[Palliative care after neonatal intensive care: Contributions of Leonetti Law and remaining challenges]. / Soins palliatifs au décours d'une réanimation néonatale : apports de la loi Léonetti et défis persistants.

The 2005 enactment of the "Patients' rights and end-of-life care" act, known as the Leonetti law, has been accompanied by practical changes in the processes of withdrawal and withholding of active life-sustaining treatments. This law has also promoted the implementation of palliative care in perinatal medicine to avoid unreasonable therapeutic interventions and to preserve the dying patient's quality of life and human dignity. Recently, a new law has been voted by the French National Assembly and new reflections on the ethical aspects of the end of life in neonatal medicine should resume again within the French Society of Neonatology in the working group on ethical issues in neonatology. This is why it appears important to discuss the perceived benefits and the persistent difficulties related to the implementation of the Leonetti law in neonatology. Collegiality in the decision-making processes as well as withdrawal and withholding of life-sustaining treatments that were already present in the practices of many centers has been stipulated within a legal framework and promoted in clinical practice. It has brought serenity within perinatal nursing and medical teams. It has helped them face the always-difficult end-of-life situations with parents and deal with decision-making processes in an intense emotional climate. However, new questions inherent to the law have appeared. The most important ones concern the withholding of artificial nutrition and hydration, the time pressure in the management of the decision-making process, and the management of the duration of palliative care. Challenges remain in addressing various persistent ethical dilemmas such as the possible survival of newborns with significant brain lesions detected after the period of life-sustaining treatments that have allowed their survival. The new law carried by Mr. Clayes and Mr. Léonetti should provide answers to some of these ethical issues, but it would probably not solve all of them.

[Role of systematic ophthalmological screening for congenital toxoplasmosis: epidemiological study of an Alsatian cohort from 1990 to 2011]. / Intérêt du dépistage ophtalmologique systématique de la toxoplasmose congénitale: étude d'une cohorte alsacienne entre 1990 et 2011.

INTRODUCTION: Ophthalmologic complications of congenital toxoplasmosis, such as retino-choroiditis, are particularly feared. Any child with confirmed congenital toxoplasmosis is systematically treated and followed regularly with multiple fundus examinations. The goal of our study is to describe the management and monitoring of a cohort of patients with congenital toxoplasmosis in Alsace, and the impact of this disease in terms of parental anxiety using a standardized questionnaire. MATERIALS AND METHODS: Our study recorded 35 children with congenital toxoplasmosis, born between 1990 and 2011 in Alsace. All patients were followed by an ophthalmologist. A standardized questionnaire concerning the experience of pregnancy and post-natal follow-up was administered to the parents. RESULTS: At birth, retinochoroiditis was detected in 2 of the 35 children, and only one child developed chorioretinitis detected during follow-up monitoring (follow-up ranged from 1 to 22 years). Brain abnormalities were noted in 3 children at birth; none of them have presented with chorioretinitis to this day. An average score of 15 out of 23 was found by our standardized questionnaire, reflecting significant anxiety due to congenital toxoplasmosis. DISCUSSION: Parental anxiety due to congenital toxoplasmosis is obvious, as demonstrated by our standardized questionnaire. Follow-up, directed by comprehensive pediatric examination at birth, including fundus examination, and good information on functional signs of ocular toxoplasmosis may improve screening, so as to avoid impact on visual function.

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.

Surgical management of congenital chylothorax in children.

PURPOSE: Aim of the study was to determine the role of surgery in the management of congenital chylothorax (CC). METHODS: We retrospectively reviewed the data of patients with CC requiring medical or surgical treatment postnatally in our institution between January 2001 and March 2009. RESULTS: Ten patients were treated for CC. We divided our population into 2 groups: group A consisted of patients in whom CC healed after conservative medical treatment (thoracocentesis, pleural drainage, total parental nutrition, somatostatin, intrapleural injections of povidone-iodine), and group B of patients who needed both medical and surgical treatment (pleural abrasion and/or pleurectomy). Conservative postnatal therapy was successful in 50% of cases. Of the 3 patients treated preoperatively with intrapleural injections of povidone-iodine, 2 presented with severe complications. Surgical treatment was successful in all cases, with no surgical complications. Patients in group B had a significantly lower birth term (p=0.0254) and birth weight (p=0.0021) compared to patients in group A. Patients with a massive chylothorax (≥50 mL/kg/day) needed surgery significantly more often than those with chylothorax <50 mL/kg/day (p=0.0119). CONCLUSION: The initial postnatal medical management of CC should consist of thoracocentesis, drainage by tube thoracostomy, and total parenteral nutrition. If this treatment fails after 10 days, we propose using alternative therapies such as somatostatin (although its efficacy is not clear) and surgery. Chemical pleurodesis by intrapleural injection of povidone-iodine must be avoided in infants and small babies. Surgical management by pleural abrasion and/or pleurectomy appears to be safe and effective. Early surgical management is proposed for babies with low birth term, birth weight and massive chylothorax >50 mL/kg/day. Long-term follow-up is needed to evaluate the potential consequences of this therapy.

[Severe acute pancreatitis in children receiving asparaginase: multicenter retrospective study]. / Pancréatites aiguës sévères à l'asparaginase chez l'enfant: étude rétrospective multicentrique.

UNLABELLED: Asparaginase is frequently used in the treatment of lymphoblastic malignancies in children and is a major cause of drug-induced acute pancreatitis. Severe cases of iatrogenic pancreatitis are uncommon but potentially lethal, and represent a diagnostic and therapeutic challenge. PATIENTS AND METHOD: We have retrospectively collected pediatric cases of severe acute pancreatitis induced by asparaginase, having occurred since January 1996 in participating centers from France and Belgium. RESULTS: Eleven patients, between four and 15 years old, have been included. Pancreatitis has been observed in all treatment phases, after 6 to 21 doses of asparaginase, 2 to 16 days after the last injection. Circulatory collapse (5/11), insulin-dependent diabetes (6/11) and pancreatic pseudokysts (7/11) were the major complications. Non-surgical treatment mainly included digestive rest, broad-spectrum antibiotic therapy and prolonged use of morphine. Asparaginase has been eventually reintroduced in three cases, and has caused a recurrence of pancreatitis in two of them. CONCLUSION: Intensive supportive management should enable a favourable outcome in most cases of acute pancreatitis induced by asparaginase in children. There is no way to predict the occurrence of this adverse event. Re-use of asparaginase should probably be ruled out.

Peritoneal dialysis in children: consider the membrane for optimal prescription.

The peritoneal dialysis prescription was, for a long time, based on clinical experience and very empirical, especially for patients on continuous ambulatory peritoneal dialysis (CAPD). Better comprehension of the peritoneal membrane as a dynamic dialysis surface allows an individualized prescription, especially for children on automated peritoneal dialysis (APD). Fill volume prescription should be scaled for body surface area (mL/m(2)) and not in a too low amount to avoid a hyperpermeable exchange. Fill volume enhancement should be done under clinical control and is best secured by intraperitoneal pressure measurement (IPP; cm H2O). A peak fill volume of 1400-1500 mL/m(2) could be prescribed both in terms of tolerance and of efficiency. The dwell times should be determined individually with respect to two opposite parameters namely: short dwell times which provide adequate small solute clearance and maintain ultrafiltration capacity and long dwell times which enhance phosphate clearance but can contribute to dialysate reabsorption. The new peritoneal dialysis fluids which are free of GPD's, have neutral pH and are not exclusively lactate buffered, appear as the best choice in the context of peritoneal exchange membrane recruitment and of peritoneal vascular hyperperfusion preservation.

Does smoking in pregnancy modify the impact of antenatal steroids on neonatal respiratory distress syndrome? Results of the Epipage study.

OBJECTIVES: To assess the relation between cigarette smoking during pregnancy and neonatal respiratory distress syndrome (RDS) in very preterm birth, and to analyse the differential effect of antenatal steroids on RDS among smokers and non-smokers. DESIGN: A population based cohort study (the French Epipage study). SETTING: Regionally defined births in France. METHODS: A total of 858 very preterm liveborn singletons (27-32 completed weeks of gestation) of the French Epipage study were included in this analysis. The odds ratio for RDS in relation to smoking in pregnancy was estimated using a logistic regression to control for gestational age. The odds ratio for RDS in relation to antenatal steroids was estimated taking into account an interaction between antenatal steroids and cigarette smoking, using multiple logistic regression to control for gestational age, birthweight ratio, main causes of preterm birth, mode of delivery, and sex. RESULTS: The odds ratio for RDS in relation to smoking in pregnancy adjusted for gestational age (aOR) was 0.59 (95% confidence interval (CI) 0.44 to 0.79). The aOR for RDS in relation to antenatal steroids was 0.31 (95% CI 0.19 to 0.49) in babies born to non-smokers and 0.63 (95% CI 0.38 to 1.05) in those born to smokers; the difference was significant (p = 0.04). CONCLUSIONS: Cigarette smoking during pregnancy is associated with a decrease in the risk of RDS in very preterm babies. Although antenatal steroids reduce the risk of RDS in babies born to both smokers and non-smokers, the reduction is smaller in those born to smokers.

[Secondary surfactant deficiencies in extremely low birth weight premature infants]. / Déficits secondaires en surfactant chez le grand prématuré

Primary deficiency of surfactant is responsible for the respiratory distress syndrome and concerns premature neonates born before 33 weeks of gestation. However, newborns may develop respiratory disorders related to a secondary deficiency or dysfunction of surfactant. We report the course of three extremely low birth weight premature infants who experienced clinical respiratory decompensation at two weeks and showed a marked improvement after exogenous natural surfactant administration.

[Secondary surfactant deficiencies]. / Les déficits secondaires en surfactant.

Preterm babies born before the 33rd week of gestation often exhibit primary surfactant deficiency responsible for the respiratory distress syndrome or hyaline membrane disease. In that situation, there is a limited and insufficient production of surfactant by type II alveolar cells of the lung due to immaturity. Secondary surfactant deficiencies occur in patients with prior normal surfactant synthesis and can be related to sepsis, hypoxia, ventilator induced lung injury or surfactant inhibition by a variety of substances reaching the alveolar spaces. They occur in full-term newborns with meconium aspiration syndrome, acute respiratory distress syndrome and congenital diaphragmatic hernia. In children and adults, acute respiratory distress syndrome and respiratory syncytial virus bronchiolitis can be responsible. In prematures they occur after the initial primary deficiency during pulmonary hemorrhage, pneumonia and bronchopulmonary dysplasia. Treatment with exogenous surfactant may be beneficial. There is a need for randomized controlled studies for evaluation of this treatment. Next generation of surfactants containing recombinant surfactant protein or synthetic peptides appear as promising agents in these situations of secondary surfactant deficiencies.

Measurement of hydrostatic intraperitoneal pressure: a useful tool for the improvement of dialysis dose prescription.

The prescription of peritoneal dialysis should be individualized based on parameters of tolerance and adequacy. Determination of the intraperitoneal fill volume is essential for optimal patient care. Fill volume enhancement is a factor of exchange surface area recruitment: the wetted, contact peritoneal dialysis membrane. Nevertheless, fill volume enhancement can also lead to patient discomfort, with the potential risk of too high an intraperitoneal pressure (hernia, gastro-esophageal reflux). The perception of the individual patient is also a subjective parameter of fill volume tolerance assessment. In contrast, measurement of the hydrostatic intraperitoneal pressure (IPP, cmH(2)O) allows an objective approach to fill volume tolerance. From our clinical experience of more than 10 years of IPP measurements in child care, we can give a recommendation for normal values in children: less than 18 cm of water, usually between 5 and 15 cm, correlated to the intraperitoneal fill volume (naturally), but individually taking into account age, gender, "accustomization" and overall body mass index.

Effects of antenatal antibiotics on the incidence and bacteriological profile of early-onset neonatal sepsis. A retrospective study over five years.

BACKGROUND: Recommendations for the use of antenatal antibiotics have been widely implemented in the past few years, notably to prevent group B streptococcal disease or to prolong pregnancy in the case of preterm premature rupture of the membranes. OBJECTIVES: We designed a retrospective study to assess the potential effects of this increasing use of antibiotics on the incidence and bacteriological profile of early-onset neonatal sepsis (EONS). METHODS: All neonates referred to our department for suspected EONS from January 1 1995 through December 31 1999 were included. Antenatal antibiotic exposure together with clinical and microbiological data from the neonatal period were gathered and analyzed on a yearly basis. RESULTS: Of the 485 newborns who met the inclusion criteria, there were 101 cases of culture-confirmed sepsis; 339 cases of suspected sepsis and 69 cases of confirmed sepsis involved children born in the hospital, among a total of 16,627 live births registered in our center over the study period. The overall incidence of EONS dropped from 6.8 to 0.6/1,000 births between 1995 and 1999 (p < 0.001), but the rate of group B streptococcal infection decreased much more rapidly than that of non-group B streptococcal infection. We observed a trend towards the emergence of ampicillin-resistant Escherichia coli strains, which were isolated in seven cases. Among E. COLI infections, ampicillin resistance was statistically linked with antenatal antibiotic use (p = 0.025). We also delineated several risk factors associated with these infections. CONCLUSION: In our center, antenatal antibiotic treatment was effective in reducing the incidence of EONS, but this benefit may come at the cost of favoring the emergence of ampicillin-resistant organisms causing severe neonatal infections. Antenatal and postnatal antibiotic treatment strategies should take this adverse effect into account.

[Role of gastroesophageal reflux in asthma in infants and young children]. / Rôle du reflux gastro-oesophagien dans l'asthme du nourrisson et du jeune enfant.

Gastroesophageal reflux (GER) occurs more frequently in asthmatic children than in general population. Esophageal pH recording data may be somewhat particular. The debate on GER increasing bronchial obstruction or GER being a parallel phenomenon remains controversial. Hypotheses are: acid microaspirations giving bronchospasm, vagally-transmitted reflex, or more probably coexisting phenomena. Pulmonary contamination is rarely seen during esophageal scintigraphy. Asthma symptoms are rarely clearly correlated to acid reflux episodes in pH-recording studies. However the esophageal acid infusion test may increase bronchial obstruction in adult asthmatics. Basically, when should one seek GER in asthmatic children? Many authors keep this for asthmatic children not responding to conventional treatment, also keeping in mind that GER-specific therapy efficacy is often difficult to appreciate in such patients. Briefly, one may speculate that GER improves with bronchodilator treatment in most cases.

[Pemphigoid gestationis and bullous lesions in the newborn]. / Pemphigoïde gravidique et lésions bulleuses chez le nouveau-né.

BACKGROUND: Pemphigoid gestations is very seldom responsible for cutaneous lesions in newborns through passive transfer of the autoimmune disease from mother to infant. CASE REPORT: We report an additional case of a newborn presenting with an extensive but transitory bullous eruption despite the absence of circulating autoantibodies. CONCLUSION: Such examples of transplacental pemphigoid are so uncommon that the pathogenic role of IgG autoantibodies is being questioned.

Developmental aspects of parathyroid hormone-related protein biology.

Parathyroid hormone-related protein (PTHrP) has been discovered as a parathyroid hormone (PTH)-like factor responsible for the humoral hypercalcaemia of malignancies. Further studies revealed that PTHrP is ubiquitously expressed, in mature as well as in developing normal tissues from various species. Although not completely understood, the biological roles of PTHrP concern a variety of domains, including calcium phosphorus metabolism and bone mineralization, smooth muscle relaxation, cell growth and differentiation, and embryonic development. As a poly-hormone, PTHrP is now acknowledged to act via the paracrine, autocrine, and even the intracrine pathways. This review focuses on the main developmental features of the biology of PTHrP. During embryonic development, PTHrP is considered to be involved as a growth factor that promotes cell proliferation and delays cell terminal maturation. PTHrP has been shown to intervene in the development of various tissues and organs such as the skeleton, skin, hair follicles, tooth, pancreas, and the kidney. In addition, through its midregion sequence, which is able to promote an active transplacental calcium transport, PTHrP may intervene indirectly in the mineralization of the foetal skeleton. PTHrP has also been shown to be necessary for the normal development of the mammary gland, while huge amounts of PTHrP are found in the human milk. Finally, observations of physiologic, vasodilating effects of PTHrP in the kidney suggest its involvment in the control of renal hemodynamics, especially in the perinatal period.

Paradoxical actions of exogenous and endogenous parathyroid hormone-related protein on renal vascular smooth muscle cell proliferation: reversion in the SHR model of genetic hypertension.

In previous studies, added parathyroid hormone-related protein (PTHrP) inhibits whereas transfected PTHrP stimulates the proliferation of A10 aortic smooth muscle cells by nuclear translocation of the peptide. In the present studies, we asked whether these paradoxical trophic actions of PTHrP occur in smooth muscle cells (SMC) cultured from small intrarenal arteries of, and whether they are altered in, 12-wk-old spontaneously hypertensive rats (SHR) as compared to normotensive Wistar-Kyoto (WKY) rats. SHR cells grew faster than WKY cells. PTHrP transcript was increased in SHR-derived cells whereas PTH1 receptor (PTH1R) transcripts were similar in both cell lines. In both strains of cells, stable transfection with human PTHrP(1-139) cDNA did not further induce proliferation, suggesting maximal effect of endogenous PTHrP in wild cells. In contrast, transfection with antisense hPTHrP(1-139) cDNA, which abolished PTHrP mRNA, decreased WKY but increased SHR cell proliferation. Added PTHrP(1-36) (1-100 pM) decreased WKY and increased SHR cell proliferation. Additional studies indicated that the preferential coupling of PTH1-R to G-protein Gi was responsible for the proliferative effect of exogenous PTHrP in SHR cells. Moreover, PTHrP was detected in the nucleolus of a fraction of WKY and SHR renal SMC, in vitro as well as in situ, suggesting that the nucleolar translocation of PTHrP might be involved in the proliferative effects of endogenous PTHrP. In renovascular SMC, added PTHrP is antimitogenic, whereas endogenously produced PTHrP is mitogenic. These paradoxical effects of PTHrP on renovascular SMC proliferation appear to be reversed in the SHR model of genetic hypertension. A new concept emerges from these results, according to which a single molecule may have opposite effects on VSMC proliferation under physiological and pathophysiological conditions.