Prevention Of Adverse Pregnancy Outcomes Research Articles

First trimester prediction and prevention of adverse pregnancy outcomes related to poor placentation.

To summarize recent research findings related to first trimester prediction and prevention of adverse pregnancy outcomes associated with poor placentation. Recent publications related to prediction and prevention of preeclampsia, intrauterine growth restriction (IUGR) and stillbirth were reviewed. Researchers continue to identify markers that will help predict pregnancies that go on to develop preeclampsia through screening at 11-13 weeks. A number of multivariate algorithms describing risks for preeclampsia have been published and some of these have been validated in independent populations. A large randomized controlled trial has proven the efficacy of a first trimester prediction - prevention programme for preeclampsia with an 80% reduction in prevalence of disease leading to delivery less than 34 weeks. Screening tools for IUGR and stillbirth are less advanced and require further validation in other populations. The value of these models in preventing disease still needs to be demonstrated. Significant progress has been made in developing predictive and preventive strategies which can affect the prevalence of severe early-onset preeclampsia. This approach could be adopted for population-based screening aiming to prevent this disease.

Tacrolimus in the prevention of adverse pregnancy outcomes and diabetes-associated embryopathies in obese and diabetic mice

BackgroundT2DM is a high-risk pregnancy with adverse fetal and maternal outcomes including repeated miscarriages and fetal malformations. Despite the established association between placental insufficiency and poor maternal Th1-adaptability to the development of pregnancy complications in T2DM, there have been no established data to assess benefits of pre-pregnancy immunosuppression relative to gestational outcomes in T2DM. We hypothesized that pre-pregnancy macrolide immune suppression can re-establish normal placental development and uterine vascular adaptation in a mouse model of obesity-associated T2DM.MethodsFetal live birth rate, postnatal variability, mid-gestational uterine and umbilical flow dynamics and certain morphological features of spiral artery modification were examined in the New Zealand Obese (NONcNZO10/Ltj) female mice (n = 56) weaned to ages of 32 weeks on a 60% calories/g high-fat diet (also referred to as HFD-dNONcNZO), and which received either tacrolimus (0.1 mg/kg s.c. q2d) , its vehicle (castor oil and ethanol) or metformin (in drinking water 200 mg/dL p.o. ad libitum). HFD-BALBc-Rag2/IL2-gc female mice (n = 24) were used as HFD-immunodeficient controls.ResultsTreatment of the HFD-dNONcNZO female mice with tacrolimus improved live birth rates and postnatal viability scores (p < 0.01), normalized OGTT (p < 0.001), inhibited fetal malformation rates, restored morphology of spiral arterial modification; and improved uterine arterial and umbilical blood flow (p < 0.01). Placental production of TNFαand IL16 in the tacrolimus-treated HFD-dNONcNZO dams were restored to non-diabetic levels and the treatment resulted in the inhibition of aberrant monocyte/macrophage activation during pregnancy in the HFD-dNONcNZO dams.ConclusionsOur present data suggest a casual association between chronic maternal overnutrition and aberrancy in the maternal Th1-immune maladaptation to pregnancy and defective spiral artery modification, placental insufficiency and adverse fetal outcomes in the T2DM subjects. Further safety studies into the use of tacrolimus in the pre-pregnancy glycemic control may be beneficial.

The Impact of Socioeconomic Position on Severe Maternal Morbidity Outcomes Among Women in Australia: A National Case-control Study

(BJOG. 2015;122(12):1601–1609) Research conducted in Australia in 2000 determined that although there had been improvements in the health of the population over previous years, increased inequalities for socioeconomically related mortality had occurred for some conditions. Studies in other developed countries, such as the United Kingdom, have suggested that socioeconomic position may be a risk factor for poorer pregnancy outcomes. Identifying high-risk parturients is critical for the prevention of adverse pregnancy outcomes because it allows targeted interventions and intensive clinical management of specific groups of women. The Australasian Maternal Outcomes Surveillance System is based on the methodology of the UK Obstetric Surveillance System and enables research and surveillance for a range of pregnancy complications across Australia and New Zealand. This study aimed to explore the independent impact of socioeconomic position on selected severe maternal morbidities among women in Australia.

Surgical Management of an Ovarian Bilateral Multiple Dermoid Cyst During Pregnancy: A Case Report Study

Introduction: Most ovarian dermoid cysts occur during the reproductive age and therefore could occur during pregnancy. They are present in 0.03% of pregnancies and the risk of torsion during pregnancy is approximately 8%. They are bilateral in approximately 10% of cases. Diagnosis is usually made by ultrasound imaging. An ovarian cystectomy is almost always possible, even if it appears that only a small amount of ovarian tissue remains. Intraoperative spill of tumor contents may be a cause of complications. Case Presentation: A 28-year-old, pregnant, primipara female with gestational age 20 weeks + four days where referred to with complaint of pelvic mass that was incidentally reported in sonography where referred to the hospital. She had undergone intact removal (without spillage) of cysts during pregnancy by laporotomy and histopathologic report confirmed bilateral, multiple, benign and dermoid cyst. She was discharged without any complication on the second day after operation. She had an uneventful pregnancy and a cesarean delivery with alive, normal, female fetus at 38 weeks of gestation because of breech presentation. Conclusions: It seems that early diagnosis and intact surgery of multiple ovarian dermoid cysts during the second trimester of pregnancy could prevent complication of cysts and probably guarantee the prevention of adverse pregnancy outcome.

Current controversies in prenatal diagnosis 2: prediction and prevention of adverse pregnancy outcomes requires a genomic rather than proteomic solution.

From both presentations, it is clear that understanding the APO associated with placental dysfunction represents one of the greatest challenges in the field of prenatal screening, diagnosis, and therapy. Their clinical impact on the health of the mother and child was well recognized by the debaters, and both have agreed that there is a paucity of knowledge in the etiophysiopathology of placental dysfunction and the associated clinical phenotypes. They also agreed that this marked limitation in our understanding is a significant problem when designing a research protocol, and both stressed the importance of proper study designs. When focusing on the specific topics of the debate, they showed different opinions about the role of genomics in the search for relevant answers. Leslie Myatt pointed out that the genome does not define the cellular phenotype, and although the proteome itself does not define phenotype, it is much closer to it than the genome. Conversely, Rossa Chiu suggested that genomic approaches offer a better chance of achieving the answers than by proteomics alone. Actually, she hypothesized that through genomic approaches, or rather through systems biology, that is, including genomics, epigenomics, transcriptomics, and proteomics, there would be a better chance of obtaining the best answers. She also raised the possibility of the potential use of cell-free fetal nucleic acids in maternal plasma, which in turn are mainly of placental origin. Finally, both debaters and the audience agreed that there was not an exclusive proteomic or genomic 'solution', but that we need a larger spectrum of research strategies to include both proteomics and genomics and other systems biology approaches, combined with detailed and standardized clinical, laboratory, and epidemiological criteria in appropriately designed studies in order to start filling the significant gaps in our knowledge about this highly complex area of placental mediated adverse pregnancy outcomes.

Applicability of a high-throughput shotgun plasma protein screening approach in understanding maternal biological pathways relevant to infant birth weight outcome

There are reports linking maternal nutritional status, smoking and environmental chemical exposures to adverse pregnancy outcomes. However, biological bases for association between some of these factors and birth outcomes are yet to be established. The objective of this preliminary work is to test the capability of a new high-throughput shotgun plasma proteomic screening in identifying maternal changes relevant to pregnancy outcome. A subset of third trimester plasma samples (N=12) associated with normal and low-birth weight infants were fractionated, tryptic-digested and analyzed for global proteomic changes using a MALDI-TOF-TOF-MS methodology. Mass spectral data were mined for candidate biomarkers using bioinformatic and statistical tools. Maternal plasma profiles of cytokines (e.g. IL8, TNF-α), chemokines (e.g. MCP-1) and cardiovascular endpoints (e.g. ET-1, MMP-9) were analyzed by a targeted approach using multiplex protein array and HPLC-Fluorescence methods. Target and global plasma proteomic markers were used to identify protein interaction networks and maternal biological pathways relevant to low infant birth weight. Our results exhibited the potential to discriminate specific maternal physiologies relevant to risk of adverse birth outcomes. This proteomic approach can be valuable in understanding the impacts of maternal factors such as environmental contaminant exposures and nutrition on birth outcomes in future work. We demonstrate here the fitness of mass spectrometry-based shot-gun proteomics for surveillance of biological changes in mothers, and for adverse pathway analysis in combination with target biomarker information. This approach has potential for enabling early detection of mothers at risk for low infant birth weight and preterm birth, and thus early intervention for mitigation and prevention of adverse pregnancy outcomes. This article is part of a Special Issue entitled: Can Proteomics Fill the Gap Between Genomics and Phenotypes?

Is TMED2 essential in the chorion for normal interaction between the allantois and the chorion in mice?

s / Placenta 34 (2013) A1–A99 A84 insufficiency and adverse fetal outcomes in the T2DM HFD-NZO mice. Translational studies in the use of Tacrolimus in the pre-pregnancy glycemic control and immuno-conditioning for women with T2DM may be deemed beneficial in the prevention of adverse pregnancy outcomes. http://dx.doi.org/10.1016/j.placenta.2013.06.247 P2.82. IS TMED2 ESSENTIAL IN THE CHORION FOR NORMAL INTERACTION BETWEEN THE ALLANTOIS AND THE CHORION IN MICE? Wenyang(Dominic) Hou , Didem Sarikaya , Loydie Jerome-Majewska 1,2 Department of Human Genetics, McGill University, Montreal, Canada; Montreal Children Hospital Research Institute, Montreal, Canada; Organismic and Evolutionary Biology Department, Harvard University,

Effect of aspirin in prevention of adverse pregnancy outcome in women with elevated alpha-fetoprotein

Background: To evaluate the effect of low-dose aspirin in prevention of adverse pregnancy outcomes (APO) in women with second trimester alpha-fetoprotein (AFP) >2.5 multiple of median (MOM) and to compare aspirin effect on women with normal and abnormal uterine artery (UtA) Doppler. The primary outcome was the adverse pregnancy outcome.Methods: This randomized controlled trial was conducted in singleton pregnant women, who had unexplained AFP >2.5 MOM and gestational age between 15 and 18 weeks of gestation. They were assigned randomly to receive either aspirin (N = 65) or control (N = 68). UtA Doppler velocimetry studies were performed at the time of targeted ultrasonographic exam.Results: Two groups were comparable regarding the maternal characteristics. The frequency of APO in aspirin and control groups were 26.1% versus 44.1% (p = 0.045), the frequency of preterm delivery before 34 weeks were 3.2% versus 22.0% in aspirin and control group, p = 0.001. Other outcomes were similar in both groups. The frequency of adverse outcomes in women with abnormal UtA Doppler was 39.1% in aspirin and 60.0% in control group, p = 0.556.Conclusion: Low-dose aspirin reduces APO and delivery before 34 weeks of gestation in pregnant women with unexplained elevated AFP.

A multi-centre phase IIa clinical study of predictive testing for pre-eclampsia. IMproved PRegnancy Outcomes Via Early Detection (IMPROVED)

1 in 20 first time pregnancies is complicated by pre-eclampsia, the leading cause of maternal death in Europe. No clinically useful early pregnancy screening test exists, consequentially clinicians are unable to offer targeted surveillance or preventative strategies. IMPROVED Consortium members have pioneered a personalised medicine approach in identifying blood-borne biomarkers through recent technological advancements, involving mapping of the blood metabolome and proteome. The Consortium recently received funding under the auspices of the 7th Framework Programme of the European Union under the call: HEALTH- 2012-INNOVATION-1.2-1 (Grant Agreement no. Health-F5-2012-305169). The objective is to develop a sensitive, specific, high-throughput and economically viable early pregnancy screening test for pre-eclampsia. We report the design of a multicentre, phase IIa clinical study to assess and refine innovative prototype tests based on emerging metabolomic and proteomic technologies. Participation involves serial maternal phlebotomy, collection of clinical data, and pregnancy outcome data. Participants will attend essential visits at 15 and 20 weeks' gestation, with optional 11 and 34 weeks' gestation. Blood samples will undergo a combination of proteomic and metabolomic tests, and diagnostic performance will be assessed in accord with a pre-approved statistical analysis plan which will report Receiver Operating Curves, and Positive Predictive Values. The study is expected to refine proteomic and metabolomic panels, combined with clinical parameters, and evaluate clinical applicability as an early pregnancy predictive test for pre-eclampsia. If 'at risk' patients can be identified, this will allow stratified care with personalised fetal and maternal surveillance, early diagnosis, timely intervention, and significant health economic savings. The IMPROVED biobank will be accessible to the European scientific community for high quality research into the cause and prevention of adverse pregnancy outcome.

PPAR‐γ – a possible drug target for complicated pregnancies

Peroxisome proliferator activated receptors (PPARs) are ligand-activated transcription factors expressed in trophoblasts, which regulate both cell differentiation and proliferation. In recent years, evidence has linked PPARs to playing an integral role in pregnancy; specifically, PPAR-β and PPAR-γ have been shown to play an integral role in placentation, with PPAR-γ additionally serving to regulate trophoblast differentiation. Recent evidence has shown that PPAR-γ expression is altered in many complications of pregnancy such as intrauterine growth restriction (IUGR), preterm birth, pre-clampsia and gestational diabetes. Thus, at present, accumulating evidence from the literature suggests both a pivotal role for PPAR-γ in the progression of a healthy pregnancy and the possibility that PPAR-γ may act as a therapeutic target in complicated pregnancies. This review aims to provide a succinct and comprehensive assessment of the role of PPAR-γ in normal pregnancy and pregnancy complications, and finally its potential as a therapeutic target in the treatment and/or prevention of adverse pregnancy outcomes.

Prevention of Adverse Pregnancy Outcomes With Low-Dose ASA in Early Pregnancy: New Perspectives for Future Randomized Trials

Recent evidence suggests that treatment with low-dose acetylsalicylic acid (ASA) started early in pregnancy could prevent preeclampsia and intrauterine growth restriction (IUGR), two complications involving placental dysfunction. Preterm birth could also potentially be prevented, suggesting that it could share mechanisms of disease with preeclampsia and intrauterine growth restriction. Because there is new evidence that placental dysfunction can be predicted as early as in the first trimester, we argue that there is a need for randomized controlled trials of lowdose ASA for the prevention of preeclampsia, IUGR, and possibly preterm birth among nulliparous women with early indicators of placental dysfunction.

Optimal timing of periodontal disease treatment for prevention of adverse pregnancy outcomes: before or during pregnancy?

Several large randomized controlled clinical trials failed to find that standard periodontal therapy during pregnancy reduces the incidence of adverse pregnancy outcomes (eg, preterm birth and low birthweight). However, treating periodontal disease during pregnancy may be too late to reduce the inflammation that is related to the adverse pregnancy outcomes. Moreover, periodontal treatment during pregnancy can cause bacteremia, which itself may initiate the pathway leading to the adverse pregnancy outcomes. Finally, the periodontal treatments provided during pregnancy are not always effective in preventing the progression of periodontal disease during pregnancy. Pregnancy may not be an appropriate period for periodontal intervention(s). We hypothesize that periodontal treatment before pregnancy may reduce the rates of adverse pregnancy outcomes. Future randomized controlled trials are needed to test if treating periodontal disease in the prepregnancy period reduces the rate of adverse pregnancy outcomes.

Screening and Management of Bacterial Vaginosis in Pregnancy

ObjectiveTo review the evidence and provide recommendations on screening for and management of bacterial vaginosis in pregnancy. OptionsThe clinical practice options considered in formulating the guideline. OutcomesOutcomes evaluated include antibiotic treatment efficacy and cure rates, and the influence of the treatment of bacterial vaginosis on the rates of adverse pregnancy outcomes such as preterm labour and delivery and preterm premature rupture of membranes. EvidenceMedline, EMBASE, CINAHL, and Cochrane databases were searched for articles, published in English before the end of June 2007 on the topic of bacterial vaginosis in pregnancy. ValuesThe evidence obtained was rated using the criteria developed by the Canadian Task Force on Preventive Health Care. Benefits, Harms, and CostsGuideline implementation will assist the practitioner in developing an approach to the diagnosis and treatment of bacterial vaginosis in pregnant women. Patients will benefit from appropriate management of this condition. ValidationThese guidelines have been prepared by the Infectious Diseases Committee of the SOGC, and approved by the Executive and Council of the SOGC. SponsorsThe Society of Obstetricians and Gynaecologists of Canada. RecommendationsThere is currently no consensus as to whether to screen for or treat bacterial vaginosis in the general pregnant population in order to prevent adverse outcomes, such as preterm birth.1.In symptomatic pregnant women, testing for and treatment of bacterial vaginosis is recommended for symptom resolution. Diagnostic criteria are the same for pregnant and non-pregnant women. (I-A)2.Treatment with either oral or vaginal antibiotics is acceptable for achieving a cure in pregnant women with symptomatic bacterial vaginosis who are at low risk of adverse obstetric outcomes. (I-A)3.Asymptomatic women and women without identified risk factors for preterm birth should not undergo routine screening for or treatment of bacterial vaginosis. (I-B)4.Women at increased risk for preterm birth may benefit from routine screening for and treatment of bacterial vaginosis. (I-B)5.If treatment for the prevention of adverse pregnancy outcomes is undertaken, it should be with metronidazole 500mg orally twice daily for seven days or clindamycin 300mg orally twice daily for seven days. Topical (vaginal) therapy is not recommended for this indication. (I-B)6.Testing should be repeated one month after treatment to ensure that cure was achieved. (III-L)

Psychosocial Stress and Pregnancy Outcome

This article is intended to help clinicians better understand the ever-expanding body of research on whether psychosocial stress (both acute and chronic) is linked to 2 major adverse pregnancy outcomes: preterm birth and low birth weight. We summarize the existing literature and then review assessment tools commonly used to diagnose various types of psychosocial stress, with attention to how and when assessments should be made. After discussing the physiologic mechanisms hypothesized to underlie these relationships, we examine the range of existing interventions aimed at reducing psychosocial stress and review their efficacy at improving birth outcomes. Future directions for prevention of adverse pregnancy outcomes are discussed and suggest that an entirely new approach may be necessary.

Micronutrients in women’s health and immune function

Lawrence J. Machlin’s contributions to elucidating the roles of nutrients in optimizing human health included the support of research in the areas of women’s health and immune function. Several essential nutrients have been shown to affect women’s health throughout the different life stages. Symptoms of premenstrual syndrome affect the vast majority of menstruating women, and calcium supplementation significantly reduces physical and emotional symptoms. Premenstrual syndrome in fact might be a predictor of osteoporosis induced by low calcium intake. Periconceptional multivitamin supplementation has reduced the risk of serious birth defects, premature delivery, and low birth weight by 50% and improved maternal health during pregnancy. Micronutrients of particular importance for prevention of adverse pregnancy outcomes are folic acid, zinc, and iron. However, if the preterm delivery is caused by preeclampsia, then data suggest that calcium supplementation and high doses of vitamins C and E significantly reduce that risk. Well-controlled studies consistently have shown that calcium supplementation, with or without vitamin D, significantly reduces the risk of hip fracture. Antioxidants such as vitamins C and E have been shown to reduce the risk of fracture in women smokers. As in the rapidly growing embryo, the immune system includes rapidly multiplying cells whose functions are dramatically affected by an individual’s micronutrient status. Multivitamins have been shown to enhance many aspects of immune response, and antioxidant micronutrients consistently have been found to enhance lymphocyte-proliferative responses and skin-test responses, especially in the elderly.

Genital tract infections and perinatal transmission of HIV.

In areas of the world where genital tract infections (GTIs) are common, the prevalence of HIV and the rate of mother-to-child transmission (MTCT) of HIV are also high. Although observational studies suggested that GTIs are associated with MTCT of HIV, no controlled clinical trial has confirmed this finding. It is likely that GTIs that cause either discharges or ulcers during pregnancy increase perinatal transmission of HIV. Several potential biological mechanisms might facilitate perinatal transmission. For example, chorioamnionitis, increased viral shedding in cervicovaginal secretions, increased HIV acquisition during pregnancy, inflammatory cytokine production, preterm labor, prolonged rupture of membranes, ascending infection, and increased intrapartum infectious secretions are factors that can be associated with GTIs. Several studies have shown that treating clinical conditions associated with inflammation might alter HIV shedding. It is conceivable that preventing ascending infection or reducing exposure of the infant to infectious material during birth could reduce MTCT. This can possibly be achieved by antimicrobial therapy during pregnancy and intrapartum. Such an approach is practical, is less expensive, and has secondary benefits related to prevention of adverse pregnancy outcomes associated with GTIs. Antibiotics might also complement reductions in MTCT of HIV obtained by antiretrovirals given to the mother around the time of delivery. In addition, antibiotics could reduce infectious causes of morbidity and mortality in infant and mother.

The immunobiology and obstetrical consequences of antiphospholipid antibodies.

Two classes of antiphospholipid antibodies (APA) are associated with adverse pregnancy outcomes. Those APA identified by immunoassays using phospholipid-coated surfaces (e.g., anticardiolipin antibodies) seem to bind to the 57 kD anticoagulant protein, beta 2-glycoprotein-I, when complexed with anionic phospholipid bilayers. Such APA may or may not prolong phospholipid-dependent clotting assays. A second class of APA are identified by their interference with phospholipid-dependent clotting assays (i.e., lupus anticoagulants). The latter bind to phospholipids present in a unique hexagonal phase either alone or complexed with prothrombin or beta 2-glycoprotein-I. There is evidence that both classes of APA are directly responsible for adverse pregnancy outcomes including spontaneous abortions, stillbirths, fetal growth retardation, thrombosis, thrombocytopenia, and preeclampsia. Putative APA-mediated pathogenic mechanisms include intervillous thrombosis, intravillous infarctions and decidual vasculopathy. The thrombogenicity of APA may result from their interference with endothelial phospholipids required for antithrombin III and protein C and S anticoagulant activity and prostacyclin synthesis and/or increased endothelial expression of the procoagulants: tissue factor, von Willebrand factor, platelet-activating factor, and plasminogen activator inhibitor type-1. Other prothrombotic properties seem to include: increased platelet aggregation, and reduced beta 2-glycoprotein-1 and annexin V anticoagulant activity. Rigorous diagnostic criteria must be applied to the detection of both classes of APA because the prevention of adverse pregnancy outcomes requires potentially hazardous anticoagulant therapy.