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Preterm infants have physiological proteinuria and values of urine protein to creatinine ratio (UPr/Cr) are higher compared to full-term infants during the first week of life. Few investigations explored the changes of proteinuria in very preterm infants (VPI, ≤ 31 weeks of gestation) older than a week, and it is unclear whether high and persistent proteinuria is associated with kidney injury in this population. This study aimed to (1) observe the changes of UPr/Cr during the first month of life in VPI and (2) describe clinical and biological variables associated with the changes of UPr/Cr.Spot urine samples for UPr/Cr were collected on the first day of life (DOL1) and then on DOL2-3, DOL5-6, second week of life (WOL2), WOL3, and WOL4 in VPI cared for in a third-level NICU. We tested the relationship of UPr/Cr with perinatal variables and diseases.A total of 1140 urine samples were obtained for 190 infants. UPr/Cr values (mg/mmol) (median with interquartile) at DOL1, DOL2, DOL3, WOL2, WOL3, and WOL4 were, respectively, 191 (114-399), 226 (152-319), 225 (156-350), 282 (200-488), 308 (188-576), and 325 (175-664). At the multivariate analysis, lower gestational age (GA) and increasing postnatal age were the only variables significantly associated with higher UPr/Cr values (p 0.001). There was wide intra- and interindividual variability in UPr/Cr, especially in infants with higher GA and clinical stability.In VPI, UPr/Cr is higher at lower GA and increases with advancing postnatal age. High persistent proteinuria is not associated with clinical and biological variables reflecting kidney injury during the first month of life. A higher resolution version of the Graphical abstract is available as Supplementary information.

To determine the impact of maternal coronavirus disease 2019 (COVID-19) on prematurity, birthweight and obstetric complications.Nationwide, population-based retrospective cohort study.National Programme de Médicalisation des Systèmes d'Information database in France.All single births from March to December 2020: 510 387 deliveries, including 2927 (0.6%) with confirmed COVID-19 in the mother and/or the newborn.The group with COVID-19 was compared with the group without COVID-19 using the chi-square test or Fisher's exact test, and the Student's t test or Mann-Whitney U test. Logistic regressions were used to study the effect of COVID-19 on the risk of prematurity or macrosomia (birthweight ≥4500 g).Prematurity less than 37, less than 28, 28-31, or 32-36 weeks of gestation; birthweight; obstetric complications.In singleton pregnancies, COVID-19 was associated with obstetric complications such as hypertension (2.8% versus 2.0%, p 0.01), pre-eclampsia (3.6% versus 2.0%, p 0.01), diabetes (18.8% versus 14.4%, p 0.01) and caesarean delivery (26.8% versus 19.7%, p 0.01). Among pregnant women with COVID-19, there was more prematurity between 28 and 31 weeks of gestation (1.3% versus 0.6%, p 0.01) and between 32 and 36 weeks of gestation (7.7% versus 4.3%, p 0.01), and more macrosomia (1.0% versus 0.7%, p = 0.04), but there was no difference in small-for-gestational-age newborns (6.3% versus 8.7%, p = 0.15). Logistic regression analysis for prematurity showed an adjusted odds ratio (aOR) of 1.77 (95% CI 1.55-2.01) for COVID-19. For macrosomia, COVID-19 resulted in non-significant aOR of 1.38 (95% CI 0.95-2.00).COVID-19 is a risk factor for prematurity, even after adjustment for other risk factors.The risk of prematurity is twice as high in women with COVID-19 after adjustment for factors usually associated with prematurity.

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.

Objectives: To identify if there is a specific neonatal morbidity/mortality among second twins relative to first twins.Study design: A 17-year (2001–2017) population-based observational cohort of a...

International audience; To describe the exposure to drugs used for the treatment of patent ductus arteriosus (PDA) in a large cohort of preterm infants born before 32 weeks of gestation. METHODS: A prospective observational cohort analysis was conducted during 2 years in 28 French level 3 NICU using the same computerized order-entry system. The main outcome was "a medically treated PDA," defined as exposure to ibuprofen, indomethacin, or paracetamol prescribed with the indication of PDA closure. Secondary outcomes were as follows: time of the first treatment administration; total exposure to furosemide during hospitalization; and rate of PDA refractory to pharmacological closure. RESULTS: The study cohort consisted of 2614 infants. Among them, 474 (18.1%) received a medical treatment for PDA, with a mean postnatal age at treatment of 4.3 ± 6.6 days. The drug used as a first-line treatment was ibuprofen in 89.5% and paracetamol in 10.5%. One hundred and ninety-five infants (7.4%) had a PDA refractory to pharmacological closure. At the multivariate analysis, factors associated with PDA refractory to pharmacological closure (OR; 95% CI) were as follows: gestational age (GA) (0.81; 0.72-0.90), paracetamol as the first-line treatment (0.32; 0.15-0.68), and pharmacological treatment before 48 h of life (0.63; 0.43-0.94). 24.6% of the study cohort was exposed to furosemide (cumulative dose 6.5 ± 12.6 mg/kg). Variables significantly associated with higher cumulative doses of furosemide were lower GA and ibuprofen treatment (both p

Objectifs : Evaluer les couts associes a la prise en charge medicale des grands prematures (≤ 32semaines d’amenorrhee : SA) en France, dans la premiere annee de vie, du point de vue de l’Assurance Maladie. Comparaison aux couts associes aux autres naissances prematurees (33-37 SA) et a terme (≥ 37 SA).Methode : Extraction des donnees medicales et de remboursements issues du systeme d’information national de l’Assurance Maladie (SNIIRAM) de l’ensemble des naissances en 2009-2010. Description et comparaison des distributions de couts a l’aide du test statistique Mann-Whitney.Resultats : Extraction de 467 106 naissances au final, dont 0,71 % de grands prematures, sur 4,96 % de prematures au total (< 37 SA). Les sejours hospitaliers des grands prematures (resp. l’ensemble des prematures) representaient 14% (resp. 26%) du cout total hospitalier. Les couts moyens associes etaient 25 fois superieurs (resp. 7) a ceux des naissances a terme. L’ensemble des soins non-hospitaliers des grands prematures representaient 3% (resp. 10%) du cout total non-hospitalier. Les couts moyens associes etaient 5 fois superieurs (resp. 2 fois) a ceux des naissances a terme. Les resultats revelent une relation inverse significative entre les couts et l’âge gestationnel a la naissance, et d’importantes differences en termes de consommation de soins des grands prematures compares aux naissances a terme.Conclusion : Cette etude du cout de la prematurite en France constitue un premier travail permettant de justifier sur le plan medico-economique la necessite d’ameliorer la prevention de la prematurite et de ses consequences.

International audience; Aims: To analyse the risk factors associated with home births and “en-route” deliveries that occurred in the south of Reunion Island. Patients and methods: Since 2001, all births have been recorded in an epidemiological database from 22 weeks’ gestation, including maternal and neonatal information. This study is based on a 15-year period (1/01/2001–31/12/2015).Results: Over this period, there were 656 cases of home births recorded across a total of 81,511 of all births in South Reunion (0.8%). Compared with births in maternity units, these deliveries occurred on the whole at night (67% vs. 54%, OR: 1.74 [1.4–2.1]), by multiparous women (OR: 5 [3.7–6.2]) and and highly multiparous women (5 or more children, OR: 4.1 [3.5–4.9]), women aged over 35 years (OR: 1.4 [1.2–1.7]), in single-parent families (women who live alone, OR: 1.47 [1.3–1.7]), households from a lower socioeconomic (without work OR: 1.24 [1.2–1.3]) and educational (primary or secondary school, OR: 2.4 [2.0–2.9]) background, and who had received fewer prenatal checkups (number of visits 6.4 vs. 9.0). From a neonatal point of view, prematurity was more common (17 vs. 9.9%, OR: 1.9 [1.6–2.4]), as was severe prematurity (< 33 weeks, 5.1 vs. 2.2%, OR: 2.38 [1.7–3.4]) and transfers to a neonatal unit (12.7 vs. 8.0%, OR: 1.67 [1.3–2.1]) were more significant (P< 0.0001). There were 43 perinatal deaths (9.4%, OR: 3.2 [2.3–4.6]) and one maternal death, in a 26-year old highly multiparous woman.Conclusions: In this context, specific monitoring of multiparous women from a low socioeconomic background appears to be a priority.; Objectifs : Analyser les facteurs de risque des accouchements à domicile et « en route » survenus dans le Sud de l’île de La Réunion. Patients et méthodes : Depuis 2001, toutes les naissances sont colligées dans une base de données épidémiologique à partir de 22 semaines d’aménorrhée avec les données maternelles et néonatales. Cette étude porte sur une période de 15 ans (1er janvier 2001–31 décembre 2015). Résultats : Pendant la période d’étude, il y a eu 656 cas recensés d’accouchements à domicile sur un total de 81 511 naissances totales dans le Sud Réunion (0,8 %). Par rapport aux naissances dans les maternités, ces accouchements surviennent surtout la nuit (67 vs 54 %, OR : 1,74 [1,4–2,1]), chez des multipares (OR : 5 [3,7–6,2]) et grandes multipares (cinq enfants et plus, OR : 4,1 [3,5–4,9]), chez des femmes de plus de 35 ans (OR : 1,4 [1,2–1,7]), dans des foyers monoparentaux (femmes vivant seules, OR : 1,47 [1,3–1,7]), des foyers niveau socio économique (sans profession, OR : 1,24 [1,2–1,3]) et éducatifs (niveau primaire ou collège, OR : 2,4 [2,0–2,9]) plus faibles, et ayant plutôt un moins bon suivi prénatal (nombre de visites : 6,4 vs 9,0). Du point de vue néonatal, on retrouve plus de prématurité (17 vs 9,9 %, OR : 1,9 [1,6–2,4]), de grande prématurité (< 33 SA, 5,1 vs 2,2 %, OR : 2,38 [1,7–3,4]) et de transferts en néonatologie (12,7 vs 8,0 %, OR : 1,67 [1,3–2,1]), de manière significative (p < 0,0001). Il y a eu 43 décès périnatals (9,4 %, OR : 3,2 [2–4,6]) et une mort maternelle chez une grande multipare de 26 ans. Conclusions : Dans notre contexte, un suivi particulier chez les multipares à bas niveau socio-économique semble prioritaire.

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.

International audience; Background: Early diagnosis is essential to improve the treatment and prognosis of newborn infants with nosocomial bacterial infections. Although cytokines and procalcitonin (PCT) have been evaluated as early inflammatory markers, their diagnostic properties have rarely been compared.Objectives: This study evaluated and compared the ability of individual inflammatory markers available for clinician (PCT, semi-quantitative determination of IL-8) and of combinations of markers (CRPi plus IL-6 or quantitative or semi-quantitative determination of IL-8) to diagnose bacterial nosocomial infections in neonates.Methods: This prospective two-center study included neonates suspected of nosocomial infections from September 2008 to January 2012. Inflammatory markers were measured initially upon suspicion of nosocomial infection, and CRP was again measured 12–24 h later. Newborns were retrospectively classified into two groups: those who were infected (certainly or probably) and uninfected (certainly or probably).Results: The study included 130 infants of median gestational age 28 weeks (range, 24–41 weeks). Of these, 34 were classified as infected and 96 as uninfected. The sensitivity, specificity, positive and negative predictive values (PPV and NPV), and positive and negative likelihood ratios (LR+ and LR-) for PCT were 59.3% (95% confidence interval [CI], 38.8–77.6%), 78.5% (95% CI, 67.8–86.9%), 48.5% (95% CI, 30.8–66.5%), 84.9% (95% CI, 74.6–92.2%), 2.7 (95% CI, 1.6–4.9), and 0.5 (95% CI, 0.3–0.8), respectively. Semi-quantitative IL-8 had the highest specificity (92.19%; 95% CI, 82.70–97.41%), PPV (72.22%; 95% CI, 46.52–90.30%) and LR+ (6.17, 95% CI, 2.67–28.44), but had low specificity (48.15%; 95% CI, 28.67–68.05%). Of all markers tested, the combination of IL-6 and CRPi had the highest sensitivity (78.12%; 95% CI, 60.03–90.72%), NPV (91.3%; 95% CI, 82.38–96.32%) and LR- (0.29; 95% CI, 0.12–0.49). The combination of IL-6 and CRPi had a higher area under the curve than PCT, but with borderline significance (p = 0.055).Conclusions: The combination of IL-6 and CRPi was superior to other methods, including PCT, for the early diagnosis of nosocomial infection in neonates, but was not sufficient for sole use. The semi-quantitative determination of IL-8 had good diagnostic properties but its sensitivity was too low for use in clinical practice.

Introduction Des la naissance, le nouveau-ne presente une proteinurie «physiologique» due a l’immaturite glomerulaire et tubulaire, d’autant plus marquee que l’âge gestationnel (AG) est faible. Chez l’enfant a terme, la proteinurie diminue au cours du premier mois et sa persistance est pathologique. La persistance d’une proteinurie chez les nouveau-nes prematures est aussi consideree comme un marqueur d’atteinte renale; toutefois, ni les valeurs physiologiques, ni le profil de l’excretion urinaire des proteines dans le premier mois de vie ne sont connus. Le ratio proteinurie/creatininurie (P/C) est un indicateur valide de proteinurie, car positivement correle au dosage de la proteinurie sur les urines des 24 heures. L’objectif de cette recherche etait d’etudier l’evolution et mesurer les centiles de reference de P/C dans les 4 premieres semaines (S) de vie postnatale dans une cohorte de grands prematures. Patients et methodes Etude prospective, observationnelle. Pendant la periode d’etude, tous les nouveau-nes d’AG Resultats Nous avons inclus 145 nouveau-nes (AG 28,9 ± 2,1 SA; PN 1115 ± 355 g). Les valeurs du 50e percentile (10e–90e) de P/C (g/mol) variaient ainsi: 196 (90–549) (P1), 233,5 (136–616) (P2), 243,5 (123–521) (P3), 296 (142–1055) (P4), 337 (121–1286) (P5), 318 (133–1023) (P6). Le P/C etait significativement plus eleve a S2, S3 et S4 par rapport aux trois prelevements de la 1ere semaine de vie (p Conclusion Cette etude a permis de decrire les variations et les percentiles de reference de P/C dans une cohorte de grands prematures. Il sera utile d’identifier les facteurs cliniques, pathologiques et medicamenteux associes a P/C > 90e percentile a un mois de vie et proposer un suivi renal adapte a ces patients. Ethique Etude financee a l’Appel d’Offres Internes (Medicaux) 2014. Consentement eclaire des parents (non opposition notifiee sur le dossier patient et information ecrite remise aux parents, comme demande par le CPP).

Introduction Peu d’etudes ont explore le risque de prematurite induit par les anti-inflammatoires non steroidiens (AINS), alors que la prematurite constitue un facteur de risque majeur de morbidite et de mortalite post-natales. Le but de cette etude etait d’evaluer le risque de naissance prematuree associe aux AINS, en mettant l’accent sur l’exposition precoce des meres (periode depuis la conception jusqu’a 22 semaines d’amenorrhee [SA]). Methodes Nous avons fait une etude de cohorte retrospective a partir des donnees du Systeme national des donnees de sante (SNDS). Ont ete incluses toutes les grossesses survenues entre janvier 2012 et decembre 2014, chez des femmes âgees de 15 a 45 ans et ayant donne lieu a une naissance vivante survenant apres 22 SA. Nous avons exclu les grossesses multiples, celles pour lesquelles des anti-inflammatoires ont ete administres apres 22 SA et celles pour lesquelles le chainage mere–enfant etait impossible. Au total, 1 598 330 grossesses ont ete incluses. La prematurite etait definie comme une naissance avant 37 SA. Nous avons egalement etudie les accouchements extremement prematures ( Resultats L’exposition precoce des femmes enceintes a des AINS non selectifs est associee a un risque significativement accru de prematurite, quelle que soit la gravite de celle-ci (extreme : ORa = 1,76 [1,54 ; 2,00], moderee : ORa = 1,28 [1,17 ; 1,40], tardive : ORa = 1,08 [1,05 ; 1,11]). Inversement, l’exposition precoce aux inhibiteurs selectifs de la COX-2 n’augmente pas le risque de naissance prematuree, pas plus que les agents biologiques utilises seuls. Le risque de prematurite differe selon l’AINS, il est accru en cas d’exposition a l’une des molecules suivantes : ketoprofene, flurbiprofene, nabumetone, etodolac, indomethacine. Discussion/Conclusion L’utilisation des AINS non selectifs au cours des 22 premieres semaines de la grossesse est associee a un risque accru de prematurite. Les differences entre les AINS devront etre confirmees. Ces resultats peuvent aider a affiner les recommandations en matiere de sante publique.

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; Background: Describe the 1-year hospitalization and in-hospital mortality rates, in infants born after 31 weeks ofgestational age (GA).Methods: This nation-wide population-based study used the French medico-administrative database to assess thefollowing outcomes in singleton live-born infants (32–43 weeks) without congenital anomalies (year 2011): neonatalhospitalization (day of life 1 – 28), post-neonatal hospitalization (day of life 29 – 365), and 1-year in-hospital mortalityrates. Marginal models and negative binomial regressions were used.Results: The study included 696,698 live-born babies. The neonatal hospitalization rate was 9.8%. Up to 40 weeks,the lower the GA, the higher the hospitalization rate and the greater the likelihood of requiring the highest levelof neonatal care (both p < 0.001). The relative risk adjusted for sex and pregnancy-related diseases (aRR) reached21.1 (95% confidence interval [CI]: 19.2-23.3) at 32 weeks. The post-neonatal hospitalization rate was 12.1%. Theraw rates for post-neonatal hospitalization fell significantly from 32 – 40 and increased at 43 weeks and thispersisted after adjustment (aRR = 3.6 [95% CI: 3.3–3.9] at 32 and 1.5 [95% CI: 1.1–1.9] at 43 compared to 40 weeks).The main causes of post-neonatal hospitalization were bronchiolitis (17.2%), gastroenteritis (10.4%) ENT diseases(5.4%) and accidents (6.2%). The in-hospital mortality rate was 0.85‰, with a significant decrease (p < 0.001)according to GA at birth (aRR = 3.8 [95% CI: 2.4–5.8] at 32 and 6.6 [95% CI: 2.1–20.9] at 43, compared to 40 weeks.Conclusion: There’s a continuous change in outcome in hospitalized infants born above 31 weeks. Birth at 40 weeksgestation is associated with the lowest 1-year morbidity and mortality.

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.

SummaryWhat is known The neonatal intensive care units (NICUs) are at the highest risk of drug dose error of all hospital wards. NICUs also have the most complicated prescription modalities. The computerization of the prescription process is currently recommended to decrease the risk of preventable adverse drug effects (pADEs) in NICUs. However, Computer Prescribing Order Entry–Clinical Decision Support (C.P.O.E./C.D.S.) systems have been poorly studied in NICUs, and their technical compatibility with neonatal specificities has been limited. Objectives We set up a performance study of the preselected prescription of drugs for neonates, which limited the role of the prescriber to choosing the drugs and their indications. Methods A single 29 bed neonatal ward used this neonatal C.P.O.E./C.D.S. system for all prescriptions of all hospitalized newborns over an 18-month period. The preselected prescription of drugs was based on the indication, gestational age, body weight and post-natal age. The therapeutic protocols were provided by a formulary reference (330 drugs) that had been specifically designed for newborns. The preselected prescription also gave complete information about preparation and administration of drugs by nurses. The prescriber was allowed to modify the preselected prescription but alarms provided warning when the prescription was outside the recommended range. The main clinical characteristics and all items of each line of prescription were stored in a data warehouse, thus enabling this study to take place. Results Seven hundred and sixty successive newborns (from 24 to 42 weeks’ gestation) were prescribed 52 392 lines of prescription corresponding to 65 drugs; About 30·4% of neonates had at least one out of licensed prescription; A prescription out of the recommended range for daily dose was recorded for 1·0% of all drug prescriptions. What is new? The C.P.O.E./C.D.S. systems can currently provide a complete preselected prescription in NICUs according to dose rules, which are specific to newborns and also comply with local specificities (therapeutic protocols and formulation of drugs). The role of the prescriber is limited to the choice of drugs and their indications. The prescriber still retains the possibility of modifying each item of the prescription, with all other prescription items being calculated by the C.P.O.E. system. In these conditions, the prescribers rarely modified the preselected prescription and the rate of out of range prescription was low. A multicentric study is required to confirm and extend these observations. Conclusions This study showed the feasibility of preselected prescription in NICUs and a low rate of out of range prescriptions. The preselected prescription could play a key role in lowering the dose error rate in NICUs.

International audience; What is known and objective The risk of dosage Prescription Medication Error (PME) among manually written prescriptions within ‘mixed’ prescribing system (computerized physician order entry (CPOE) + manual prescriptions) has not been previously assessed in neonatology. This study aimed to evaluate the rate of dosage PME related to manual prescriptions in the high-risk population of very preterm infants (GA \textless 33 weeks) in a mixed prescription system. Methods : The study was based on a retrospective review of a random sample of manual daily prescriptions in two neonatal intensive care units (NICU) A and B, located in different French University hospitals (Dijon and La Reunion island). Daily prescription was defined as the set of all drugs manually prescribed on a single day for one patient. Dosage error was defined as a deviation of at least ±10% from the weight-appropriate recommended dose. Results and discussion : The analyses were based on the assessment of 676 manually prescribed drugs from NICU A (58 different drugs from 93 newborns and 240 daily prescriptions) and 354 manually prescribed drugs from NICU B (73 different drugs from 131 newborns and 241 daily prescriptions). The dosage error rate per 100 manually prescribed drugs was similar in both NICU: 3·8% (95% CI: 2·5–5·6%) in NICU A and 3·1% (95% CI: 1·6–5·5%) in NICU B (P = 0·54). Among all the 37 identified dosage errors, the over-dosing was almost as frequent as the under-dosing (17 and 20 errors, respectively). Potentially severe dosage errors occurred in a total of seven drug prescriptions. None of the dosage PME was recorded in the corresponding medical files and information on clinical outcome was not sufficient to identify clinical conditions related to dosage PME. Overall, 46·8% of manually prescribed drugs were off label or unlicensed, with no significant differences between prescriptions with or without dosage error. The risk of a dosage PME increased significantly if the drug was included in the CPOE system but was manually prescribed (OR = 3·3; 95% CI: 1·6–7·0, P \textless 0·001). What is new and conclusion : The presence of dosage PME in the manual prescriptions written within mixed prescription systems suggests that manual prescriptions should be totally avoided in neonatal units.

Parmi les 139 196 femmes qui ont accouche en Bourgogne de 2000 a 2009, 11 135 habitaient a plus de 30 minutes d’une maternite et 467 a plus de 45 minutes.L’objectif de notre etude etait d’analyser l’impact du temps de trajet du domicile a la maternite la plus proche sur les indicateurs de perinatalite.Methodes : Les donnees utilisees sont celles du PMSI « elargi » du reseau perinatal de Bourgogne (RPB). Les temps de trajet ont ete calcules du centroide du code PMSI du domicile a celui de la commune de la maternite la plus proche. Pour evaluer l’impact du temps de trajet nous avons utilise des regressions logistiques multiniveaux. L’ajustement a ete fait sur les donnees individuelles, l’environnement socio-demographique et la typologie du lieu de residence.Resultats : Pour des temps superieurs a 45 minutes, les taux bruts de mortinatalite passent de 0,46% a 0,86% et ceux de la mortalite perinatale de 0,64% a 1,07%. Apres ajustement, il persiste une liaison positive entre les risques de souffrance fœtale aigue (anomalies du RCF et LAM), de mortinatalite, de mortalite perinatale, d’hospitalisations antenatales et d’accouchement hors-hopital.Discussion et conclusion : Nos resultats montrent qu’en Bourgogne, la duree du trajet a la maternite la plus proche a un impact sur la sante perinatale. D’autres etudes sont necessaires car s’ils se confirmaient, ces effets negatifs seraient a prendre en compte lors de toute evaluation des benefices, tant medicaux qu’economiques, attendus des restructurations et des fermetures des maternites.

International audience; Maternity unit closures in France have increased travel time for pregnant women in rural areas. We assessed the impact of travel time to the closest unit on perinatal outcomes and care in Burgundy using multilevel analyses of data on deliveries from 2000 to 2009. A travel time of 30min or more increased risks of fetal heart rate anomalies, meconium-stained amniotic fluid, out-of-hospital births, and pregnancy hospitalizations; a positive but non-significant gradient existed between travel time and perinatal mortality. The effects of long travel distances on perinatal outcomes and care should be factored into closure decisions.

SUMMARYThe aim of this study was to describe the incidence and risk factors for respiratory morbidity during the 12-month period following the first respiratory syncytial virus (RSV) season in 242 preterm infants [vs. 11%,P = 0·007) and recurrent wheezing episodes (4%vs. 1%,P = 0·049). The 17 infants (14 preterms, three full-terms) who had been hospitalized for RSV-confirmed bronchiolitis during their first RSV season had significantly more wheezing episodes during the follow-up period than subjects who had not been hospitalized for RSV-confirmed bronchiolitis (odds ratio 4·72, 95% confidence interval 1·71–13·08,P = 0·003). Male gender, birth weight

International audience; OBJECTIVE: To assess the impact of household smoking and palivizumab prophylaxis on the risk of respiratory syncytial virus (RSV) hospitalisation in late-preterm (32-35 weeks' gestational age) infants. METHODS: Familial smoking and other RSV risk factor data from the FLIP, FLIP-2 and IMpact studies and datasets from France, Germany and Italy, together with palivizumab prophylaxis data from the FLIP-2 and IMpact studies, were analysed using cross-correlation and Bayesian meta-analytical modelling employing Markov Chain Monte Carlo sampling. RESULTS: There were 2.35 times (95% confidence interval [CI] 1.37-4.02) as many hospitalisations amongst infants from smoking compared with those from non-smoking families. Among non-prophylaxed infants, there were 2.53 times (95% CI 1.27-4.94) as many RSV hospitalisations from smoking than from non-smoking families and that excess hospitalisation was reduced to 1.03 times (95% CI 0.38-2.99) amongst prophylaxed infants. Familial smoking correlates significantly (p \textless 0.01) with other RSV risk factors: positive correlation with number of school-age siblings, history of family atopy, family wheeze and gestational age; negative correlation with birth weight and breast feeding. CONCLUSIONS: Late-preterm infants from smoking families appear to be at heightened risk for severe RSV infection requiring hospitalisation of which the risk may be reduced with RSV prophylaxis.

Cefotaxime is one of the most frequently prescribed antibiotics for the treatment of Gram-negative bacterial sepsis in neonates. However, the dosing regimens routinely used in clinical practice vary considerably. The objective of the present study was to conduct a population pharmacokinetic study of cefotaxime in neonates and young infants in order to evaluate and optimize the dosing regimen. An opportunistic sampling strategy combined with population pharmacokinetic analysis using NONMEM software was performed. Cefotaxime concentrations were measured by high-performance liquid chromatography-tandem mass spectrometry. Developmental pharmacokinetics-pharmacodynamics, the microbiological pathogens, and safety aspects were taken into account to optimize the dose. The pharmacokinetic data from 100 neonates (gestational age [GA] range, 23 to 42 weeks) were modeled with an allometric two-compartment model with first-order elimination. The median values for clearance and the volume of distribution at steady state were 0.12 liter/h/kg of body weight and 0.64 liter/kg, respectively. The covariate analysis showed that current weight, GA, and postnatal age (PNA) had significant impacts on cefotaxime pharmacokinetics. Monte Carlo simulations demonstrated that the current dose recommendations underdosed older newborns. A model-based dosing regimen of 50 mg/kg twice a day to four times a day, according to GA and PNA, was established. The associated risk of overdose for the proposed dosing regimen was 0.01%. We determined the population pharmacokinetics of cefotaxime and established a model-based dosing regimen to optimize treatment for neonates and young infants.

International audience; Objective: To investigate the association between birth weight and respiratory syncytial virus (RSV) hospitalisation during the first year of life in 33°–356 weeks’ gestational age (wGA) infants.Study design: Pooled analysis of data (n = 1218) from Spain, Germany, France and Italy.Result: RSV hospitalised infants overall had a significantly higher birth weight than non-hospitalised infants (2.24 versus 2.14 kg; p \textless 0.001) for both males (2.25 versus 2.18 kg; p = 0.049) and females (2.22 versus 2.11 kg, p = 0.007). The effect was significant only in 34 wGA infants (33 wGA: hospitalised 1.95 kg versus non-hospitalised 1.95 kg, p = 0.976; 34 wGA: 2.26 versus 2.14 kg, p = 0.007; 35 wGA: 2.37 versus 2.29 kg, p = 0.070), particularly female 34 wGA infants (female: 2.24 versus 2.08 kg, p = 0.019; male: 2.27 versus 2.20, p = 0.191). Birth weight was shown to be an independent risk factor for RSV hospitalisation.Conclusions: In 33–35 wGA infants, a higher birth weight appeared independently associated with an increased risk of RSV hospitalisation.

International audience; OBJECTIVES: To describe the maternal and neonatal outcomes of a large cohort of adolescent pregnancies in a tertiary care hospital at Reunion Island. METHODS: Retrospective study of all primiparous singleton pregnancies over 10.5 years. Adolescent (\textless18 years) were compared to 18-29 years pregnancies. The maternal outcomes were obstetric illness, labor complications, and way of delivery. Neonatal outcomes were preterm birth, low birth weight (LBW), small for gestational age, birth asphyxia, need for mechanical ventilation, and mortality. RESULTS: We analyzed 1839 adolescent pregnancies and 11,445 controls. Adolescents had worse prenatal care than older mothers, (4.4 vs. 1.4%; p \textless 0.0001), higher rates of smoking and alcohol assumption (13 vs. 11% and 0.7 vs. 0.4%, both p \textless 0.05). They showed less pregnancy-related illness and labor complications and higher rates of normal vaginal delivery (80 vs. 69%; p \textless 0.0001), without increased risk of episiotomy or postpartum hemorrhage. Offspring mortality, preterm birth, and LBW were higher in adolescent pregnancies (3.3 vs. 2.2%; p = 0.001, 14 vs. 12%; p = 0.0008; 17 vs. 14%; p = 0.002). CONCLUSIONS: In this population, adolescents had an obstetrical outcome better than controls, but their offspring short-term outcomes were unfavorable. Furthers studies are needed to better elucidate the link between adolescent pregnancy and impaired neonatal outcome.

International audience; OBJECTIVE: Evidence supports the efficacy of probiotics in reducing necrotizing enterocolitis (NEC) in very low-birth-weight infants, although concerns remain with regard to their routine use. Since 2008 in our neonatal intensive care unit, a low dose of probiotics (unique strain) is administered as standard of care in all preterm babies born at 24 to 31 weeks' gestation. This study reports outcomes in infants receiving probiotic cohort (PC) compared with the historical cohort. DESIGN: Treatment with Lactobacillus rhamnosus Lcr35 (Lcr Restituo) (2 × 108 colony-forming units/12 h) was started early after birth and intention to treat was up to 36 weeks' gestation. The main outcome was definite NEC. Secondary outcomes were mortality, late-onset sepsis (LOS), cholestasis, isolated rectal bleeding (IRB), and time to reach full enteral feeding (FEF). RESULTS: A total of 1130 patients were included. No adverse effects were observed. Infants in PC presented a reduced rate of NEC (odds ratio [OR] 0.20; 95% confidence interval [CI] 0.07 to 0.58), mortality (OR 0.46; 95% CI 0.21 to 1.00), and LOS (OR 0.60; 95% CI 0.40 to 0.89) and achieved FEF significantly earlier. IRB was significantly reduced among infants receiving the complete scheduled treatment. CONCLUSION: Administration of Lcr Restituo was well tolerated and associated with lower mortality and morbidities in this cohort. Our results provide evidence in support of the hypothesis that this probiotic may reduce IRB.

International audience; Background: Recent guidelines for preterm parenteral nutrition (PN) recommend an earlier and higher intake of amino acids (AA) and energy to avoid postnatal catabolism and approximate normal foetal growth. Few investigations explored how early PN may affect electrolyte and water homeostasis. We performed a prospective observational trial to assess the effect of nutrient intake on electrolyte homeostasis and balance. Methods: During 16 months all infants ≤32 weeks were eligible. In the first week of life we recorded daily: electrolytes (plasma and 8-hour urine collection), nutritional intake, urine output, body weight and we calculated sodium (Na) and potassium (K) balance. Infants were divided, for analysis, into 3 groups of AA intake: Low 2g/kg/day (HAA). Results: 154 infants were included. HAA group presented lower weight loss. Na balance was influenced by urine output and postnatal age, with little contribution of nutrition. Kalemia and K balance were mainly influenced by AA intake. K balance differed among groups: LAA -2.3 mol/kg/wk, MAA 1.1 mmol/kg/wk and HAA 2.6 mmol/kg/wk (p

OBJECTIVE: To identify the best combination of serum cytokines and clinical parameters to diagnose rapidly early-onset neonatal infection (EONI) in critically ill preterm infants. At birth, most critically ill neonates are receiving broad-spectrum antibiotics pending bacterial culture results, because distinguishing infected from noninfected infants at birth is difficult. DESIGN: Prospective study. SETTING: Neonatal intensive care unit in a tertiary care hospital. PATIENTS: Two hundred thirteen infants, born before 33 wks' gestation, admitted to the neonatal intensive care unit within 6 hrs of life with a presumptive diagnosis of EONI. INTERVENTION: A presumptive diagnosis of EONI was associated with a 300-μL blood sample to measure six cytokine (interleukin [IL]-1β, IL-6, IL-8, IL-10, IL-12, tumor necrosis factor-α) concentrations, using the cytometric bead array technique. MEASUREMENTS AND MAIN RESULTS: Of the 213 infants included, 31 had a definite or possible EONI and 182 were not infected. Concentrations of IL-6, IL-8, and IL-10 were significantly increased in infected neonates, in comparison with infants without EONI. In contrast, IL-1β, IL-12, and tumor necrosis factor-α concentrations were not. Logistic regression analyses were performed to construct multivariate predictive models that could distinguish infected from noninfected infants at birth. A clinical score was based on three parameters independently associated with EONI (i.e., interval of >12 hrs between the membranes rupture and delivery, prenatal maternal colonization and mechanical ventilation at birth). This score was compared with scores including clinical parameters and serum cytokines, alone or in combination. The best predictive model combined the three clinical parameters, IL-6 (positive threshold, 300 pg/mL) and IL-8 (positive threshold, 300 pg/mL) concentrations. CONCLUSION: A predictive model combining serum IL-6 and IL-8 measurements and selected clinical variables could distinguish infected from noninfected preterm infants at birth and should help the clinician in reducing or shortening the unnecessary use of antibiotics.

International audience; Abstract: In severe perinatal asphyxia, the prognostic value of apparent diffusion coefficient (ADC) measurements is still open to question. We hypothesized that temporal and anatomical changes of brain ADC values occurring early after the hypoxic ischemic insult could predict the outcome at 36 months. To demonstrate this, mean ADC values were calculated for 16 brain structures in 59 term neonates who underwent an MR examination during the first month of life. Neonates were divided into two groups according to their 36-month outcome: unfavorable (death/severe disability) or favorable outcome. ADC values were plotted against age at scan. In neonates with favorable outcomes (n=32), ADC values were constant over the study period. In babies with unfavorable outcomes (n=27), ADCs exhibited two different patterns. In infratentorial structures, ADCs were constant and normal. In supratentorial areas, ADCs followed a biphasic temporal evolution: ADC values were at their lowest at day 2, showed a rapid increase until Days 5-7, and were thereafter similar to those of neonates with favorable outcomes. Using receiver operating characteristic analysis, during the first 3-5 days of life, all neonates with decreased ADC had an unfavorable outcome. These temporal and anatomical changes of ADC values imply that individual prognosis of asphyxiated neonates can only be predicted by measurement of ADC in supratentorial areas within the first 3-5 days of life.

Background: The persistence of a patent ductus arteriosus (PDA) in preterm infants complicates their clinical course and may contribute to increased morbidity. Intravenous preparations of ibuprofen constitute one of the standard therapies for closure of a PDA. However, the unavailability of intravenous ibuprofen in certain regions of the world and the availability of inexpensive oral preparations has led to off-label nasogastric administration of oral ibuprofen in preterm infants with PDA. Objective: This article reviews and comments on the evidence for the enteral use of oral formulations of racemic ibuprofen for PDA closure in preterm infants, with a focus on the risk of necrotizing enterocolitis (NEC). Methods: MEDLINE, Current Contents, and Google Scholar were searched in April 2010 for trials of enteral ibuprofen in the treatment of PDA in preterm or low-birth-weight infants using the terms treatment, pharmacokinetics, ibuprofen, oral, enteral, patent ductus arteriosus, PDA, preterm, premature, low birth weight, infant , and newborn . Relevant congress Web sites were also searched for relevant abstracts. Results: The literature search identified 2 pharmacokinetic studies involving 32 infants and 13 clinical efficacy studies involving 306 infants treated with enteral ibuprofen. The clinical studies reported some benefit for enteral ibuprofen relative to the comparators. However, these studies had methodologic limitations, including small numbers of subjects, lack of blinding, inclusion of preterm infants with a higher gestational age, customized treatment regimens, and second-order statistical error that prevented conduct of a systematic review. When the results of all studies were pooled, NEC was reported in a total of 46 of 281 infants (16%) receiving enteral ibuprofen and 21 of 83 infants (25%) receiving indomethacin. This rate of NEC with enteral ibuprofen was twice that reported for intravenous ibuprofen in a recent meta-analysis (27/356 [8%]). Conclusions: The evidence supporting the off-label use of enteral ibuprofen for PDA in preterm infants is weak. Well-designed, appropriately powered pharmacologic and controlled clinical studies are needed before use of enteral ibuprofen can be recommended. In countries where an intravenous formulation of racemic ibuprofen is approved, off-label use of enteral racemic ibuprofen cannot be supported.

Resume Objectifs Evaluer l’impact de l’augmentation de l’âge des meres et du diagnostic prenatal sur la prevalence de la trisomie 21 dans un echantillon de la population francaise. Patients et methodes Les donnees sur la trisomie 21 ont ete obtenues a partir du registre de malformations congenitales REMERA entre 1978 et 2005. La population surveillee correspond a environ 10 % des naissances francaises. Nous avons etudie la prevalence totale, la prevalence des naissances vivantes ainsi que la prevalence des interruptions de grossesse apres diagnostic prenatal positif. Resultats L’âge moyen des meres a augmente passant de 26 a 30 ans sur la duree de l’etude. La prevalence totale de la trisomie 21 est passee de 14/10 000 en 1978 a 23/10 000 naissances vivantes en 2005. L’augmentation progressive du nombre d’interruption de grossesse apres diagnostic prenatal atteint 78 % des cas en 2005. La prevalence a la naissance a diminue, passant de 14/10 000 en 1978 a 5,1/10 000 en 2005. Conclusion Il est important de continuer la surveillance epidemiologique de la trisomie 21 en France, notamment du fait des changements dans les caracteristiques demographiques de la population mais egalement dans les politiques de depistage prenatal de la trisomie 21.