Administering atropine and ketamine before less invasive surfactant administration resulted in low pain scores in a prospective study of premature neonates.

AIM: Less invasive surfactant administration (LISA) can avoid tracheal intubation for neonatal respiratory distress syndrome, but can be painful because it requires laryngoscopy. The aim of this study was to assess the efficacy and tolerance of intravenous atropine plus ketamine administration before LISA. METHODS: We conducted a prospective observational study of all premature infants hospitalised in our French neonatal intensive care unit treated with LISA between March 2015 and March 2016. Ketamine was titrated by 0.5 mg/kg increments. The technical conditions, pain scores, emergent intubations and vital signs were collected and analysed. RESULTS: Values are reported as medians (interquartile ranges). We included 29 patients with a gestational age of 29.6 (28.6-30.9) weeks and birth weight of 1290 (945-1600) grams. Technical conditions were satisfying for 24 infants (83%). The Faceless Acute Neonatal Pain Scale score was 2 (2-4); seven infants (24%) required tracheal intubation before LISA could be performed; 17 (59%) had a pulse oxymetry value under 80% that lasted more than 60 seconds. Heart rate and mean arterial blood pressure transiently increased. CONCLUSION: Atropine plus ketamine before LISA resulted in low pain scores and stable haemodynamic parameters, but prolonged desaturations or apnoea leading to tracheal intubation were frequently observed.

[Video recording of newborn resuscitation in the delivery room: technique and advantages]. / Enregistrement vidéo de situations réelles de réanimation en salle de naissance: technique et avantages.

An extreme attentiveness is mandatory when caring about extremely-low-gestational-age neonates at birth because of their innate vulnerability. The interventions performed during resuscitation of these infants may have direct influence on the immediate survival and also on long-term morbidity. Although stressfull, each resuscitation step is crucial and needs to be precise, fast and harmless. In order to determine our compliance to the international guidelines and to assess our neonatal performances in delivery room, we used a Mobotix camera to record all resuscitations of extremely-low-gestational-age neonates during the decisive first minutes of life. Neonatal medical and nursing staff agreed to be recorded. Our local ethics committee approved that videotaping neonatal resuscitation is an audit of clinical practice and thus does not require informed consent. During debriefing sessions, we reviewed the videotaped recordings, which allowed us to identify frequent deviations from the international guidelines and to re-educate and improve performance. The most frequent errors we recognized were errors of hygiene, not re-evaluating oxygen titration and airway obstruction during mask ventilation. We observed team behaviour and coordination during resuscitation and focused on quality of care. We believe that this method may be very effective as a teaching tool.

OASIS: an assessment tool of epidemiological surveillance systems in animal health and food safety.

The purpose of this study was to develop a standardized tool for the assessment of surveillance systems on zoonoses and animal diseases. We reviewed three existing methods and combined them to develop a semi-quantitative assessment tool associating their strengths and providing a standardized way to display multilevel results. We developed a set of 78 assessment criteria divided into ten sections, representing the functional parts of a surveillance system. Each criterion was given a score according to the prescription of a scoring guide. Three graphical assessment outputs were generated using a specific combination of the scores. Output 1 is a general overview through a series of pie charts synthesizing the scores of each section. Output 2 is a histogram representing the quality of eight critical control points. Output 3 is a radar chart representing the level reached by ten system attributes. This tool was applied on five surveillance networks.

Automated early warning system for the surveillance of Salmonella isolated in the agro-food chain in France.

Non-typhic Salmonella is one of the major bacterial pathogens that cause foodborne infections as well as economic losses for the food production industry. There is therefore a need to improve early detection to prevent the emergence and spread of Salmonella within the agro-food chain. The passive laboratory-based surveillance system of the Salmonella network has been integrated into the French Food Safety Agency's working plan. The objective of this study was to evaluate the ability of this network to detect unusual Salmonella contamination as early as possible in the agro-food chain. Three statistical methods were used to detect unusual events from the time-series of counts. After an experimental period of more than 1 year, this approach detected several unusual events linked to contamination in the agro-food chain that were confirmed in a timely manner at national or regional levels. This evaluation also reinforced the position of the Salmonella network as an integral part of the national public health surveillance system.

Nationwide outbreak of Salmonella enterica serotype 4,12:i:- infections in France, linked to dried pork sausage, March-May 2010.

In May 2010, a nationwide excess of infections with the specific monophasic variant Salmonella enterica serotype 4,12:i:- was investigated in France. Subtyping with multilocus variable number of tandem repeats analysis revealed a distinct epidemic strain within this excess. Epidemiological investigations identified a dried pork sausage sold by a particular chain of supermarkets as the likely vehicle of transmission. The suspected batches have been withdrawn and recalled.

[Palliative care in the neonatal period. Part one: general considerations]. / Réflexions et propositions autour des soins palliatifs en période néonatale : 1(re) partie considérations générales.

In France, the law dated 22 April 2005 required that all practitioners offer palliative care to patients as an alternative to unreasonable obstinacy. The practical development of palliative care during the neonatal period is not easy, even though obstetricians and neonatologists have always been aware of the ethical necessity of comfort in the dying newborn. The decision leading to palliative care begins with the recognition of patent or potential unreasonable obstinacy, followed by withdrawing treatment and technical support, and finally a palliative care plan is drawn up with the medical team and the parents.

[Evidence versus experience in neonatal practice: the example of extremely premature infants]. / Niveaux de preuves versus pratiques cliniques: l'exemple de l'extrême prématurité

We focused on current nutritional and ventilation strategies of extremely preterm infants and reviewed the evidence and the practical experience in four French neonatal intensive care units. The recommendations from reviews and the local clinical guidelines were compared and were overall in agreement. We wanted then to evaluate if different ventilatory and nutritional styles existed between four French intensive neonatal units, and if these approaches had an effect on short term outcomes. 399 infants delivered at a gestational age <28 weeks between January 2005 and December 2006 were retrospectively studied (unit I = 141, unit II = 97, unit III = 85, unit IV = 76). Data were collected from birth to discharge. The study groups were similar with regard to gestational age, birth weight, gender, prenatal steroids, rate of inborn. There were significant differences in ventilatory and nutritional strategies between the units. Incidence of NEC, IVH grade 3-4 and PVL were similar between the units. Mortality rate during the hospitalization stay was 14.9 %, 35.0 %, 29.4 % and 29 % (p<0.05). A national database would be useful to analyse differences in strategies and long term outcomes.

Disseminated bronchoalveolar keratinocyte plugs in severe neonatal congenital lamellar ichthyosis.

We present here a case of congenital lamellar ichthyosis responsible for neonatal death immediately after delivery due to obstruction by bonchoalveolar keratinocyte plugs. The main interest of this case was to confirm in utero amniotic fluid movement into the distal airways by fetal breathing or gasping.

Mosaic trisomy 15 and hemihypertrophy.

We report a case of mosaic trisomy 15 with mental retardation, facial dysmorphism, and hemihypertrophy, but no manifestations of Prader-Willi or Angelman syndromes. Mosaic trisomy 15 (11%) was discovered at the amniocentesis. Uniparental disomy for chromosome 15 was excluded by molecular analysis. Post-natal blood karyotype and examination were normal. Mosaic was confirmed on skin fibroblasts, placenta and cord. Evolution was marked by progressive right hemi-hypertrophy, and developmental delay. Our case is the first patient reported with hemihypertrophy associated with mosaic trisomy 15. The relevant literature is reviewed.

Food supplementation with milk fermented by Lactobacillus casei DN-114 001 protects suckling rats from rotavirus-associated diarrhea.

Group A rotavirus is the leading cause of diarrhea among children aged 3-36 mo worldwide. Introducing fermented milk products into the infant diet has been proposed for the prevention or treatment of rotavirus diarrhea. The preventive effect of milk fermented by the Lactobacillus casei strain DN-114 001 was studied in a model of germfree suckling rats supplemented daily from d 2 of life and infected with SA11 rotavirus at d 5 (RF group). One group was supplemented with nonfermented milk (RM) and two uninfected groups (CM and CF) received either nonfermented or fermented milk. Frequency and severity of diarrhea were observed. Rats were killed at various times from 0 to 120 h postinfection (p.i.). Bacteria were measured in the intestine, and rotavirus antigens were detected by ELISA in fecal samples and in different parts of the intestine. Histologic observations were made, including vacuolation, morphology of intestinal villi and number of mucin cells. RM rats had diarrhea for 6 d; compared with the CM group, they had alterations of the intestinal mucosa characterized by cellular vacuolation 48 and 72 h p.i. and a lower number of sulfated mucin cells 72 and 96 h p.i. (P: < 0.05). Early supplementation with fermented milk significantly decreased the clinical signs of diarrhea from 24 to 144 h p.i. (P: < 0.05) and prevented rotavirus infection in all sections of the intestine. Histologic lesions of the small intestine were greatly reduced (P: < 0.05) and the number of mucin cells remained unchanged. The data are discussed with respect to the possibility of reducing rotavirus diarrhea in young children by consumption of fermented milk.

Continuous tracheal gas insufflation in preterm infants with hyaline membrane disease. A prospective randomized trial.

In mechanically ventilated neonates, the instrumental dead space is a major determinant of total minute ventilation. By flushing this dead space, continuous tracheal gas insufflation (CTGI) may allow reduction of the risk of overinflation. We conducted a randomized trial to evaluate the efficacy of CTGI in reducing airway pressure over the entire period of mechanical ventilation while maintaining oxygenation. A total of 34 preterm newborns, ventilated in conventional pressure-limited mode, were enrolled in two study arms, to receive or not receive CTGI. Transcutaneous Pa(CO(2)) (tcPa(CO(2))) was maintained at 40 to 46 mm Hg in both groups to ensure comparable alveolar ventilation. Respiratory data were collected several times during the first day and daily until Day 28. Both groups were similar at the time of inclusion. During the first 4 d of the study, the difference between peak pressure and positive end-expiratory pressure was significantly lower in the CTGI group by 18% to 35%, with the same tcPa(CO(2)) level and with no difference in the ratio of tcPa(O(2)) to fraction of inspired oxygen (245 +/- 29 versus 261 +/- 46 mm Hg [mean +/- SD] over the first 4 d). Extubation occurred sooner in the CTGI group (p < 0.05), and the duration of mechanical ventilation was shorter (median: 3.6 d; 25th to 75th quartiles: 1.5 to 12.0 d; versus median: 15.6 d; 25th to 75th quartiles: 7.9 to 22.2; p < 0.05) than in the non-CTGI group. CTGI allows the use of low-volume ventilation over a prolonged period and reduces the duration of mechanical ventilation.

[The incidence of prescriptions without marketing product license in a neonatal intensive care unit]. / Incidence des prescriptions hors autorisation de mise sur le marché en réanimation néonatale.

UNLABELLED: Most of the drugs prescribed in pediatric units have no product licence. The lack of clinical studies in children and appropriate drug formulations decrease their safety. The lack of a legal framework makes the prescriber insecure. Even if the debate is not recent, few studies have been carried out in this field. The aim of the present study was to evaluate the rate of prescriptions of unlicensed and off-label drugs in a neonatal intensive care unit. PATIENTS AND METHODS: The present study was carried out in our neonatal intensive care unit, from January 12 to February 12, 1998. Forty babies aged 0 to 128 days were included (90% newborns), with a gestational age between 25 to 40 weeks (88% were premature, with a birth weight lower than 1000 g). RESULTS: Two hundred and fifty-seven prescriptions were administered with 55 different types of drugs during this period. Ten percent of the prescribed drugs had no product licence. Sixty-two percent were off-label for premature infants and 64% for newborns: 90% due to age, 9.3% due to dose and 0.7% to method of administration. No therapeutic alternatives to these prescriptions were found among the few available licensed drugs. CONCLUSION: The prescriptions of unlicensed and off-label drugs in neonatal intensive care units are daily and repeated events. The prescribers are usually not aware of the exact status of the drug and do not realize neither he importance of the problem nor the legal and potential consequences. The lack of pediatric clinical studies is to a large extent responsible for the absence of drug registration in pediatrics. The pharmaceutical industry has few incentives to develop the pediatric product licences.

Evaluation of parental mitochondrial inheritance in neonates born after intracytoplasmic sperm injection.

Intracytoplasmic sperm injection (ICSI) is now used when severe male-factor infertility has been documented. Since defective mitochondrial functions may result in male hypofertility, it is of prime importance to evaluate the risk of paternal transmission of an mtDNA defect to neonates. DNA samples from the blood of 21 infertile couples and their 27 neonates born after ICSI were studied. The highly polymorphic mtDNA D-loop region was analyzed by four PCR-based approaches. With denaturing gradient gel electrophoresis (DGGE), which allows 2% of a minor mtDNA species to be detected, the 27 newborns had a DGGE pattern identical to that of their mother but different from that of their father. Heteroplasmy documented in several parents and children supported an exclusive maternal inheritance of mtDNA. The parental origin of the children's mtDNA molecules also was studied by more-sensitive assays: restriction-endonuclease analysis (REA) of alpha[32P]-radiolabeled PCR products; paternal-specific PCR assay; and depletion of maternal mtDNA, followed by REA. We did not detect paternal mtDNA in nine neonates, with a sensitivity level of 0.01% in five children, 0.1% in two children, and 1% in two children. The estimated ratio of sperm-to-oocyte mtDNA molecules in humans is 0.1%-1.5%. Thus, we conclude that, in these families, the ICSI procedure performed with mature spermatozoa did not alter the uniparental pattern of inheritance of mtDNA.

Continuous tracheal gas insufflation enables a volume reduction strategy in hyaline membrane disease: technical aspects and clinical results.

OBJECTIVE: Instrumental dead space wash-out can be used to improve carbon dioxide clearance. The aim of this study was to define, using a bench test, an optimal protocol for long-term use, and to assess the efficacy of this technique in neonates. DESIGN: A bench test with an artificial lung model, and an observational prospective study. Dead space wash-out was performed by continuous tracheal gas insufflation (CTGI), via six capillaries molded in the wall of a specially designed endotracheal tube, in 30 preterm neonates with hyaline membrane disease. SETTING: Neonatal intensive care unit of a regional hospital. RESULTS: The bench test study showed that a CTGI flow of 0.5 l/ min had the optimal efficacy-to-side-effect ratio, resulting in a maximal or submaximal efficacy (93 to 100%) without a marked increase in tracheal and CTGI circuit pressures. In the 30 newborns, 15 min of CTGI induced a significant fall in arterial carbon dioxide tension (PaCO2), from 45 +/- 7 to 35 +/- 5 mmHg (p = 0.0001), and in 14 patients allowed a reduction in the gradient between Peack inspirating pressure and positive end-expiratory pressure from 20.8 +/- 4.6 to 14.4 +/- 3.7 cmH2O (p < 0.0001) while keeping the transcutaneous partial pressure of carbon dioxide constant. As predicted by the bench test, the decrease in PaCO2 induced by CTGI correlated well with PaCO2 values before CTGI (r = 0.58, p < 0.002) and with instrumental dead space-to-tidal volume ratio (r = 0.54, p < 0.005). CONCLUSION: CTGI may be a useful adjunct to conventional ventilation in preterm neonates with respiratory disease, enabling an increase in CO2 clearance or a reduction in ventilatory pressure.

Development of a heterologous model in germfree suckling rats for studies of rotavirus diarrhea.

Germfree suckling rats were infected with an SA11 rotavirus strain. Infected pups developed diarrhea associated with histopathological changes. The virus was detected in feces and in the small intestine. Cellular vacuolation was observed in the villi of the jejunum. These results provide a new model for further investigations of group A rotavirus infection.

Exhaustive scanning approach to screen all the mitochondrial tRNA genes for mutations and its application to the investigation of 35 independent patients with mitochondrial disorders.

To gain a better understanding of the molecular basisof mitochondrial (mt) encephalomyopathies, a highly heterogeneous condition, we developed a denaturing gradient gel electrophoresis-based approach that allows rapid and exhaustive screening for mutations of all 22 mt tRNA-encoding genes and their flanking regions in large cohorts of patients. This method, that detects heteroplasmy (i.e. co-existence of mutant and wild-type mtDNA species in various ratios) directly, was applied to the investigation of 35 independent patients with a disease phenotype compatible with a mitochondrial encephalomyopathy. Twenty-five of the 35 patients investigated displayed a sequence variation in at least one tRNA gene. A total of 46 different sequence variations (41 point mutations, four short insertions and one short deletion), among which 20 are new, were characterized. Forty of them were present in a homoplasmic state, whereas six were heteroplasmic. Twenty-two were located in tRNA genes, among which 10 are new homoplasmic or heteroplasmic sequence variations; 24 were located in flanking regions (12 in mRNA-encoding genes, seven of them leading to missense sequence variations; two in rRNA genes; and 10 in non-coding regions). This study demonstrates (i) the high frequency of homoplasmic tRNA gene sequence variations in our patient sample, and (ii) the existence of several polymorphic sites in tRNA gene regions that may be helpful for defining haplogroups in different populations. It relies on a screening method that can now be applied easily to other population samples.

Milk fermented with yogurt cultures and Lactobacillus casei compared with yogurt and gelled milk: influence on intestinal microflora in healthy infants.

Ingestion of fermented dairy products induces changes in the equilibrium and metabolism of the intestinal microflora and may thus exert a healthful influence on the host. We compared the effects of consumption of a traditional yogurt, a milk fermented with yogurt cultures and Lactobacillus casei (YC), and a nonfermented gelled milk on the fecal microflora of healthy infants. Thirty-nine infants aged 10-18 mo were randomly assigned to one of three groups in which they received 125 g/d of one of the three products for 1 mo. The following indexes were not modified during the supplementation period or for 1 wk after the end of supplementation: total number of anaerobes, bifidobacteria, bacteroides, and enterobacteria; pH; water content; concentrations of acetate, butyrate, propionate, and lactate; and bacterial enzyme activity of beta-galactosidase and alpha-glucosidase. In contrast, in the yogurt group the number of enterococci in fecal samples increased (P < 0.05), whereas the percentage of branched-chain and long-chain fatty acids, which are markers of proteolytic fermentation, decreased (P < 0.05). In the YC group, the percentage of children with > 6 log10 colony-forming units lactobacilli/g feces increased (P < 0.05), whereas the potentially harmful enzyme activity of beta-glucuronidase and beta-glucosidase decreased (P < 0.05). These decreases were particularly marked in those infants in the YC group in whom activity of the enzymes was initially unusually high.

Pattern of metabolism and composition of the fecal microflora in infants 10 to 18 months old from day care centers.

BACKGROUND: From 5 months of age, infants are progressively introduced to a variety of foods which influence the equilibrium of the intestinal microflora. METHODS: Thirty-five children age 10-18 months from 8 day care centers in France were studied. Fecal specimens were examined for their biochemical and microbiological criteria. RESULTS: Bifidobacteria and Bacteroides belong to the predominant populations (9.7 and 8.6 log 10 cfu/g, respectively). The mean level of enterobacteria and enterococci were 8.0 and 7.8 log 10 cfu/g, respectively. Only 10% of the infants presented a lactobacilli amount above 6 log 10 cfu/g. Most feces had similar pH values (mean 6.4), percentage of water (mean 76.4%), and short chain fatty acid, ammonia and lactic acid concentrations (means 77, 6.7 and 2.3 mumol/g, respectively). beta-galactosidase had the highest activity (106 IU/g of protein) and nitroreductase, the lowest (0.1 IU/g of protein). alpha-glucosidase and nitrate reductase showed intermediate values of 17 and 4 IU/g of protein, respectively. With the exception of 4 infants, beta-glucosidase and beta-glucuronidase values were low (4 and 2 IU/g of protein). Age and day care center were not significant factors for most parameters studied, except that rotavirus was related to day care center, with detection in 5 infants from the same center. CONCLUSIONS: Many biochemical parameters were comparable to those found in adults, with the exception of ammonia concentration and beta-galactosidase activity. The fecal bacterial profile was different than in adults, with more Bifidobacteria than Bacteroides and higher levels of facultative anaerobes. One infant suffering from gastroenteritis had distinctive biochemical and bacterial parameters.

[Progressive external ophthalmoplegia of mitochondrial origin: contribution of morphological and molecular studies]. / Ophtalmoplégies externes progressives d'origine mitochondriale: apport des investigations morphologiques et moléculaires.

We performed a comparative analysis of the clinical, morphological and molecular characteristics of 62 patients affected with progressive external ophthalmoplegia with ragged-red fibres in muscle. Twenty-seven patients had only muscular disease, and 35 had a multisystemic disease with neurological, cardiac, sensory, or endocrine symptoms. Quantitation of mitochondrial accumulation and numbering of cytochrome c oxidase deficient muscle fibres were done in 43 patients. Muscle mitochondrial DNA deletions were detected, quantitated and localised by Southern Blot analysis. Point mutations were screened in five mitochondrial DNA transfer RNA genes by denaturing gradient gel electrophoresis technique. This study further emphasized the relationships between progressive external ophthalmoplegia and mitochondrial DNA mutations that were present in 46/62 patients (40 deletions, 4 h point mutations in the tRNA leucine gene and 2 further families with maternal inheritance but no mutation identified to-date). Family history was positive in 12 patients: 4 with a maternally inherited disease (2 of whom had an identified mitochondrial DNA mutation), and 4 with an autosomal dominant inherited disease, none of which was associated with multiple mitochondrial DNA deletions. Interestingly, 2 of our patients with an identified mitochondrial DNA mutation appeared as sporadic cases. No morphological or molecular parameters was correlated with the tissular extension of the disease. However, mitochondrial DNA deletions were significantly associated with ocular symptoms which had an earlier onset and were more severe. Clinical features of the patients with a multisystemic disease and a mitochondrial DNA deletion were essentially related to Kearns-Sayre syndrome. In particular, a cardiac conduction defect was present in 12 patients out of 18 with a multisystemic disease associated with a mitochondrial DNA deletion; it was never encountered in 17 patients with a multisystemic disease but no mitochondrial DNA deletion.