U Simeoni

University of Lausanne, Lausanne, Vaud, Switzerland

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Publications (157)329.84 Total impact

  • C. Yzydorczyk · D. Mitanchez · F. Boubred · U. Simeoni
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    ABSTRACT: In the 1980s, David Barker and his colleagues proposed that the major causes of cardiovascular mortality in industrialized countries may have their roots in early development. They notably observed an association between birth weight and coronary heart disease mortality rates later in life. Further epidemiological, clinical, and animal experimental studies have suggested that the time period that extends from conception through pregnancy to early infancy, also mentioned as the first 1000 days, is a critical window for the programming of lifelong health or disease. During this period, environmental stimuli potentially lead to physiological malprogramming determining final health outcomes. We review here how the early exposure to factors such as maternal undernutrition, glucocorticoids, placental insufficiency, maternal diabetes/obesity, preterm birth, oxidative stress, and epigenetic modifications can set the scene for later hypertension, obesity, and type 2 diabetes, features of the metabolic syndrome and other noncommunicable diseases.
    No preview · Chapter · Dec 2015
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    ABSTRACT: The survival of preterm babies has increased over the last few decades. However, disorders associated with preterm birth, known as oxygen radical diseases of neonatology, such as retinopathy, bronchopulmonary dysplasia, periventricular leukomalacia, and necrotizing enterocolitis are severe complications related to oxidative stress, which can be defined by an imbalance between oxidative reactive species production and antioxidant defenses. Oxidative stress causes lipid, protein, and DNA damage. Preterm infants have decreased antioxidant defenses in response to oxidative challenges, because the physiologic increase of antioxidant capacity occurs at the end of gestation in preparation for the transition to extrauterine life. Therefore, preterm infants are more sensitive to neonatal oxidative stress, notably when supplemental oxygen is being delivered. Furthermore, despite recent advances in the management of neonatal respiratory distress syndrome, controversies persist concerning the oxygenation saturation targets that should be used in caring for preterm babies. Identification of adequate biomarkers of oxidative stress in preterm infants such as 8-iso-prostaglandin F2α, and adduction of malondialdehyde to hemoglobin is important to promote specific therapeutic approaches. At present, no therapeutic strategy has been validated as prevention or treatment against oxidative stress. Breastfeeding should be considered as the main measure to improve the antioxidant status of preterm infants. In the last few years, melatonin has emerged as a protective molecule against oxidative stress, with antioxidant and free-radical scavenger roles, in experimental and preliminary human studies, giving hope that it can be used in preterm infants in the near future. Copyright © 2015 Elsevier Masson SAS. All rights reserved.
    No preview · Article · Jul 2015 · Archives de Pédiatrie
  • U. Simeoni · D. Haumont
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    ABSTRACT: Les naissances « à la limite de la viabilité » sont souvent considérées comme des situations extrêmes dans le champ médical et comme des situations emblématiques dans le débat sur l’excès thérapeutique, l’« obstination déraisonnable » mentionnée dans la loi française sur la fin de vie. Le contexte de ces situations est certainement spécifique, pour de multiples raisons naturelles, médicales, psychologiques et socio-économiques. Il a pu faire penser que des règles de portée collective, appuyées sur un poids de naissance ou une durée de grossesse limite, soient d’indispensables garde-fous pour les interventions ou abstentions médicales engageant la vie. Toutefois, tant les données scientifiques actuellement disponibles, qu’une réflexion éthique protégée de toute connotation symbolique ou phantasmatique liée au contexte, indiquent que le principe du respect du droit fondamental de l’enfant, fut-il extrêmement prématuré, à une prise en compte et des décisions individualisées, orientée vers son intérêt supérieur, s’applique dans ce domaine comme dans les autres domaines médicaux. Les dilemmes, parmi les plus complexes, soulevés par les interventions anténatales autour de la limite de viabilité, ne peuvent que bénéficier de ce principe de conduite.
    No preview · Article · Jun 2015
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    ABSTRACT: Method Data were obtained from the PMSI (medical Information system program) and the SNIIRAM (inter-regimens national system of information) of the French health insurance. All the childbirths and the terminations of pregnancy (TOP) after 22 weeks were selected. The mother’s diabetic status was determined by an algorithm based on the consumption of antidiabetics and hospitalisation diagnoses before and during the pregnancy. An identifier in the PMSI links mothers and children. Macrosomia was defined as a birth weight (BW) > 4 kg or > 90th percentile for gestational age. Results 806 579 childbirths /TOP > 22 weeks were identified in the PMSI. The motherchild chaining was obtained for 474 614 births. 16.7% of the newborn had BW >4 kg in type 1 diabetes (T1D), 13.4% in type 2 diabetes (T2D), 9.0% in GD, and 6.6% in the normal population. 42.5% (n = 354) of the newborn had a BW >90th percentile in T1D, 30.4% (n = 348) in T2D, 15.7% (n = 5096) in GD and 9.4% in the absence of diabetes. The OR compared with the absence of diabetes were respectively 7.0 [6.1–8.0], 3.9 [3.4–4.4] and 1.7 [1.6–1.8]. The median BW was significantly higher whatever the term of birth in cases of GD compared to the normal population. Conclusion the risk of macrosomia is the highest in case of T1D, but it remains in case of GD, although it is lower.
    Preview · Article · Oct 2014 · Archives of Disease in Childhood
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    ABSTRACT: Method Data were obtained from the PMSI (medical Information system program) and the SNIIRAM (inter-regimens national system of information) of the French health insurance. All the childbirths and the terminations of pregnancy (TOP) after 22 weeks were selected. The mother’s diabetic status was determined by an algorithm based on the consumption of anti diabetics and hospitalisation diagnoses before and during pregnancy. An identifier in the PMSI links mothers and children, thus enabling analyses of associations between the diabetic status and complications in neonates. Results 806 579 childbirths/TOP > 22 weeks were identified in the PMSI. Mother- child chaining was obtained for 474 614 births. In the case of type 1 and type 2 diabetes, the risk was respectively increased for the following complications (OR adjusted on mother age [95%CI]): perinatal death (2.2 [1.4–3.4] and 3.0 [2.2–4.1]), perinatal asphyxia (3.3 [2.2–5.1] and 2.5 [1.6–3.7]), respiratory distress syndrome (OR adjusted on mother age and gestational age: 2.6 [2.0–3.4] and 1.9 [1.5–2.5]), brachial plexus trauma and/or collarbone fractures in cases of vaginal delivery (8.5 [4.9–14.8] and 2.9 [1.5–5.9]), cardiac malformations (4.4 [3.0–6.5] and 3.2 [2.2–4.7]). In cases of GD, the risk was not increased for these complications compared to the population without diabetes, except for the respiratory distress syndrome (1.2 [1.1–1.3]). Conclusion The risk of severe perinatal complications remains high in case of pregestational diabetes.
    Preview · Article · Oct 2014 · Archives of Disease in Childhood
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    ABSTRACT: Recent studies have shown that a low birth weight is a risk factor for increased systemic blood pressure (BP) in adulthood. Further, systemic BP and arterial stiffness (AS) are reported to be increased in adolescents born prematurely. The purpose of this study was to characterize systemic BP and AS in young adults born preterm. Systemic BP was measured using an automated oscillometric device. AS was assessed by measuring the right carotid-radial pulse wave velocity (PWV) using a validated non-invasive automated method. Systemic BP, pulse pressure, and PWV [mean (confidence intervals)] were compared between 16 adults (age 21 years) born preterm (age at birth 32 weeks of gestation) with a birth weight (1710 g) appropriate for their gestational age and 15 adults (21 years) born at term (40 weeks of gestation) with a birth weight (3430 g) appropriate for their gestational age. Adults born preterm had a significantly higher systolic BP [122 mmHg (114-144) v. 112 (106-127)], mean BP [89 mmHg (86-98) v. 84 (81-91)], diastolic BP [69 mmHg (66-76) v. 65 (62-78)], pulse pressure [54 mmHg (47-72) v. 47 (42-60)], and PWV [7 m/s (6.3-8.6) v. 6.4 (5.8-8)] than did those born at term. Our findings suggest that young adults with a low birth weight due to preterm birth have increased systemic BP and AS. Accordingly, preterm birth may predispose individuals to cardiovascular diseases in adulthood due to increased AS.
    No preview · Article · Aug 2014 · Journal of Developmental Origins of Health and Disease
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    ABSTRACT: In the 1980s, David Barker and Colleagues proposed that the major causes of cardiovascular and metabolic diseases have their roots in early development. There is now robust evidence that an hyperglycemic intrauterine environment is responsible not only for significant short-term morbidity in the fetus and the neonate but also for an increased risk of developing diabetes as well as other chronic, noncommunicable diseases at adulthood. The risk is higher in pregestational diabetes, but unrecognized and/or poorly managed gestational diabetes (GDM) may have similar consequences. Although a relatively clear picture of the pathogenesis of the fetal and neonatal complications of maternal diabetes and of their interrelationship is available today, the intimate molecular mechanisms involved in the long term are far from being understood. While the rate of GDM is sharply increasing in association with the pandemic of obesity and of type 2 diabetes over the world, we review here the current understanding of short- and long-term outcomes of fetuses exposed to a diabetic environment.
    No preview · Article · Aug 2014 · Bailli&egrave re s Best Practice and Research in Clinical Obstetrics and Gynaecology
  • U Simeoni · G H A Visser · H L Halliday

    No preview · Article · Aug 2014 · Zeitschrift für Geburtshilfe und Neonatologie
  • M Saint-Faust · F Boubred · U Simeoni
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    ABSTRACT: The structural and functional development of the kidney is responsible for a significant impact on postnatal adaptation to extrauterine life. Prenatal or neonatal impairment of nephrogenesis may carry long term, lifelong consequences in terms of reduced nephron endowment, chronic kidney disease, and cardiovascular risks at adulthood. Intrauterine growth restriction, preterm birth, congenital renal, and urinary tract anomalies are for long widely incriminated. Neonatal administration of nephrotoxic drugs has been associated with short-term acute kidney injury and longer chronic kidney disease. This review attempts at offering a comprehensive understanding of the renal development, the neonatal renal transition to extrauterine life and subsequent maturation phase during early infancy. It also focuses on developmental and maturational changes that impact lifelong renal function and adult health.
    No preview · Article · Mar 2014 · American Journal of Perinatology
  • U. Simeoni
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    ABSTRACT: La prematuridad, un importante desafío de salud pública, afecta al 7-14% de los nacimientos en todo el mundo. Aunque los considerables adelantos técnicos y científicos han hecho posible la supervivencia de niños cada vez más inmaduros, los casos más frecuentes se refieren a la prematuridad tardía. En condiciones de gran prematuridad (antes de las 33 semanas de amenorrea), el nacimiento se programa en un centro de nivel 3 y la madre es trasladada en el período prenatal. La asistencia médica es perinatal y se inicia con la corticoterapia prenatal para acelerar la maduración fetal ante una amenaza de parto prematuro. La estabilización en la sala de parto está relativamente exenta de dificultades. Sin embargo, una serie de complicaciones posibles en la unidad de reanimación neonatal puede alterar la estancia hospitalaria, con una mortalidad y morbilidad que por lo general son proporcionales al grado de inmadurez. Los cuidados se orientan hoy hacia una conducta menos agresiva, centrada en el desarrollo del niño de forma personalizada y con la estrecha cooperación de los padres. La etapa posthospitalaria y el seguimiento a largo plazo son claves para la calidad de la vida futura de estos niños, algunos de los cuales están expuestos a trastornos del desarrollo psicomotor e incluso a una mayor incidencia de enfermedades no transmisibles del adulto como la hipertensión arterial y la diabetes de tipo 2.
    No preview · Article · Mar 2014
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    ABSTRACT: Cardiovascular diseases are one of the leading causes of mortality. Hypertension (HT) is one of the principal risk factors associated with death. Chronic kidney disease (CKD), which is probably underestimated, increases the risk and the severity of adverse cardiovascular events. It is now recognized that low birth weight is a risk factor for these diseases, and this relationship is amplified by a rapid catch-up growth or overfeeding during infancy or childhood. The pathophysiological and molecular mechanisms involved in the "early programming" of CKD are multiple and partially understood. It has been proposed that the developmental programming of arterial hypertension and chronic kidney disease is related to a reduced nephron endowment. However, this mechanism is still discussed. This review discusses the complex relationship between birth weight and nephron endowment and how early growth and nutrition influence long term HT and CKD. We hypothesize that fetal environment reduces moderately the nephron number which appears insufficient by itself to induce long term diseases. Reduced nephron number constitutes a "factor of vulnerability" when additional factors, in particular a rapid postnatal growth or overfeeding, promote the early onset of diseases through a complex combination of various pathophysiological pathways.
    Full-text · Article · Aug 2013 · International Journal of Nephrology
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    D. Mitanchez · U. Siméoni · B. Carbonne

    Full-text · Article · Dec 2012 · Revue de médecine périnatale
  • C. Grosse · U. Simeoni
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    ABSTRACT: Las posibilidades de la reanimación neonatal han permitido una disminución drástica de la mortalidad perinatal de los grandes prematuros nacidos antes de las 33 semanas de amenorrea en los últimos 15 años. Sin embargo, estos progresos no han permitido disminuir en las mismas proporciones las secuelas sobre el neurodesarrollo que presentan estos niños. En el período neonatal, los recién nacidos prematuros están expuestos a un riesgo de lesiones hemorrágicas, lesiones de la sustancia blanca y lesiones corticales o cerebelosas. En los recién nacidos prematuros, la sustancia blanca cerebral es especialmente sensible a los fenómenos de origen isquémico o inflamatorio. Un episodio isquémico o inflamatorio desencadenará una cascada biológica que consta de la liberación de citocinas proinflamatorias y de radicales libres. Estas moléculas tienen una acción tóxica sobre los precursores de los oligodendrocitos y pueden causar lesiones de necrosis focal o de astrogliosis difusa. Por otra parte, los recién nacidos prematuros tienen un riesgo especial de desarrollar hemorragias intraventriculares. La zona periventricular, donde se desarrollan los precursores neuronales, se caracteriza por una gran fragilidad vascular. Cualquier aumento súbito del flujo sanguíneo cerebral puede inducir una hemorragia a este nivel, que saldrá a la cavidad ventricular en una segunda fase. El diagnóstico de estas lesiones se basa en la ecografía transfontanelar (ETF) y la resonancia magnética (RM) cerebral. La ETF es la prueba de elección para el cribado de las lesiones hemorrágicas que se producen en la mayoría de los casos durante la primera semana. La RM cerebral es la prueba de referencia en el diagnóstico de las lesiones cerebrales asociadas a la prematuridad y las nuevas técnicas permiten una detección precoz y un análisis microestructural. La RM es una exploración clave para establecer el pronóstico neuromotor. Sin embargo, la ausencia de detección de lesiones cerebrales en el período neonatal no descarta la aparición de trastornos del desarrollo posterior. La comprensión de los mecanismos fisiopatológicos causantes de las lesiones cerebrales de la prematuridad es esencial para elaborar estrategias de neuroprotección.
    No preview · Article · Dec 2012
  • C. Grosse · U. Simeoni
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    ABSTRACT: El tratamiento de la hiperbilirrubinemia en el recién nacido prematuro sigue constituyendo un motivo importante de preocupación para el neonatólogo. En el recién nacido prematuro, la hiperbilirrubinemia es más frecuente y su evolución es más prolongada que en el recién nacido a término. La elevación de la bilirrubina se debe al aumento de la destrucción de eritrocitos en el período neonatal, así como a la inmadurez de los sistemas de depuración, en particular a nivel hepático. La bilirrubina no unida es tóxica para el sistema nervioso central, tanto más cuanto menor sea la edad gestacional o si existen enfermedades graves. La ictericia nuclear, complicación grave de la hiperbilirrubinemia, se debe a la toxicidad directa de la bilirrubina sobre el sistema nervioso central. Aunque la incidencia de esta complicación ha disminuido considerablemente, las preocupaciones persisten, ya que se han comunicado casos de ictericia nuclear con cifras bajas de bilirrubinemia en recién nacidos prematuros. La determinación de los niveles sanguíneos es el método de referencia, que debe repetirse en la detección precoz y cuando se instaura el tratamiento. Éste se basa en la fototerapia, que se establece en función de un umbral de bilirrubinemia que depende de la edad gestacional y de las enfermedades del niño. La utilización corriente de la fototerapia ha permitido limitar el recurso a la exanguinotransfusión, práctica no exenta de complicaciones, en particular en el recién nacido prematuro. La intervención sobre la hiperbilirrubinemia del recién nacido prematuro requiere un control cuidadoso, tanto en la evaluación del riesgo como en la instauración del tratamiento, con el fin de limitar el riesgo de complicaciones neurosensoriales posteriores.
    No preview · Article · Dec 2012
  • M. Saint-Faust · U. Simeoni
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    ABSTRACT: Incidence of gestational diabetes is increasing worldwide, which is a great global health concern. In utero exposure to increasing maternal blood concentrations is associated with early perinatal consequences, increased risk for diabetes and obesity during childhood, and cardiovascular diseases at adulthood. These adverse effects during early life have led to the concept of developmental “programming”. The “critical window of development” is the best opportunity for intervention and prevention, but also a way to consider the preconceptional period. Obstetricians and pediatricians have an increased concern about these vulnerable infants. This review aimed at emphasizes the short- and long term outcomes of children in offspring of maternal diabetes.
    No preview · Article · Sep 2012 · Médecine des Maladies Métaboliques
  • I Ligi · F Boubred · I Grandvuillemin · U Simeoni
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    ABSTRACT: The kidney is a major organ for drug elimination. The function of the neonatal kidney is markedly immature with a reduction of renal blood flow, of glomerular filtration and of active tubular secretion, even in healthy, term infants. Maturation of renal function in particular of glomerular filtration rate is gestational age and postnatal age-dependant. Moreover, many neonatal pathological conditions such as preterm birth, sepsis or perinatal asphyxia can also affect renal function. These developmental changes have a major impact on drug metabolism and elimination. Alterations in renal clearance can influence significantly both drugs efficacy and toxicity. Moreover, nephrogenesis is a still ongoing process in a number of premature infants before 36 wks postconceptional age. Drugs and toxic factors that may alter the constitution of the congenital nephron number endowment during this period may have long term consequences on arterial pressure and renal function at adulthood.
    No preview · Article · Aug 2012 · Current Drug Metabolism
  • C. Grosse · U. Simeoni

    No preview · Article · Jul 2012
  • C. Grosse · U. Simeoni

    No preview · Article · Jul 2012
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    ABSTRACT: Smooth muscle cells (SMCs) participate to the regulation of peripheral arterial resistance and blood pressure. To assume their function, SMCs differentiate throughout the normal vascular development from a synthetic phenotype towards a fully differentiated contractile phenotype by acquiring a repertoire of proteins involved in contraction. In human fetal muscular arteries and umbilical arteries (UAs), no data are available regarding the differentiation of SMCs during the last trimester of gestation. The objective of this study was to characterize the phenotype of SMCs during this gestation period in human UAs. We investigated the phenotype of SMCs in human UAs from very preterm (28-31 weeks of gestation), late preterm (32-35 weeks) and term (37-41 weeks) newborns using biochemical and immunohistochemical detection of α-actin, smooth muscle myosin heavy chain, smoothelin, and non-muscle myosin heavy chain. We found that the number of SMCs positive for smoothelin in UAs increased with gestational age. Western blot analysis revealed a higher content of smoothelin in term compared to very preterm UAs. These results show that SMCs in human UAs gradually acquire a fully differentiated contractile phenotype during the last trimester of gestation and thus that premature birth is associated with not fully differentiated contractile SMCs in human UAs.
    No preview · Article · Apr 2012 · Placenta

  • No preview · Article · May 2011 · Archives de Pédiatrie

Publication Stats

1k Citations
329.84 Total Impact Points

Institutions

  • 2014
    • University of Lausanne
      Lausanne, Vaud, Switzerland
    • University Hospital of Lausanne
      Lausanne, Vaud, Switzerland
  • 2009-2014
    • Aix-Marseille Université
      Marsiglia, Provence-Alpes-Côte d'Azur, France
    • Hôpital Européen, Marseille
      Marsiglia, Provence-Alpes-Côte d'Azur, France
  • 2004-2013
    • Assistance Publique Hôpitaux de Marseille
      Marsiglia, Provence-Alpes-Côte d'Azur, France
    • Unité Inserm U1077
      Caen, Lower Normandy, France
  • 2010
    • Centre Hospitalier Universitaire de Rennes
      Roazhon, Brittany, France
    • Assistance Publique – Hôpitaux de Paris
      Lutetia Parisorum, Île-de-France, France
  • 1993-2002
    • Hôpital Universitaire Necker
      • Service d’Anatomie-Pathologique
      Lutetia Parisorum, Île-de-France, France
  • 1993-2001
    • University of Strasbourg
      • • Faculty of Medicine
      • • Institut de Bactériologie
      Strasburg, Alsace, France
  • 1994
    • IHU de Strasbourg
      Strasburg, Alsace, France
  • 1992
    • CHRU de Strasbourg
      Strasburg, Alsace, France