Using Discharge Abstracts to Evaluate a Regional Perinatal Network: Assessment of the Linkage Procedure of Anonymous Data

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

Disparate effects of chronic and acute theophylline on cyclosporine A nephrotoxicity

Abstract : 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 administratio

Chloride Balance in Preterm Infants during the First Week of Life

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

Facteurs cliniques périnatals et paramètres biologiques prédictifs du pronostic chez l'enfant prématuré

L objectif de ce travail était de décrire les facteurs biologiques précoces influençant le pronostic des enfants grands prématurés. A partir d une population de 1 067 enfants admis en réanimation néonatale au CHU de Dijon de 2001 à 2008 et faisant l objet d un recueil prospectif de données clinico-biologiques périnatales, deux objectifs de recherche ont été identifiés : 1) évaluer l impact des troubles de la chlorémie au cours de l adaptation postnatale sur la morbidité neurologique; 2) caractériser la possible association entre l hypoprotidémie du premier jour de vie(J1) et le pronostic défavorable. Ces objectifs ont été approfondis dans 4 études, réalisées sur la population initiale et sur 3 autres cohortes de grands prématurés. Nous avons observé que l hyperchlorémie entraine une acidose métabolique sévère dans les 7 à 10 premiers jours de vie sans que ceci ne s associe à un pronostic neurologique défavorable (hémorragie intraventriculaire et/ou paralysie cérébrale à 18 mois d âge corrigé). Les résultats ont montré l importance de contrôler les apports de chlore des médicaments et de la nutrition parentérale, afin de prévenir toute acidose métabolique indésirable après la naissance. Les études sur la protidémie ont montré que l hypoprotidémie à J1 est un facteur indépendant associé au décès ou à la survie avec anomalies neurologiques sévères et que son pouvoir prédictif de pronostic défavorable est comparable à celui d autres scores de gravité validés. Ce travail contribue à la compréhension des facteurs périnatals influençant le pronostic du grand prématuré et ouvre de nouvelles perspectives de recherche sur la prise en charge de ces enfants vulnérables.Our aim was to identify early biochemical abnormalities associated with adverse outcome in very preterm infants. Based on an 8-year population-study for assessing the outcome in 1067 very preterm babies admitted to the neonatal intensive care unit of Dijon university hospital, two research axes were explored: 1) the impact of plasma chloride abnormalities on neurological morbidities; 2) the association between hypoproteinemia on the first day of life (D1) and adverse outcome. These issues were assessed by 4 studies, performed on the initial population and on 3 other cohorts.We found that hyperchloremia results in severe metabolic acidosis during the first 7-10 days of life, but this is not associated with adverse neurological outcome (intraventricular haemorrhage and/or cerebral palsy at 18 months of corrected age). The tight control of chloride intake by parenteral nutrition or inadvertent administration represents a good means for lowering the incidence of metabolic acidosis after birth.We also showed that hypoproteinemia (D1) has prognostic value for impaired outcome (death or survival with severe cerebral ultrasound findings) and that total plasma protein has a predictive performance comparable with other validated illness severity scores. These results provide additional insight into factors influencing mortality and morbidity for preterm babies. Our findings raise the interest in addressing the above issues in future investigations on: 1) pathophysiological mechanisms underlying the association between biological abnormalities and impaired outcome, 2) their possible therapeutic implications and 3) the development of new severity scores for very preterm babies.DIJON-BU Doc.électronique (212319901) / SudocSudocFranceF

Paraben exposure through drugs in the neonatal intensive care unit: a regional cohort study

Background and objectives: Environmental factors influence the development of very preterm infants (VPIs, born at less than 32 weeks of gestation). It is important to identify all potential sources of paraben exposure in these vulnerable infants. We aimed to quantify paraben exposure via drug administration in a cohort of VPI cared for in neonatal intensive care units (NICUs).Methods: A prospective, observational study was carried out over a five-year period in a regional setting (two NICUs using the same computerized order-entry system). The main outcome was exposure to paraben-containing drugs. The secondary outcomes were: time of the first exposure, daily intake, number of infants exceeding paraben acceptable daily intake (ADI: 0–10 mg/kg/d), duration of exposure, and cumulative dose.Results: The cohort consisted of 1,315 VPIs [BW 1129.9 (±360.4) g]. Among them, 85.5% were exposed to paraben-containing drugs. In 40.4% of infants, the first exposure occurred during the second week of life. Mean paraben intake and duration of exposure were, respectively, 2.2 (±1.4) mg/kg/d and 33.1 (±22.3) days. The cumulative paraben intake was 80.3 (±84.6) mg/kg. The ADI was exceeded in 3.5% of exposed infants. Lower GA was associated with higher intake and longer exposure (p < 0.0001). The main molecules involved in paraben exposure were: sodium iron feredetate, paracetamol, furosemide, and sodium bicarbonate + sodium alginate.Conclusion: Commonly used drugs are potential source of parabens, and ADI can be easily exceeded in VPIs cared for in NICUs. Efforts are needed to identify paraben-free alternative formulations for these vulnerable infants

Clinical Study Chloride Balance in Preterm Infants during the First Week of Life

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 (tCO 2 ) 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 tCO 2 . 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 tCO 2 . Chloride intake was the main independent factor associated with high plasma chloride, low SID, and low plasma tCO 2 , 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

Early Inflammatory Markers for the Diagnosis of Late-Onset Sepsis in Neonates: The Nosodiag Study

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