently the first ultrasound-documented case of perimortem hemorrhage in twin-twin transfusion syndrome and its treatment by emergent ultrasound-guided percutaneous cord occlusion followed by percutaneous fetal intravascular transfusion. The case illustrates three important pathophysiologic events. First, it confirms acute twin-to-twin hemorrhage occurs and reveals it can begin before the first twin dies. Thus, delivery of the survivor after its dead co-twin is discovered is unlikely to protect the survivor. Second, the elevated fetal middle cerebral artery peak systolic velocity due to acute anemia requires hours to develop. And thirdly, intracardiac epinephrine can correct the acute fetal bradycardia associated with hemorrhage that is presumably due to fetal hypotension.

Preterm birth contributes to 0.5 million deliveries in the United States (one of eight pregnancies) and poses a huge burden on public health with costs in the billions. Of particular concern is that the rate of earliest preterm birth (

Prelabor rupture of membranes (PROM) is a common obstetrical problem, but its diagnosis is frequently problematic. Lacking a gold standard, the diagnosis is equivocal in some 10% of cases. We performed a systematic review to assess the accuracy of several tests for the diagnosis of PROM in these equivocal cases. We performed an electronic search in PubMed, Embase, DARE and the Cochrane Library and reference lists for potentially missed articles. No language restrictions were used. Only accuracy studies for diagnostic methods for PROM in women with equivocal PROM were selected. The studies were scored according to STARD and QUADAS guidelines. Based on the full description of reference and index tests, an expert panel finally decided whether the selected articles were of sufficient quality to be included. We identified 3864 studies of which 146 full manuscripts were obtained. We excluded 133 due to multiple reasons. The remaining 13 studies were scored by an expert panel. Only three articles with a total of 155 patients fulfilled all criteria. These articles tested three different methods, pH measurement (64 patients), insulin-like growth factor binding protein-1 (ILGBP-1, 83 patients) and alpha fetoprotein (AFP, 8 patients). Sensitivity varied from 88% (pH) to 100% (AFP), specificity varied from 56% (ILGPP-1) to 100% (AFP). Based on the limited evidence on the accuracy of tests to diagnose ruptured membranes, we conclude that the use of a particular test cannot be recommended.

The prevalence of cerebral palsy (CP) shows little temporal or geographic variation and is associated with preterm birth, maternal/fetal infection/inflammation, and fetal growth restriction (IUGR), a potential surrogate for chronic fetal hypoxemia (CHX). We previously demonstrated CHX causes a fetal inflammatory response syndrome (FIRS). Herein, we test the hypothesis that CHX may cause fetal brain injury by upregulating inflammatory cytokine cascades, culminating in apoptosis pathway activation. Time-mated guinea pigs were housed in 12% or 10.5% O(2) for the last 21% of gestation. Chronic fetal hypoxemia increased the lactate/pyruvate and decreased the glutathione (GSH)/oxidized glutathione (GSSH) ratios, confirming a shift to a prooxidant state. The end result was a >30% decrease in hippocampal neuron density. Based on a microarray spotted with 113 cytokines and receptors, 22 genes were upregulated by CHX in proportion to the degree of hypoxia; the findings were confirmed by quantitative polymerase chain reaction (PCR). Thus, CHX triggers fetal brain inflammation inversely proportional to its severity characterized by increased apoptosis and neuronal loss. We suggest CHX fetal brain injury is not directly caused by oxygen deprivation but rather is an adaptive response that becomes maladaptive.

Confidential enquiries into poor perinatal outcomes have identified deficiencies in team working as a common factor and have recommended team training in the management of obstetric emergencies. Isolated aviation-based team training programmes have not been associated with improved perinatal outcomes when applied to labour ward settings, whereas obstetric-specific training interventions with integrated teamwork have been associated with clinical improvements. This commentary reviews obstetric emergency training programmes from hospitals that have demonstrated improved outcomes to determine the active components of effective training. The common features identified were: institution-level incentives to train; multi-professional training of all staff in their units; teamwork training integrated with clinical teaching and use of high fidelity simulation models. Local training also appeared to facilitate self-directed infrastructural change.

One of the least-developed areas of clinical pharmacology and drug research is the use of medication during pregnancy and lactation. This article is the first in a two-part series designed to familiarize physicians with many aspects of the drugs they commonly prescribe for pregnant and breast-feeding women. Almost every pregnant woman is exposed to some type of medication during pregnancy. Although the majority of pregnant and breast-feeding women consume clinically indicated or over-the-counter drug preparation regularly, only few medications have specifically been tested for safety and efficacy during pregnancy. There is scant information on the effect of common pregnancy complications on drug clearance and efficacy. Often, the safety of a drug for mothers, their fetuses, and nursing infants cannot be determined until it has been widely used. Absent this crucial information, many women are either refused medically important agents or experience potentially harmful delays in receiving drug treatment. Conversely, many drugs deemed "safe" are prescribed despite evidence of possible teratogenicity. Novel research and diagnostic applications evolving from the opportunities presented by the advances in genomics and proteomics are now beginning to affect clinical diagnosis, vaccine development, drug discovery, and unique therapies in a modern diagnostic-therapeutic framework-part of the new scientific field of theranostics. This review critically explores a number of recently raised issues in regard to the use of several classes of medications during gestation and seeks to provide a general and concise resource on drugs commonly used during pregnancy and lactation. It also seeks to make clinicians more aware of the controversies surrounding some drugs in an effort to encourage safer prescribing practices through consultation with a maternal-fetal medicine specialist and through references and Web sites that list up-to-date information.

Preterm premature rupture of the fetal membranes (PPROM) is associated with intra-uterine infection. Early detection of intra-uterine infection may help prevent neonatal sepsis. C-reactive protein (CRP) is an acute phase protein often elevated when inflammation is present. The aim of this review was to assess whether CRP accurately predicts chorioamnionitis and/or neonatal sepsis in women with PPROM. We searched Medline and Embase databases for articles reporting on CRP and chorioamnionitis and/or neonatal sepsis. Two reviewers extracted clinical and methodological study characteristics and test accuracy data. Accurate data were used to form 2 x 2 data tables comparing CRP and the occurrence of infection. For the selected studies, sensitivity and specificity of CRP in the prediction of histological chorioamnionitis, clinical chorioamnionitis and neonatal sepsis were calculated separately. A bivariate meta-regression model was used to calculate pooled estimates of sensitivity and specificity. The search revealed 200 articles, of which only five met the inclusion criteria. These five articles reported on 381 patients, of which four articles (227 patients) reported on CRP as a predictor for histological chorioamnionitis and four studies (330 patients) reported on CRP as a predictor for clinical chorioamnionitis. None of the selected articles fulfilled our criteria for the use of CRP as a predictor of neonatal sepsis. CRP was moderately predictive of histological chorioamnionitis. Unfortunately, the studies of clinical chorioamnionitis were too heterogeneous to pool data. Current literature does not support the use of CRP in women with PPROM. (C) 2009 Elsevier Ireland Ltd. All rights reserved

We aim to demonstrate that Brain Natriuretic Peptide (BNP) is synthesized and released from the fetal membranes and mediates pregnancy myometrial quiescence. Myometrium and fetal membranes (FM) were obtained from term and preterm pregnancies at the time of cesarean section, either in labor or not in labor. BNP was measured in term and preterm FM, in culture cells, and conditioned media. We found BNP (but not ANP or CNP) inhibited contractions of preterm, but not term, human myometrium. BNP (both protein and mRNA) was detected in all tissues, conditioned media and cultured cells. BNP was higher in samples from preterm women not in labor compared to those at term not in labor. BNP concentrations were significantly reduced in women in spontaneous preterm labor. We conclude that locally produced BNP may be involved in generating myometrial quiescence during pregnancy. Further, a premature decrease of BNP production may cause preterm labor.

Inertial and magnetic sensors are commonly used to determine orientation as they do not rely on a line of sight [1, 2]. There are many different techniques to fuse inertial measurement unit (IMU) data and obtain useful rotational data [1–3]. This study uses two separate data fusion techniques; a direction cosine matrix-based (DCM) technique and a quaternion-based Extended Kalman Filter (EKF) technique [1–3]. These techniques were altered based on performance metrics to weight sensor data when certain sensors proved not as reliable as others [2]. IMU sensors were tested on a hand mannequin and filters were developed using MATLAB software. Simulation results displayed a root-mean-squared error of less than .06° for each rotation angle. Experimental results maintained errors of less than 8° in each rotation angle.Copyright © 2015 by ASME

Birth is less safe than it can be. We adapted the UK-developed PROMPT (PRactical Obstetric Multi-Professional Training) course to local practices and initiated annual training.This observational study used quality assurance data from University of Kansas Hospital 2 years before and 7 years after intervention encompassing 14,309 consecutive deliveries from January 2006 through December 2014. An events/trials approach was applied to changes in proportions over time.PROMPT was associated with progressive decreases in rates (P0.05) of brachial plexus injury and umbilical artery pH7.00 exclusive of catastrophic events. Reduced rates (P0.05) of cesarean section, episiotomy and higher perception of nurse/physician communication were documented. Hypoxic ischemic encephalopathy (HIE) rates declined progressively by50% (P=NS). These improvements occurred despite younger faculty and higher rates of complicated pregnancies (P0.05). Estimated health-care costs avoided exceeded annual training costs.Local annual multi-professional training as provided by PROMPT was temporally associated with improved obstetric outcomes.

Whether the isolated VSD (i-VSD) is associated with aneuploidy to the same degree as a more severe heart anomaly is unclear. Our objective was to determine the likelihood of aneuploidy in pregnancies at a tertiary referral center when an i-VSD is detected before 24 weeks.A retrospective chart review of all detailed anatomy ultrasounds before 24 weeks performed at the University of Kansas Medical Center from 08/23/2006 to 06/07/2012 was conducted. A complete evaluation of the fetal heart was accomplished using gray scale and spectral/color Doppler examinations. The outcomes of each pregnancy were reviewed for any diagnoses of aneuploidy. Odds ratios were calculated.A total of 4078 pregnancies with complete obstetric and neonatal data were reviewed. The prevalence of an i-VSD was 2.7% (112/4078). The odds ratio of aneuploidy when an i-VSD was present was (OR: 36.0, 95% CI: 5.0, 258.1). This odds ratio remained large when either an abnormal or unknown serum screen was present.The presence of an i-VSD present before 24 weeks does increase the risk of fetal aneuploidy. Whether a normal serum screen or first trimester screen for aneuploidy negates the association of an i-VSD with aneuploidy still remains undetermined.

Training for intrapartum emergencies is a promising strategy to reduce preventable harm during birth; however, not all training is clinically effective. Many myths have developed around such training. These principally derive from misinformed beliefs that all training must be effective, cheap, independent of context and sustainable. The current evidence base for effective training supports local, unit-based and multi-professional training, with appropriate mannequins, and practice-based tools to support the best care. Training programmes based on these principles are associated with improved clinical outcomes, but we need to understand how and why that is, and also why some training is associated with no improvements, or even deterioration in outcomes. Effective training is not cheap, but it can be cost-effective. Insurers have the fiscal power to incentivise training, but they should demand the evidence of clinical effect; aspiration and proxies alone should no longer be sufficient for funding, in any resource setting.

Objective We tested the hypothesis that long-term neurodevelopmental outcomes of successfully treated fetuses with immune hydrops are similar to their unaffected siblings according to a protocol that addresses the underlying pathophysiologic condition. Study design Sixteen of 18 consecutive hydropic fetuses (89%) who were treated in a dedicated fetal medicine unit between July 1985 and October 1995 survived. The transfusion protocol used a 2-step correction over a 2 to 4 day interval, combined with umbilical venous pressure measurements to avoid over transfusion and bicarbonate administration to assure a posttransfusion UV pH of >7.30. Survivors were evaluated at a mean age of 10 years. Statistical analyses included t -test, Wilcoxon rank-sum test, Fisher's exact test, and Pearson coefficients. Results Overall, death or major neurologic morbidity occurred in 4 of 18 of the fetuses (22%) who were treated (2/16 of survivors [12.5%]). Among the survivors, the children with immune hydrops had physical, neurologic, and cognitive outcomes statistically similar to their siblings, except for a measure of visual attention. Two of the children (12%) had major neurologic sequelae. Brain volumes were statistically smaller than unrelated control subjects by 8.8%, but these control subjects were not matched for height at testing or gestational age at birth. Both groups had brain volumes within the normal range. Conclusion Intravascular transfusion of fetuses with profoundly anemic immune hydrops results in high survival rates and favorable long-term neuropsychological outcomes.

Screening tests have become increasingly popular in women's health care over the last two decades. The initiative for screening is typically generated by either an agency or the health care professional being consulted for some reason. In many instances, however, the demand for screening tests is patient driven with the health care provider being poorly prepared to determine the usefulness of screening. This review illustrates the complexity of screening using three disorders where early detection and treatment have the potential to improve the quality and longevity of life. Prenatal diagnosis of Down's syndrome does not offer the parents the opportunity for cure but does offer the opportunity for education and rational choice as the impact of the diagnosis on the family is weighed. The evidence for breast cancer screening is more persuasive for older than younger women, but even in older women, there is a balance of risks and benefits. Treatment options for osteoporosis have improved in terms of reductions in fracture risk as well as beneficial effects on bone density, but evidence of the effectiveness of a screening programme for this condition in an unselected population is lacking. Ultimately, it is crucial that women be provided with clear and comprehensive information about the screening programme, in terms of possible gains but also costs of various kinds: physical, economic and psychological.

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 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 P =.025) groups. This difference was preserved at the fundus (PPROM vs P-CTR, P 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.

Summary Thousands of pregnant and breast-feeding women take a prescribed or over-the-counter drug preparation daily. Few of these products have been specifically tested for safety and efficacy during normal pregnancy, and there is only scant information on the impact of common pregnancy complications on drug clearance and efficacy. The safety of a drug for fetuses and nursing infants often cannot be determined until it is widely used. Governmental safety categories do not inform on how either pregnancy or lactation may alter the patient's response to therapy compared with the non-pregnant state, nor do they indicate the impact of common medical diseases on a drug's efficacy. In the absence of information many women are inappropriately denied medically important agents. Funding agencies should address these knowledge deficits in a comprehensive fashion, and pharmaceutical houses should be offered incentives to perform clinically relevant studies of drugs that might be used in reproductive-age women before these drugs are marketed. Until the large gaps in the body of knowledge are filled, caregivers should seek and frequently utilise references that are updated regularly throughout the year.

The origin of incompetent cervix is multifactorial, and the success of rescue cerclage is unpredictable. We tested amniotic fluid from women who were preparing to undergo rescue cerclage for proteomic biomarkers and correlated their presence with clinical outcome.Amniocentesis was performed to facilitate rescue cerclage in 37 consecutive women with painless dilation (2 cm) and no detectable uterine activity for 4 hours (range, 1-24 hours) before cerclage. Thirty-nine consecutive women with a sonographically normal pregnancy and cervix who underwent amniocentesis for chromosomal testing during the same study interval at the same clinical site provided the control samples. A proteomic fingerprint was generated with the discarded sample and the Mass-Restricted score (MR score) for inflammation calculated. Peaks corresponding to free hemoglobin chains were sought as evidence of decidual hemorrhage or intra-amniotic bleeding.Amniocentesis was performed at 23.5 weeks in cerclage (mean dilation, 4 cm) versus 19.5 weeks in control subjects. Cerclage subjects were delivered at 28.8 weeks; control subjects were delivered at 39.2 weeks. Thirty-two of 37 of cerclage subjects (86%) were delivered prematurely. Ten of 37 of cerclage subjects (27%), but no control subject, had a MR score that was indicative of inflammation (P.001). Hemoglobin peaks were present in 12 of 37 of cerclage subject (32%), but no control subjects. Among cerclage subjects, those with a MR score of 3 to 4 were delivered earlier than those with a MR score of 0 to 2 (P.001). Women with a MR score of 3 to 4 had a shorter latency period (days from amniocentesis to delivery; 3 days) and a shorter percentage of prolongation (1.8%) than women with a MR score of 0 to 2 (35 days; P.05; 17.9%; P.05). Women with hemoglobin had a shorter latency period (6 days) and a shorter percentage of prolongation (3.8%) than women without hemoglobin (38 days; P.05; 21.8%; P.05). Hemoglobin was present in 7 of 10 of the cerclage subjects (70%) with a MR score of 3 to 4. Women with both a MR score of 3 to 4 and hemoglobin had the shortest intervals to delivery.These findings illustrate 2 pathologic mechanisms that are associated with preterm delivery are also associated with incompetent cervix. Either an intrauterine inflammatory response or decidual hemorrhage predates surgery in one half the women whose condition requires rescue cerclage. The activation of either mechanism predicts cerclage failure.

Objective Vaginal birth after a prior low transverse caesarean section (VBAC) is advocated as a safe and effective method to reduce the total caesarean section rate. However, the risk of uterine rupture has dampened the enthusiasm of practising clinicians for VBAC. Uterine rupture occurs more frequently in women receiving prostaglandins in preparation for the induction of labour. We hypothesised that similar to the cervix, prostaglandins induces biochemical changes in the uterine scar favouring dissolution, predisposing the uterus to rupture at the scar of the lower segment as opposed to elsewhere. Design We tested aspects of this hypothesis by investigating the location of uterine rupture associated with prostaglandins and compared it with the sites of rupture in the absence of prostaglandins. Settings Two North American University Hospitals. Population Twenty-six women with a prior caesarean section, experiencing uterine rupture in active labour. Methods Retrospective review of all pregnancies complicated by uterine rupture at two North American teaching hospitals from 1991 to 2000. Main outcome measure Site of the uterine rupture. Results Thirty-four women experienced rupture after a previous caesarean section with low transverse uterine incision. Ten of the women who ruptured (29%) received prostaglandins for cervical ripening (dinoprostone: n= 8 or misoprostol: n= 2) followed by either spontaneous contractions (n= 3) or oxytocin augmentation during labour (n= 7). In 16 women (47%), oxytocin alone was sufficient for the induction/augmentation of labour. Eight (23%) women ruptured at term before reaching the active phase of labour in the absence of pro-contractile agents or attempted VBAC. There were no differences among the groups in terms of age, body mass index, parity, gestational age, fetal weight or umbilical cord pH measurements. Women treated with prostaglandins experienced rupture at the site of their old scar more frequently than women in the oxytocin-alone group whose rupture tended to occur remote from their old scar (prostaglandins 90%vs oxytocin 44%; OR: 11.6, 95% CI: 1.2–114.3). Conclusion Women in active labour treated with prostaglandins for cervical ripening appear more likely to rupture at the site of their old scar than women augmented without prostaglandins. We propose that prostaglandins induce local, biochemical modifications that weaken the scar, predisposing it to rupture.

Objective Cyclic nucleotide phosphodiesterases (PDEs) are a diverse enzyme group with multiple regulatory properties and wide tissue distribution. Such activity includes cyclic adenosine (cAMP) and guanosine monophosphate (cGMP) breakdown. The type 5 isoform (PDE-5, cGMP specific) is the target of specific antagonists (ie, sildenafil, Viagra). We tested the hypothesis that PDE-5 is present in rat myometrium and modulates myometrial activity. Study design Full-thickness uterine wall was collected from nonpregnant (n = 3) and pregnant Sprague-Dawley rats on days 10 (n = 4), 17 (n = 6), 22 nonlabor (n = 5), and 22 during term labor (TL, n = 4). Preterm labor (PTL, n = 3) was induced in some animals on day 16 with 15 mg/kg mifepristone (RU 486). Tissue samples were prepared for Western blotting using a monoclonal antibody against rodent PDE-5. In a second series, cumulative doses of sildenafil (0.005, 0.05, 0.5, 5 mg/kg, intraperitoneal) were administered and the effect on uterine contractility recorded in vivo during term (TL, n = 7) and preterm labor (PTL, n = 6). Saline solution–injected rats provided temporal control. Uterine contractility was estimated from intrauterine pressure (IP) measured electronically with a sensor tip pressure catheter. Heart rate was recorded simultaneously using electrodes attached to the chest and connected to the same data acquisition system. Results PDE-5 immunoreactivity was present in the nonpregnant rat uterus and at all gestational times studied, although the expression was unaffected by either pregnancy or the state of labor (preterm or term). A dominant antibody-specific band was identified at 86 kd in the uterine samples, contrasting with lung where the 100-kd PDE-5 isoform was most abundant. Two additional lower molecular weight (55 and 32 kd) bands were also identified as antibody specific. Despite the lack of change in PDE-5 during pregnancy, sildenafil reduced IP during TL and PTL beginning at 0.5 mg/kg. The highest dose of sildenafil reduced IP during both TL and PTL by 45% and 59% of baseline, respectively (two-way analysis of variance, P Conclusion PDE-5 is constitutively present in the rat uterine wall. There was no observed change in the PDE-5 protein expression throughout pregnancy. In contrast to the lung, the uterus expresses an 80-kd PDE-5 isoform. Sildenafil in pharmacologic doses inhibits mechanical uterine activity and might be of benefit if selectively used for treatment of preterm labor.

The length of mammalian pregnancy is tightly regulated to assure the delivery of a newborn mature enough to survive the extra-uterine environment. A successful pregnancy requires near complete relaxation of the uterus for more than ninety-five percent of gestation, overcoming the inherent tendency of the myometrium to contract with stretch. This active and highly regulated process is called myometrial quiescence. It requires not only the near absence of myometrial contractions, but also its refractoriness to contractile agents.