Preeclampsia As Modulator of Offspring Health (original) (raw)
Reproductive Sciences, 2007
Development of the National Institutes of Health sponsored a 2-day workshop titled "Preeclampsia-A Pressing Problem." The purpose of the workshop was to bring together leaders in the field to present and discuss their diverse research areas, which ranged from basic science to clinical trials and management, and to identify scientific gaps. This article is a summary of the proceedings of that workshop. Although much progress is being made in understanding the underpinnings of preeclampsia, a number of research gaps are identified that, if filled, would hasten progress in the field. It is the overall consensus that preeclampsia is a multifactorial disease whose pathogenesis is not solely vascular, genetic, immunologic, or environmental but a complex combination of factors. In addition, a number of specific scientific gaps are identified including insufficient multidisciplinary and collaborative research, clinical trials and studies of patient management, and a lack of in-depth mechanistic research. The research community needs to focus on these gaps to better understand the disease, with the ultimate goal of preventing the disorder.
Opinion article Preeclampsia and human reproduction. An essay of a long term reflection
2003
Gestational hypertension/preeclampsia, is a major disease of human reproduction, with 10% of human births being affected. It is due to the failure of extravillous cytotrophoblast to invade the maternal uterine spiral arteries to a sufficient depth at the second physiological invasion around the 14-16th week of gestation, inducing poor vascular exchanges between the mother and the placenta. The rise of blood pressure in the human mother is then a compensatory mechanism to increase the exchanges and try to save the fetus from poor supplies. Indeed, it is only in the late 1970s that a puzzling phenomenon has been described: in human pregnancy, in contrast with other mammals, implantation of the embryo occurs by two physiological invasions of the cytotrophoblast inside the uterine wall: (a) at the beginning of pregnancy after fecundation (like all mammals); (b) then follows an apparent long pause (6-8 weeks) and (c) late at the end of first trimester (14-16th week) of gestation, a second very deep (1/3 of the uterine wall) invasion. This two-wave physiological endovascular trophoblast invasion represents a remarkable immunological placental-maternal interaction. Moreover, preeclampsia which has been considered as 'the disease of primigravidae' during all the XXth century may be in fact associated with new paternity especially in couples conceiving very shortly after the beginning of their sexual relationship. 'Primipaternity', rather than primigravidity, is probably the leading cause of preeclampsia. Comprehension in the near future of the physiological immunological tolerance in normal pregnancies and immunological rejection (preeclampsia) of the second trophoblastic invasion will give the biological clue of this puzzling disease, real plague of human reproduction.
Preeclampsia: Pathophysiology and management
Journal of Gynecology Obstetrics and Human Reproduction, 2020
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Pre-eclampsia has an adverse impact on maternal and fetal health
Translational Research, 2015
Pre-eclampsia (preE) is a multifaceted complication found uniquely in the pregnant patient and one that has puzzled scientists for years. PreE is not a single disorder, but a complex syndrome that is produced by various pathophysiological triggers and mechanisms affecting about 5% of obstetrical patients. PreE is a major cause of premature delivery and maternal and fetal morbidity and mortality. PreE is characterized by de novo development of hypertension and proteinuria after 20 weeks of gestation and affects nearly every organ system, with the most severe consequences being eclampsia, pulmonary edema, intrauterine growth restriction, and thrombocytopenia. PreE alters the intrauterine environment by modulating the pattern of hormonal signals and activating the detrimental cellular signaling that has been transported to the fetus. The fetus has to adapt to this intrauterine environment with detrimental signals. The adaptive changes increase the risk of disease later in life. This review defines the predisposition and causes of preE and the cellular signaling detrimental to maternal health during preE. Moreover, the risk factors for diseases that are transmitted to the offspring have been addressed in this review. The detrimental signaling molecules that have been overexpressed in preE patients raises the possibility that those signals could be therapeutically blocked one day.
Journal of Reproductive Immunology
The 11th workshop on Immunology of preeclampsia in Reunion 2018 celebrated its 20th candle In this paper we try to summarize the main tracks of reflections during these two decades. First, of course, the advances in immunology of reproduction in the field of preeclampsia, which was poorly developed 2 decades ago when we first started in 1998. But, this workshop has not been dedicated only to immunology. Second, one of the main reflections has always been, workshop after workshop: "why does preeclampsia exists in humans?" in an evolutionary view, as we have no established natural animal models in the other some 4500 other mammal species. Third, besides the reflections on the biological plausibility of preeclampsia-disease-of-first-pregnancies-at-a-level-of-a-couple (primipaternity rather than primigravidity), i.e. immunology, paternal-maternal conflict, we had to face an apparent conundrum: the human species should have disappeared (almost 40-50% incidence of hypertensive disorders of pregnancy in couples conceiving within the first 4 months of sexual cohabitation). We report then the dialogues we were obliged to have with zoologists who themselves had no clues on our apparent "extravagant sexuality" and strange reproduction (ridiculous low fertility rate of the human female: 25%). Fourth, debates on the main difference between early onset ("rather immunological") and late onset PE ("rather maternal vascular predispositions"). Further, the debate of why high income countries report 90% of their PE being LOP, while other countries describe epidemiologically very high incidences of EOP. Finally, and always present at all workshops, the physiopathology of the reversible systemic maternal vascular inflammation.
Journal of reproductive immunology, 2015
This workshop had four main objectives: (A) Trying to look at the preeclampsia (PE) problem "from the Space Shuttle": why preeclampsia has emerged in humans (a specific human reproductive feature among 4300 mammal species)? (B) Epidemiology: there are major geographical differences concerning early onset PE and late onset PE throughout the world. (C) Vascular: The very promising use of pravastatin in the treatment of the vascular maternal syndrome (based on the metabolism of carbon monoxide (CO), the role of inositol phosphate glycans P-type (IPG-P), a major role in comprehending the insulin resistance phenotype in preeclampsia. (D) Immunology: the specialty of these workshops since their start in 1998; our understanding of the role of the immune system and the regulation of the deep implantation of the human trophoblast (and the obligatory compromises between the fetal/placental unit and the mother) have reached a kind of "maturity," following the pivotal studie...
Chinese Medical Journal, 2018
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Preeclampsia: Still a Disease of Theories
Donald School Journal of Ultrasound in Obstetrics and Gynecology
Preeclampsia is one of the causes of increased maternal morbidity and mortality of the fetus or newborn. 1-13 Historically the triad of hypertension, proteinuria, and edema was considered preeclampsia, but we stress that the definition does not require the presence of proteinuria to meet the diagnostic criteria. The inclusion of fetal growth restriction in this definition may increase the number of women who meet the diagnostic criteria for preeclampsia and therefore represents a significant change, compared to the previous historical definition. The aim of the paper is to present the characteristics of pregnant women presenting with different types of preeclampsia, with an overview of the pathophysiological mechanism.
Preeclampsia: Effect on the Fetus and Newborn
NeoReviews, 2011
Preeclampsia (PE) is the most common medical complication in pregnancy and a major cause of maternal and fetal morbidity and mortality. This disease is a great challenge for obstetricians because there are no effective interventions to treat or prevent it, and antenatal care involves a difficult balance between the risks for women to continue pregnancy and the risks for the baby's early birth. Fetal complications in PE are directly related to gestational age and the severity of maternal disease and include increased rates of preterm delivery, intrauterine growth restriction, placental abruption, and perinatal death. The major complications for the newborn are related to prematurity, although the data on the morbidity and outcome for preterm infants of women who have PE are conflicting, and few studies address this issue. The pathogenesis of PE involves abnormal placentation associated with immune and vascular events that result in endothelial dysfunction and clinical manifestations of PE. This disease has been associated with imbalance in angiogenic factors and oxidative stress. Nevertheless, only a limited number of studies have been carried out on fetuses and newborns that suggest that infants born from women
Review Article, 2023
Preeclampsia is a pregnant hypertension condition. It has a significant negative impact on maternal and perinatal health and affects 2-8% of pregnancies worldwide. The disease's main features are hypertension and proteinuria, though systemic organ damage could follow. The aberrant placentation that precedes the release of antiangiogenic markers, which is predominantly mediated by soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin, is the first sign of the clinical condition.(sEng). Every maternal organ system, including the fetus, may be adversely affected by high levels of sFlt-1 and sEng due to endothelial dysfunction, vasoconstriction, and immunological dysregulation. With an emphasis on the mechanisms underlying the clinical symptoms, this article thoroughly investigates the pathogenesis of preeclampsia. The only permanent remedy is delivery. In high-risk populations, low-dose aspirin is advised for prophylaxis. There are few other therapy alternatives. The pathophysiology of this common disease has to be clarified in order to find possible therapeutic targets for better treatment and, ultimately, outcomes. The three most common causes of maternal morbidity and mortality worldwide are preeclampsia and eclampsia. Rates of eclampsia, maternal mortality, and maternal morbidity in wealthy nations have significantly decreased during the past 50 years. In contrast, maternal mortality, problems during pregnancy, and eclampsia rates are still high in developing nations. In industrialised nations, preeclampsia-eclampsia patients are properly managed, and prenatal care is widely accessible. These discrepancies are mostly attributable to these factors.
Interest in preeclampsia for researchers in reproduction
Journal of Reproductive Immunology, 2002
Gestational hypertension/preeclampsia, is a major disease of human reproduction, with 10% of human births being affected. It is due to the failure of extravillous cytotrophoblast to invade the maternal uterine spiral arteries to a sufficient depth at the second physiological invasion around the 14-16th week of gestation, inducing poor vascular exchanges between the mother and the placenta. The rise of blood pressure in the human mother is then a compensatory mechanism to increase the exchanges and try to save the fetus from poor supplies. Indeed, it is only in the late 1970s that a puzzling phenomenon has been described: in human pregnancy, in contrast with other mammals, implantation of the embryo occurs by two physiological invasions of the cytotrophoblast inside the uterine wall: (a) at the beginning of pregnancy after fecundation (like all mammals); (b) then follows an apparent long pause (6-8 weeks) and (c) late at the end of first trimester (14-16th week) of gestation, a second very deep (1/3 of the uterine wall) invasion. This two-wave physiological endovascular trophoblast invasion represents a remarkable immunological placental-maternal interaction. Moreover, preeclampsia which has been considered as 'the disease of primigravidae' during all the XXth century may be in fact associated with new paternity especially in couples conceiving very shortly after the beginning of their sexual relationship. 'Primipaternity', rather than primigravidity, is probably the leading cause of preeclampsia. Comprehension in the near future of the physiological immunological tolerance in normal pregnancies and immunological rejection (preeclampsia) of the second trophoblastic invasion will give the biological clue of this puzzling disease, real plague of human reproduction.
Preeclampsia: a view through the danger model
Journal of Reproductive Immunology, 2007
Classical thinking suggests that the immune system undergoes activation on the basis of discrimination between 'self' and 'non-self'. Accordingly, the fetus activates the mother's immune system because the fetus is in part 'non-self'. Thus, successful pregnancy depends on constraint of maternal immunity. Preeclampsia is an outcome of lost constraint. Instead, the danger model suggests that normal pregnancy, regardless of the expression of 'non-self' antigens, does not activate the maternal immune system unless that pregnancy expresses danger signals. Thus, preeclampsia stems from stress or abnormal cell death in pregnancy-related tissues. This compels expression of specific danger signals and potential activation of anti-fetal immunity, which secondarily feeds the syndrome. Study of preeclampsia from this perspective may bring forth novel mechanisms and indicators of vascular and metabolic dysfunction during pregnancy.
Pregnancy Hypertension, 2018
Introduction: Preeclampsia is a leading cause of maternal and fetal morbidity and mortality. Regarding the offspring, little is known about the long-term complications. The objective of the current study is to assess whether in utero exposure to preeclampsia increases the risk of long-term cardiovascular morbidity in the offspring. Materials and methods: A population-based cohort study compared the incidence of cardiovascular disease between singletons exposed and unexposed to preeclampsia. Deliveries occurred between 1991 and 2014 in a regional tertiary medical center. A Cox proportional hazard model was used to control for confounders. Results: During the study period 231,298 deliveries met the inclusion criteria; 4.1% of the births were to mothers diagnosed with preeclampsia, of which 3.2% with mild preeclampsia (n = 7286), 0.9% with severe preeclampsia (n = 2174) and 0.03% with eclampsia (n = 73). A significant linear association was noted between preeclampsia (no preeclampsia, mild preeclampsia, severe preeclampsia and eclampsia) and cardiovascular disease of the offspring (0.24%, vs. 0.33% vs. 0.51% vs. 2.73% respectively, p < 0.001 using the chi-square test for trends). In the offspring born at term, severe preeclampsia was found to be an independent risk factor for cardiovascular morbidity (adjusted HR = 2.32; 95% CI 1.15-4.67). In offspring born preterm, neither severe preeclampsia (adjusted HR = 1.36; 95% CI 0.53-3.48) nor mild preeclampsia (adjusted HR = 0.37; 95% CI 0.52-2.71) were associated with cardiovascular morbidity of the offspring. Conclusion: Exposure to severe maternal preeclampsia is an independent risk factor for long-term cardiovascular morbidity in the offspring born at term.