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Intrauterine growth restriction (IUGR) affects 10-15% of all pregnancies worldwide. IUGR may result from maternal, placental or fetal origin. Maternal malnutrition before and during pregnancy represents the most prevalent non-genetic or placental cause. IUGR reflects an abnormal adaptive fetal growth in a deleterious environment. Individuals born after IUGR are more susceptible to develop diseases related to subsequent stressors through a lifetime. Animal models help to decipher the underlying causes of dysregulated pathways and molecular modifications conditioning health and disease in adult offspring born after IUGR. The aim of this review is to summarize current knowledge on long term consequences of IUGR, integrating animal models and human studies for a better care of IUGR-born individuals in a life course perspective.

Infants born after intrauterine growth restriction (IUGR) are at risk of developing arterial hypertension at adulthood. The endothelium plays a major role in the pathogenesis of hypertension. Endothelial colony-forming cells (ECFCs), critical circulating components of the endothelium, are involved in vasculo-and angiogenesis and in endothelium repair. We previously described impaired functionality of ECFCs in cord blood of low-birth-weight newborns. However, whether early ECFC alterations persist thereafter and could be associated with hypertension in individuals born after IUGR remains unknown. A rat model of IUGR was induced by a maternal low-protein diet during gestation versus a control (CTRL) diet. In six-month-old offspring, only IUGR males have increased systolic blood pressure (tail-cuff plethysmography) and microvascular rarefaction (immunofluorescence). ECFCs isolated from bone marrow of IUGR versus CTRL males displayed a decreased proportion of CD31+ versus CD146+ staining on CD45− cells, CD34 expression (flow cytometry, immunofluorescence), reduced proliferation (BrdU incorporation), and an impaired capacity to form capillary-like structures (Matrigel test), associated with an impaired angiogenic profile (immunofluorescence). These dysfunctions were associated with oxidative stress (increased superoxide anion levels (fluorescent dye), decreased superoxide dismutase protein expression, increased DNA damage (immunofluorescence), and stress-induced premature senescence (SIPS, increased beta-galactosidase activity, increased p16INK4a, and decreased sirtuin-1 protein expression). This study demonstrated an impaired functionality of ECFCs at adulthood associated with arterial hypertension in individuals born after IUGR.

Metabolic syndrome (MetS) is a cluster of several disorders, such as hypertension, central obesity, dyslipidemia, hyperglycemia, insulin resistance and non-alcoholic fatty liver disease. Despite health policies based on the promotion of physical exercise, the reduction of calorie intake and the consumption of healthy food, there is still a global rise in the incidence and prevalence of MetS in the world. This phenomenon can partly be explained by the fact that adverse events in the perinatal period can increase the susceptibility to develop cardiometabolic diseases in adulthood. Individuals born after intrauterine growth restriction (IUGR) are particularly at risk of developing cardiovascular diseases (CVD) and metabolic disorders later in life. It has been shown that alterations in the structural and functional integrity of the endothelium can lead to the development of cardiometabolic diseases. The endothelial progenitor cells (EPCs) are circulating components of the endothelium playing a major role in vascular homeostasis. An association has been found between the maintenance of endothelial structure and function by EPCs and their ability to differentiate and repair damaged endothelial tissue. In this narrative review, we explore the alterations of EPCs observed in individuals with cardiometabolic disorders, describe some mechanisms related to such dysfunction and propose some therapeutical approaches to reverse the EPCs dysfunction.

Children's food allergies are a significant public health burden in industrialized countries. Their prevalence is also increasing in developing countries, reflecting the impact of modern globalized food that challenges humanity to adapt to unprecedented allergenic stress. The understanding of the multiple mechanisms involved in the emergence of these allergies has greatly improved over the past two decades. On the therapeutic level, the eviction regime has shown its limitations and risks in growing individuals. Personalized nutrition represents a promising field of investigation in therapeutic innovations.Les allergies alimentaires de l’enfant sont un fardeau de santé publique important dans les pays industrialisés. Leur prévalence augmente également dans les pays en croissance, témoignant de l’impact d’une alimentation moderne globalisée qui met l’humanité au défi de s’adapter à un stress allergénique inédit. La compréhension des multiples mécanismes impliqués dans l’émergence de ces allergies a largement progressé depuis deux décennies. Sur le plan thérapeutique, le régime d’éviction a montré ses limites et ses risques chez des individus en croissance. La nutrition personnalisée représente un champ d’investigations, prometteur en innovations thérapeutiques.

Early malnutrition, the first environmental cause of intra-uterine growth restriction, impairs development of the thymus. Alterations of the thymic structure and function are reported at young ages in murine and ovine models. However, descriptions of thymic consequences of fetal malnutrition at adulthood are scarce. The present study investigates thymic structure, protein expression and cell selection process observed at postnatal day 180 (PND180) in male offspring of rats exposed to maternal low-protein diet (mLPD) compared with control diet during gestation. The thymic index was lower in adult offspring exposed to mLPD (P P β receptor (P P P P

A previously healthy 9-year-old boy presented with a history of fatigue for 3 weeks, pain in both calves for 2 days, and a mild cough, without fever. His medical history was negative and vaccinations were up to date. Examination by his pediatrician only showed decreased deep tendon reflexes (DTR) in both lower limbs. Blood count (white blood cells [WBC] 5.4 G/L, hemoglobin [Hb] 138 g/L, thrombocytes [Tc] 251 G/L), thyroid-stimulating hormone (1.76 mU/L), creatine kinase (CK) level (104 U/L), and erythrocyte sedimentation rate (3 mm/h) were all normal. Epstein-Barr virus monotest was negative and blood serology suggested a past infection.

The continuing rise in the global prevalence of diabetes and overweight or obesity has become a major burden for global health, as the pandemic is affecting both high and low-middle income countries (LMIC). At the same time, a similar pattern has been observed for all forms of hyperglycemia in pregnancy (HIP), diabetes during pregnancy and gestational diabetes. The offspring of mothers with HIP and/or overweight-obesity is receiving increasing attention as advances in early detection and treatment of HIP did not completely prevent macrosomia and its associated short-term perinatal disorders, whilst long term consequences are observed in the mother and in offspring as it reaches adulthood. This review discusses the current developments in the consequences of HIP in the offspring, with a particular focus on its long-term health at adulthood, and on intergenerational and transgenerational effects. HIP is emerging as one of the factors that can contribute, during the window of sensitivity to environmental cues constituted by the preconception, pregnancy, and early childhood, and as an amplifying factor linked to reproduction, to the current global epidemic of diabetes and non-communicable diseases (NCDs).

International audience; Impaired early nutrition influences the risk of developing metabolic disorders in later life. We observed that transient postnatal overfeeding (OF) in mice induces long-term hepatic alterations, characterized by microsteatosis, fibrosis associated with oxidative stress (OS), and stress-induced premature senescence (SIPS). In this study, we investigated whether such changes can be reversed by moderate calorie restriction (CR). C57BL/6 male mice pups were maintained during lactation in litters adjusted to nine pups in the normal feeding (NF) group and three pups in the transient postnatal OF group. At six months of age, adult mice from the NF and OF groups were randomly assigned to an ad libitum diet or CR (daily energy supply reduced by 20%) for one month. In each group, at the age of seven months, analysis of liver structure, liver markers of OS (superoxide anion, antioxidant defenses), and SIPS (lipofuscin, p53, p21, p16, pRb/Rb, Acp53, sirtuin-1) were performed. CR in the OF group reduced microsteatosis, decreased levels of superoxide anion, and increased protein expression of catalase and superoxide dismutase. Moreover, CR decreased lipofuscin staining, p21, p53, Acp53, and p16 but increased pRb/Rb and sirtuin-1 protein expression. CR did not affect the NF group. These results suggest that CR reduces hepatic disorders induced by OF.

The adolescent's painful functional disorders deserve management by a specialized interdisciplinary team. In recent years, intensive interdisciplinary physical therapy (IIPT) programs have developed in a hospital environment in Europe and around the world. While the short-term objective is often to restore trust between the patient and the therapists by relieving parents of the need to coordinate a network of multidisciplinary practitioners. These programs have proven to be effective in the medium and long term in improving the patient's clinical performance and for the benefits associated with restoring normal life for the family. Finally, these programs can have a positive impact in a cost-benefit approach when considering these often long and complex care arrangements.Les troubles fonctionnels douloureux chroniques de l’adolescent méritent une prise en charge interdisciplinaire spécialisée. Depuis quelques années, des programmes de thérapie physique intensive interdisciplinaire (intensive interdisciplinary physical therapy, IIPT) se sont développés dans un environnement hospitalier en Europe et dans le monde. Si l’objectif à court terme est souvent de remettre les patients en mouvement, un autre objectif est de restaurer une confiance entre le patient et les professionnels de la santé en soulageant notamment les parents de la coordination d’un réseau de praticiens multidisciplinaires. Ces programmes ont montré leur efficacité à moyen et long termes sur l’amélioration clinique du patient et sur les bénéfices associés à la reprise d’une vie normale pour la famille. Enfin, ces programmes peuvent avoir un impact positif en termes de coût/bénéfice dans ces prises en charge souvent longues et complexes.

Intrauterine growth restriction (IUGR) has been identified as a risk factor for adult chronic kidney disease (CKD), including hypertension (HTN). Accelerated postnatal catch-up growth superimposed to IUGR has been shown to further increase the risk of CKD and HTN. Although the impact of excessive postnatal growth without previous IUGR is less clear, excessive postnatal overfeeding in experimental animals shows a strong impact on the risk of CKD and HTN in adulthood. On the other hand, food restriction in the postnatal period seems to have a protective effect on CKD programming. All these effects are mediated at least partially by the activation of the renin–angiotensin system, leptin and neuropeptide Y (NPY) signaling and profibrotic pathways. Early nutrition, especially in the postnatal period has a significant impact on the risk of CKD and HTN at adulthood and should receive specific attention in the prevention of CKD and HTN.

Epidemiological and experimental studies have shown that the peri-conception period, pregnancy, and infancy are windows of particular sensibility to environmental clues which influence lifelong trajectories across health and disease. Nutrition, stress, and toxins induce epigenetic marks that control long-term gene expression patterns and can be transmitted transgenerationally. Chronic diseases of adulthood such as hypertension, diabetes, and obesity thus have early, developmental origins in the perinatal period. The early epigenome, in interaction with other actors such as the microbiome, add powerful layers of diversity to the biological predisposition generated by the genome. Such “programming” is a normal, adaptive component of development, including in normal pregnancies and births. However, perinatal disease, either maternal (such as pre-eclampsia, ges­tational diabetes, or inflammatory disease) or fetal, and neonatal diseases (such as intrauterine growth restriction and preterm birth) are major conditions of altered programming, translated into an increased risk for chronic disease in these patients when they reach adulthood. Early prevention, optimal perinatal nutrition, and specific follow-up measures are key factors in the early preservation of long-term health.

Functional disorder during adolescence is a very complex problem too often limited to a psychological origin. Its pathogenesis remains unclear but it definitively associates individual and environmental factors. Recent data show anatomo-functional evidence of neural networks of the brain that is involved in pain and its psychological representation as well as the representation of pain in the body. We describe a holistic approach to manage functional disorders that include the family and promote adolescent centered care in order to reach a rapid and optimal rehabilitation.Le trouble fonctionnel de l’adolescent est une pathologie complexe trop souvent réduite à un abord exclusivement psychologique. Sa genèse est encore insuffisamment comprise, mais elle associe certainement des facteurs individuels et environnementaux. Les données récentes montrent qu’il existe un support anatomo-fonctionnel au sein des réseaux neuronaux cérébraux impliqués dans la douleur et sa représentation psychique et corporelle. A l’instar des réseaux neuronaux, il s’agit souvent aussi d’une difficulté de travailler en réseau interdisciplinaire. Nous proposons ici une approche holistique de ces troubles, incluant les familles et plaçant l’adolescent au centre d’une prise en charge qui vise une réhabilitation rapide.

International audience; Background and aims: The prevalence of obesity is increasing worldwide at an alarming rate. Altered early nutrition, in particular postnatal overfeeding (PNOF), is a risk factor for impaired cardiac function in adulthood. In the understanding of the initiation or progression of heart diseases, NLRP3 inflammasome and non-coding RNAs have been proposed as key players. In this context, the aim of this study was to decipher the role of NLRP3 inflammasome and its post transcriptional control by micro-RNAs in the regulation of cardiac metabolic function induced by PNOF in mice. Methods and results: Based on a model of mice exposed to PNOF through litter size reduction, we observed increased cardiac protein expression levels of NLRP3 and ETS-1 associated with alterations in insulin signaling. Additionally, miR-193b levels were down-regulated in the adult hearts of overfed animals. In a cardiomyocyte cell line, transfection with miR-193b induced down-regulation of ETS-1 and NLRP3 and improved insulin signaling. Conclusions: These findings suggest that the miR-193b could be involved in cardiac phenotypic changes observed in adulthood induced by PNOF likely through the regulation of ETS-1 and NLRP3 expression, and through this of insulin signaling.

Introduction Healthcare students should comply with the same vaccination recommendations as employed healthcare professionals. Vaccination coverage data for healthcare students are lacking Materials and methods This cross-sectional survey was carried out on medical, nursing and midwifery students in 15 hospitals of the Assistance Publique – Hopitaux de Paris with a maternity ward. All midwifery students were surveyed, and a subset of medical and nursing students were selected from 10 hospitals by three-stage random sampling. Data were collected by face-to-face interviews and verified from health records. Results A total of 432 students were included in the study (178 medical, 147 nursing, 107 midwifery), of whom 376 (87%) had proof of vaccination. The confirmed coverage for compulsory vaccinations was 96.9% for the booster dose of diphtheria–tetanus–poliomyelitis vaccine, 93.6% for BCG and 91.8% for at least three doses of hepatitis B. The coverage for recommended vaccinations confirmed by a vaccine booklet was 44% for pertussis (booster at 11–13 or 16–18 years of age), and 79.3% and 49.6% for the first and second doses of measles, respectively. The rate for influenza vaccination was 39.6%, based on self-reported information. Of the 27 students without any history of varicella infection, six had been vaccinated. Discussion Vaccination coverage of healthcare students is high for compulsory vaccinations, but largely insufficient for recommended vaccinations. Increased awareness regarding the required vaccinations is necessary in this population, as well as stronger enforcement prior to initiating clinical work.

Unbalanced nutrition early in life is increasingly recognized as an important factor in the development of chronic, non-communicable diseases at adulthood, including metabolic diseases. We aimed to determine whether transient postnatal overfeeding (OF) leads to liver stress-induced premature senescence (SIPS) of hepatocytes in association with liver structure and hepatic function alterations. Litters sizes of male C57BL/6 mice were adjusted to 9 pups (normal feeding, NF) or reduced to 3 pups during the lactation period to induce transient postnatal OF. Compared to the NF group, seven-month-old adult mice transiently overfed during the postnatal period were overweight and developed glucose intolerance and insulin resistance. Their livers showed microsteatosis and fibrosis, while hepatic insulin signaling and glucose transporter protein expressions were altered. Increased hepatic oxidative stress (OS) was observed, with increased superoxide anion production, glucose-6-phosphate dehydrogenase protein expression, oxidative DNA damage and decreased levels of antioxidant defense markers, such as superoxide dismutase and catalase proteins. Hepatocyte senescence was characterized by increased p21WAF, p53, Acp53, p16INK4a and decreased pRb/Rb and Sirtuin-1 (SIRT-1) protein expression levels. Transient postnatal OF induces liver OS at adulthood, associated with hepatocyte SIPS and alterations in liver structure and hepatic functions, which could be mediated by a SIRT-1 deficiency.

An association between viral infection and late-onset disease caused by group B Streptococcus (GBS), was systematically looked for in neonates hospitalized for fever during a 3 1/2 year period. Five neonates between 5 to 12.5 months of age presented with meningitis (2 cases) or with septicemia (3 cases) caused by GBS. Viral culture, immunofluorescence, and assay of IFNalpha in blood and cerebrospinal fluid were performed. A viral infection was proved in 4 cases and suspected in 1 case (rash and pharyngitis). We speculate that viral infection may provoke late-onset disease in colonized infants with GBS.

Author for correspondenceService des urgences pediatriques, Hopital d’enfants Armand Trousseau, 26, Avenue du Dr A Netter, 75012 Paris, France; and INSERM, UMR S149, UPMC Paris the immaturity of the nervous system in 06, Epidemiological Research on Perinatal Health and Women’s Health, Paris, France Tel.: +33 144 736 487 Fax: +33 144 737 479 ricardo.carbajal@ trs.aphp.fr

False-negative findings of polymerase chain reaction (PCR) for genuine pertussis as well as the numerous atypical forms of whooping cough make it difficult to diagnose this disease in young babies.For two years, real-time PCR was performed to test for Bordetella pertussis in 86 infants younger than 6 months hospitalized for apnea or paroxysmal and/or vomiting cough and in 205 of their household contacts, whether or not they coughed.Group 1 included 30 infants for whom PCR detected B. pertussis (25 of whom were also RSV+). PCR was also positive for at least one household contact in 25/30 families. This group included 16 babies with apnea and 12 who developed a whooping cough during follow-up. Group 2 comprised 12 infants whose PCR was negative while at least one household contact had positive results. Five of these infants had severe apnea and 6 developed a whooping cough. Group 3 included 44 infants (28 RSV +) for whom PCR was negative in the index case and in the household contacts: none developed a whooping cough during follow-up. Only 3 of the 54 positive household contacts had a paroxysmal cough or a typical whooping cough and 12 had no cough at all.Positive PCR in a household contact, symptomatic or not, is helpful for the diagnosis of atypical whooping cough in young infants.

To the Editor: A measles epidemic is currently occurring in several countries in Europe (1,2). Although most cases concern unvaccinated children and young adults, health care professionals (HCPs) are also affected. Cases occur mostly in unvaccinated persons, but also in those who have received a single dose of vaccine. In France, the measles vaccine was introduced in the childhood-immunization schedule in 1983. Current guidelines recommend 2 doses: one at 12 months of age and the second between 13 and 24 months of age. For persons born after 1992, one catch-up dose is recommended (3). Coverage by >1 dose, by the age of 2 years, remained at 83%–87% during 1997–2005. The latest figures show a slight increase to 90% in 2007 (4). The risk for measles in HCPs has been estimated as 13× higher than that for the general population (5) and is also higher among students (6). Vaccination against measles is recommended, not mandatory, for HCPs and health care students (HCSs) (medicine, nursing, and midwifery) who have no history of measles. The objective is to prevent transmission to a nonimmunized patient or another HCP, and from patients to susceptible HCPs. HCSs are in close and repeated contact with patients and therefore targeted by the recommendations. We conducted a cross-sectional survey in the university hospitals in Paris, France, to assess measles vaccination coverage in HCSs. The sampling frame included 15 hospitals with an obstetrics department. All midwifery students were selected. Other students were selected through a multistage random sampling. Sampling units were selected at each stage by simple random sampling. We selected 10 hospitals at the first stage, 10 clinical wards by hospital at the second stage, and all nursing students and half the medical students by ward at the third stage. A total of 116 students were required from each profession to estimate 50% coverage with 10% precision. Students gave oral informed consent. Information was collected by face-to-face interview. Vaccination-status was assessed from a document when available. Measles vaccination coverage was defined as the number of students with no history of measles who had received >1 dose of vaccine divided by the total number of students with no history of measles. The study was approved by the French Ethics Board and conducted from March 2009 through July 2009. Of the 106 selected wards, 10 could not be included (clearance from the head of department was not given). Of the 488 selected students, 432 were enrolled in the study (participation rate 88.5%); 178 (41%) were medical students, 147 (34%) nursing students, and 107 (25%) midwifery students. A document confirming the student's vaccination status was available for 376 (87%) students; 38 (10.1%) had a history of measles (removed from analysis). Median age was 22 years (interquartile range 21–24 years); 74% were female. Measles vaccination was cited by 61.5% (95% confidence interval [CI] 50.0%–71.9%) as a recommended vaccination. Measles vaccination coverage was 79.3% (95% CI 71.0%–75.8%) for >1 dose and 49.6% (95% CI 40.3%–59.1%) for 2 doses (Table). When considering only the students’ accounts (without written confirmation), 1- and 2-dose vaccination coverage was 93.3% (95% CI 88.0%–96.3%) and 83.6% (95% CI 68.0%–92.4%), respectively. In multivariate analysis, younger students (

Western Blots for the following proteins in the mouse kidney at weaning and adulthood: P-Rb, Rb, P16, P21, P53, Sirt1. Actin was used for for normalization. CTRL: control group. OF: overfeeding group.

Western Blots for the following proteins in the mouse kidney at weaning and adulthood: P-Rb, Rb, P16, P21, P53, Sirt1. Actin was used for for normalization. CTRL: control group. OF: overfeeding group.&nbsp