Klebsiella pneumoniae and Klebsiella oxytoca meningitis in infants. Epidemiological and clinical features.

BACKGROUND: The incidence of meningitis caused by Klebsiella pneumoniae (Kp) and Klebsiella oxytoca (Ko) in high-income countries is unknown, and no series have been published to date. METHODS: We conducted a nationwide multicenter observational study in France between 2006 and 2016. All children from the French national registry for paediatric bacterial meningitis under the age of 1 year and hospitalized for Kp or Ko meningitis were included. Virulence factors of four Klebsiella spp. strains were explored by whole genome sequencing. RESULTS: Of 1859 cases of meningitis in children under the age of 1 year, 13 cases (0.7%) of Klebsiella spp. meningitis (nine for Kp meningitis and four for Ko meningitis) were registered in the French national registry. Three of the patients died and 50% of the survivors had developmental delays. CONCLUSIONS: Prematurity, low birth weight, and congenital anomalies of the urinary tract appear to be risk factors for Klebsiella spp. meningitis as well as virulence factors of the strain.

[Increased success rate in umbilical venous catheter positioning by posterior liver mobilization]. / Intérêt du refoulement hépatique pour repositionner un cathéter veineux ombilical « sous-hépatique ¼ dans la veine cave inférieure.

OBJECTIVE: To evaluate prospectively the benefit of posterior liver mobilization during umbilical venous catheterization to place the umbilical venous catheter (UVC) in the central position (inferior vena cava). PATIENTS AND METHODS: Sixty-five successive newborn infants admitted in 3 neonatal intensive care units who required a UVC were enrolled over a 4-month period. UVC positions were assessed by X-ray. UVCs were placed either in an adequate position (at the right atrial-inferior vena cava junction, indicating success) or inserted within the portal system (failure). In this case, the UVC was drawn back to the 3cm mark and then, an additional attempt to insert the UVC was made during lateroposterior liver mobilization by the operator's hand. The success and failure rates at 1st and 2nd attempts were evaluated and compared. Characteristics of the population and possible catheter-related complications were recorded. RESULTS: A total of 31 of 65 (55%) UVC insertions failed at the 1st attempt. Among these UVCs, 16 (52%) were correctly repositioned in the central position by hepatic mobilization. The success rate increased by 50% (p<0.05). No life-threatening complications were observed during the procedure. CONCLUSION: Hand liver mobilization during umbilical venous catheterization improves the rate of adequate insertion of the UVC into the inferior vena cava. It is a simple, quick, and safe procedure.

Early hemodynamic consequences of patent ductus arteriosus in preterm infants with intrauterine growth restriction.

OBJECTIVE: To test the hypothesis that significant patent ductus arteriosus (PDA) may occur very early after birth in preterm infants with intrauterine growth restriction (IUGR), we compared the longitudinal changes in left-to-right shunting through DA between eutrophic and preterm infants with IUGR. STUDY DESIGN: The preterm infants -26 to 32 weeks gestational age (GA), admitted in our neonatal intensive care unit from February to May 2004 were included. They were separated into an "IUGR of placental origin" group and an "eutrophic" group. Significant PDA was assessed by Doppler echocardiography at 6, 24, and 48 hours of age. RESULTS: Thirty-one eutrophic (GA = 29 +/- 1.4 weeks; birth weight [BW] = 1300 +/- 160 g) and 17 infants with IUGR (GA = 29.3 +/- 1.5 weeks; BW = 810 +/- 140 g) were studied. Six hours after birth, the rate of significant PDA was higher in the IUGR than in the eutrophic group (10/17 [60%] vs 5/31 [15%]; P < .05). More DA became significant in infants with IUGR (11/17 [65%]) than in eutrophic infants (12/31 [40%]) (P < .05) within the 48 hours after birth. CONCLUSION: Markers of high pulmonary blood flow and systemic vascular steal occur more frequently and earlier after birth in IUGR of placental origin than in eutrophic preterm infants. The management of preterm infants with severe IUGR of placenta origin should include early echocardiographic monitoring to assess for markers of significant PDA.

[Fatal neonatal respiratory distress in Niemann-Pick C2 and prenatal diagnosis with mutations in gene HE1/NPC2]. / Forme respiratoire néonatale létale de la maladie de Niemann-Pick C2 et diagnostic anténatal par l'étude des mutations du gène HE1/NPC2.

UNLABELLED: We report the fifth case of neonatal form of type C2 (NP-C2) Niemann-Pick disease with early and fatal respiratory distress. Eleven families presenting such cases are known to date in the world. Since December 2000, isolation of the underlying gene HE1/NPC2 and its mutations has allowed major advances in diagnosis. CASE REPORT: Elisa was born in May 2000. NP-C2 disease was associated with severe respiratory distress leading to death at the age of four months. On the next pregnancy in September 2000, prenatal diagnosis was performed by means of biological tests that required four weeks response time. In December 2000, isolation of the HE1/NPC2 gene located to 14q24.3 and of some of its mutations allowed to characterize the patient as being homozygote for the nonsense mutation E20X. On the the two next pregnancies, prenatal diagnosis was performed at 12 SA, in 48 hours, by the means of mutation analysis. The last fetus was heterozygote for the mutation E20X, allowing the birth at term of a healthy male newborn baby. CONCLUSION: Niemann-Pick type C disease is a rare lysosomal lipid storage disease with severe prognosis. It is characterized by abnormalities of intracellular transport of endocytosed cholesterol. Diagnosis relies on biological tests that require cultured cells. Genetic heterogeneity defines two different genetic complementation groups C1 and C2. Severe and early respiratory distress is more likely to be associated with the rare type C2. Since December 2000, after identification of the disease-causing mutations in the proband, mutation analysis of gene HE1/NPC2 on direct chorionic villus samples allows early and fast (48 hours) prenatal diagnosis.

[Very preterm infant (< 32 weeks) vs very low birth weight newborns (1500 grammes): comparison of two cohorts]. / Grands prématurés infant (< 32 semaines) vs nouveau-nés de très faible poids de naissance (< 1500 grammes): comparison de deux cohortes.

UNLABELLED: Studies concerning very preterm newborns are either defined by birth weight (<1500 g) or gestational age (<32 weeks). The aim of our study was to underline limits of cohort definitions by birth weight. METHODS: Data come from the Nord Pas de Calais EPIPAGE cohort. Every birth occurring in 1997 before 32 weeks or with a birth weight less than 1500 g and transferred in a neonatal unit was included. Two cohorts were defined, one by gestational age (<32 weeks), the other by birth weight (<1500 g). Two subgroups could be defined from these to cohorts: group A (<32 weeks and > or =1500 g), from cohort (<32 weeks), group B (> or =32 weeks and <1500 g) from cohort (<1500 g). RESULTS: Five hundred nine newborns were included. Perinatal characteristics of both cohorts seemed comparable. The analysis by subgroups A and B revealed an excess of pulmonary and neurological morbidity in very preterm infant compared to very low birth weight newborn. This was linked to an excess of growth restricted newborns in this cohort with more advanced gestational ages. CONCLUSION: Cohorts of very preterm newborns should rather be defined by gestational age. If not possible, results in very low birth weight cohorts should also be given by gestational age and rate of growth restriction should be described.

[Multicentric study on neonatal medical pain management in the Nord-Pas-de-Calais]. / Enquête multicentrique sur la prise en charge médicamenteuse de la douleur en néonatologie dans le Nord-Pas-de-Calais.

UNLABELLED: The aim of this study was to describe pain management for newborn infants in neonatal intensive care units and neonatal units in the Nord-Pas-de-Calais. PATIENTS AND METHODS: A questionnaire was distributed to the 52 physicians practising in the six neonatal intensive care units and six neonatal units. The questions were in reference to pain assessment, treatment and prevention. RESULTS: Forty questionnaires were completed (77%). Eleven units proclaimed an interest in neonatal pain management. The tool for assessing pain was the EDIN scale (Echelle Douleur Inconfort Nouveau-né, neonatal pain and discomfort scale). Analgesic treatment was administered in 100% of cases for the insertion of chest tube, in 92% of cases for the insertion of percutaneous central catheter in a ventilated newborn infant and in 91% of cases for necrotizing enterocolitis requiring a mechanical ventilation. Prescribed analgesic drugs were propacetamol, nalbuphin or fentanyl; a sedation by midazolam or diazepam was occasionally associated. Emla cream was used before lumbar puncture in 80% of cases in the neonatal intensive care units and in 92% of cases in the neonatal units. Three neonatal intensive care units and four neonatal units administered a sucrose solution for blood samples. CONCLUSION: At the time of study, the interest in the pain of the physicians working in neonatal intensive care units and neonatal units was inadequate to guarantee an optimum management of pain in newborn infants. Physicians' approach remained heterogeneous.

[Congenital pulmonary lymphangiectasia revealed by cardiac arrest]. / Lymphangiectasies pulmonaires congénitales révélées par un arrêt cardiorespiratoire précoce.

UNLABELLED: Congenital pulmonary lymphangiectasia is a rare cause of respiratory distress in the neonatal period. Cardiac arrest may be its first manifestation. CASE REPORT: We report the case of a full term newborn who suffered at 30 min of life a sudden cardiac arrest. Despite intensive support, the patient died 5 h later. Lung examination showed pulmonary lymphangiectasia. CONCLUSION: Congenital pulmonary lymphangiectasia may be revealed by a sudden neonatal cardiac arrest. Pulmonary lymphangiectasia should be suspected in any newborn who develops early in life an unexplained refractory hypoxemia with radiographic reticulonodular images and uni or bilateral pneumothorax. The diagnosis is established at lung microscopy.

Effects of catecholamines on the pulmonary circulation in the ovine fetus.

High levels of circulating catecholamines are found in the fetus, and fetal stress and birth induce a marked surge in catecholamine secretion. Little is known about the role of catecholamines on the fetal pulmonary circulation. To determine the effects of catecholamines on the pulmonary vascular tone, we tested the hemodynamic response to norepinephrine and dopamine infusion in chronically prepared late-gestation fetal lambs. We found that norepinephrine infusion (0.5 microg. kg(-1). min(-1)) increased pulmonary artery pressure (PAP) by 10 +/- 1% (P < 0.01), left pulmonary artery blood flow by 73 +/- 14% (P < 0.01), and decreased pulmonary vascular resistance (PVR) by 33 +/- 6% (P < 0.01). The pulmonary vasodilator effect of norepinephrine was abolished after nitric oxide synthase inhibition. Dopamine infusion at 5 microg. kg(-1). min(-1) did not significantly change PVR. Conversely, dopamine infusion at 10 microg. kg(-1). min(-1) increased PAP (P < 0.01) and progressively increased PVR by 30 +/- 14% (P < 0.01). These results indicate that catecholamines may modulate basal pulmonary vascular tone in the ovine fetus. We speculate that catecholamines may play a significant role in the maintenance of the fetal pulmonary circulation and in mediating changes in the transitional pulmonary circulation.

Effects of inhaled nitric oxide on gas exchange and acute lung injury in premature lambs with moderate hyaline membrane disease.

OBJECTIVE: The purpose of this study was to examine whether inhaled nitric oxide (iNO) may change lung injury in moderate hyaline membrane disease (HMD). METHODS: Fifteen moderately premature lambs (128 days gestation, term=147 days) were randomly assigned to treatment with 20 ppm inhaled NO (n=7) from the onset of ventilation or control (n=8). Except for inhaled NO, treatments were intentionally similar to those applied in clinical situations. After porcine surfactant administration (Curosurf, 100 mg/kg), mechanical ventilator settings were modified during the course of the study to maintain PaCO(2) between 40 and 50 mmHg and post-ductal SpO(2) between 90 and 95%. The main studied parameters were gas exchanges parameters, respiratory mechanics (static compliance and functional residual capacity) and pulmonary vascular permeability and/or filtration rate indices. RESULTS: We found that 20 ppm of inhaled NO for 5 h significantly reduce ventilatory and oxygen requirements, but only during the first hour of mechanical ventilation. No increase in extravascular lung water content (5.41+/-0.96 vs. 5.46+/-1.09 ml/g bloodless dry lung in the control group and in the NO group, respectively) and no impairment of the respiratory mechanics could be found in the NO-treated group. However, inhaled NO increased the albumin lung leak index in this model (6.09+/-1.51 in the NO-treated group vs. 4.08+/-1.93 in the control group; P<0.05). CONCLUSIONS: Our results do not therefore support a detrimental effect of short-term exposure to low doses of NO inhalation in moderate HMD. However, it may induce an increase in lung vascular protein leakage. The pathophysiological consequences of this finding remain to be elucidated.

[Non-medical factors in perinatal health. A study of socioeconomic anc cultural features of women admitted to the maternity hospital in Lens (Pas-de-Calais)]. / Rôle des facteurs non médicaux dans la santé périnatale. Etude des caractéristiques socioéconomiques et culturelles de la population accueillie à la maternité du centre hospitalier de Lens (Pas-de-Calais).

BACKGROUND: The aim of this study was to determine the influence of medical and non-medical factors on perinatal health in an underpriviledged area, the ex-coal mines of Lens (Pas-de-Calais). POPULATION AND METHODS: This prospective study concerned 1,000 women who delivered in the maternity hospital of Lens between January 5, 1993 and May 13, 1993. The relationships between preterm delivery, low birth weight and maternal socioeconomic and cultural characteristics were analyzed. RESULTS: The women included presented adverse pregnancy outcomes. Preterm delivery, low birth weight and neonatal transfer rates were respectively 6.9%, 7.3% and 12.7% higher than the average regional rates. In contrast with these results, antenatal care could be considered correct or even better. The poor socioeconomic status of the population appeared to be a very significant perinatal risk factor. CONCLUSION: At present, in an unfavourable regional conjuncture, socioeconomic and cultural factors have adverse effects on perinatal morbidity and mortality independent of medical factors like prenatal care. The prevention of poor perinatal outcome should be based on these data. Not the access to the health care system but the manner of dispensing health care should require great consideration.

Combined effects of inhaled nitric oxide (iNO) and oxidant agents on the production of methemoglobinemia in newborn piglets.

OBJECTIVE: To investigate the effects of the association of inhaled nitric oxide (iNO) and oxidant drugs (acetaminophen, phytomenadione, and EMLA cream) on methemoglobinemia during the neonatal period. DESIGN: Prospective, randomized, experimental study. SETTING: University Experimental Pharmacology laboratory. SUBJECTS: Sixty newborn piglets weighing 1.5-2.0 Kg. INTERVENTIONS: Twelve groups of five piglets were anaesthetized, mechanically ventilated, and studied for 3 hrs. Eight groups received iNO (40 ppm or 80 ppm) alone or in association with a single intravenous dose of acetaminophen (120 mg/kg propacetamol), phytomenadione (5 mg vitamin K1) or EMLA cream (2.5 g) applied to the ventral lower abdomen for 3 hrs. Three other groups received, respectively, acetaminophen, phytomenadione, or EMLA cream without iNO. The last group (control group) received neither drugs nor iNO. MEASUREMENTS AND MAIN RESULTS: Methemoglobinemia was measured before the beginning of each experiment, 30 mins later, and every hour for 3 hrs. There was no significant difference in methemoglobinemia at any time between groups receiving acetaminophen (0.90%+/-0.12%), phytomenadione (0.88%+/-0.11%), or EMLA cream alone (0.97%+/-0.11%) and the control group (0.92%+/-0.12%). At 3 hrs, methemoglobinemia was slightly but significantly increased in group receiving iNO alone (1.04%+/-0.17% at 40 ppm iNO and 1.14%+/-0.16% at 80 ppm iNO; p < .05). Conversely, methemoglobinemia increased as a function of time in groups in which iNO was associated to drug administration and was significantly greater than the control group at 3 hrs (80 ppm iNO + acetaminophen, 2.80%+/-0.47%; 80 ppm iNO + phytomenadione, 2.38%+/-0.45%; 80 ppm iNO + EMLA cream, 2.33%+/-046%; p < .001). CONCLUSIONS: These results demonstrate that if oxidant drugs (acetaminophen, phytomenadione, or EMLA cream) did not increase blood methemoglobinemia in neonatal piglets, their association with iNO caused an increase in methemoglobin. Special care should be taken to monitor methemoglobinemia when iNO is combined to such drugs in newborn infants.

Combined effects of inhaled nitric oxide and hyperoxia on pulmonary vascular permeability and lung mechanics.

OBJECTIVE: To determine whether inhaled nitric oxide (NO) may alter pulmonary vascular permeability and respiratory function in an in vivo model. DESIGN: Prospective, randomized, controlled, experimental study. SETTING: University experimental pharmacology laboratory. SUBJECTS: Mechanically ventilated newborn piglets, 1 to 2 days old, exposed to 100% oxygen for 76 hrs. INTERVENTIONS: The piglets were randomly assigned either to a treatment group receiving 20 ppm inhaled NO from the onset of ventilation (n = 5) or to a control group (n = 6) receiving no treatment. MEASUREMENTS AND MAIN RESULTS: The main variables studied were gas exchange (PaO2/F(IO2) ratio, lung diffusing capacity), respiratory mechanics (static compliance of the respiratory system, stat, quasi-static hysteresis area, functional residual capacity), and pulmonary vascular permeability assessed by simultaneous intravenous administration of iodine-125-labeled albumin and chromium-51-labeled red blood cells. Extravascular albumin space of the lung and dry lung weight were significantly higher in the NO group vs. the control group (albumin space, 1.08+/-0.16 vs. 0.70+/-0.26 [SD] mL/kg body weight [p < .05]; dry lung weight, 3.20+/-0.34 vs. 2.66+/-0.14 g/kg body weight [p < .05]). Moreover, the hysteresis area was higher from 24 hrs of NO exposure. Conversely, NO inhalation altered neither the extravascular lung water content (12.98+/-2.79 mL/kg body weight in the NO group vs. 12.18+/-2.26 mL/kg body weight in the control group [not significant]) nor the main respiratory mechanical variables (static compliance, functional residual capacity) and gas exchange (lung diffusing capacity, PaO2/F(IO2) ratio). CONCLUSION: These results do not support the hypothesis that NO inhalation combined with hyperoxia can alter the main lung-function variables in neonates. However, it may induce an increase in lung vascular protein leakage. The pathophysiologic consequences of this finding remain to be elucidated.

[Use of double-lumen umbilical vein catheters in a neonatal intensive care unit]. / Utilisation de cathéters veineux ombilicaux double voie en unité de soins intensifs néonatals.

BACKGROUND: The aim of the study was to compare the success/failure rate and complications of insertion into the umbilical vein, of either double-lumen catheters (Charrière diameter 04, length 13 and 30 cm) or single-lumen catheters (Charrière diameter 05, length 40 cm) in a population of neonates admitted to a neonatal intensive care unit. The numbers of insertions of additional peripheral venous catheters were also compared. PATIENTS AND METHODS: The population was divided into two groups according to the severity of the respiratory failure. Group 1 (n = 52): normal hemodynamic parameters and moderate respiratory failure (FiO2 < 0.6): only single-lumen catheters were used. Group 2 (n = 56): low systemic pressure requiring vascular filling and/or inotropic drugs infusion and/or severe respiratory failure (FiO2 > 0.6): in this group, either single-lumen catheters or double-lumen catheters were inserted. RESULTS: The success rate of insertion of double-lumen catheters and of single-lumen catheters were similar (61% vs 71%: P = 0.7). Nineteen double-lumen catheters were inserted in the group 2. The average duration of double-lumen umbilical catheterization was not significantly different from simple-lumen catheterization (4.9 +/- 2.2 vs 4.6 +/- 2.2 days). Complications relating to the umbilical venous catheterization were uncommon: three catheter obstructions (two with single-lumen catheter, one with double-lumen catheters), two nosocomial infections (both with single-lumen catheter), one hydropericardium (with single-lumen catheter). In group 2, more peripheral venous catheters were required during the first 72 hours of life after insertion of single-lumen catheter than after insertion of double-lumen catheters (average number of peripheral venous catheters per infant: 1.6 +/- 0.83 vs 1 +/- 0.35 respectively; P < 0.01). CONCLUSION: Feasibility and complication rate of umbilical double-lumen catheters were similar to those of single-lumen catheters. The use of umbilical double-lumen catheters reduces the need of peripheral venous catheters.

Inhaled nitric oxide neither alters oxidative stress parameters nor induces lung inflammation in premature lambs with moderate hyaline membrane disease.

The purpose of this investigation was to examine whether inhaled nitric oxide (NO) may alter oxidative stress parameters and induce lung inflammation in moderate hyaline membrane disease (HMD). Eighteen moderately premature lambs (130 days gestation, term = 147 days) were randomly assigned to treatment with 20 ppm inhaled NO (n = 8) from the onset of ventilation or used as control (n = 10). Except inhaled NO, treatments were intentionally similar to those applied in clinical situations. The main studied parameters were oxidative stress index measurements on lung parenchyma and in circulating blood, lung parenchyma microscopic examination and bronchoalveolar lavage cell count. We found that 20 ppm of inhaled NO for 5 h did not change significantly either malondialdehyde and total antioxidant status levels in circulating blood, or malondialdehyde, reduced glutathione, glutathione peroxidase and glutathione reductase in lung parenchyma. Amino-imino-propene bond generation, which are lipoperoxidation markers, was similar in both groups. Furthermore, no significant changes in the number of inflammatory cells in lung lavage products and in lung parenchyma microscopic examination could be found. Therefore, these data do not support the hypothesis that short-term NO inhalation increases oxidative stress and lung inflammation in an experimental model of moderate HMD.