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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.

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).

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.

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.

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

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: 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

We previously developed a model of acute cyclosporine A (CsA)-induced vasomotor nephrotoxicity in rabbits. As exogenous adenosine infusion mimics the haemodynamic changes that characterize acute renal failure (ARF), we wanted to know whether adenosine was a mediator in this model and whether an adenosine receptor blocker could prevent the CsA-induced ARF. Group 1 were untreated controls. Group 2 received CsA (25 mg/kg per day) for 5 days. Renal function parameters were measured, showing ARF in all animals compared to controls. Theophylline (1 mg/kg i.v. bolus) was then administered and renal function was reassessed. Theophylline significantly reduced renal vascular resistance (-8%) and increased renal blood flow (RBF) (+20%), glomerular filtration rate (GFR) (+50%), filtration fraction (+24%) and diuresis (+73%), suggesting that adenosine was involved in the CsA-induced ARF. In group 3, theophylline (30 mg/kg per day) was given concomitantly with CsA for 5 days. GFR was normalized, but theophylline did not hinder the drop in RBF seen with CsA alone in group 2. Microscopy observation of the kidneys showed that chronic theophylline administration aggravated the morphological changes induced by CsA alone. We conclude that CsA administration for 5 days induced a vasomotor nephropathy with an adenosine-mediated afferent arteriolar constriction which cannot be prevented by concomitant theophylline administration

The renal effects of acute hypoxemia and the ability of perindoprilat, a potent angiotensin-converting enzyme inhibitor, to prevent these effects were assessed in 31 anesthetized and mechanically ventilated newborn (5 to 8 d of age) rabbits. Renal blood flow (RBF) and GFR were determined by the clearances of para-aminohippuric acid and inulin, respectively. Each animal acted as its own control. In eight normoxemic rabbits (group 1), the i.v. infusion of saline did not change renal and hemodynamic functions. In eight additional rabbits, acute hypoxemia (PaO2= 40 mm Hg) induced a significant decrease in mean blood pressure (-8+/-2%), RBF (-36+/-3%), and GFR (-31+/-3%) and an increase in renal vascular resistance (+50+/-12%). A third group of newborn animals (n=7) was used to determine the renal effects of perindoprilat administration (20 microg/kg) under normoxemic conditions. RBF significantly increased (+15+/-2%) and renal vascular resistance significantly decreased (-15+/-3%), whereas GFR, mean blood pressure, and filtration fraction did not change significantly. In group 4 (n=7), perindoprilat infusion completely prevented the hypoxemia-induced alterations in GFR and renal vascular resistance and partially prevented the fall in RBF. These results demonstrate that angiotensin II modulates the renal immature microcirculation and that inhibition of its formation effectively prevents the hypoxemia-induced decrease in GFR.

International audience; Background : Aim of this study was to provide a detailed description of a Methicillin-resistant Staphylococcus aureus (MRSA) outbreak management strategy in the neonatal intensive care unit of a university hospital.MethodsThis was a retrospective, “before-after” study, over two consecutive 18-month periods. The outbreak management strategy was performed by a multidisciplinary team and included: extensive healthcare workers (HCW) involvement, education, continuous hand-hygiene training and active MRSA colonization surveillance. The actions implemented were identified based on an anonymous, voluntary, reporting system, carried out among all the HCW, and regular audit and feedback were provided to the nursing staff.The main measured outcome was the rate of MRSA infections before and after the implementation of the outbreak management strategy. Piecewise linear Poisson regression was performed and the model adjusted for confounding variables. The secondary outcome was the rate of laboratory-confirmed bloodstream infections before and after the outbreak management strategy. The rates of MRSA colonization, implementation of proposed actions, observed compliance for hand-hygiene and insertion/care of central lines were also recorded during the second period.Results1015 newborns were included. The rate of MRSA infections throughout the two periods fell from 3.5 to 0.7 cases per 1000 patient-days (p=0.0005). The piecewise Poisson regression analysis adjusted for confounding variables showed a significant decrease in the MRSA infection rate after the outbreak management strategy (p=0.046). A significant decrease in positive laboratory confirmed blood cultures was observed over the two periods (160 vs 83; p\textless0.0001). A significant decline in the MRSA colonization rate occurred over the second period (p=0.001); 93% of the proposed actions were implemented. The compliance rate for hand-hygiene and insertion/care of central lines was respectively 95.9% and 62%.ConclusionsThe implementation of multiple, simultaneous, evidence-based management strategies is effective for controlling nosocomial infections. Outbreak management strategies may benefit from tools improving the communication between the institutional and scientific leadership and the ground-level staff. These measures can help to identify individualized solutions addressing specific unit needs.

Background Bronchiolitis is a distressing respiratory condition and the most common cause of hospitalization during the first year of life. The hospitalization of an infant is a stressful event for parents and deserves careful consideration. The objective of this work was to develop and validate a self-administered instrument that comprehensively assesses the impact on parents of the hospitalization of their infant for bronchiolitis. Methods The Impact of Bronchiolitis Hospitalization Questionnaire (IBHQ©) was developed using a literature review and pre-study interviews with both parents and clinicians. For finalization and psychometric validation, it was included in a multicenter, longitudinal, observational study conducted in France. Parents of infants under the age of 1 year and hospitalized for bronchiolitis were asked to complete the questionnaire at hospital discharge, and 3 months after. Results Seven hundred and seven questionnaires were completed by the parents of the 463 eligible infants. After finalization, based on principal component analyses, the IBHQ included 30 core items allowing the calculation of 7 dimension core scores (Worries and distress; Fear for future; Guilt; Impact on daily organization; Physical impact; Impact on behavior with hospitalized infant; Financial impact), as well as 16 optional items, allowing the calculation of 5 optional dimension scores (Disturbed breastfeeding; Physical reaction of hospitalized infant; Impact on feeding; Impact on behavior with other infants; Siblings’ reaction). Internal consistency reliability and construct validity of the IBHQ were satisfactory. The highest impact was observed for “Worries and distress”, “Fear for future” and “Impact on daily organization” scores. Conclusions The IBHQ is a reliable and valid instrument for assessing the multifaceted impact on parents of the hospitalization of their infant for bronchiolitis.

International audience; OBJECTIVE: We aimed to investigate the predictive value for severe adverse outcome of plasma protein measurements on day one of life in very preterm infants and to compare total plasma protein levels with the validated illness severity scores CRIB, CRIB-II, SNAP-II and SNAPPE-II, regarding their predictive ability for severe adverse outcome. METHODS: We analyzed a cohort of infants born at 24-31 weeks gestation, admitted to the tertiary intensive care unit of a university hospital over 10.5 years. The outcome measure was "severe adverse outcome" defined as death before discharge or severe neurological injury on cranial ultrasound. The adjusted odd ratio (aOR) and 95% confidence interval (95% CI) of severe adverse outcome for hypoproteinemia (total plasma protein level \textless40 g/L) was calculated by univariate and multivariate analyses. Calibration (Hosmer-Lemeshow goodness-of-fit) was performed and the predictive ability for severe adverse outcome was assessed for total plasma protein and compared with CRIB, CRIB-II, SNAP-II and SNAPPE-II, by calculating receiver operating characteristic (ROC) curves and their associated area under the curve (AUC). RESULTS: 761 infants were studied: 14.4% died and 4.1% survived with severe cerebral ultrasound findings. The aOR of severe adverse outcome for hypoproteinemia was 6.1 (95% CI 3.8-9.9). The rank order for variables, as assessed by AUCs and 95% CIs, in predicting outcome was: total plasma protein [0.849 (0.821-0.873)], SNAPPE-II [0.822 (0.792-0.848)], CRIB [0.821 (0.792-0.848)], SNAP-II [0.810 (0.780-0.837)] and CRIB-II [0.803 (0.772-0.830)]. Total plasma protein predicted severe adverse outcome significantly better than CRIB-II and SNAP-II (both p\textless0.05). Calibration for total plasma protein was very good. CONCLUSIONS: Early hypoproteinemia has prognostic value for severe adverse outcome in very preterm, sick infants. Total plasma protein has a predictive performance comparable with CRIB and SNAPPE-II and greater than other validated severity scores.

SUMMARYThis study was conducted during the 2008–2009 respiratory syncytial virus (RSV) season in France to compare hospitalization rates for bronchiolitis (RSV-confirmed and all types) between very preterm infants (

Objective. To describe the chloride balance in infants born 25–32-week gestation, analyze the association of chloride changes with hydroelectrolytic status and their relationship with perinatal conditions, morbidities, and neurological outcome.Methods. For 7 days after birth, sodium and chloride balance, plasma potassium, phosphate, and total carbon dioxide (tCO2) were prospectively determined and strong ion difference (SID) calculated. Three multivariate regression analyses were performed to identify factors associated with high plasma chloride concentration, low SID, and low tCO2.Results. 107 infants were studied. Plasma chloride concentration was significantly positively associated with plasma sodium concentration. Higher plasma chloride and lower SID were significantly associated with lower plasma tCO2. Chloride intake was the main independent factor associated with high plasma chloride, low SID, and low plasma tCO2, with lesser contribution of sodium intake and low gestational age (GA). Also, patent ductus arteriosus and birth weight loss were independent factors affecting plasma chloride and SID. Neither high chloride levels nor low SID were associated to impaired neurological outcome.Conclusions. In preterm infants, chloride balance is influenced by GA and by interrelationship between sodium and chloride intake. High chloride levels are associated with metabolic acidosis but not related to increased risk of impaired neurological outcome.

International audience; BACKGROUND: While intrauterine insemination (IUI), a simple, inexpensive and non-invasive technique, is the most used assisted reproduction technology (ART) worldwide, the risk of major birth defects following IUI is paradoxically not well documented. METHODS: Retrospective cohort study performed in Burgundy, France, over a 9-year period which consisted of the cross analysis of two prospective databases, the Burgundy perinatal network database and the database of the assisted conception units in Burgundy. A total of 1348 ART singletons [in vitro fertilization technologies (IVFT): n= 903; IUI: n= 445] matched with 4044 infants conceived naturally, 552 ART twins (IVFT: n= 362; IUI: n= 190) matched with 1656 twins who were conceived naturally. The major birth defects were categorized according to the European Surveillance of Congenital Anomalies classification EUROCAT. RESULTS: Compared with naturally conceived singletons, singletons born after IUI and IVFT had a higher prevalence of major congenital malformations, with adjusted odd ratios (AOR) of 2.0 [95% confidence interval (CI) 1.0-3.8] and 2.0 (CI 1.3-3.1); 3.6 and 4.2% of infants born, respectively. All twins and unlike-sex twins born after IVFT but not IUI, have an increased prevalence of major birth defects compared with naturally conceived twins; AOR of 3.0 (CI 1.6-5.6) and 3.7 (CI 1.1-16.9), respectively. When comparing IUI with IVFT, no differences were observed for singletons (AOR 1.0; CI 0.4-2.2), all twins (AOR 0.4; CI 0.1-1.2) and unlike-sex twins (AOR 0.3; CI 0.1-4.5). CONCLUSIONS: The risk of major birth defects in singletons conceived through IUI was increased over naturally conceived singletons. This risk was no different from that observed after IVFT.

International audience; OBJECTIVE: We aimed to investigate the relationship between day-1 hypoproteinemia and severe adverse outcome (SAO) in very preterm infants admitted to the neonatal intensive care unit (NICU). STUDY DESIGN: Retrospective study of all patients born from 24 to 31 weeks gestation and cared for in our NICU over an 8-year period. Infants were excluded if the serum protein value on the first day of life was not available. RESULT: A total of 913 patients were included. In all, 14.6% presented with SAO (death or severe neurological injury on cranial ultrasound). Hypoproteinemia (total protein level \textless40 g l(-1)) on day 1 of life occurred in 19.5 % of all patients. The rate of SAO was 33.7% in patients with hypoproteinemia and 9.9% in those with normoproteinemia (P\textless0.0001). Logistic and multiple regression analysis confirmed that the association hypoproteinemia-SAO remained significant after adjustment for the other major predictors of outcome present at baseline (odds ratio 3.4; 95% confidence interval 2.1-5.4; P\textless0.0001). CONCLUSION: Hypoproteinemia was highly associated with SAO in this cohort of critically ill preterm infants. We are unable to explain the link between hypoproteinemia and adverse outcome in our population. This investigation serves as a hypothesis-generating report of a large preterm infants sample, and suggests the need to assess the predictive accuracy for adverse outcome of hypoproteinemia in future prospective studies.

Background and Purpose— Perinatal arterial ischemic stroke (PAIS) is a common cause of hemiplegic cerebral palsy in children. The diagnosis of PAIS is based on cerebral imaging. The objective of our study was to determine prenatal risk factors associated with PAIS. Methods— A retrospective case–control study was nested in the whole population of Burgundy, France, from January 2000 to December 2007. Case patients were confirmed by review of brain imaging and medical records. Three control subjects per case were randomly selected from the study population by sex, term, place, and year of birth. Results— PAIS was confirmed in 32 patients and its incidence was one per 4400 live births. In comparison to control subjects, clinical conditions significantly associated to cases were gestational diabetes (16.1% versus 4.2%; P =0.04), fetal heart rate abnormalities (35.5% versus 10.9%; P =0.001), and meconium-stained liquor (40% versus 12%; P P =0.08) and during pregnancy (32.1% versus 16.7%; P =0.07), cord abnormalities (29% versus 14.1%; P =0.06), and cesarean delivery (28.1% versus 14.6%; P =0.08). In the multivariate analysis, maternal smoking during pregnancy (OR, 3.1; 95% CI, 1.1–8.8; P =0.04) was the only risk factor significantly associated with PAIS. Conclusions— This study is the first to identify maternal smoking during pregnancy as an independent prenatal risk factor of PAIS. Additional prospective studies are needed to confirm this result and to investigate the role of maternal smoking in fetal and neonatal thrombogenesis.

The renal effects of endothelin-1 were investigated in 16 anesthetized and mechanically ventilated newborn rabbits. Renal blood flow and glomerular filtration rate were determined by the clearance of para-aminohip-puric acid and inulin, respectively. Each animal acted as its own control. In eight newborn rabbits, a bolus injection of 5 nmol·kg-1 of endothelin-1 caused an initial fall in mean arterial blood pressure followed by a gradual, significant increase in mean arterial blood pressure that lasted for 45 min. The dramatic increase in renal vascular resistance (+28 ± 4%) induced by endothelin led to a fall in glomerular filtration rate (-12 ± 4%) and renal blood flow (-16 ± 3%). In spite of the reduction of glomerular filtration rate and renal blood flow, urine flow and sodium excretion rates increased significantly (+20 ± 5% and +49 ± 9%, respectively). In eight additional newborn rabbits, a bolus injection of 1 nmol · kg-1 of endothelin—a dose that usually induces marked renal and systemic vasoconstriction in adult models—did not affect systemic or renal hemodynamics. In conclusion, endothelin induces renal and systemic vasoconstriction and affects water and sodium homeostasis during the neonatal period. These effects occur under higher doses than those used in adult animals. This age difference in systemic and renal responsiveness is probably mediated by receptor immaturity and/or interference of high levels of counteracting hormones present during the neonatal period.

OBJECTIVE: To evaluate the effects of maternal smoking during pregnancy on foetal growth in preterm infants with gestational age (GA)

International audience; Background: Approximately 75% of preterm births are late-preterm (340/7 to 366/7 weeks' gestation). This group has usually been considered as a whole in studies assessing the outcome of these preterm infants by comparison with term infants. However, the respective contribution to prognosis of each week of gestation has not been fully clarified. Methods: A population-based study of 150,426 live-born singleton neonates with gestational ages ranging from 34 to 41 weeks of gestation. Results: The rate of severe respiratory disorders (treated by mechanical ventilation and/or nasal continuous positive airway pressure) markedly declined with gestational age from 19.8% at 34 weeks to 0.28% at 39-41 weeks. Between 34 to 38 weeks, each additional week diminished the relative risk (crude or adjusted) of severe respiratory disorders by a factor varying from 2 to 3. The rate of poor prognosis (death and/or severe neurological condition) significantly declined between 34 to 38 weeks and remained stable thereafter. A multivariate analysis showed that antepartum hemorrhage and hypertensive disorders during pregnancy were significantly associated with severe respiratory disorders and poor outcome. Diabetes was an additional factor associated with severe respiratory disorders. Conclusions: Future studies should delineate more precisely the respective contribution of gestational age, maternal complication and induced delivery in the prognosis of infants born between 33 and 39 weeks' gestation.

To assess the Burgundy perinatal network (18 obstetrical units; 18 500 births per year), discharge abstracts and additional data were collected for all mothers and newborns. In accordance with French law, data were rendered anonymous before statistical analysis, and were linked to patients using a specific procedure. This procedure allowed data concerning each mother to be linked to those for her newborn(s). This study showed that all mothers and newborns were included in the regional database; the data for all mothers were linked to those for their infant(s) in all cases. Additional data (gestational age) were obtained for 99.9% of newborns.

Here we describe the clinical, histopathological and molecular studies of a female proband that died at 2 months of age in the context of a syndromic polymicrogyria. There was no significant family history. Clinical and radiological features included poor contact, cleft palate, facial dysmorphic features with frontal bossing, down-slanting and small palpebral fissures, inferior epicanthic folds, low-set and malformed ears, flat nose, retrognathism and short neck, minor limb anomalies, polymicrogyria that appear more severe in the perisylvian regions and cerebellar vermis hypoplasia. Autopsy findings revealed a patent foramen ovale with persistent left superior vena cava, left renal hypoplasia and microphthalmia. This description does not fit with any of the known syndromes with polymicrogyria and cytogenetic analyses including standard and high resolution chromosome analyses, telomeric FISH studies and array-CGH were normal. Consequently, the reported features in this child are unique and are likely to represent a new syndrome.

The number of pregnant women who receive cyclosporin A (CsA) after transplantation or for autoimmune disease has increased. CsA and its metabolites can cross the placental barrier and thus interfere with fetal development. It was shown previously that rabbits that were exposed in utero to 10 mg/kg per d CsA from the 14th to the 18th day of gestation presented a 25% nephron reduction. Thus, this study was conducted to assess the long-term systemic and renal effects of a CsA-induced nephron reduction. Twenty-two pregnant New Zealand white rabbits were randomly divided into two groups: Twelve received 10 mg/kg per d CsA from day 14 to day 18 of gestation, and 10 were used as controls. Rabbits that were born to these animals were evaluated at 4, 11, 18, and 35 wk of life. Pups that were exposed antenatally to CsA presented first a permanent nephron deficit; second, glomerular, tubular, and intrarenal hemodynamics dysfunction; third, enlarged kidneys with numerous tubular and glomerular lesions; and, fourth, an endothelin-dependent systemic hypertension that worsened with age. In utero exposure to CsA induced a nephron reduction that led to systemic hypertension and progressive chronic renal insufficiency in adulthood. A long-term clinical survey is mandatory in infants who are born to mothers who were treated with cyclosporin during pregnancy.

Perinatal care networks are defined as an organized group of several persons or facilities scattered throughout a given territorial area. They were granted legal authority in France in 1998. The establishments were then requested to coordinate their activities so as to put at the disposal of mothers and newborns the technical support centres that correspond to their needs. Institutional obstacles due to the lack of an administrative framework appeared. Another difficulty relates to assessment of the quality of care within the networks. In order to deal with these difficulties and promote the development of these networks, there is a need for methodological and budget support., Les réseaux de soins périnatals se définissent comme un ensemble organisé de plusieurs personnes physiques ou morales dispersées dans une zone territoriale donnée. Ils ont reçu un fondement légal en France en 1998. Il a alors été demandé aux établissements de coordonner leurs activités pour mettre à la disposition des mères et des nouveaunés les plateaux techniques correspondant à leurs besoins. Des obstacles d’ordre institutionnel, liés à l’absence de cadre administratif, sont apparus. Une autre difficulté est celle de l’évaluation de la qualité des soins au sein des réseaux. Pour lever ces difficultés et favoriser le développement des réseaux, un accompagnement méthodologique et budgétaire est nécessaire., Gouyon-Cornet Béatrice, Quantin Catherine, Sagot Paul, Gouyon Jean-Bernard. Mise en place et évaluation des réseaux de soins périnatals : expériences françaises et étrangères. In: Santé, Société et Solidarité, n°1, 2004. Naître en France et au Québec. pp. 129-136.

Cyclosporin A (CsA) is an immunosuppressive agent used to prevent graft rejection and to treat autoimmune disorders. Successful pregnancies can be achieved among CsA-treated women, although it is known that CsA is nephrotoxic and crosses the human placenta. The aim of this study was to evaluate the harmlessness of CsA toward the embryonic kidney. Twenty-one pregnant rabbits were divided into four groups. Groups of six and four female animals were subjected to daily injections of 10 mg/kg per d CsA (administered subcutaneously) for 5 d, from day 14 to day 18 of gestation or from day 20 to day 24 of gestation, respectively. In the third group, five female animals received the CsA diluent (Cremophor) from day 14 to day 18 of gestation. The fourth group consisted of six untreated female animals. Pregnancy outcomes among CsA-treated does demonstrated a reduced number of living pups, which were also growth-retarded, with exposure to CsA from day 20 to day 24 of gestation. However, pups exposed to CsA from day 14 to day 18 of gestation exhibited normal fetal growth, and blood concentrations of CsA matched human data. Examinations of kidneys at birth demonstrated vacuolation of proximal and collecting tubules and ureteric bud ends. Increased glomerular volumes and decreased nephron densities suggested nephron mass reduction, which was quantitatively evaluated in 1-mo-old animals. The nephron numbers were reduced by 25 and 33% in day 14 to 18 CsA-treated and day 20 to 24 CsA-treated animals, respectively, which displayed compensatory adaptation of the existing nephrons. However, foci of segmental glomerular sclerosis were already present, which would possibly jeopardize renal function later in life.

Background—Cisapride administration for 48 hours has been shown to increase heart rate corrected QT (QTc) interval in preterm neonates. Accumulation of the drug because of liver enzyme immaturity has been suggested to be the reason. If this is correct, a longer survey of QTc interval should disclose an increase even in term neonates. Objective—A prospective survey of the eVects of cisapride on QTc interval in term neonates administered cisapride. Setting—Neonatal Unit of the University Hospital of Dijon, France. Design—QTc interval was determined just before and 48 hours, seven days, and 15 days after the start of treatment. Subjects—Twenty one term newborn infants (mean gestational age 39.3 weeks) given the recommended dose of cisapride (0.2 mg/kg, four times a day). Results—Administration of cisapride caused a significant increase in QTc interval (p < 0.01). The mean value increased from 0.397 before treatment to 0.418 after 48 hours, 0.431 by day 7, and 0.447 by day 15. A QTc interval exceeding 0.450 was found in six neonates: three at 48 hours, one at day 7, and two at day 15. In two infants, withdrawal of the drug was associated with normalisation of the QTc interval. Conclusions—These results support the hypothesis of cisapride accumulation in newborns due to enzymatic immaturity and indicate that QTc interval should be monitored in neonates receiving this drug. (Arch Dis Child Fetal Neonatal Ed 2001;84:F44‐F46)

Background The objective of this work was to explore the impact on parents of the bronchiolitis hospitalization of their infant using the Impact of Bronchiolitis Hospitalization Questionnaire (IBHQ©). Methods Four hundred sixty-three infants aged less than 1 year and hospitalized for bronchiolitis were included in a French observational study during the 2008–2009 season. Parents were asked to complete the IBHQ at hospital discharge and 3 months later. IBHQ scores, ranging from 0 (no impact) to 100 (highest impact), were compared according to gestational age (full-term, 33–36 wGA, ≤ 32 wGA) and the presence of congenital heart disease (CHD). The potential drivers of impact were explored using multivariate linear regressions. Results The study included 332 full-terms, 71 infants born at 33–36 wGA, and 60 at ≤ 32 wGA; 28 infants had a CHD. At hospital discharge, 9 of the 12 IBHQ mean scores were above 40, indicating a marked impact on parents. Three months later, all mean scores were lower but 5 were still greater than 40. At discharge, the length of hospitalization had a significant effect on IBHQ worries and distress, fear for future, guilt and impact on daily organization scores (p Conclusions Bronchiolitis hospitalization has conspicuous emotional, physical and organizational consequences on parents and siblings, which persist 3 months after hospital discharge. The main drivers of the impact were length of hospital stay and parents’ educational level, while infants’ gestational age or the presence of a CHD had little influence.

Eight preterm infants were given intravenous nicardipine, a calcium channel blocker, to treat systemic hypertension (renal artery thrombosis (n=3); dexamethasone for management of bronchopulmonary dysplasia (n=2); unexplained (n=3)). Nicardipine doses ranged from 0.5 to 2.0 µg/kg/min and were given for three to 36 days (mean (SD) 15.9 (10.3) days). Systolic blood pressure had significantly decreased after 12 and 24 hours of nicardipine treatment (-17 (17)% and -21 (10) %, respectively). Diastolic blood pressure significantly decreased after 24 hours of treatment (-22 ± 16%). The decrease in blood pressure remained significant over the subsequent days of treatment. No hypotension or other clinical side effects were observed. It is concluded that intravenous nicardipine could be a first line treatment for hypertension in preterm infants. Keywords: nicardipine; hypertension; blood pressure.