Respiratory morbidity of preterm infants of less than 33 weeks gestation without bronchopulmonary dysplasia: a 12-month follow-up of the CASTOR study cohort.

The 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 [<33 weeks gestational age (GA)] without bronchopulmonary dysplasia and 201 full-term infants (39-41 weeks GA) from the French CASTOR study cohort. Preterm infants had increased respiratory morbidity during the follow-up period compared to full-terms; they were more likely to have wheezing (21% 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 <3330 g and hospitalization for RSV bronchiolitis during the infant's first RSV season were independent risk factors for the development of wheezing episodes during the subsequent 12-month follow-up period.

Hospitalizations for respiratory syncytial virus bronchiolitis in preterm infants at <33 weeks gestation without bronchopulmonary dysplasia: the CASTOR study.

This 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 (<33 weeks' gestational age, WGA) without bronchopulmonary dysplasia and full-term infants (39-41 WGA) matched for date of birth, gender and birth location, and to evaluate the country-specific risk factors for bronchiolitis hospitalization. Data on hospitalizations were collected both retrospectively and prospectively for 498 matched infants (249 per group) aged <6 months at the beginning of the RSV season. Compared to full-term infants, preterm infants had a fourfold [95% confidence interval (CI) 1·36-11·80] and a sevenfold (95% CI 2·79-17·57) higher risk of being hospitalized for bronchiolitis, RSV-confirmed and all types, respectively. Prematurity was the only factor that significantly increased the risk of being hospitalized for bronchiolitis. The risk of multiple hospitalizations for bronchiolitis in the same infant significantly increased with male gender and the presence of siblings aged ⩾2 years.

Synthesis and antibacterial activity of ketolides (6-O-methyl-3-oxoerythromycin derivatives): a new class of antibacterials highly potent against macrolide-resistant and -susceptible respiratory pathogens.

In the search for new antibiotics active against macrolide-resistant pneumococci and Haemophilus influenzae, we synthesized a new class of 3-oxo-6-O-methylerythromycin derivatives, so-called "ketolides". A keto function was introduced in position 3 after removal of L-cladinose, a sugar which has long been thought essential. Further modifications of the macrolactone backbone allowed us to obtain three different series of 9-oxime, 11,12-carbamate, and 11, 12-hydrazonocarbamate ketolides. These compounds were found to be very active against penicillin/erythromycin-resistant pneumococci and noninducers of MLSB resistance. The 11,12-substituted ketolide 61 (HMR 3004) demonstrated a potent activity against multiresistant pneumococci associated with a well-balanced activity against all bacteria involved in respiratory infections including H. influenzae, Mycoplasma catarrhalis, group A streptococci, and atypical bacteria. In addition HMR 3004 displayed high therapeutic activity in animals infected by all major strains, irrespective of their resistance phenotype.

Emergence of Enterobacter cloacae as a common pathogen in neonatal units: pulsed-field gel electrophoresis analysis.

In the first week of December 2002, three infants hospitalized in the neonatal department of our hospital had blood cultures positive with Enterobacter cloacae. Screening cultures and genotyping showed that 10 of 25 screened patients also carried E. cloacae and that nine isolates belonged to the same clone as that responsible for all three bacteraemias. This epidemic cluster was limited to one of the two units of the department. Surveillance of both units continued until the end of March 2003; 51 of 159 neonates screened were colonized with E. cloacae, 38 out of 80 (47.5%) in the premature unit (PU) and 13 out of 79 (16.4%) in the paediatric intensive care unit (PICU). Pulsed-field gel electrophoresis (PFGE) analysis of 130 available isolates revealed 30 different pulsotypes, including 24 unique pulsotypes from individual patients and six from multiple patients. Antibiotic (particularly beta-lactam) use did not significantly vary from 1999 to 2003. The consumption of alcohol-based hand rub (four-fold higher in the PICU than in the PU) and nurse-to-patient ratio (1:2 in the PICU and 1:4 in the PU) might explain the higher cross-transmission rate in the PU. Finally, despite an epidemiological survey, we failed to identify the causes of the emergence of E. cloacae in our neonatology units. However, improved hygiene practices combined with restriction of admission led to the progressive disappearance of the epidemic strain. The increasing importance of this type of unit and the dramatic consequences of infections emphasize the need for additional research on the constitution of the flora of newborns and the mode of acquisition Gram-negative multi-resistant bacteria.

[Value of the subxiphoid approach in 2-dimensional echocardiography for the diagnosis of ductus arteriosus in premature infants and infants]. / Intérêt de la voie sous-xiphoïdienne en échocardiographie bidimensionnelle pour le diagnostic du canal artériel du prématuré et du nourrisson.

The preliminary results of our experience with the "inverted" subxiphoid approach for 2D echocardiographic visualisation of patent ductus arteriosus (PDA) in premature neonates and infants are reported. Eight premature ventilated neonates weighting 870 to 1,200 g with an isolated PDA were examined by this technique using a mechanical sector scanner and a 7.5 MHz transducer; three views were obtained (left ventricular outflow tract or "long axis"; an oblique view through the two atria and aortic arch; short axis view of the ventricles). A PDA was directly visualised in 6 of the 8 patients. It was possible to measure its diameter and observe its tortuous or rectilinear trajectory; the outcome of Indomethacin therapy or surgical ligature could also be evaluated. In the 2 patients in whom the PDA was not visualised, there were no clinical symptoms or echocardiographic signs of shunt: these PDA were therefore probably extremely small. In the neonate and infant, it is relatively easy to demonstrate a PDA by this approach. The PDA can also be followed up in "ductus dependent" congenital heart disease during treatment with Prostaglandin E. In conclusion, the subxiphoid approach represents an interesting alternative for the visualisation of PDA, especially in premature neonates in whom the suprasternal and parasternal views are often difficult to obtain.

[Carcinomatous meningitis presenting with isolated headache]. / Céphalées isolées révélatrices d'une méningite carcinomateuse.

INTRODUCTION: Carcinomatous meningitis reveals a solid cancer in 10 percent of cases. OBSERVATION: Our patient developed isolated headache which progressively worsened. Cranial Computerized Tomography (CT) was normal. Brain MRI showed multiples areas of contrast enhancements meningeal tissue associated with small nodulars deposits. Repeated cerebrospinal fluid (CSF) examinations revealed elevated tumor markers suspect cells. The diagnosis of pulmonary adenocarcinoma was established during systematic follow-up. CONCLUSION: The diagnosis of carcinomatous meningitis can be difficult to establish because of the non-specific clinical presentation and the absence of suggestive context; negative CSF-cytology is frequent. MRI and elevated tumor markers in the CSF compared with the serum level contribute significantly to diagnosis.

[Juvenile xanthogranuloma localized in the parotid gland]. / Xanthogranulome juvénile de localisation parotidienne.

Juvenile xanthogranuloma of parotid gland is reported in a 9-year-old boy. This kind of tumor is thought to be very rare in salivary glands. Histological, immunohistochemical and ultrastructural data showed characteristic features and excluded a Langerhans cell histiocytosis. Follow-up was uneventful after 18 months.

[Smith-Lemli-Opitz syndrome]. / Le syndrome de Smith-Lemli-Opitz.

BACKGROUND: Smith-Lemli-Opitz syndrome (SLOS) is an autosomic recessive metabolic affection. Children affected by SLOS exhibit a defect in cholesterol biosynthesis associated with a high concentration of cholesterol precursor 7 dehydrocholesterol (7 DHC) and its isomers, which is due to an enzymatic block at the level of delta-7-DHC reductase. SLOS has been subdivided into two types on the basis of clinical severity: type I is the classic and type II is the severe one. CASE REPORT: A full term female was born from a pregnancy complicated by oligoamniosis and intra-uterine growth retardation. The neurologic status was immediately impaired with severe hypotonia, absence of reflexes, and abnormal crying. She exhibited multiple congenital anomalies with a facial dysmorphia, anomalies of members, unicornus uterus and a pyloric stenosis. Plasmatic concentration exhibited a normal cholesterolemia contrasting with an elevated level of 7 and 8 DHC. Major alimentary tract defect led to enteral and parenteral nutrition. The severe neurological defect led to death on the 16th day of life. CONCLUSION: Despite normal blood cholesterol levels that can be attributed to enteral and parenteral nutrition, the severity of clinical findings and the lethal course permit to classify this case as type II.

[Neurologic development in premature infants under 33 weeks of gestational age: determination of risk of neurological abnormalities in a prospective regional survey with a control group]. / Devenir neurologique des prématurés de moins de 33 semaines: détermination du risque d'anomalie neurologique dans une enquête régionale prospective avec groupe témoin.

AIM: The purpose of this population-based study was to compare the incidence of neurodevelopmental disability and its risk factors between preterm and full-term infants matched as control group. POPULATION AND METHODS: The preterm cohort included 203 infants born between 25 and 33 weeks of gestational age in the region of Franche-Comté (France) during a two-year-period. The control group included 196 full-term infants born in the same maternities. Survival up to the date of follow-up was 171/203 (84%) for preterms and 195/196 (99.5%) for full-term infants (uncorrected age, mean 12 months). Neurodevelopmental assessments were performed by pediatricians or physicians on 164/171 surviving preterms (96% follow-up) and 179/195 full-terms (92%). RESULTS: Thirty-two (19.5%) preterm infants had disability, ten of these (6%) showing severe disability. Five (2.8%) full-term infants had disability, one of these (.5%) having severe disability. Risk factors predicting a disability included in a multivariate approach: prematurity (odds-ratio [OR]: 7.8), maternal age > 37 (OR: 3.0), lack of profession for both parents (OR: 3.7), male gender (OR: 2.9). The pediatrician observed a disability more frequently than the physician (OR: 2.46). Likewise, risk factors predicting a severe disability included: prematurity (OR: 10.8), lack of profession for both parents (OR: 5.8) and monochorial twin-placentation (OR: 4.5). CONCLUSIONS: Prematurity is not the only risk factor to be taken into account for neurodevelopmental evaluation of premature infants, but its influence still remains widely predominant.

[Neurodevelopmental outcome of premature infants born at less than 33 weeks of gestational age and not cerebral palsy at the age of 5 years]. / Devenir neurodéveloppemental à cinq ans des prématurés nés avant 33 semaines d'aménorrhée et indemnes d'infirmité motrice d'origine cérébrale.

AIM: To appreciate the impact of prematurity, fetal hypotrophy and familial environment on the neurodevelopmental performances of very premature infants without cerebral palsy at the age of five years. POPULATION AND METHODS: We followed a regional cohort of 171 very premature infants (< or = 32 weeks of gestation) until they were five years of age. Cognitive functions were tested with the WPPSI test and the development quotient was assessed by the ability to draw a "bonhomme". Twenty-two premature infants suffered from cerebral palsy diagnosed before the age of two years. Another infant had a moderate diplegia at the five-year examination. We had no information for 16 prematures (9.3% of survivors). Twenty-eight premature infants were considered as having no severe disability on phone or mailed contact, and another child had a severe isolated mental retardation. We examined 104/148 infants, and 96/148 survivors without cerebral palsy passed the tests. The cognitive functions of these premature infants are compared to the performances of a control group made up of 108 children born at term > or = 37 weeks, matched for birthplace and single or twin characteristics of the pregnancy. RESULTS: The values of the different quotients are significantly decreased in the preterm group. The global IQ and the performance IQ are 0.8 SD, verbal IQ is 0.5 SD and the development quotient is 0.4 SD below the values observed in the control group. A performance IQ less than -2 SD for the mean of the control group is observed three times more than in the controls (13.5% vs 3.7%, P < 0.01). Multiple linear regression shows that prematurity explains, independent of hypotrophy and socioeconomic environment, 8% of the variation of the performance IQ (P < 0.01), 2% of the variation of the verbal IQ and 2% of the development quotient (P < 0.05). CONCLUSION: The five-year neurologic outcome of the children born prematurely in this regional study is similar to the results observed in regional studies conducted in Europe: 13.4% of the survivors have cerebral palsy, and the cognitive functions of the children with no cerebral palsy are significantly lower than the term control group. Other risk factors such as hypotrophy, which modulates the developmental quotient, and the socioeconomic status, which modulates the verbal IQ, are underlined.

[Comparative study of 2 protocols for antibiotic therapy. Maternal-fetal non-specific bacterial infections during labor]. / Etude comparative de 2 protocoles d'antibiothérapie. Infections materno-foetales bactériennes non spécifiques au cours du travail.

Two protocols for prophylaxis by antibiotics in labour were compared to see how effective they were in preventing materno-fetal infection in patients who had signs of chorio-amnionitis. There was in increase in E. coli infections in 40% of liquor which were resistant to amoxycillin which had been used right up to now. 135 cases of patients who had received antibiotic treatment in labour were studied. 61 of these were treated with amoxycillin and 74 with piperacillin. The results show that there was a drop of 11.05% in the number of newborns who were infected in the group of patients who were treated with piperacillin. It was not possible using piperacillin to avoid all infections of the mother and fetus. The severity of the infection in the fetus, as judged by the Apgar score and the opinion of the paediatricians, was less serious in the group that was treated with piperacillin. The death rate for both groups was identical: one in each group. Both were caused by E. coli infections. A drop of 11% in post partum maternal infections was noted. Its was shown that piperacillin was more efficacious, but this way of preventing of infections in the mother and fetus lay in finding as early as possible the situation that could increase the risk of infection.

[Subcutaneous fat necrosis of the newborn with hypercalcemia]. / Cytostéatonécrose du nouveau-né compliquée d'une hypercalcémie.

INTRODUCTION: Hypercalcemia associated with subcutaneous fat necrosis of the newborn is a well known but rare event. CASE REPORT: A newborn with a history of cesarean section, fetomaternal infection, neurological and respiratory distress was admitted with anorexia, adynamia, vomiting, polyuria and polydipsia at the age of 37 days. Physical examination showed red and violaceous infiltrated skin lesions. Skin biopsy revealed focal areas of fat necrosis with crystal-like structures. Calcium and 1,25 (OH(2) ) vitamin D serum levels were increased. Diagnostic of subcutaneous fat necrosis of the newborn with symptomatic hypercalcemia was made. Evolution was favorable after treatment including furosemide, prednisone and a diet low in calcium and vitamin D. DISCUSSION: Hypercalcemia must be detected in infants with subcutaneous fat necrosis. This major complication may have fatal outcome. Treatment of hypercalcemia includes dietary changes associated with classic treatment of hypercalcemia. Routine evaluation of serum calcium level is essential.

[Iatrogenic acrodermatitis enteropathica-like syndrome in leucinosis]. / Pseudo-acrodermatite entéropathique per carence alimentaire en isoleucine chez un nourrisson atteint de leucinose.

INTRODUCTION: Leucinosis (maple syrup urine disease) is a metabolic disorder caused by an enzymatic deficiency involved in the degradative pathways of the three branched-chain amino acids. We report an observation of acrodermatitis enteropathica-like syndrome induced by essential amino acid deficiency in a child with leucinosis. CASE REPORT: A child with leucinosis was referred to our hospital for exfoliative dermatitis of the perioral and anogenital regions associated with diarrhea and pancytopenia. The diagnosis of iatrogenic acrodermatitis enteropathica-like syndrome was confirmed after screening showing isoleucine deficiency. Rapid response was observed after adequate isoleucine supplementation. DISCUSSION: The acrodermatitis enteropathica-like eruption in our patient was due to an iatrogenic amino acid nutritional imbalance. Our observation underlines the risk of using a branched-chain amino acid-free formula without adequate supplementation of deficient amino acids. In addition, dietary insufficiency of isoleucine, associated with the treatment of organic aciduria should be added to the causes of acrodermatitis enteropathica-like syndrome.

[Search for early indications for reintubation after mechanical ventilation weaning of the newborn]. / Recherche de critères précoces de réintubation après sevrage de la ventilation mécanique du nouveau-né.

Early predictive factors for successful extubation were investigated, in order to determine the best moment for respiratory weaning of the newborn, and the risk of subsequent reintubation. PaO2/FiO2 ratio, PCO2 and respiratory rate were measured 2 h after extubation in 100 newborn infants. There was no statistically significant difference for the PaO2/FiO2 ratio and PCO2 between infants who were successfully extubated (group 1) and those who required subsequent reintubation (group 2). By contrast, the respiratory rate 2 h after extubation was significantly higher in group 2, and a respiratory rate greater than 70/min appears to be the earliest ventilatory modification predictive of the need for further mechanical ventilation before the occurrence of hypoxemia and respiratory acidosis.

[Efficacy of nifedipine on refractory hypoxemia associated with diaphragmatic hernia in the newborn infant. Apropos of a case]. / Efficacité de la nifédipine sur l'hypoxémie réfractaire associée à la hernie diaphragmatique du nouveau-né. A propos d'une observation.

A 3,200 g birth weight, 38-week gestational age neonate developed very severe persistent pulmonary hypertension following surgical repair of a left diaphragmatic hernia. Despite administration of dopamine, dobutamine, and tolazoline, a significant alveolar-arterial oxygen difference (660 mmHg) was found at age 41 hours. Nifedipine was then administered sublingually in a dose of 1 mg/kg and produced an immediate and dramatic improvement in the right radial artery pO2 that was sustained despite persistence of the right-to-left shunt. We discuss the mode of action of this vasodilating agent that, when added to major therapeutic agents, proved capable of completely reversing a hazardous neonatal situation.

Beta-keto-ester chemistry and ketolides. Synthesis and antibacterial activity of 2-halogeno, 2-methyl and 2,3 enol-ether ketolides.

The effect of 2,3 modifications on the antibacterial activity of ketolides was evaluated by introducing substituents in position 2 and converting the C-1, C-2, C-3 beta-keto-ester into stable 2,3 enol-ether or 2,3 anhydro derivatives. Introduction of a fluorine in C-2 is beneficial with regard to the overall antibacterial spectrum whereas the enol-ether and 2,3 unsaturated compounds, as well as the bulky gem dimethyl or 2-chloro derivatives, are less active particularly against erythromycin resistant strains. A 2-fluoro ketolide derivative demonstrates good antibacterial activity and in vivo efficacy against multi-resistant Streptococcus pneumoniae. Compared to azithromycin against Haemophilus influenzae, this compound is equivalent in vitro and slightly more active in vivo. These results demonstrate that within the ketolide class, to retain good antibacterial activity, position 2 needs to remain tetrahedral and tolerates only very small substituents such as fluorine.

[Pain in newborn infants hospitalized in pediatric intensive care unit]. / La douleur chez le nouveau-né hospitalisé en réanimation pédiatrique.

The increasing aggressivity of the modern technology connected with neonatal resuscitation had led to the recognition by paediatricians of the existence of pain in the newborn, and of the necessity to treat this condition. The neurophysiological development of the neonate is such that it allows pain perceptions even in premature infants; a number of clinical parameters have therefore been described for pain recognition in neonates. An antalgic therapeutic scheme to be used for treatment of pain in the intensive care unit is proposed.