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Objective To compare the demographical, clinical and laboratory features, and outcomes of neonates with enteroviral meningitis (EVM) with those with bacterial meningitis (BM). Methods A retrospective two-center study was performed in La Réunion Island between January 2008 and December 2018 in hospitalized neonates aged less than 29 days. Patients positive for enterovirus real-time polymerase chain reaction from the cerebrospinal fluid (CSF) were diagnosed with EVM. Neonates with positive CSF culture results for a potentially pathogenic bacterium were diagnosed with BM. Results Compared with their EVM peers (n = 20), BM-infected neonates (n = 14) had lower birth weight, and were more likely to present hypotension and neurological symptoms on admission. Thrombocytopenia, elevated serum procalcitonin, hyperproteinorachia, hypoglycorrhachia, CSF pleocytosis, a bacterial meningitis score >0 were more frequent in the BM-infected group. All BM-infected neonates had at least one abnormal cutoff value in the CSF, while nine neonates (45%) in the EVM group had no CSF abnormality (p = 0.004). BM-infected neonates also had a longer length of hospital stay, needed more supportive care, received more prolonged antimicrobial courses, and developed respiratory and neurological complications. Conclusion Recognition of some clinical and laboratory features can help clinicians in differentiating BM from EVM when managing this high-risk patient group.

Background: Aminoglycosides are the most prescribed antibiotics in neonatal intensive care units (NICU). Reducing exposure to antibiotics in the NICU is highly desirable, particularly through benchmarking methods. Methods: Description of aminoglycosides prescriptions in 23 French NICU using the same computerized system over a 4-year period (2017–2020). A benchmarking program of antibiotics prescription was associated. Results: The population included 53,818 patients. Exposition rates to gentamicin and amikacin were 31.7% (n = 17,049) and 9.1% (n = 4894), respectively. Among neonates exposed to gentamicin, 90.4% of gentamicin and 77.6% of amikacin treatments were started within the 1st week of life. Among neonates exposed to amikacin, 77.6% started amikacin within the 1st week. The average daily dose of gentamicin at first prescription increased over the study period from 3.9 in 2017 to 4.4 mg/kg/d in 2020 (p &lt, 0.0001). Conversely, the corresponding amikacin daily doses decreased from 13.0 in 2017 to 12.3 mg/kg/d in 2020 (p = 0.001). The time interval between the first 2 doses of gentamicin was mainly distributed in 3 values during the first week of life: 49.4% at 24 h, 26.4% at 36 h, and 22.9% at 48 h. At first amikacin prescription, the time interval was distributed in 4 categories: 48% at 24 h, 4.1% at 30 h, 8.5% at 36 h, and 37.1% at 48 h. As compared to literature guidelines, the rates of overdose and underdose in gentamicin (1.5% and 2.7%) and amikacin (0.3% and 1.0%). They significantly decreased for gentamicin over the study period. In multivariate analysis, the factors significantly associated with GENT overdose were the year of admission, prematurity, length of stay, and duration of the treatment. Conclusion: This prescription strategy ensured a low rate of overdose and underdose, and some benefits of the benchmarking program is suggested.

Aim To examine the rates of follow-up at two years of age and perinatal factors associated with non-compliance in an observational population-based cohort of very preterm children enrolled in a routine follow-up program. Method Data review of infants born between 2008 and 2012 in the Observatoire de La Grande Prematurite, Reunion Island cohort. All singletons born alive before 33 weeks of gestational age and resident on the island at two years of age were included. Patients were considered compliant if they were timely evaluated between 20–28 months of age, or non-compliant if they were not evaluated or evaluated after 28 months of age. Results Of the 802 survivors (mean gestational age of 30.3 ± 2.0 months, mean birthweight of 1364 ± 396 g), 468 (58.4%) were examined between 20–28 months, 119 (14.8%) after 28 months of age, and 215 (26.8%) were never evaluated, respectively. In multivariate analysis, factors associated with non-compliance were higher parity (> 2), past history of preterm delivery, maternal diabetes (preexisting or gestational), appropriate for gestational status, and centre of birth. Conclusion Sustainable follow-up of vulnerable neonates remains a challenge in clinical practice. Early predictors of non-compliance can be used to define individualized and local follow-up strategies in these infants at high risk for developmental disabilities.

ObjectivesThe primary objective of this study is to determine the current level of patient medication exposure in Level 3 Neonatal Wards (L3NW). The secondary objective is to evaluate in the first month of life the rate of medication prescription not cited in the Summary of Product Characteristics (SmPC). A database containing all the medication prescriptions is collected as part of a prescription benchmarking program in the L3NW.Material and methodsThe research is a two-year observational cohort study (2017-2018) with retrospective analysis of medications prescribed in 29 French L3NW. Seventeen L3NW are present since the beginning of the study and 12 have been progressively included. All neonatal units used the same computerized system of prescription, and all prescription data were completely de-identified within each hospital before being stored in a common data warehouse.ResultsThe study population includes 27,382 newborns. Two hundred and sixty-one different medications (International Nonproprietary Names, INN) were prescribed. Twelve INN (including paracetamol) were prescribed for at least 10% of patients, 55 for less than 10% but at least 1% and 194 to less than 1%. The lowest gestational ages (GA) were exposed to the greatest number of medications (18.0 below 28 weeks of gestation (WG) to 4.1 above 36 WG) (pConclusionNeonates remain therapeutic orphans. The consequences of polypharmacy in L3NW should be quickly assessed, especially in the most immature infants.

Table S1. Consensual definitions of neonatal outcomes between the Observatoire de La Grande Prématurité, La Réunion (OGP) cohort and the EPIPAGE 2 mainland France cohort. (DOCX 17 kb)

To evaluate the maternal-fetal management and follow-up of infants at risk for congenital syphilis.Monocentric retrospective cohort study at the Félix Guyon Hospital, Saint-Denis, La Réunion between January 2008 and December 2014. Management of 38 pregnancies (35 women, 39 fetuses) with a positive syphilis serology was evaluated according to the Centers for Disease Control and Prevention (CDC) guidelines.A total of 68% (n=26) of pregnancies were screened before 16 weeks of gestation, and 26% (n=10) had appropriate treatment. Adverse outcomes were noted in 45% of pregnancies. Neonatal serology was not performed in 7 live-born neonates (19%) and 33 infants were classifiable according to the four CDC scenarios. In the infants, adequate complementary evaluation and appropriate treatment were noted in 42% (n=13) and 55% (n=17) of cases, respectively. Rate of infant follow-up was 76% (n=16). No treatment failure was observed in infants.Reinforcement of public health policies and a better sensitization, training and collaboration among perinatal caregivers are warranted given the gaps revealed in our study.

Background: Acute kidney injury (AKI) is a frequent complication in preterm infants, and the identification of early markers of renal hypoperfusion is a chief challenge in neonatal intensive care units. Objectives: To describe the association between early markers of cardiovascular function and renal perfusion with AKI occurrence in a cohort of preterm infants < 32 weeks’ gestation. Methods: 128 infants were prospectively included from birth to discharge. During the first day of life, we assessed cardiovascular function, systemic and organ blood flow by Doppler ultrasound, and monitored cerebral and renal regional oxygen saturation (rSO2) using near-infrared spectroscopy (NIRS). These measures were analyzed in relation to developing AKI and serum creatinine (SCr) peak from day 2 to 7 of life. Results: 12 of 128 infants presented with AKI (9.4%). SCr peak was 155.3 ± 30.2 µmol/L in infants with AKI versus 82.0 ± 16.5 in non-AKI infants (p < 0.001). Among all measures of cardiovascular function and renal perfusion, low mean cerebral and renal rSO2 during the first day of life and a low resistive index at renal artery Doppler were significantly associated with developing AKI. After adjustment for possible confounding factors, low renal rSO2 on the first day of life remained associated with a high SCr peak from day 2 to 7 of life. Conclusion: Low renal rSO2 values during the first day of life correlate with developing AKI in preterm infants < 32 weeks’ gestation. NIRS monitoring of renal function during adaptation seems promising, and its very early use after birth to detect kidney hemodynamic dysfunction deserves further investigations.

International audience; IntroductionUne avancée récente dans l’approche à l’IRA néonatale repose sur l’identification de différents degrés de réduction aiguë de la fonction rénale, comprenant un continuum pathologique dont l’IRA est le stade le plus sévère et où les variations de la créatinine plasmatique (Crp) sont corrélées à la dysfonction rénale. Selon cette conception, l’exploration de paramètres précoces d’hypoperfusion rénale permet une anticipation de l’IRA et une prise en charge plus précoce et préventive de ses complications. Cette étude souhaitait caractériser le lien entre l’hémodynamique dans les premières 24 h et la fonction rénale dans la première semaine de vie dans une cohorte de grands prématurés, population très sensible aux perturbations de la fonction rénale.MéthodesAu total, 128 prématurés < 32 SA ont été inclus dès la naissance. Pendant les premières 24 h de vie, les paramètres hémodynamiques cliniques, échographiques (volémie, débit cardiaque, contractilité, résistances vasculaires, canal artériel–diamètre et shunt à 6 h de vie), la perfusion d’organe (Doppler) et l’oxygénation tissulaire par le NIRS (rSO2 cérébrale et rénale) ont été enregistrés. L’association entre ces paramètres, ainsi qu’entre les facteurs de risques connus d’IRA et la mesure de la créatinine plasmatique (Crp) dans la première semaine de vie a été analysée. L’IRA a été définie par un taux de Crp > 130 mmol/L à j2.RésultatsDouze enfants (9,4%) ont présenté une IRA. La Crp maximale (mmol/L) était de 155 ± 30 dans le groupe IRA vs 82 ± 16 dans le groupe sans IRA. Les facteurs significativement associés à l’IRA étaient : l’AG, le poids de naissance, la voie d’accouchement, la protidémie à H12, la rSO2 cérébrale, le canal artériel traité, la rSO2 rénale, l’index de résistance dans l’artère rénale. L’analyse multivariée a montré que les facteurs de risque indépendants liés à l’augmentation de la Crp étaient : le canal artériel traité (p = 0,002), l’hypoprotidémie à H12 (p = 0,01), une plus basse mesure de rSO2 rénale (p = 0,02) et un plus faible AG (p = 0,03).ConclusionsNos résultats montrent pour la première fois que l’hypoprotidémie à H12 et l’hypoxie tissulaire rénale mesurée par le NIRS sont des facteurs de risque précoces d’anomalie de la fonction rénale chez le grand prématuré.

International audience; Fryns syndrome (FS) is a multiple malformations syndrome with major features of congenital diaphragmatic hernia, pulmonary hypoplasia, craniofacial dysmorphic features, distal digit hypoplasia, and a range of other lower frequency malformations. FS is typically lethal in the fetal or neonatal period. Inheritance is presumed autosomal recessive. Although no major genetic cause has been identified for FS, biallelic truncating variants in PIGN, encoding a component of the glycosylphosphatidylinositol (GPI)-anchor biosynthesis pathway, have been identified in a limited number of cases with a phenotype compatible with FS. Biallelic variants in PIGN, typically missense or compound missense with truncating, also cause multiple congenital anomalies-hypotonia-seizures syndrome 1 (MCAHS1). Here we report six further patients with FS with or without congenital diaphragmatic hernia and recessive loss of function PIGN alleles, including an intragenic deletion with a likely founder effect in La Réunion and other Indian Ocean islands. Our results support the hypothesis that a spectrum of phenotypic severity is associated with recessive PIGN variants, ranging from FS at the extreme end, caused by complete loss of function, to MCAHS1, in which some residual PIGN function may remain. Our data add FS resulting from PIGN variants to the catalog of inherited GPI deficiencies caused by the disruption of the GPI-anchor biosynthesis pathway.

Purpose To suggest a novel technique for omphalocele closure which uses the circular base of the umbilical cord, thus allowing for a more physiological healing process and natural-looking scar. Methods Among 16 neonates operated for omphalocele between 2011 and 2016, 12 were closed with a one-stage procedure using a Z omphaloplasty (ZORRO). Median gestational age was 36.5 weeks; median birth weight was 3210 g. The umbilical arteries were divided and ligated outside the peritoneal cavity above the parietal musculocutaneous plane. The upper part of the defect was closed vertically in the midline, while the lower part was closed in a circular fashion by imbricating 2 lateral cutaneous Z flaps thus forming a new cordonal base. Results The postoperative course was uneventful in all cases. The reconstructed cordonal bases healed as would a normal umbilical cord, with central umbilication surrounded by healthy skin. With a median follow-up period of 11 months, the umbilicus was in the normal position, with a 0.6 xyphoumbilical/xyphopubic ratio. Conclusions This technique mimics the natural necrosis mechanism and physiological healing of the umbilicus thus allowing for an esthetic and “natural looking” umbilicus.

Background: Retrospective studies suggest that early hypoproteinemia has prognostic value for adverse outcome in preemies, but the underlying pathophysiology is unknown. We hypothesized that the prognostic relevance of hypoproteinemia could be related to its association with impaired cardiovascular function and organ perfusion during transition. Objectives: To describe the plasma protein status and the measures of cardiovascular function according to the outcome in infants Methods: One hundred and twenty-eight infants were prospectively included from birth to discharge. During the first 24 h of life, we assessed the cardiovascular function and systemic and organ blood flow by Doppler ultrasound, and monitored cerebral and renal regional oxygen saturation (cRSO2, rRSO2) using near-infrared spectroscopy. These measures were analyzed in relationship to hypoproteinemia (total plasma protein level Results: Hypoproteinemia was associated with a higher risk of a severe adverse outcome after adjustment of confounding variables (adjusted OR = 6.8; 95% CI 1.3-34). Compared to normoproteinemic infants and after adjustment for gestational age, hypoproteinemic ones had more significantly: hypotension (7 vs. 13%, p = 0.03), abnormal capillary refilling time (20 vs. 36%, p < 0.001), abnormal renal blood flow (resistive index 0.78 ± 0.11 vs. 0.85 ± 0.09, p = 0.04), lower rRSO2 (82.9 ± 9.2 vs. 73.6 ± 10.5%, p = 0.04), and lower systemic vascular resistance (0.155 ± 0.058 vs. 0.108 ± 0.037 mm Hg/L/kg; p = 0.04). The cRSO2 patterns were significantly decreased in infants with severe adverse outcome and independent from protein status. Conclusion: Hypoproteinemia is associated with impaired cardiovascular function. Further studies are required to elucidate the interplay between changes in protein levels, postnatal hemodynamics and clinical outcome.

To describe conservative management of spontaneous intestinal perforation (SIP) in preterm infants using peritoneal needle aspiration (PNA). Monocentric retrospective review of SIP cases treated primarily by PNA between 1999 and 2015 (n=31). Mean gestational age was 29.2±2.4 weeks and birthweight 1149±428 g. SIP occurred at 3.7±2.2 days of life. PNA achieved definitive treatment in 18 patients (60%) with a mean of 1.8 (±0.8) procedures. All patients requiring more than three PNAs had secondary laparotomy. Two patients died and five presented severe cerebral lesions. Full enteral feeding was achieved 42±18 days after SIP. Intestinal morbidity included cholestasis (n=6), intestinal stricture (n=1) and growth restriction (n=22). On follow-up (n=25, median=4 years), no severe impairment was noted. Seventeen children (68%) had a normal development. PNA as primary therapy for SIP is a viable option, resulting in definitive treatment in 60% of cases, with limited mortality and morbidity.

Fetal edema can present as limited subcutaneous edema, fluid accumulation in body cavities or hydrops fetalis. Hydrops fetalis is the end stage of a variety of fetal/maternal disorders and nonimmune etiology represents more than 3/4 of cases. Lymphatic dysplasia may account for a subset of patients with nonimmune and "idiopathic" hydrops fetalis, fetal chylous ascites or chylothorax. We present two unrelated patients with antenatal features of hereditary lymphedema syndrome, in whom Milroy disease was diagnosed after birth. At least, 20 genes have been identified to cause primary lymphedema, with sometimes antenatal features. Hereditary lymphedema syndrome should be considered in cases of nonimmune hydrops fetalis/fetal edema after ruling out the more common etiologies.

Resume Objectifs Le but de cette etude de cohorte retrospective etait de determiner la prevalence et la gravite de la dysplasie bronchopulmonaire (DBP) ainsi que ses facteurs predictifs dans une cohorte regionale de grands prematures (GP) de l’ile de La Reunion. Methodes Tous les GP autochtones nes vivants avant la 33 e semaine d’amenorrhee (SA) entre le 1 er janvier 2008 et le 31 decembre 2009, etaient eligibles. Seuls les GP ayant survecu au moins 28 j, dont les parametres etaient connus depuis la naissance, ont participe a l’etude cas temoin des facteurs predictifs de DBP moderee ou severe (DBP mo/s ). Resultats Chez les moins de 33 SA, le taux global de DBP (3 stades de gravite) etait de 30,7 %. Parmi ceux ayant survecu 28 j ou plus, le taux de DBP mo/s etait de 13,1 % (intervalle de confiance [IC] 95 % : 10,2–15,9 %). Dans un modele logistique a effet fixe ajuste sur l’âge gestationnel (AG), la croissance post-natale et le mode ventilatoire a 24 h, 4 facteurs etaient predictifs de DBP mo/s : le retard de croissance intra-uterin (RCIU), le surfactant, le retard energetique et l’infection neonatale tardive. Dans un modele logistique a effet mixte ajuste sur ces memes cofacteurs, le site etait associe a la DBP mo/s , en raison d’un effet centre (absence d’effet de composition). Conclusion La prevalence de la DBP mo/s dans la population metissee de l’ile de La Reunion est comparable a celles observees en Europe, quoique contrastee par site. Dans notre contexte, les facteurs predictifs de DBP mo/s etaient similaires a ceux deja identifies.

International audience; SummaryBackground Bronchopulmonary dysplasia, a major complication of extreme prematurity, has few treatment options. Postnatal steroid use is controversial, but low-dose hydrocortisone might prevent the harmful effects of inflammation on the developing lung. In this study, we aimed to assess whether low-dose hydrocortisone improved survival without bronchopulmonary dysplasia in extremely preterm infants. Methods In this double-blind, placebo-controlled, randomised trial done at 21 French tertiary-care neonatal intensive care units (NICUs), we randomly assigned (1:1), via a secure study website, extremely preterm infants inborn (born in a maternity ward at the same site as the NICU) at less than 28 weeks of gestation to receive either intravenous low-dose hydrocortisone or placebo during the first 10 postnatal days. Infants randomly assigned to the hydrocortisone group received 1 mg/kg of hydrocortisone hemisuccinate per day divided into two doses per day for 7 days, followed by one dose of 0·5 mg/kg per day for 3 days. Randomisation was stratified by gestational age and all infants were enrolled by 24 h after birth. Study investigators, parents, and patients were masked to treatment allocation. The primary outcome was survival without bronchopulmonary dysplasia at 36 weeks of postmenstrual age. We used a sequential analytical design, based on intention to treat, to avoid prolonging the trial after either efficacy or futility had been established. This trial is registered with ClinicalTrial.gov, number NCT00623740. Findings 1072 neonates were screened between May 25, 2008, and Jan 31, 2014, of which 523 were randomly assigned (256 hydrocortisone, 267 placebo). 255 infants on hydrocortisone and 266 on placebo were included in analyses after parents withdrew consent for one child in each group. Of the 255 infants assigned to hydrocortisone, 153 (60%) survived without bronchopulmonary dysplasia, compared with 136 (51%) of 266 infants assigned to placebo (odds ratio [OR] adjusted for gestational age group and interim analyses 1·48, 95% CI 1·02–2·16, p=0·04). The number of patients needed to treat to gain one bronchopulmonary dysplasia-free survival was 12 (95% CI 6–200). Sepsis rate was not significantly different in the study population as a whole, but subgroup analyses showed a higher rate only in infants born at 24–25 weeks gestational age who were treated with hydrocortisone (30 [40%] of 83 vs 21 [23%] of 90 infants; sub-hazard ratio 1·87, 95% CI 1·09–3·21, p=0·02). Other potential adverse events, including notably gastrointestinal perforation, did not differ significantly between groups. Interpretation In extremely preterm infants, the rate of survival without bronchopulmonary dysplasia at 36 weeks of postmenstrual age was significantly increased by prophylactic low-dose hydrocortisone. This strategy, based on a physiological rationale, could lead to substantial improvements in the management of the most premature neonates. Funding Assistance Publique-Hôpitaux de Paris

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.

International audience; Major epidemics of Chikungunya have re-emerged with millions of cases worldwide. What was once largely a tropical disease in poorer countries is now recognized as a major global health issue. The disease is perpetuated by the alphavirus Chikungunya, and is transmitted by Aedes mosquitoes. The infection is highly symptomatic, with fever, skin rash and incapacitating arthralgia, which can evolve to chronic arthritis and rheumatism in elderly patients. Mother-to-child transmission, encephalitis, Guillain–Barré syndrome and deaths have been noted. In this article, we will highlight the epidemiological, clinical, virological and immunological aspects of the disease and mention the therapies that have been used during recent epidemics. Novel prevention measures to control the mosquito and a new vaccine are highly warranted.

Chikungunya fever is an arbovirosis caused by an alphavirus (CHIKV) belonging to the Togaviridae family. Its main vectors are Aedes mosquitoes. In its classic form, Chikungunya consists in a flu-like illness that can be very disabling, especially by incapacitating arthralgia. In children, the arthropathy is well known to be better tolerated than in adulthood but severe manifestations and complications can occur owing to neurologic, cardiac, hematologic or cutaneous dysfunctions, all carrying a fatality risk in the absence of appropriate intensive care. Out of these, the most singular is a severe encephalopathy, even in some cases genuine encephalitis. More rare, but quite specific of small infants, skin blisters have been reported, sometimes complicated by extensive detachments. Mother-to-child infections were demonstrated on La Reunion island with a fifty-percent probability of vertical transmission when the mother was highly viremic around the term of pregnancy. The diagnosis can be made by detecting CHIKV RNA using RT-PCR or specific IgM antibodies using MAC-Elisa serology. Chikungunya is a notifiable disease. The epidemic that emerged in Indian Ocean islands during 2005-2006, its progressive extension to Asia and even to Italy in July 2007, highlighted a very important capacity of CHIKV to cause huge outbreaks wherever Aedes sp. can proliferate. In France, Aedes albopictus is definitively endemic in the departments of Alpes-Maritimes since 2004, Corsica since 2005, and Var since 2007. Therefore, the risk of introduction of CHIKV from an epidemic area to Europe and especially in France is real.

International audience; Résumé Durant l’été austral 2005–2006 une épidémie de Chikungunya (Chik) a touché plus du tiers de la population de l’île de la Réunion. Objectifs Notre objectif a été de décrire les cas pédiatriques observés. Matériel et méthodes Du 1er janvier au 30 avril 2006, au pic de l’épidémie, nous avons effectué une étude descriptive, rétrospective, monocentrique, clinique et biologique sur les cas de Chik en pédiatrie, confirmés biologiquement au centre hospitalier départemental de Saint-Denis. Résultats Nous avons retenu 86 enfants de 10 j de vie à 18 ans. Nous avons observé plusieurs formes cliniques en dehors de la forme typique. Des formes compliquées, neurologiques, cardiaques, digestives, déjà connues, ont été mieux décrites grâce à un plateau technique moderne. Des formes sévères ont entraîné le décès de 2 enfants de 9 ans ayant eu une forme neurologique pour le premier et une atteinte polyviscérale neurologique, cardiaque et hémorragique pour le second. Les autres formes sévères hospitalisées ont surtout concerné des enfants de moins de 6 mois et ceux présentant une atteinte cardiaque, dermatologique et neurologique. Nous avons également mis en évidence des cas d’épidermolyse bulleuse non mentionnée dans la littérature. Conclusion Les recherches doivent être poursuivies afin de proposer un traitement adapté en cas d’infection à Chik, compte tenu des complications sévères possibles. Summary During the southern-hemispheric 2005–2006 summer, Reunion Island was struck by an epidemic of Chikungunya (Chik), which affected more than a third of the overall population. Objectives Our objective was to describe pediatric cases of Chick. Material and methods We conducted a retrospective descriptive monocentric study of confirmed pediatric cases of Chik recruited at Saint-Denis’ departemental hospital during the peak of the epidemic (January 1st to April 30th 2006). Results Eighty-six children aged 10 days to 18 years were included. In addition to the typical clinical presentation, we observed other phenotypes. Well-known complicated forms with neurologic, cardiac, gastro-intestinal (plus dehydration) involvement were thoroughly investigated using modern medical technology. We observed 2 fatal cases of acute disease in 9-year-old children: death resulted from a central nervous system insult in one case, and multisystemic neurological, cardiac, haemorrhagic involvement in another. Severe acute presentations requiring hospital admission involved mainly children aged less than 6 months, and those with cardiac, skin and neurologic impairment. The study identified 3 cases of epidermolysis bullosa, which to our knowledge, have never been described previously. Conclusion Chik in children warrants further research in order to propose early and appropriate treatments to avoid complications.

Resume Le syndrome de Fryns est un syndrome de transmission recessive autosomique habituellement letal associant une hernie diaphragmatique congenitale (HDC), une hypoplasie pulmonaire, une dysmorphie crânio-faciale avec facies grossier, fente labiopalatine et opacites corneennes, une hypoplasie des phalanges distales et des malformations diversement associees cardiaques, neurologiques, gastro-intestinales, genito-urinaires et squelettiques. Cas cliniques Nous presentons trois observations de nouveau-nes decedes avec syndrome de Fryns a La Reunion et a Mayotte. Les signes constants etaient un polyhydramnios important, une dysmorphie faciale evocatrice et une hypoplasie nette des phalanges distales et des ongles. Les nouveau-nes presentaient un etat de mort apparente et une hypoxemie lies a une HDC pour deux d'entre eux et a un syndrome alveolaire persistant pour le troisieme. Les caryotypes sur fibroblastes et lymphocytes etaient normaux. Conclusions Le syndrome de Fryns est le syndrome le plus communement associe a une HDC. L'association d'une HDC et d'une brachytelephalangie est fortement evocatrice de syndrome. Le diagnostic differentiel comprend des associations de malformations d'origine chromosomique dont la tetrasomie 12p en mosaique et des microdeletions chromosomiques actuellement reperees par de nouvelles techniques cytogenetiques d'hybridation genomique comparative. L'obtention d'un caryotype normal sur fibroblastes est un prealable au diagnostic de syndrome de Fryns et a un conseil genetique adapte. Pour les cas sporadiques, la recherche poussee de microdeletions chromosomiques est souhaitable.

Background Little is known about the neurocognitive outcome in children exposed to perinatal mother-to-child Chikungunya virus (p-CHIKV) infection. Methods The CHIMERE ambispective cohort study compared the neurocognitive function of 33 p-CHIKV-infected children (all but one enrolled retrospectively) at around two years of age with 135 uninfected peers (all enrolled prospectively). Psychomotor development was assessed using the revised Brunet-Lezine scale, examiners blinded to infectious status. Development quotients (DQ) with subscores covering movement/posture, coordination, language, sociability skills were calculated. Predictors of global neurodevelopmental delay (GND, DQ≤85), were investigated using multivariate Poisson regression modeling. Neuroradiologic follow-up using magnetic resonance imaging (MRI) scans was proposed for most of the children with severe forms. Results The mean DQ score was 86.3 (95%CI: 81.0–91.5) in infected children compared to 100.2 (95%CI: 98.0–102.5) in uninfected peers (P, Author Summary Chikungunya virus (CHIKV), an alphaviral infection transmitted by day-biting Aedes mosquitoes, is widespread in Asia and in Africa. Usually, CHIKV causes a self-limiting arthritide, except in debilitated people and in neonates, for whom it can lead to severe disease. Mother-to-child perinatal transmission of CHIKV is a rare event that can occur in the setting of large-scale outbreaks when the risk of maternal viremia at the term of pregnancy becomes non-negligible. In that event, CHIKV can give rise to neonatal infection with a probability of 50%, and prostration and encephalopathy, the two leading clinical pictures in the neonate, represent a continuum in the gradation of an undiscovered central nervous system involvement. We have followed-up 33 children infected at birth between June 2005 and April 2006 on the island of La Réunion, Indian Ocean, and 135 uninfected controls, for assessing their neurodevelopmental performance around the age of two years. Fifty-one percent of infected children had a global neurodevelopmental delay compared to 15% of uninfected peers. Multivariate analysis and neuroradiology suggest without irrefutable evidence a causal relationship between CHIKV infection and neurocognitive outcomes. Our findings suggest that CHIKV infection, acquired in the perinatal period, can cause severe disease with lifelong expected disability.

International audience; We report on six patients (five unpublished patients) from the Indian Ocean islands, with coarse face, cleft lip or palate, eye anomalies, brachytelephalangy, nail hypoplasia, various malformations (genitourinary or cerebral), abnormal electroencephalograms with impaired neurological examination and lethal outcome. Massive polyhydramnios was noted in the third trimester of pregnancy and neonatal growth was normal or excessive. The combination of the features is consistent with the diagnosis of Fryns syndrome (FS) without congenital diaphragmatic hernia. Besides chromosomal aberrations and microdeletion syndrome, differential diagnoses include conditions overlapping with FS such as Simpson-Golabi-Behmel, and conditions with hypoplasia/absence of the distal phalanges such as DOOR syndrome, Schinzel-Giedion syndrome, and Rudiger syndrome.

International audience; To search for serological evidence of congenital infection in apparently healthy neonates born to women infected with the Chikungunya virus (CHIKV) during pregnancy, monitoring for CHIKV-specific antibodies was performed within the CHIMERE cohort study (Reunion island, 2006-2008). CHIKV-specific antibody kinetics showed no evidence of asymptomatic congenital infection as neonates were tested negative for CHIKV-specific IgM antibodies at birth and 368 infants with CHIKV-specific IgG antibodies seroreversed completely (mean seroreversion time: 7.7 months). Seroreversion time of transplacental CHIKV IgG antibodies was inversely correlated with the stage of pregnancy at which exposure took place and end-term small for gestational infants seroreversed earlier.

Introduction Le recrutement dans les essais en pediatrie est souvent plus long et difficile compare aux essais chez les adultes. Les methodes sequentielles permettent de limiter la duree d’un essai randomise et de conclure plus rapidement. Une des methodes les plus utilisees est le test triangulaire (Whitehead et Stratton, 1983). Le test triangulaire tronque est un cas particulier du test triangulaire permettant de conclure lorsque l’essai est arrete prematurement. L’objectif de ce travail est d’illustrer l’utilisation de cette methode dans l’analyse d’un essai pediatrique (PREMILOC). Methodes L’etude PREMILOC est un essai therapeutique multicentrique, randomise, en double insu, contre placebo. L’objectif etait d’evaluer l’utilite de l’administration precoce d’hydrocortisone (HSHC) chez de grands prematures nes dans un contexte d’infection perinatale sur la mortalite neonatale et la survenue de la dysplasie bronchopulmonaire. Cet essai etait planifie avec des analyses sequentielles selon un test triangulaire. Les taux de succes attendus etaient de 56 % dans le bras placebo (C) et 66 % dans le bras HSHC (E). Les risques alpha et beta ont ete fixes a 5 % et 20 %. A partir de ces hypotheses, les bornes du triangle ont ete estimees et les analyses intermediaires ont ete planifiees tous les 100 patients inclus. Dans le cadre d’une analyse triangulaire, a chaque analyse intermediaire, la statistique de test B et l’information de Ficher V sont calculees. En fonction de la position du point (B, V) dans le triangle, une decision sur la poursuite de l’essai doit etre prise. Tant que le point (B, V) est a l’interieur du triangle, il est impossible de conclure, l’essai continue alors jusqu’a la prochaine analyse intermediaire. Dans le cadre de cet essai, un defaut de recrutement a ete observe, necessitant l’arret premature des inclusions. Une decision de tronquer le triangle a ete prise en accord avec l’investigateur (celui-ci etant en aveugle des precedentes analyses). Un nombre maximum L de patients pouvant etre inclus a ete estime par l’investigateur. Une valeur critique B* a ete calculee permettant de conclure au point tronque L. La valeur critique B* a ete estimee avec la PROC IML et la fonction SEQ du logiciel SAS © 2002–2012 par SAS Institute Inc., Cary, NC, Etats-Unis en s’assurant que l’erreur commise par les analyses intermediaires et l’analyse tronquee ne depassait jamais le risque alpha. Si B L > B* alors l’essai conclue que E > C. Si B L C. B L etant le test statistique estime au point tronque L. Resultats Apres la quatrieme analyse intermediaire, une analyse triangulaire tronquee a 521 patients a ete realisee. A l’arret des inclusions, 255 patients ont recu l’HSHC contre 266 pour le placebo. La valeur critique B* valait 10,40 dans le cadre d’un test unilateral avec une erreur alpha egale a 0,025. La statistique B L estimee a 521 patients etait egale a 10,87. B L > B*, l’essai a conclu que E > C ( p = 0,021). La puissance estimee a ce point etait egale a 59 % mettant en exergue une perte de puissance. Conclusion Le test triangulaire tronque permet de conclure sur une etude sequentielle contrainte de s’arreter prematurement au detriment d’une perte de puissance. Cette methode ne doit donc etre utilisee qu’en dernier recours a l’initiative d’une personne en aveugle des precedentes analyses intermediaires.

Prenatal exposure to valproic acid (VA) is associated with an increased risk of congenital malformations, especially limb defects like radial ray defects. Tibial developmental field defect in VA embryopathy remains exceptional. We report on three patients presenting with tibial hypo/aplasia associated with either femoral bifurcation or radial ray defect following prenatal exposure to VA. Femoral bifurcation and tibial agenesis has been described in the Gollop–Wolfgang complex and in the tibial agenesis-ectrodactyly syndrome. Tibial agenesis has also been reported in VACTERL association. The relation between prenatal exposure to VA and tibial agenesis is discussed. © 2010 Wiley-Liss, Inc.

Purpose: Apple-peel atresia is a rare form of bowel atresia associating proximal jejunal atresia with a typical coil-shaped distal small bowel. Many of the children suffering from this condition are still managed with initial enterostomy followed by delayed anastomosis.Patients and method: Between 2000 and 2007, we managed four patients with apple-peel atresia. Three by primary anastomosis and one by initial enterostomy with delayed anastomosis.Results: Total duration of total parenteral nutrition (TPN) was an average 109 days. Survival rate was 100% with an average follow-up of 4.3 years.Conclusion: Nowadays, the prognosis of apple-peel atresia depends mainly on prolonged TPN-related morbidity rather than immediate postoperative complications. We therefore recommend that those infants affected be managed by primary anastomosis in order to reduce the duration of parenteral nutrition, followed by careful nutrition by teams experienced in neonatal TPN and short bowel syndrome.

International audience; no abstract

Except for prenatal hospital admissions for those infected, this virus had no effect on outcomes., Mother-to-child transmission of chikungunya virus was reported during the 2005–2006 outbreak on Réunion Island, France. To determine the effects of this virus on pregnancy outcomes, we conducted a study of pregnant women in Réunion in 2006. The study population was composed of 1,400 pregnant women (628 uninfected, 658 infected during pregnancy, 27 infected before pregnancy, and 87 infected on unknown dates). We compared pregnancy outcomes for 655 (628 + 27) women not infected during pregnancy with 658 who were infected during pregnancy. Infection occurred during the first trimester for 15% of the infected women, the second for 59%, and the third for 26%. Only hospital admission during pregnancy differed between infected and uninfected women (40% vs. 29%). Other outcomes (cesarean deliveries, obstetric hemorrhaging, preterm births, stillbirths after 22 weeks, birthweight, congenital malformations, and newborn admissions) were similar. This virus had no observable effect on pregnancy outcomes.

The aim of this study was to describe a pediatric case series of Chikungunya infection associated with extensive bullous skin lesions, a severe and unknown form of the disease, during the 2005-2006 outbreak in La Réunion Island.Retrospective descriptive hospital-based study in children presenting blistersor = 10% of total body surface area with laboratory-confirmed Chikungunya infection.Eight boys and five girls with a mean age of 3.4 months were included. Blistering began after an average of 2 days after onset of fever and affected 21.5% (10% to 35%) of the total body surface area. Reverse transcription-polymerase chain reaction of blister fluid (n = 5) was positive with a mean viral load sometimes higher than in concurrent serum. Histopathologic examination (n = 10) showed intraepidermal blisters. Hospitalization and repeated dressing changes under general anesthesia were required. No death occurred. On follow-up, long term repigmentation was excellent with sometimes cosmetic sequelae.Chikungunya should be included in the differential diagnosis of febrile blistering dermatoses in small infants in epidemic areas.

International audience; Chikungunya virus (CHIKV) is transmitted by Aedes mosquitoes and causes an acute symptomatic illness with fever, skin rash, and incapacitating arthralgia, which can evolve into chronic rheumatoid arthritis in elderly patients. This is a tropical disease originally described in central/east Africa in the 1960s, but its 2004 re-emergence in Africa and rapid spread in lands in and around the Indian Ocean (Reunion island, India, Malaysia) as well as Europe (Italy) led to almost 6 million cases worldwide. The risk of importation and spreading diseases with long-term sequelae is even greater today given the global distribution of the vectors (including in the Americas), increased tourism and the apparent capacity of CHIKV to produce high levels of viremia (10(9)-10(12) virus/ml of blood) and new mutants. CHIKV-associated neuropathology was described early in the 1960s, but it is the unprecedented incidence rate in Indian Ocean areas with efficient clinical facilities that allowed a better description of cases with severe encephalitis, meningoencephalitis, peripheral neuropathies and deaths among newborns (mother-to-child infection), infants and elderly patients. Death rates following CHIKV infection were estimated at 1:1000 cases in la Reunion's outbreak. These clinical observations have been corroborated by experimental infection in several mouse models, leading to CNS pathologies. We further describe in this review the capacity of CHIKV to infect neurons and glial cells, delineate the fundamental innate (intrinsic) immune defence mechanisms to protect from infection and argue about the possible mechanisms involved in the encephalopathy.

Perlman syndrome is a rare overgrowth syndrome characterized by polyhydramnios with neonatal macrosomia, nephromegaly, distinctive facial appearance, renal dysplasia, nephro-blastomatosis, and predisposition to Wilms tumor (WT). We report on a newborn with prenatal sonographic signs of Perlman syndrome, large fetal ascites, nephromegaly and macrosomia. The clinical course was marked by neonatal distress, renal failure and refractory hypoxemia leading to death at 2 days of life. Renal histologic examination showed bilateral nephroblastomatosis. Genetic or epigenetic alterations of the 11p15 region (involved in the BWS), including mutation of the CDKN1C gene were excluded. No mutation of the GPC3 gene was identified. We review the 28 patients who have been reported with Perlman syndrome. The prognosis of Perlman syndrome is poor with a high neonatal mortality rate. Among the infants who survived beyond the neonatal period, 64% developed a WT and all had a developmental delay. Fetal macrosomia, ascites and polyhydramnios are frequent manifestations. Clinical overlaps with other overgrowth syndromes particularly Beckwith-Wiedemann syndrome and Simpson-Golabi-Behmel syndrome have been emphasized. Perlman syndrome is considered as an autosomal recessive condition. We review 19 patients from seven sibships with parental consanguinity in two families only. The other cases were sporadic. The 28 reported patients had only 10 unaffected sibs. The low percentage of consanguinity among parents is also puzzling for a rare recessive condition. The molecular basis of Perlman syndrome is unknown. (Epi)genetic anomalies of 11p15 and mutations in GPC3 were not studied in most of the previous reports.

Chikungunya virus, a mosquito-borne arbovirus, was responsible for a massive epidemic in La Réunion Island during 2005 to 2006. The disease is usually benign, but neurologic involvement, with sometimes fatal outcome, has been described. We report a retrospective hospital-based pediatric series of 30 children (23 boys and 7 girls) who presented neurologic manifestations of chikungunya such as encephalitis (n = 12), febrile seizures (n = 10), meningeal syndrome (n = 4), and acute encephalopathy (n = 4). Cerebrospinal fluid biological and cytological analyses (n = 23) were unremarkable except for 1 case of acute disseminated encephalomyelitis. The presence of viral genome in cerebrospinal fluid was inconstantly positive. Brain magnetic resonance imaging (MRI) scans (n = 14) were abnormal in 5 cases. Electroencephalography was nonspecific. Two patients died. At discharge and 6 months later, 5 children had neurologic sequelae. Patients with initial severe neurologic presentation and having pathological brain MRI had more sequelae or fatal disease.

International audience; We report results of the prospective surveillance system established in the largest intensive care unit (ICU) of Reunion Island (25 beds). This system covers 500,000 residents (62% of the total population) and monitors the daily status of patients >17 years of age who had a positive reverse transcription–PCR (RT-PCR) for pandemic (H1N1) 2009 virus. Reunion Island is a French overseas territory in the Southern Hemisphere, with health care facilities similar to those of mainland France. Patients were followed up until discharge from the ICU or death. Data were collected during July 15–September 30, 2009.

Objectif Presenter les caracteristiques des grands prematures (GP) enroles en 2008 et 2009 dans la cohorte de l’Observatoire regional (OGP) reunionnais de la GP. Sujets/materiels et Methodes Tous les GP admis dans les deux services de medecine neonatale de niveau III de l’ile de La Reunion (CHD Saint-Denis, GHSR Saint-Pierre) en 2008-20009. Description des causes de prematurite, de la morbidite et de la mortalite neonatales des GP. Resultats principaux Pres de 600 GP ont ete inclus dans la cohorte de l’OGP (deux tiers au CHD, un tiers au GHSR). Le taux de corticotherapie antenatale etait de 85 %. La GP etait spontanee ou induite dans la moitie des cas. Sa principale cause etait l’HTA/pre-eclamspie, presente dans un quart des naissances. Le taux d’inborn etait superieur a 90 %. La pathologie etait superposable a celle observee en metropole a l’exception d’une prevalence moindre de la maladie des membranes hyalines et de la dysplasie bronchopulmonaire. La mortalite etait compatible avec celle rencontree en Europe. Conclusions L’OGP a permis de disposer de donnees quasi exhaustives sur les GP de l’ile de La Reunion. Il a mis en evidence une preponderance des causes induites et une moindre prevalence des complications respiratoires, elements contrastant avec la situation europeenne.

Objectif Le syndrome d’Apple peel est une forme rare d’atresie grele liee a l’occlusion de l’artere mesenterique superieure et se presentant sous la forme d’une atresie proximale avec le segment distal enroule en queue de cochon autour d’un vaisseau unique. Le traitement chirurgical « classique » de ce type d’atresie se fait en deux temps, comprenant la mise en double stomie, d’amont et d’aval, en raison de l’importante disparite de calibre entre les deux segments et de la vascularisation precaire du segment distal, suivie secondairement d’un retablissement de la continuite. Nous rapportons notre experience d’enfants traites en un temps par anastomose directe. Materiel et methode Entre 2000 et 2007, quatre patients ont ete pris en charge au CHD Felix Guyon pour atresie jejunale de type Apple Peel. Trois patients (deux filles et un garcon) ont ete traites en un temps par anastomose primaire, le quatrieme patient a ete mis en double stomie et retabli secondairement. Resultats Le poids moyen des enfants traites en un temps etait de 1950 g, avec un terme moyen de 33 semaines. L’intervention a consiste en une anastomose termino-terminale avec modelage du segment proximal. La longueur totale d’intestin etait estimee respectivement a 30, 60 et 120 cm. La duree totale de nutrition parenterale etait respectivement de 8 mois, 66 jours et 32 jours. Un patient a presente un pneumoperitoine postoperatoire spontanement resolutif. L’enfant traite en deux temps l’a ete parce qu’il presentait une vascularisation precaire du segment distal avec decoloration de l’anse lors des tentatives de mobilisation. Il a ete retabli a J60, la duree totale de nutrition parenterale a ete de 127 jours. Conclusion Dans certains cas, lorsque la situation vasculaire le permet, le traitement chirurgical du syndrome d’Apple Peel en un temps, avec anastomose directe, est possible, evitant ainsi une seconde intervention. Notre serie ne permet pas d’affirmer un benefice en ce qui concerne la duree totale de nutrition parenterale.

Objectif Etablir les caracteristiques des complications associees a la pandemie grippale a virus influenza A (H1N1) chez l’enfant. Materiel et Methode Analyse retrospective des patients de moins de 18 ans, avec RT- PCR H1N1 positive entre le premier juillet 2009 et le 31 octobre 2009 a La Reunion. Resultats 113 patients inclus, 60 % de sexe masculin, âge moyen de 2,03 ans (0,17-17,42). 58,4 % avaient au moins un facteur de risque. 41,6 % hospitalises dont 6 (5,3 %) en reanimation. 85 complications etaient relevees chez 43 patients (38 %) : complication pulmonaire 61 fois (71,8 % des complications) : 23 pneumonie, 21 crise d’asthme, 13 oxygenodependance superieure a 48 h, 2 pleuresie, 2 œdeme aigu pulmonaire; d’ordre cardiaque 5 fois (5,9 %) : (3 myocardite, 2 choc cardiogenique) ; Neurologique 4 fois (4,7 %), ((3 crises convulsives, 1 encephalopathie) ; renale 4 fois (4,7 %) : (4 insuffisance renale aigue), une crise vaso-occlusive et 2 otites sont retrouvees. Un deces est note. Un enfant a presente une myocardite fulminante peroperatoire. Conclusion Les principales complications sont pulmonaires. Le virus H1N1 semble etre responsable de myocardite fulminante plus frequemment que la grippe saisonniere. Nous suggerons de surseoir a toute chirurgie non urgente en periode de pandemie grippale.

Table S4. Adverse neonatal outcomes according to other severe morbidities, obstetrical and neonatal characteristics in the EPIPAGE-2 2011 cohort. (DOCX 27 kb)

Table S3. Adverse neonatal outcomes according to other severe morbidities, obstetrical and neonatal characteristics in the OGP 2008–2013 cohort. (DOCX 25 kb)