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Pregnancy Complications (pregnancy + complications)
Selected AbstractsORIGINAL ARTICLE: Haplotype-dependent Differential Activation of the Human IL-10 Gene Promoter in Macrophages and Trophoblasts: Implications for Placental IL-10 Deficiency and Pregnancy ComplicationsAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 3 2010Surendra Sharma Citation Sharma S, Stabila J, Pietras L, Singh AR, McGonnigal B, Ernerudh J, Matthiesen L, Padbury JF. Haplotype-dependent differential activation of the human IL-10 gene promoter in macrophages and trophoblasts: Implications for placental IL-10 deficiency and pregnancy complications. Am J Reprod Immunol 2010; 64: 179,187 Problem, Polymorphic changes in the IL-10 gene promoter have been identified that lead to altered IL-10 production. We hypothesized that because of these genotypic changes, the IL-10 promoter might be expressed in a cell type,specific manner and may respond differentially to inflammatory triggers. Method of study, We created reporter gene promoter constructs containing GCC, ACC, and ATA haplotypes using DNA from patients harboring polymorphic changes at ,1082 (G,A), ,819 (C,T), and ,592 (C,A) sites in the IL-10 promoter. These individual luciferase reporter constructs were transiently transfected into either primary term trophoblasts or THP1 monocytic cells. DNA-binding studies were performed to implicate the role of the Sp1 transcription factor in response to differential promoter activity. Results, Our results suggest that the GCC promoter construct was activated in trophoblast cells in response to lipopolysaccharide (LPS), as demonstrated by reporter gene expression, but not in monocytic cells. The ACC construct showed weaker activation in both cell types. Importantly, while the ATA promoter was constitutively activated in both cell types, its expression was selectively repressed in response to LPS, but only in trophoblasts. DNA-nuclear protein binding assays with nuclear extracts from LPS treated or untreated cells suggested a functional relevance for Sp1 binding differences at the ,592 position. Conclusions, These results demonstrate cell type,specific effects of the genotypic changes in the IL-10 gene promoter. These responses may be further modulated by bacterial infections or other inflammatory conditions to suppress IL-10 production in human trophoblasts. [source] Pregnancy complications associated with childhood anxiety disordersDEPRESSION AND ANXIETY, Issue 3 2004Dina R. Hirshfeld-Becker Ph.D. Abstract To determine whether perinatal complications predict childhood anxiety disorders independently of parental psychopathology, we systematically assessed pregnancy and delivery complications and psychopathology in a sample of children (mean age=6.8 years) at high risk for anxiety disorders whose parents had panic disorder with (n=138) or without (n=26) major depression, and in contrast groups of offspring of parents with major depression alone (n=47), or no mood or anxiety disorders (n=95; total N=306). Psychopathology in the children was assessed by structured diagnostic interviews (K-SADS), and pregnancy and delivery complications were assessed using the developmental history module of the DICA-P. Number of pregnancy complications predicted multiple childhood anxiety disorders independently of parental diagnosis (odds ratio=1.6 [1.4,2.0]). This effect was accounted for by heavy bleeding requiring bed-rest, hypertension, illness requiring medical attention, and serious family problems. Associations remained significant when lifetime child mood and disruptive behavior disorders were covaried. Results suggest that prenatal stressors may increase a child's risk for anxiety disorders beyond the risk conferred by parental psychopathology alone. Depression and Anxiety 19:152,162, 2004. © 2004 Wiley-Liss, Inc. [source] Thrombophilia and pregnancy outcomesJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 8 2005I. PABINGER Summary., Pregnancy complications are still a challenge for physicians, because knowledge of pathomechanisms and prophylactic measures is still limited. In recent years thrombophilia as a risk factor for pregnancy complications has gained much attention in the scientific community. However, data on this topic in the literature are conflicting. Besides an established association between antiphospholipid antibodies and pregnancy loss, available data suggest additional associations for antithrombin deficiency, hyperhomocysteinemia and also for factor (F)V Leiden, prothrombin G20210A variation, and protein S-deficiency. The contribution of thrombophilia to the risk of pre-eclampsia is less well established and recent studies did not confirm earlier data suggesting an association between thrombophilia and pre-eclampsia. A limited number of prospective studies have failed to reveal an increased risk of pregnancy complications in unselected women with thrombosis risk factors. Low-molecular weight heparin (LMWH) seems to have a positive effect on pregnancy outcome after single or recurrent abortions, however, data from only one controlled trial are available. Experience in the prevention of pre-eclampsia by prophylactic heparin is very limited, and in addition, data on pregnancy complications in women with known heritable thrombophilia or a history of thrombosis are inconsistent. These women will usually have a favorable pregnancy outcome referring to the European Prospective Cohort on Thrombophilia Study. In conclusion, thrombophilia screening might be justified in women with pregnancy loss and treatment with LMWH might be considered in those with pregnancy loss and thrombophilia. Further prospective studies and controlled interventional trials are urgently needed. [source] Pregnancy complications among women who took folic acid during early pregnancy , Sino,US NTD ProjectPAEDIATRIC & PERINATAL EPIDEMIOLOGY, Issue 4 2001No abstract is available for this article. [source] A Novel Three-Dimensional In Vitro System to Study Trophoblast,Endothelium Cell InteractionsAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 2 2007Paulomi B. Aldo Introduction Pregnancy complications have been linked to improper trophoblast migration and failure of spiral artery transformation. Endothelial cells play an essential role in directing trophoblast migration and transformation, although by an unknown mechanism. We describe a novel in vitro model to evaluate endothelial,trophoblast interaction and signaling in a three-dimensional system. Method of study Immortalized human endometrial endothelial cell line and first trimester trophoblast cells were co-cultured. Endothelial transformation into vessel-like structures occurred in MatrigelTM OpenLab Image Analysis software was used to monitor labeled trophoblast migration and endothelium transformation. Cytokine/chemokine production was determined using Multiplex. Results Trophoblast migrates toward endothelial cells in Matrigel, aligns on top of the endothelium within 4,8 hr and achieves complete replacement of the endothelium by 72,96 hr. Lipopolysaccharide treatment damages the endothelium and disrupts endothelium,trophoblast interaction. Conclusion We report a novel three-dimensional in vitro and in vivo system of trophoblast,endothelium cell interaction. Significant changes in endothelial cells' phenotype are observed upon differentiation in Matrigel. These changes may be necessary for endothelium to direct trophoblast migration and transformation. [source] Escherichia coli: a growing problem in early onset neonatal sepsisAUSTRALIAN AND NEW ZEALAND JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Issue 6 2004Bronwyn JONES Abstract Aims: To review the demographic characteristics, antecedents and outcome for early neonatal Escherichia coli sepsis. Secondary aims were to identify antenatal antibiotic use and to review the antimicrobial susceptibility. Methods: A retrospective chart review was performed for all infants with a positive culture for E. coli from either blood or CSF samples obtained between January 1998 and October 2002. Results: Nineteen liveborn infants with early onset sepsis and one stillborn baby with a positive maternal blood culture for E. coli were identified. Pregnancy complications included multiple pregnancy in five (25%), preterm rupture of membranes 10 (50%) and maternal urinary tract infection in five (25%). Eighteen of the cases were born preterm and two at term. The mortality was 8/20 (40%), and for nine cases with developmental outcome data available, 67% were within normal limits and 33% were abnormal. Of the 20 E. coli isolates 11 (55%) were resistant to amoxycillin and 1 (5%) was resistant to gentamicin. Conclusions: Infants with early onset E. coli sepsis had a poor outcome with high mortality and a third of the survivors manifesting neurodevelopmental impairment. Although amoxycillin resistance is common, there is a low prevalence of gentamicin resistance in local isolates. [source] Pregnancy complications associated with childhood anxiety disordersDEPRESSION AND ANXIETY, Issue 3 2004Dina R. Hirshfeld-Becker Ph.D. Abstract To determine whether perinatal complications predict childhood anxiety disorders independently of parental psychopathology, we systematically assessed pregnancy and delivery complications and psychopathology in a sample of children (mean age=6.8 years) at high risk for anxiety disorders whose parents had panic disorder with (n=138) or without (n=26) major depression, and in contrast groups of offspring of parents with major depression alone (n=47), or no mood or anxiety disorders (n=95; total N=306). Psychopathology in the children was assessed by structured diagnostic interviews (K-SADS), and pregnancy and delivery complications were assessed using the developmental history module of the DICA-P. Number of pregnancy complications predicted multiple childhood anxiety disorders independently of parental diagnosis (odds ratio=1.6 [1.4,2.0]). This effect was accounted for by heavy bleeding requiring bed-rest, hypertension, illness requiring medical attention, and serious family problems. Associations remained significant when lifetime child mood and disruptive behavior disorders were covaried. Results suggest that prenatal stressors may increase a child's risk for anxiety disorders beyond the risk conferred by parental psychopathology alone. Depression and Anxiety 19:152,162, 2004. © 2004 Wiley-Liss, Inc. [source] Assessment of gestational age and neuromaturationDEVELOPMENTAL DISABILITIES RESEARCH REVIEW, Issue 1 2005Marilee C. Allen Abstract Neuromaturation is the functional development of the central nervous system (CNS). It is by its very nature a dynamic process, a continuous interaction between the genome and first the intrauterine environment, then the extrauterine environment. Understanding neuromaturation and being able to measure it is fundamental to infant neurodevelopmental assessment. Fetal and preterm neuromaturation has become easier to observe with the advent of prenatal ultrasonography and neonatal intensive care units. A number of measures of degree of fetal maturation have been developed and used to estimate gestational age (GA) at birth. The most reliable measures of GA are prenatal measures, especially from the first trimester. Postnatal GA measurements tend to be least accurate at the extremes of gestation, that is, in extremely preterm and post-term infants. Observations of measures of neuromaturation in infants born to mothers with pregnancy complications, including intrauterine growth restriction, multiple gestation, and chronic hypertension, have led to the discovery that stressed pregnancies may accelerate fetal pulmonary and CNS maturation. This acceleration of neuromaturation does not occur before 30 weeks' gestation and has a cost with respect to cognitive limitations manifested in childhood. The ability to measure fetal and preterm neuromaturation provides an assessment of neurodevelopmental progress that can be used to reassure parents or identify at risk infants who would benefit from limited comprehensive follow-up and early intervention services. In addition, measures of neuromaturation have the potential to provide insight into mechanisms of CNS injury and recovery, much-needed early feedback in intervention or treatment trials and a measure of early CNS function for research into the relationships between CNS structure and function. © 2005 Wiley-Liss, Inc. MRDD Research Reviews 2005;11:21,33. [source] Epidemiology of gestational diabetes mellitus and its association with Type 2 diabetesDIABETIC MEDICINE, Issue 2 2004A. Ben-Haroush Abstract Gestational diabetes (GDM) is defined as carbohydrate intolerance that begins or is first recognized during pregnancy. Although it is a well-known cause of pregnancy complications, its epidemiology has not been studied systematically. Our aim was to review the recent data on the epidemiology of GDM, and to describe the close relationship of GDM to prediabetic states, in addition to the risk of future deterioration in insulin resistance and development of overt Type 2 diabetes. We found that differences in screening programmes and diagnostic criteria make it difficult to compare frequencies of GDM among various populations. Nevertheless, ethnicity has been proven to be an independent risk factor for GDM, which varies in prevalence in direct proportion to the prevalence of Type 2 diabetes in a given population or ethnic group. There are several identifiable predisposing factors for GDM, and in the absence of risk factors, the incidence of GDM is low. Therefore, some authors suggest that selective screening may be cost-effective. Importantly, women with an early diagnosis of GDM, in the first half of pregnancy, represent a high-risk subgroup, with an increased incidence of obstetric complications, recurrent GDM in subsequent pregnancies, and future development of Type 2 diabetes. Other factors that place women with GDM at increased risk of Type 2 diabetes are obesity and need for insulin for glycaemic control. Furthermore, hypertensive disorders in pregnancy and afterwards may be more prevalent in women with GDM. We conclude that the epidemiological data suggest an association between several high-risk prediabetic states, GDM, and Type 2 diabetes. Insulin resistance is suggested as a pathogenic linkage. It is possible that improving insulin sensitivity with diet, exercise and drugs such as metformin may reduce the risk of diabetes in individuals at high risk, such as women with polycystic ovary syndrome, impaired glucose tolerance, and a history of GDM. Large controlled studies are needed to clarify this issue and to develop appropriate diabetic prevention strategies that address the potentially modifiable risk factors. Diabet. Med. 20, ***,*** (2003) [source] Pregnancy and rare bleeding disordersHAEMOPHILIA, Issue 5 2009R. KADIR Summary., Rare bleeding disorders include deficiency of fibrinogen, prothrombin, factor V, factor VII, factor X, factor XI and factor XIII together with combined deficiency disorders, factor V+VIII deficiency, and deficiency of the vitamin K-dependent factors (factor II, VII, IX and X). They account for 3,5% of all inherited coagulation disorders. Due to their rarity, information about pregnancy complications and management is limited and mostly derived from case reports. Deficiency of fibrinogen and FXIII are both found to be strongly associated with increased risk of recurrent miscarriage and placental abruption. Factor replacement is used to reduce these risks. However, the risk of miscarriage and ante-partum complications is less clear in women with other bleeding disorders. Haemostatic abnormalities in women with rare bleeding disorders seem to persist throughout pregnancy especially if the defect is severe. Therefore women affected with these disorders are at risk of post-partum haemorrhage. The fetus can also be affected and potentially at risk of bleeding complications. Specialised multidisciplinary management is essential to minimise the potential maternal and neonatal complications and ensure an optimal outcome. This paper presents literature review for pregnancy complications in each of the rare bleeding disorders. In addition general principles for management of pregnancy, labour and delivery are discussed. [source] An Analysis of Possible Mechanisms of Unexpected Death Occurring in Hydatid Disease (Echinococcosis)JOURNAL OF FORENSIC SCIENCES, Issue 4 2009Roger W. Byard M.B.B.S. Abstract:, Most cases of hydatid disease in human populations are due to Echinococcus granulosus. The hydatid life cycle involves passage between definitive hosts such as dogs and intermediate hosts such as sheep. Humans become accidental intermediate hosts following ingestion of food or water contaminated with eggs or by contact with infected dogs. Although hydatid disease may remain asymptomatic, occasional cases of sudden and unexpected death present to autopsy. Causes of rapid clinical decline involve a wide range of mechanisms including anaphylaxis (with or without cyst rupture), cardiac outflow obstruction or conduction tract disturbance, pulmonary and cerebral embolism, pericarditis, cardiac tamponade, myocardial ischemia, pulmonary hypertension, peritonitis, hollow organ perforation, intracerebral mass effect, obstructive hydrocephalus, seizures, cerebral ischemia/infarction, and pregnancy complications. The autopsy assessment of cases therefore requires careful examination of all organ systems for characteristic cystic lesions, as multiorgan involvement is common, with integration of findings so that possible mechanisms of death can be determined. Measurement of serum tryptase and specific IgE levels should be undertaken for possible anaphylaxis. [source] The Reliability and Validity of Birth CertificatesJOURNAL OF OBSTETRIC, GYNECOLOGIC & NEONATAL NURSING, Issue 1 2006Sally Northam Objectives:, To summarize the reliability and validity of birth certificate variables and encourage nurses to spearhead data improvement. Data sources:, A Medline key word search of reliability and validity of birth certificate, and a reference review of more than 60 articles were done. Study selection:, Twenty-four primary research studies of U.S. birth certificates that involved validity or reliability assessment. Data extraction:, Studies were reviewed, critiqued, and organized as either a reliability or a validity study and then grouped by birth certificate variable. Data synthesis:, The reliability and validity of birth certificate data vary considerably by item. Insurance, birthweight, Apgar score, and delivery method are more reliable than prenatal visits, care, and maternal complications. Tobacco and alcohol use, obstetric procedures, and delivery events are unreliable. Birth certificates are not valid sources of information on tobacco and alcohol use, prenatal care, maternal risk, pregnancy complications, labor, and delivery. Conclusions:, Birth certificates are a key data source for identifying causes of increasing U.S. infant mortality but have serious reliability and validity problems. Nurses are with mothers and infants at birth, so they are in a unique position to improve data quality and spread the word about the importance of reliable and valid data. Recommendations to improve data are presented. JOGNN, 35, 3-12; 2006. DOI: 10.1111/J.1552-6909.2006.00016.x [source] Smoking Cessation Counseling for Pregnant Women Who Smoke: Scientific Basis for Practice for AWHONN's SUCCESS ProjectJOURNAL OF OBSTETRIC, GYNECOLOGIC & NEONATAL NURSING, Issue 3 2004FAAN, Susan A. Albrecht PhD Objectives: To review the literature addressing smoking cessation in pregnant women. To develop the project protocol for the Association of Women's Health, Obstetric and Neonatal Nurse's (AWHONN) 6th research-based practice project titled "Setting Universal Cessation Counseling, Education and Screening Standards (SUCCESS): Nursing Care of Pregnant Women Who Smoke." To evaluate the potential of systematic integration of this protocol in primary care settings in which women seek care at the preconception, pregnant, or postpartum stages. Literature Sources: Computerized searches in MEDLINE and CINAHL, as well as references cited in articles reviewed. Key concepts in the searches included low-birth-weight infants and effects of prenatal smoking on the infant and the effects of preconception and prenatal smoking cessation intervention on premature labor and birth weight. Literature Selection: Comprehensive articles, reports, and guidelines relevant to key concepts and published after 1964 with an emphasis on new findings from 1996 through 2002. Ninety-eight citations were identified as useful to this review. Literature Synthesis: Tobacco use among pregnant women and children's exposure to tobacco use (secondhand smoke) are associated with pregnancy complications such as placental dysfunction (including previa or abruption), preterm labor, premature rupture of membranes, spontaneous abortions, and decreased birth weight and infant stature. Neonates and children who are exposed to secondhand smoke are at increased risk for developing otitis media, asthma, other respiratory disorders later in childhood; dying from sudden infant death syndrome; and learning disorders. The "5 A's" intervention and use of descriptive statements for smoking status assessment were synthesized into the SUCCESS project protocol for AWHONN's 6th research-based practice project. Conclusions: The literature review generated evidence that brief, office-based assessment, client-specific tobacco counseling, skill development, and support programs serve as an effective practice guideline for clinicians. Implementation and evaluation of the guideline is under way at a total of 13 sites in the United States and Canada. [source] Does continuous use of metformin throughout pregnancy improve pregnancy outcomes in women with polycystic ovarian syndrome?JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH (ELECTRONIC), Issue 5 2008Fauzia Haq Nawaz Abstract Aim:, Polycystic ovarian syndrome (PCOS) is one of the most common endocrinopathies in women of reproductive age. It is associated with hyperinsulinemia and insulin resistance which is further aggravated during pregnancy. This mechanism has a pivotal role in the development of various complications during pregnancy. In the past few years, metformin, an insulin sensitizer, has been extensively evaluated for induction of ovulation. Its therapeutic use during pregnancy is, however, a recent strategy and is a debatable issue. At present, evidence is inadequate to support the long-term use of insulin-sensitizing agents during pregnancy. It is a challenge for both clinicians and researchers to provide good evidence of the safety of metformin for long-term use and during pregnancy. This study aimed to evaluate pregnancy outcomes in women with PCOS who conceived while on metformin treatment, and continued the medication for a variable length of time during pregnancy. Methods:, This case-control study was conducted from January 2005 to December 2006 at the antenatal clinics of the Department of Obstetrics and Gynecology, Aga Khan University, Karachi, Pakistan. The sample included 137 infertile women with PCOS; of these, 105 conceived while taking metformin (cases), while 32 conceived spontaneously without metformin (controls). Outcomes were measured in three groups of cases which were formed according to the duration of use of metformin during pregnancy. Comparison was made between these groups and women with PCOS who conceived spontaneously. Results:, All 137 women in this study had a confirmed diagnosis of PCOS (Rotterdam criteria). These women were followed up during their course of pregnancy; data forms were completed once they had delivered. Cases were divided into three groups: group A, 40 women who stopped metformin between 4,16 weeks of pregnancy; group B, 20 women who received metformin up until 32 weeks of gestation; and group C; 45 women who continued metformin throughout pregnancy. All the groups were matched by age, height and weight. Comparison was in terms of early and late pregnancy complications, intrauterine growth restriction and live birth rates. In groups A, B and C the rate of pregnancy-induced hypertension/pre-eclampsia was 43.7%, 33% and 13.9% respectively (P < 0.020). Rates of gestational diabetes requiring insulin treatment in groups A and B were 18.7% and 33.3% compared to 2.5% in group C (P < 0.004). The rate of intrauterine growth restriction was significantly low in group C: 2.5% compared to 19.2% and 16.6% in groups A and B respectively (P < 0.046). Frequency of preterm labor and live birth rate was significantly better in group C compared to groups A and B. Overall rate of miscarriages was 7.8%. Controls were comparable to group A in terms of early and late pregnancy complications. Conclusion:, In women with PCOS, continuous use of metformin during pregnancy significantly reduced the rate of miscarriage, gestational diabetes requiring insulin treatment and fetal growth restriction. No congenital anomaly, intrauterine death or stillbirth was reported in this study. [source] Bartter's Syndrome in Pregnancy: A Case Report and ReviewJOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH (ELECTRONIC), Issue 2 2000Dr. Ivy C. F. Li Abstract Bartter's syndrome is a rare renal tubular disorder, involving juxtaglomerular cells hyperplasia, characterized by normotensive hyper-reninism and secondary hyperaldosteronism, marked renal loss of potassium and profound hypokalaemia. Both clinical and biochemical features are heterogeneous, ranging from the incidental finding in an asymptomatic patient to marked clinical features of hypokalaemia. Inheritance is likely to be an autosomal recessive. We present a case of Bartter's syndrome complicating pregnancy in a Chinese woman. We documented an increasing demand for potassium supplement during pregnancy which stabilized by mid-trimester. The absence of pregnancy complications such as polyhydramnios indicated that the fetus was unlikely to be affected by the condition. [source] Thrombophilia and pregnancy outcomesJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 8 2005I. PABINGER Summary., Pregnancy complications are still a challenge for physicians, because knowledge of pathomechanisms and prophylactic measures is still limited. In recent years thrombophilia as a risk factor for pregnancy complications has gained much attention in the scientific community. However, data on this topic in the literature are conflicting. Besides an established association between antiphospholipid antibodies and pregnancy loss, available data suggest additional associations for antithrombin deficiency, hyperhomocysteinemia and also for factor (F)V Leiden, prothrombin G20210A variation, and protein S-deficiency. The contribution of thrombophilia to the risk of pre-eclampsia is less well established and recent studies did not confirm earlier data suggesting an association between thrombophilia and pre-eclampsia. A limited number of prospective studies have failed to reveal an increased risk of pregnancy complications in unselected women with thrombosis risk factors. Low-molecular weight heparin (LMWH) seems to have a positive effect on pregnancy outcome after single or recurrent abortions, however, data from only one controlled trial are available. Experience in the prevention of pre-eclampsia by prophylactic heparin is very limited, and in addition, data on pregnancy complications in women with known heritable thrombophilia or a history of thrombosis are inconsistent. These women will usually have a favorable pregnancy outcome referring to the European Prospective Cohort on Thrombophilia Study. In conclusion, thrombophilia screening might be justified in women with pregnancy loss and treatment with LMWH might be considered in those with pregnancy loss and thrombophilia. Further prospective studies and controlled interventional trials are urgently needed. [source] Functions of corticotropin-releasing hormone in anthropoid primates: From brain to placentaAMERICAN JOURNAL OF HUMAN BIOLOGY, Issue 4 2006Michael L. Power Corticotropin-releasing hormone (CRH) is an ancient regulatory molecule. The CRH hormone family has at least four ligands, two receptors, and a binding protein. Its well-known role in the hypothalamic-pituitary-adrenal (HPA) axis is only one of many. The expression of CRH and its related peptides is widespread in peripheral tissue, with important functions in the immune system, energy metabolism, and female reproduction. For example, CRH is involved in the implantation of fertilized ova and in maternal tolerance to the fetus. An apparently unique adaptation has evolved in anthropoid primates: placental expression of CRH. Placental CRH stimulates the fetal adrenal zone, an adrenal structure unique to primates, to produce dehydroepiandrosterone sulfate (DHEAS), which is converted to estrogen by the placenta. Cortisol induced from the fetal and maternal adrenal glands by placental CRH induces further placental CRH expression, forming a positive feedback system that results in increasing placental production of estrogen. In humans, abnormally high placental expression of CRH is associated with pregnancy complications (e.g., preterm labor, intrauterine growth restriction (IUGR), and preeclampsia). Within anthropoid primates, there are at least two patterns of placental CRH expression over gestation: monkeys differ from great apes (and humans) by having a midgestational peak in CRH expression. The functional significance of these differences between monkeys and apes is not yet understood, but it supports the hypothesis that placental CRH performs multiple roles during gestation. A clearer understanding of the diversity of patterns of placental CRH expression among anthropoid primates would aid our understanding of its role in human pregnancy. Am. J. Hum. Biol. 18:431,447, 2006. © 2006 Wiley-Liss, Inc. [source] PLAC1 (Placenta-specific 1): a novel, X-linked gene with roles in reproductive and cancer biologyPRENATAL DIAGNOSIS, Issue 6 2010Michael Fant Abstract Placenta-specific 1 (PLAC1) is a recently described X-linked gene with expression restricted primarily to cells derived from trophoblast lineage during embryonic development. PLAC1 localizes to a region of the X chromosome thought to be important in placental development although its role in this process has not been defined. This review summarizes our current understanding of its expression, regulation, and function. PLAC1 is expressed throughout human pregnancy by the differentiated trophoblast and localizes to membranous structures in the syncytiotrophoblast, including the microvillous plasma membrane surface. Recent studies have demonstrated that PLAC1 is also expressed by a wide variety of human cancers. Studies of the PLAC1 promoter regions indicate that its expression in both normal placenta and cancer cells is driven by specific interactions involving a combination of transcription factors. Although functional insight into PLAC1 in the normal trophoblast is lacking, preliminary studies suggest that cancer-derived PLAC1 has the potential to promote tumor growth and function. In addition, it also appears to elicit a specific immunologic response that may influence survival in some cancer patients, suggesting that it may provide a therapeutic target for the treatment of some cancers. We also discuss a potential role for PLAC1 as a biomarker predictive of specific pregnancy complications, such as preeclampsia. Copyright © 2010 John Wiley & Sons, Ltd. [source] Assessing the role of placental trisomy in preeclampsia and intrauterine growth restrictionPRENATAL DIAGNOSIS, Issue 1 2010Wendy P. Robinson Abstract Objective Prenatally diagnosed confined placental trisomy is associated with increased risk for intrauterine growth restriction (IUGR) and preeclampsia. However, it is unclear how often this might underlie pregnancy complications. Our objective was to evaluate the frequency and distribution of trisomic cells in placentae ascertained for IUGR and/or preeclampsia. Method Comparative genomic hybridization was applied to two uncultured biopsies from each of 61 placentae referred with maternal preeclampsia and/or IUGR, 11 cases with elevated maternal serum hCG and/or AFP but no IUGR or preeclampsia, and 85 control placentae. Results Trisomy was observed in four placentae among the IUGR group (N = 43) but in no case of preeclampsia in the absence of IUGR (N = 18). Trisomy was observed in 1 of the 11 cases ascertained for abnormal maternal serum screen. Each of these five cases was mosaic and not all sampled sites showed the presence of trisomy. None of the 84 control placentas showed mosaic trisomy, although 1 case of nonmosaic 47,XXX was identified in this group. Conclusion In cases in which diagnosis of the cause of IUGR may provide some benefit, testing should be performed using uncultured cells from multiple placental biopsies for the accurate diagnosis of trisomy mosaicism. Copyright © 2009 John Wiley & Sons, Ltd. [source] SAFE,The Special Non-invasive Advances in Fetal and Neonatal Evaluation Network: aims and achievementsPRENATAL DIAGNOSIS, Issue 2 2008Lyn S. Chitty Abstract In this short review, the objectives and work of SAFE,the Special Non-invasive Advances in Fetal and Neonatal Evaluation Network, a European Union Framework VI network of excellence is described. We demonstrate how this network facilitates the implementation of non-invasive prenatal diagnosis (NIPD) for single gene disorders, fetal rhesus typing, aneuploidy and pregnancy complications. Copyright © 2008 John Wiley & Sons, Ltd. [source] REVIEW ARTICLE: Placental Apoptosis in Health and DiseaseAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 3 2010Andrew N. Sharp Citation Sharp AN, Heazell AEP, Crocker IP, Mor G. Placental apoptosis in health and disease. Am J Reprod Immunol 2010; 64: 159,169 Apoptosis, programmed cell death, is an essential feature of normal placental development but is exaggerated in association with placental disease. Placental development relies upon effective implantation and invasion of the maternal decidua by the placental trophoblast. In normal pregnancy, trophoblast apoptosis increases with placental growth and advancing gestation. However, apoptosis is notably exaggerated in the pregnancy complications, hydatidiform mole, pre-eclampsia, and intrauterine growth restriction (IUGR). Placental apoptosis may be initiated by a variety of stimuli, including hypoxia and oxidative stress. In common with other cell-types, trophoblast apoptosis follows the extrinsic or intrinsic pathways culminating in the activation of caspases. In contrast, the formation of apoptotic bodies is less clearly identified, but postulated by some to involve the clustering of apoptotic nuclei and liberation of this material into the maternal circulation. In addition to promoting a favorable maternal immune response, the release of this placental-derived material is thought to provoke the endothelial dysfunction of pre-eclampsia. Widespread apoptosis of the syncytiotrophoblast may also impair trophoblast function leading to the reduction in nutrient transport seen in IUGR. A clearer understanding of placental apoptosis and its regulation may provide new insights into placental pathologies, potentially suggesting therapeutic targets. [source] ORIGINAL ARTICLE: Haplotype-dependent Differential Activation of the Human IL-10 Gene Promoter in Macrophages and Trophoblasts: Implications for Placental IL-10 Deficiency and Pregnancy ComplicationsAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 3 2010Surendra Sharma Citation Sharma S, Stabila J, Pietras L, Singh AR, McGonnigal B, Ernerudh J, Matthiesen L, Padbury JF. Haplotype-dependent differential activation of the human IL-10 gene promoter in macrophages and trophoblasts: Implications for placental IL-10 deficiency and pregnancy complications. Am J Reprod Immunol 2010; 64: 179,187 Problem, Polymorphic changes in the IL-10 gene promoter have been identified that lead to altered IL-10 production. We hypothesized that because of these genotypic changes, the IL-10 promoter might be expressed in a cell type,specific manner and may respond differentially to inflammatory triggers. Method of study, We created reporter gene promoter constructs containing GCC, ACC, and ATA haplotypes using DNA from patients harboring polymorphic changes at ,1082 (G,A), ,819 (C,T), and ,592 (C,A) sites in the IL-10 promoter. These individual luciferase reporter constructs were transiently transfected into either primary term trophoblasts or THP1 monocytic cells. DNA-binding studies were performed to implicate the role of the Sp1 transcription factor in response to differential promoter activity. Results, Our results suggest that the GCC promoter construct was activated in trophoblast cells in response to lipopolysaccharide (LPS), as demonstrated by reporter gene expression, but not in monocytic cells. The ACC construct showed weaker activation in both cell types. Importantly, while the ATA promoter was constitutively activated in both cell types, its expression was selectively repressed in response to LPS, but only in trophoblasts. DNA-nuclear protein binding assays with nuclear extracts from LPS treated or untreated cells suggested a functional relevance for Sp1 binding differences at the ,592 position. Conclusions, These results demonstrate cell type,specific effects of the genotypic changes in the IL-10 gene promoter. These responses may be further modulated by bacterial infections or other inflammatory conditions to suppress IL-10 production in human trophoblasts. [source] Phagocytosis of Apoptotic Trophoblast Cells by Human Endometrial Endothelial Cells Induces Proinflammatory Cytokine ProductionAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 1 2010Bing Peng Citation Peng B, Koga K, Cardenas I, Aldo P, Mor G. Phagocytosis of apoptotic trophoblast cells by human endometrial endothelial cells induces proinflammatory cytokine production. Am J Reprod Immunol 2010; 64: 12,19 Problem, Apoptosis is a normal constituent of trophoblast turnover in the placenta; however in some cases, this process is related to pregnancy complications such as preeclampsia. Recognition and engulfment of these apoptotic trophoblast cells is important for clearance of dying cells. The aim of this study was to show the cross talk between human endometrial endothelial cells (HEECs) and apoptotic trophoblast cells in an in vitro coculture model and its effect on cytokine production by HEECs. Method of study, Fluorescent-labeled HEECs were cocultured with fluorescent-labeled apoptotic human trophoblast cells. Confocal microscopy and flowcytometry were used to show the interaction between these two types of cells. Cytokine profiles were determined using multiplex analysis. Results, HEECs are capable to phagocytose apoptotic trophoblasts. This activity is inhibited by the phagocytosis inhibitor cytochalasin B. Phagocytosis of apoptotic trophoblast cells induced the secretion of the proinflammatory cytokines interleukin-6 and monocyte chemoattractant protein-1 by HEECs. Conclusion, This study provides the first evidence that HEECs have an ability to phagocytose apoptotic trophoblasts. Furthermore, we demonstrated an inflammatory response of HEECs after phagocytosing the apoptotic trophoblast cells. This event may contribute to the inflammatory response in both normal pregnancy and pathologic pregnancy such as preeclampsia. [source] REVIEW ARTICLE: The Contribution of Macrophages to Normal and Pathological PregnanciesAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 6 2010Takeshi Nagamatsu Citation Nagamatsu T, Schust DJ. The contribution of macrophages to normal and pathological pregnancies. Am J Reprod Immunol 2010 Macrophages represent one of the major leukocyte subsets in the uterine decidua. Owing to their remarkable phenotypic plasticity, decidual macrophages can participate in diverse activities during pregnancy. At baseline, decidual macrophages are characterized by an immunosuppressive phenotype and M2 polarization, supporting feto-maternal immune tolerance. In early pregnancy, macrophage-derived pro-angiogenic factors prompt vascular remodeling within the uterine wall to ensure appropriate utero-placental circulation. Upon invasion by pathogens, pattern recognition receptors on decidual macrophages help to alter the characteristics of these malleable cells toward an M1, inflammatory phenotype. Similar inflammatory characteristics are seen in those macrophages that accumulate in the lower segment of the uterus to drive cervical ripening. Disturbances in the tight control that balances macrophage function during pregnancy can trigger the development of pregnancy complications. Here, we discuss the physiologic role of uterine macrophages at different stages of pregnancy and describe their relevance in selected pregnancy disorders. [source] ORIGINAL ARTICLE: Soluble Human Leukocyte Antigen-G Isoforms in Maternal Plasma in Early and Late PregnancyAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 5 2009Roberta Rizzo Problem Human Leukocyte Antigen (HLA)-G is a class Ib gene located in the human major histocompatibility complex (MHC). Several lines of investigation indicate that the HLA-G molecule is involved in the maternal acceptance of the semi-allogenic fetus during pregnancy and in the development of tolerance. Expression of soluble HLA-G (sHLA-G) is positively correlated with successful in vitro fertilization (IVF) treatments, and aberrant expression of HLA-G in certain complications of pregnancy, such as pre-eclampsia and spontaneous abortion, has been reported. The main purpose of this study was to investigate the levels of different soluble HLA-G isoforms in maternal plasma in early and late pregnancy. Method of study Soluble HLA-G (sHLA-G) can be detected in maternal blood, and in this study, two different isoforms of sHLA-G, namely sHLA-G1 generated by shedding of membrane-bound HLA-G1 and HLA-G generated by specific HLA-G transcripts, have been investigated early [median of 16.4 weeks of gestation (GW)] and late (median: 38.9 GW) in pregnancy in an original cohort of 580 pregnant Caucasian women. Results Lower concentrations of sHLA-G1 were found late in pregnancy (>32 GW) in a group of women with severe pre-eclampsia compared with controls with uncomplicated pregnancies (P = 0.029, PC = 0.09; Mann,Whitney; Logistic regression analysis: P = 0.024, OR = 0.920, 95% CI: 0.855,0.989). However, this was not the case with HLA-G5, and significantly more of the cases with severe pre-eclampsia had detectable plasma HLA-G5 compared with that of the control group (P = 0.013, PC = 0.04; Mann,Whitney). Similar findings were not observed in women with gestational hypertension or existing hypertension continuing into pregnancy. Furthermore, there was a trend toward lower maternal plasma sHLA-G1 in a group of women with premature birth (<37 GW) compared with that of the control group (P = 0.028, PC = 0.17; Mann,Whitney). On the contrary, HLA-G5 was lower in the control group compared with that in the premature group (P = 0.004, PC = 0.02; Mann,Whitney). Conclusion This study shows in line with other published studies that a high, detectable soluble HLA-G concentration in maternal plasma or serum is not mandatory for a successful pregnancy. However, complications during pregnancy, such as (severe) pre-eclampsia, spontaneous abortion, IUGR, and premature birth, are associated with a low or undetectable level of soluble HLA-G in the maternal blood circulation. Also, this study indicates that sHLA-G1 is the interesting soluble HLA-G isoform in pre-eclampsia, and that low or undetectable levels of HLA-G5 at the end of pregnancy seem to be associated with an uncomplicated normal pregnancy, whereas in severe pre-eclampsia and possibly other pregnancy complications, such as preterm birth and IUGR, the level of HLA-G5 is higher. [source] Anti-DNA Antibodies Cross-reacting with Laminin Inhibit Trophoblast Attachment and Migration: Implications for Recurrent Pregnancy Loss in SLE PatientsAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 3 2000FAISAL QURESHI PROBLEM: Systemic lupus erythematosus (SLE), an autoimmune disease, is associated with reduced fetal survival, recurrent abortions, and other pregnancy complications. Some of the autoantibodies found in SLE bind to laminins (LNs), which play an important role in the implantation of the fertilized ovum in humans. METHOD OF STUDY: To elucidate the role of these specific autoantibodies, chorionic villous explants from 6,7-week-old human placentas were established as organ cultures on laminin-1 (LN-1), collagen IV (CN-IV) or uncoated culture dishes. The cultures were then exposed to a mouse monoclonal anti-DNA/anti-LN-1 antibody, to human polyclonal lupus antibodies cross-reacting with LN-1, a function-blocking polyclonal antibody to LN-1, polyclonal antibodies to CN-IV, or IgG control. RESULTS: The explants attached to LN-1 and CN-IV, but not to uncoated culture dishes. LN-1 promoted migration of trophoblast, whereas CN-IV promoted migration of fibroblast-like cells. Trophoblast attachment and migration were abolished in a dose-dependent manner by all three antibodies to LN-1, but not by antibodies to CN-IV or IgG control. Furthermore, the effect of anti-LN antibodies was abolished by preincubating them with LN-1. CONCLUSIONS: These studies suggest that anti-DNA antibodies cross-reacting with LNs may play a role in early pregnancy failure in SLE patients by interfering with placental implantation. [source] Human First-Trimester Decidua Vascular Density: An Immunohistochemical Study Using VE-Cadherin and Endoglin as Endothelial Cell MarkersAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 1 2000BRUNO VAILHÉ PROBLEM: Angiogenesis and vasculogenesis appear to be of critical importance for the success of pregnancy. Recent data have emphasized that pregnancy complications, such as abortion or pre-eclampsia, are linked with vascular pathologies. The aim of this study was to quantify human first-trimester decidua microvascular density, using two novel, highly specific endothelial cell markers, VE-cadherin and endoglin. METHOD OF STUDY: We collected decidua from women undergoing termination of normal pregnancies. VE-cadherin and endoglin were localized by immunohistochemistry. The blood vessel densities detected by VE-cadherin or endoglin-stainings were microscopically quantified per mm2. RESULTS: Endothelial cells in first-trimester human decidua both express VE-cadherin and endoglin. The microvascular density detected by VE-cadherin-staining varied from 32.2±1.7 in decidua basalis, to 30±0.6 in decidua parietalis. For the endoglin-staining, the values varied from 37.5±3 in decidua basalis, and 26.7±1.2 in decidua parietalis. CONCLUSIONS: Our data shows that both VE-cadherin and endoglin are good candidates to highlight the decidual endothelial cells, and to quantify the blood vessels density of endometrium. [source] Comment on: The early pregnancy assessment project: The effect of cooperative care in the emergency department for management of early pregnancy complications.AUSTRALIAN AND NEW ZEALAND JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Issue 5 2009Aust N Z J Obstet Gynaecol 2009; 49: 110 No abstract is available for this article. [source] The early pregnancy assessment project: The effect of cooperative care in the emergency department for management of early pregnancy complicationsAUSTRALIAN AND NEW ZEALAND JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Issue 1 2009David O'ROURKE Background: Early pregnancy assessment clinics (EPAC) have been introduced and accepted as the gold standard for management of early pregnancy problems (EPP). However, EPAC are not universally available and management of EPP within the emergency department (ED) can result in prolonged waiting times, inappropriate use of resources and no clear treatment or follow-up plan being implemented. Aim: To assess the effect of an early pregnancy assessment protocol (EPAP) in the ED, designed to create a cultural change among doctors in relation to EPP in order to minimise use of resources, improve treatment times for patients and establish a clear management plan where dedicated EPAC services are not available. Methods: An intervention, the EPAP was introduced to the ED and retrospective and prospective audits of the patients were carried out to assess the effect. Results: Implementation of the EPAP decreased treatment time by 55%, representations by 48%, pathology blood tests by 56% and formal imaging services by 85%. Gynaecological consultation increased by 37% for each patient visit to the ED and by 9% for each EPP. Total direct cost saving was 63% per patient and no adverse outcomes were recorded. Conclusion: Introduction of the EPAP was successful in creating cultural change and delivering clinical and financial benefits to the hospital, patients and staff. Early gynaecological consultation and bedside ultrasound scanning within the ED were key factors. Similar benefits could be reproduced in other institutions and for other clinical scenarios where a need has been identified. [source] Maternal obesity and pregnancy complications: A reviewAUSTRALIAN AND NEW ZEALAND JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Issue 3 2008Jonathan RAMACHENDERAN Obesity in women of reproductive age is increasing at an unprecedented rate in western societies. Maternal obesity is associated with an unequivocal increase in maternal and fetal complications of pregnancy. Excessive maternal weight gain in pregnancy also appears to be an independent risk factor, regardless of prepregnancy weight. Few guidelines exist regarding appropriate weight gain in pregnancy in obese women. We review the association of maternal obesity with pregnancy complications. We also suggest that appropriate diet and lifestyle intervention can enable women with severe prepregnancy obesity to safely achieve quite strict targets for limited weight gain in pregnancy. [source] | ||||||||||||||||||||||||||||