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Low weight in early infancy is a known risk factor for cardio-metabolic syndrome in adult life. However, little is known either about developmental programming in subjects of normal birthweight or about events between the ages which separate early programming and the occurrence of disease at late adulthood. We tested the hypothesis that circulating concentrations of leptin, adiponectin and insulin in young, healthy adults, born with a birth size within the normal range, are influenced by early life growth patterns. In an observational study of 188 healthy volunteers aged 18–25 years (97 males, 91 females) we investigated the association of metabolic function with their birth size, their growth during childhood and their body composition. High plasma leptin in early adulthood, a risk factor for cardio-metabolic syndrome, was associated with low weight at age 2 years (correlation coefficient controlled for adult weight = −0.21, P P

International audience; ObjectiveTo determine whether neighbourhood socioeconomic status (SES) was associated with large for gestational age (LGA) while considering key sociodemographic and clinical confounding factors.Setting and patientAll singleton infants whose parents were living in the city of Marseilles, France, between 2013 and 2016.MethodPopulation-based study based on new-born hospital birth admission charts from the French National Uniform Hospital Discharge Data Set Database. LGA infants were compared to appropriate-for-gestational-age (AGA) infants. Multiple generalized logistic model analysis was used to examine factors associated with LGA.ResultsA total of 43,309 singleton infants were included, and 4,747 (11%) were born LGA. LGA infants were more likely to have metabolic and respiratory diseases and to be admitted to the neonatal intensive care unit. Multiparity, advanced maternal age, obesity and diabetes were associated with an increased risk of LGA. Lower neighbourhood SES was associated with LGA (aOR = 1.24, 95% CI: 1.14; 1.36; p 35 years old.ConclusionNeighbourhood SES could be considered an important factor for clinicians to better identify mothers at risk of having LGA births in addition to well-known risk factors such as maternal diabetes, obesity and age. The intensification of the association between SES and LGA with increasing maternal age suggests that neighbourhood disadvantage may act on LGA cumulatively over time.

Background: Cardiovascular and chronic kidney diseases are a part of non-communicable chronic diseases, the leading causes of premature death worldwide. They are recognized as having early origins through altered developmental programming, due to adverse environmental conditions during development. Preterm birth is such an adverse factor. Rates of preterm birth increased in the last decades, however, with the improvement in perinatal and neonatal care, a growing number of preterm born subjects has now entered adulthood. Clinical and experimental evidence suggests that preterm birth is associated with impaired or arrested structural or functional development of key or-gans/systems making preterm infants vulnerable to cardiovascular and chronic renal diseases at adult-hood. This review analyzes the evidence of such cardiovascular and renal changes, the role of perina-tal and neonatal factors such as antenatal steroids and potential pathogenic mechanisms, including de-velopmental programming and epigenetic alterations. Conclusion: Preterm born subjects are exposed to a significantly increased risk for altered cardio-vascular and renal functions at young adulthood. Adequate, specific follow-up measures remain to be determined. While antenatal steroids have considerably improved preterm birth outcomes, repeated therapy should be considered with caution, as antenatal steroids induce long-term cardio-vascular and metabolic alterations in animals’ models and their involvement in the accelerated cellular senescence observed in human studies cannot be excluded.

International audience; Objective To investigate the impact of neighborhood conditions on respiratory-related hospital admissions in the first year after discharge from the neonatal unit in a population of infants born very preterm with bronchopulmonary dysplasia (BPD).Study design Very preterm infants (gestational age

Individuals born after intrauterine growth restriction (IUGR) are at increased risk of developing cardiovascular diseases in adulthood, notably hypertension (HTN). Alterations in the vascular system, particularly impaired endothelium-dependent vasodilation, may play an important role in long-term effects of IUGR. Whether such vascular dysfunction precedes HTN has not been fully established in individuals born after IUGR. Moreover, the intimate mechanisms of altered endothelium-dependent vasodilation remain incompletely elucidated. We therefore investigated, using a rat model of IUGR, whether impaired endothelium-dependent relaxation precedes the development of HTN and whether key components of the l-arginine-nitric oxide (NO) pathway are involved in its pathogenesis. Pregnant rats were fed with a control (CTRL, 23% casein) or low-protein diet (LPD, 9% casein) to induce IUGR. Systolic blood pressure (SBP) was measured by tail-cuff plethysmography in 5- and 8-wk-old male offspring. Aortic rings were isolated to investigate relaxation to acetylcholine, NO production, endothelial NO synthase (eNOS) protein content, arginase activity, and superoxide anion production. SBP was not different at 5 wk but significantly increased in 8-wk-old offspring of maternal LPD (LP) versus CTRL offspring. In 5-wk-old LP versus CTRL males, endothelium-dependent vasorelaxation was significantly impaired but restored by preincubation with l-arginine or the arginase inhibitor S-(2-boronoethyl)-l-cysteine; NO production was significantly reduced but restored by l-arginine pretreatment; total eNOS protein, dimer-to-monomer ratio, and arginase activity were significantly increased; superoxide anion production was significantly enhanced but normalized by pretreatment with the NO synthase inhibitor Nω-nitro-l-arginine. In this model, IUGR leads to early-impaired endothelium-dependent vasorelaxation, resulting from arginase upregulation and eNOS uncoupling, which precedes the development of HTN.

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.

International audience; BACKGROUND: Intrauterine growth restriction (IUGR) and postnatal nutrition are risk factors for cardiovascular and renal diseases in both humans and animals. The long-term renal effects of protein intake early in life remain unknown. The objective was to evaluate the effects of a neonatal feeding with high protein (HP) milk on renal functions and structure in IUGR male rats. METHODS: Maternal gestational low protein diet was used to produce IUGR. At day 5, IUGR pups were gastrostomized in the "pup-in-the cup" model and received either normal protein (NP) milk or HP (+50% protein content) milk until day 21. After weaning, the animals were fed the same standard diet. Renal functions and structure were assessed at postnatal day 18 (D18) and in adult offspring. RESULTS: During the preweaning period, the postnatal weight gain between the two groups was unaffected. On D18, kidneys from HP offspring were heavier with significant glomerular hypertrophy (+40%, P < 0.05). HP diet was associated with significant proteinuria and glomerulosclerosis (+49%, P < 0.05). Glomerular number was unaltered. CONCLUSION: Neonatal HP feeding. following IUGR affects renal functions and structure at adulthood. These alterations may result from a single nephron glomerular hyperfiltration.

International audience; Neonatal hypoxic-ischemic encephalopathy (NHIE) is a dramatic perinatal complication, associated with poor neurological prognosis despite neuroprotection by therapeutic hypothermia, in the absence of an available curative therapy. We evaluated and compared ready-to-use human umbilical cord blood cells (HUCBC) and bankable but allogeneic endothelial progenitors (ECFC) as cell therapy candidate for NHIE. We compared benefits of HUCBC and ECFC transplantation 48 hours after injury in male rat NHIE model, based on the Rice-Vannucci approach. Based on behavioral tests, immune-histological assessment and metabolic imaging of brain perfusion using single pho-ton emission computed tomography (SPECT), HUCBC, or ECFC administration provided equally early and sustained functional benefits, up to 8 weeks after injury. These results were associated with total normalization of injured hemisphere cerebral blood flow assessed by SPECT/CT imaging. In conclusion, even if ECFC represent an efficient candidate, HUCBC autologous criteria and easier availability make them the ideal candidate for hypoxic-ischemic cell therapy. STEM CELLS TRANSLATIONAL Neonatal hypoxic ischemic encephalopathy is a dramatic perinatal complication. Neurological and neurosensory sequelae are frequent in survivors, including motor or learning disabilities, cerebral palsy, or epilepsy. Facing the absence of effective curative therapy, many hopes have been credited in cell therapy strategies. Based on behavioral tests, immune-histological assessment and metabolic imaging of brain perfusion using single photon emission computed tomog-raphy, we report in this work that cell transplantation of both human umbilical cord blood cells and endothelial progenitors provided equally early and sustained functional benefits, up to adulthood.

Objective Limiting early intubation and mechanical ventilation in extremely low gestational age neonates (ELGAN) may decrease neonatal morbidity and mortality. The aim of our study was to demonstrate the feasibility, efficacy, and tolerability of a delivery room respiratory management protocol, including delayed umbilical cord clamping (DUCC) in combination with optimized nCPAP with high PEEP levels and less invasive surfactant administration (LISA). Study Design This cohort quality improvement study analyzed the respiratory and neonatal outcomes of all consecutive infants born between 24+0 and 26+6 weeks' gestation before (period 1, n = 40) and after (period 2, n = 52) implementing the new protocol. Results Compared with the period 1 infants, the period 2 infants had a lower rate of intubation in the delivery room (31 vs. 90%, p = 0.001) and were less likely to need mechanical ventilation on day 3 (28 vs. 62%, p = 0.002) and during the hospital stay (75 vs. 92.5%, p Conclusion A delivery room respiratory management protocol based on DUCC, optimized nCPAP with high PEEP levels, and LISA procedure is both feasible and safe, and improved ELGAN respiratory outcomes.

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.

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.

Background: Intrauterine growth restriction (IUGR) is a risk factor for hypertension (HT) and chronic renal disease (CRD). A reduction in the nephron number is proposed to be the underlying mechanism; however, the mechanism is debated. The aim of this study was to demonstrate that IUGR-induced HT and CRD are linked to the magnitude of nephron number reduction, independently on its cause. Methods: Systolic blood pressure (SBP), glomerular filtration rate (GFR), proteinuria, nephron number, and glomerular sclerosis were compared between IUGR offspring prenatally exposed to a maternal low-protein diet (9% casein; LPD offspring) or maternal administration of betamethasone (from E17 to E19; BET offspring) and offspring with a normal birth weight (NBW offspring). Results: Both prenatal interventions led to IUGR and a similar reduction in birth weight. In comparison to NBW offspring, BET offspring had a severe nephron deficit (-50% in males and -40% in females, p < 0.01), an impaired GFR (-33%, p < 0.05), and HT (SBP+ 17 mmHg, p < 0.05). Glomerular sclerosis was more than twofold higher in BET offspring than in NBW offspring (p < 0.05). Long-term SBP, GFR, and glomerular sclerosis were unchanged in LPD offspring while the nephron number was moderately reduced only in males (-28% vs. NBW offspring, p < 0.05). Conclusion: In this study, the magnitude of nephron number reduction influences long term renal disease in IUGR offspring: a moderate nephron number is an insufficient factor. Extremely long-term follow-up of adults prenatally exposed to glucocorticoids are required.

The patency of the ductus arteriosus has ever been considered as a pathological situation in preterm infants and one likely cause of mortality and morbidity, including broncho-pulmonary dysplasia, necrotizing enterocolitis, intraventricular haemorrhage, retinopathy of prematurity. The incidence of patent ductus arteriosus is inversely proportional to gestational age and infants with the lowest gestational ages are the most exposed to the complications of prematurity. So, associations between patent ductus arteriosus and the other morbidities may not be causative and patent ductus arteriosus could be more a sign of immaturity and severity of disease than the cause of these problems. Non-steroidal anti-inflammatory agents, such as indomethacin or ibuprofen, have been shown to be effective in closing or preventing patent ductus arteriosus, with differences in side effects. However nearly all randomized controlled trials have been designed with the closure of the ductus arteriosus, not mortality or morbidity, as the main endpoint. Thus, evidence is still lacking on the eventual benefits for the patient of pharmacological or surgical intervention on PDA. Moreover, both ibuprofen and indomethacin efficacy seems markedly reduced in extremely low gestational age infants, who are the most likely to benefit from such intervention. The explanation of the reduced pharmacodymanic effect in such population is unclear; so far, studies using increased dosing of ibuprofen have failed to show a clear benefit. Prophylaxis with indomethacin or ibuprofen has failed to show sustained benefits on neurodevelopment at 2 years of age in low gestational age infants. New curative trials may aim at investigating the effects of early curative administration of ibuprofen, which has reduced side effects compared to indomethacin, on immature kidney function, on mortality and morbidity in very low gestational age infants, ideally with a combined endpoint such as survival in the absence of severe neurodevelopmental alteration at 2 years age. Despite an understandable reluctance given the historical background of systematic, therapeutic closure of ductus arteriosus in preterm infants, there are no definite ethical obstacles to a placebo-controlled design.

Patency of the ductus arteriosus (PDA), a common complication of preterm birth, has been associated to increased risk for intraventricular cerebral hemorrhage, necrotizing enterocolitis, bronchopulmonary dysplasia and death. Consequently, prophylactic or curative treatment has been advocated before the critical left-to-right shunting occurs. A host of studies has shown that both pharmacological agents and surgical closure are effective in closing the ductus arteriosus in premature infants. Indomethacin has long been the drug of choice. However, renal and cerebral haemodynamic side effects have been frequently reported. Strategies to minimise adverse effects of indomethacin, such as the association with frusemide, dopamine or the use of low-dose prolonged treatment with indomethacin have failed or shown partial benefit. Other NSAIDs have been investigated. But either the profile of adverse effects was unfavourable, as in the case of mefenamic acid, or their efficacy was less than that of indomethacin for PDA closure. More recently, ibuprofen has been proposed for the treatment of PDA as it was shown to induce less adverse effects on cerebral blood flow, intestinal and renal hemodynamics, while retaining similar efficacy to indomethacin. However, since renal perfusion, GFR and diuresis in early neonatal life strongly depend on the vasodilator effects of PGs on the afferent glomerular arterioles, ibuprofen, as other COX-inhibitors may not be exempt of some renal undesirable effects. While numerous studies have shown that PDA is a risk factor associated with immaturity and with increased incidence of complications of preterm birth, including broncho-pulmonary dysplasia, retinopathy of prematurity, necrotizing enterocolitis and death, there is little evidence that such association is causative. Moreover, still little evidence exists from even recent randomized controlled trials that the pharmacological closure of PDA benefits to premature infants in terms of clinically significant short-term or medium-term outcomes, beyond a positive effect on DA patency. The use of COX-inhibitors for the prophylaxis or closure of PDA during the first hours or days of life should thus be cautious and based on an individual evaluation of benefit and risk. There is need of a randomized, placebo-controlled trials designed to assess the benefits in terms of mortality and morbidity outcomes of an early, or even very early pharmacological closure of PDA in extremely low gestational age infants.

In this study, low birth weight was induced in rats by feeding the dams with a low-protein diet during pregnancy. Kidneys from the fetuses at the end of gestation were collected and showed a reduction in overall and relative weight, in parallel with other tissues (heart and liver). This reduction was associated with a reduction in nephrons number. To better understand the molecular basis of this observation, a transcriptome analysis contrasting kidneys from control and protein-deprived rats was performed, using a platform based upon long isothermic oligonucleotides, strengthening the robustness of the results. We could identify over 1800 transcripts modified more than twice (772 induced and 1040 repressed). Genes of either category were automatically classified according to functional criteria, making it possible to bring to light a large cluster of genes involved in coagulation and complement cascades. The promoters of the most induced and most repressed genes were contrasted for their composition in putative transcription factor binding sites, suggesting an overrepresentation of the AP1R binding site, together with the transcription induction of factors actually binding to this site in the set of induced genes. The induction of coagulation cascades in the kidney of low-birth-weight rats provides a putative rationale for explaining thrombo-endothelial disorders also observed in intrauterine growth-restricted human newborns. These alterations in the kidneys have been reported as a probable cause for cardiovascular diseases in the adult.

International audience; Objectives - Recent guidelines for preterm neonates recommend early initiation of parenteral nutrition (PN) with high protein and relatively high caloric intake. This review considers whether these changes could influence homeostasis in very preterm infants during the first few postnatal weeks. Methods - This systematic review of relevant literature from searches of PubMed and recent guidelines was reviewed by investigators from several perinatal centers in France. Results - New recommendations for PN could be associated with metabolic acidosis via the increase in the amino acid ion gap, hyperchloremic acidosis, and ammonia acidosis. The introduction of high-intake amino acids soon after birth could induce hypophosphatemia and hypercalcemia, simulating a "repeat feeding-like syndrome" and could be prevented by the early intake of phosphorus, especially in preterm infants born after fetal growth restriction. Early high-dose amino acid infusions are relatively well tolerated in the preterm infant with regard to renal function. Additional studies, however, are warranted to determine markers of protein intolerance and to specify the optimal composition and amount of amino acid solutions. Conclusions - Optimal PN following new guidelines in very preterm infants, despite their demonstrated benefits on growth, may induce adverse effects on ionic homeostasis. Clinicians should implement appropriate monitoring to prevent and/or correct them.

The number of pregnant women and women of childbearing age who are receiving drugs is increasing. A variety of drugs are prescribed for either complications of pregnancy or maternal diseases that existed prior to the pregnancy. Such drugs cross the placental barrier, enter the fetal circulation and potentially alter fetal development, particularly the development of the kidneys. Increased incidences of intrauterine growth retardation and adverse renal effects have been reported. The fetus and the newborn infant may thus experience renal failure, varying from transient oligohydramnios to severe neonatal renal insufficiency leading to death. Such adverse effects may particularly occur when fetuses are exposed to NSAIDs, ACE inhibitors and specific angiotensin II receptor type 1 antagonists. In addition to functional adverse effects, in utero exposure to drugs may affect renal structure itself and produce renal congenital abnormalities, including cystic dysplasia, tubular dysgenesis, ischaemic damage and a reduced nephron number. Experimental studies raise the question of potential long-term adverse effects, including renal dysfunction and arterial hypertension in adulthood. Although neonatal data for many drugs are reassuring, such findings stress the importance of long-term follow-up of infants exposed in utero to certain drugs that have been administered to the mother.

Sartans are selective type 1 angiotensin II receptor-antagonists that are used in the treatment of arterial hypertension. Few reports are available concerning the use of sartans during pregnancy. We report two cases of adverse fetal outcome in hypertensive pregnancies exposed to sartans. In the first case, anamnios and fetal renal failure due to severe tubular dysgenesia led to termination of pregnancy in the 27th week. The second patient presented with hypocalvaria and developed fetal renal failure. The use of sartans during the two last trimesters of pregnancy should be strictly avoided.

Objective To investigate the impact of social inequalities on the risk of rehospitalization in the first year after discharge from the neonatal unit in a population of preterm-born children. Study design Preterm infants were included if they were born between 2006 and 2013 at ≤32 + 6 weeks of gestation and who received follow-up in a French regional medical network with a high level of healthcare. Socioeconomic context was estimated using a neighborhood-based socioeconomic deprivation index. Univariate and logistic regression analyses were used to identify risk factors associated with rehospitalization. Results For the 2325 children, the mean gestational age was 29 ± 2 weeks and the mean birth weight was 1315 ± 395 g. In the first year, 22% were rehospitalized (n = 589); respiratory diseases were the primary cause (44%). The multiple rehospitalization rate was 18%. Multivariable analysis showed that living in the most deprived neighborhoods (socioeconomic deprivation index of 5) was associated with overall rehospitalization (OR, 2.2; 95% CI, 1.5-3.6; P .001), and multiple rehospitalizations (OR, 2.5; 95% CI, 1.2-4.9; P .01); with socioeconomic deprivation index of 1 (least deprived) as reference. Deprivation was associated with all causes of hospitalization. Female sex ( P .001) and living in an urban area ( P = .001) were protective factors. Conclusions Despite regional routine follow-up for all children, rehospitalization after very preterm birth was higher for children living in deprived neighborhoods. Families' social circumstances need to be considered when evaluating the health consequences of very preterm birth.

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.

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.

Epidemiological and experimental studies show that the risk of cardiovascular and metabolic diseases at adulthood is inversely related to the weight at birth. Although with less evidence, low birth weight has been suggested to increase the risk of chronic kidney disease (CKD). It is well established that the developmental programming of arterial hypertension and of renal disease involves in particular renal factors, especially nephron endowment, which is reduced in low birth weight and maternal diabetes situations. Experimental studies, especially in rodents, have demonstrated the long-term influence of postnatal nutrition and/or postnatal growth on cardiovascular, metabolic and renal functions, while human data are scarce on this issue. Vascular and renal diseases appear to have a “multihits” origin, with reduced nephron number the initial hit and rapid postnatal growth the second hit. This review addresses the current understanding of the role of the kidney, both as a mechanism and as a target, in the developmental origins of adult disease theory, with a particular focus on the long-term effects of postnatal growth and nutrition.

Low birth weight is associated with an increased risk of hypertension and renal dysfunction at adulthood. Such an association has been shown to involve a reduction of nephron endowment and to be enhanced by accelerated postnatal growth in humans. However, while low-birth-weight infants often undergo catch-up growth, little is known about the long-term vascular and renal effects of accelerated postnatal growth. We surimposed early postnatal overfeeding (OF; reduction of litter size during the suckling period) to appropriate-birth-weight (NBW+OF) and intrauterine growth restriction (IUGR; IUGR+OF) pups, obtained after a maternal gestational low-protein diet. Blood pressure (systolic blood pressure; SBP) and renal function (glomerular filtration rate; GFR) were measured in young and aging offspring. Glomerulosclerosis and nephron number were determined in aging offspring (22 mo). Nephron number was reduced in both IUGR and IUGR+OF male offspring (by 24 and 26%). GFR was reduced by 40% in 12-mo-old IUGR+OF male offspring, and both NBW+OF and IUGR+OF aging male offspring had sustained hypertension (+25 mmHg) and glomerulosclerosis, while SBP and renal function were unaffected in IUGR aging offspring. Female offspring were unaffected. In conclusion, in this experimental model, early postnatal OF in the neonatal period has major long-lasting effects. Such effects are gender dependent. Reduced nephron number alone, associated with IUGR, may not be sufficient to induce long-lasting physiological alterations, and early postnatal OF acts as a “second hit.” Early postnatal OF is a suitable model with which to study the long-term effects of postnatal growth in the pathogenesis of vascular disorders and renal disease.

Introduction: Cardiovascular disease is a major cause of premature death. The severity of such diseases has been suggested to result from insufficient angiogenesis processes. Low birth weight is now recognized as a risk factor of mortality for such disease. However, the vascular repair capacity after ischemia in IUGR adult offspring is unknown. Objective: To show how postischemic neovascularization capacity is affected in 12 mo-old adult IUGR rat offspring (maternal gestational low protein diet). Material and Methods: The unilateral hind limb ischemia model by femoral artery resection was used to study the neovascular capacity; the controlateral hind limb served as a reference for each animal. Laser Doppler imaging was used to assess blood flow perfusion in both hind limb after ischemia. Capillary densities of the anterior tibial muscle from both controlateral and ischemic limbs was measured at day 21. Results: After ischemia, IUGR offspring showed marked decreased blood flow in ischemic hind limb from day 1 (-60 % vs -40 % in IUGR and control offspring, p < 0.05). At day 21, while ischemia promoted neovascularization in control offspring (+ 22 %), vascular density was decreased in IUGR ischemic hind limb by 30 % (p < 0.05). Moreover, muscle capillary density of non-ischemic hind limb was higher in IUGR as compared with control offspring (+ 20 %, p < 0.05). Conclusion: Postischemic neovascularization capacity following hind limb ischemia is affected in IUGR adult rat offspring. Angiogenic repair pathways, more than basal capillary density, may be affected in such condition.

Introduction: Epidemiological and experimental studies demonstrate that low birth weight is associated with increased risk of arterial hypertension and metabolic diseases in adulthood. Rapid postnatal catch-up growth may constitute an additional risk factor.

Introduction: Low birth weight is associated with increased risk of arterial hypertension and metabolic diseases in adulthood. Rapid postnatal catch-up growth may constitute an additional risk factor. Aim: To investigate the effects of postnatal overfeeding (OF) after intrauterine growth restriction (IUGR) in 12 month old, adult rats. Methods: 4 groups of animals were investigated: group I, controls: offspring of dams fed normal diet (NP, casein 22 %); group II: offspring of dams fed isocaloric low-protein diet (LP, casein 9 %); group III: postnatal OF (obtained by reduction of litter size); group IV: LP rats exposed to postnatal OF. Systolic blood pressure (SBP), glomerular number, renal function, fasting glycaemia and intraperitoneal glucose tolerance test were obtained Results: (mean +/- SEM). Offspring of dams fed LP diet had a 20 % birth weight and 38 % glomerular number reduction (p < 0.01). Catch-up growth was associated with an elevated SBP from the age of 4 weeks (110 +/-3; 117 +/- 2; 116 +/- 3; 127 +/- 2 mmHg in groups NP, LP, OF, LP+OF rats respectively; p < 0.05). But the difference in SBP between LP and controls rats disappeared at the age of 12 months. Creatinine clearance decreased with age in LP+OF rats but reached statistical significance in males at 12 months (3.34 +/- 0.2; 4.26 +/-0.3; 4.61+/-1.6; 5.48 +/-1.6 ml/min/kg in LP+OF, LP, OF, controls respectively). Proteinuria was significantly higher in LP+OF rats than in controls at 4 months. At the age of 12 months, glucose tolerance was significantly altered in OF and LP+OF rats. Conclusion: Early catch-up growth in IUGR rats enhances alteration of SBP, glucose tolerance and renal function in adulthood. Early postnatal overfeeding may amplify single nephron hyperfiltration, and insulin-resistance associated with IUGR, resulting in cardiovascular and metabolic diseases at adulthood.

Introduction: Intrauterine growth restriction (IUGR) is associated with increased risk of cardiovascular and metabolic diseases in adulthood. Nephron number reduction has been proposed as a key mechanism for later hypertension. Aim: To compare the long term effects of two models of IUGR on arterial systolic blood pressure (SBP) and renal function in adult rats. Methods: 3 groups of animals were investigated: group I, controls: offspring of dams fed normal diet (NP, casein 22 %); group II: offspring of dams fed isocaloric low-protein diet (LP, casein 9 %); group III: offspring of dams that received 3 daily intramuscular injections of betamethasone (0.25 mg/kg) on gestational days 17,18, 19 (BET). SBP, glomerular number, and renal function were obtained in 12 months old animals. Results: (mean +/- SEM). Glomerular number was significantly reduced in IUGR rats (38 % in LP rats and 50 % in BET rats vs. controls p

Background: Benefit and tolerance of early nCPAP, applied in the delivery room, in combination with surfactant therapy are still discussed in the management of respiratory distress syndrome (RDS) in extremely low birth weight infants (ELBWI) Objective: To assess the feasability and safety of early nCPAP in combination with early curative surfactant therapy (nCPAP + surfactant) in less than 28 wks gestational age (GA) preterm infants and its eventual effects on neonatal morbidity. Design/Methods: Outcomes of two groups of preterm infants with GA

36 Effects of Intrauterine Growth Restriction (Iugr) and Postnatal Catch-Up Growth on Arterial Blood Pressure (Bp), Glucose Tolerance (Gt) and Renal Function in Adult Rats