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Abstract: Background: Little is known about the influence of anaesthesia for caesarean section on outcome in very preterm infants. Methods: A prospective, population-based, cohort study (the EPIPAGE cohort) included all births before 33 weeks in nine French regions in 1997. Of 2360 infants live-born between 27 and 32 weeks, 1338 were delivered by caesarean section with general anaesthesia (n=711, 53.1%), spinal anaesthesia (n=419, 31.3%), or epidural anaesthesia (n=208, 15.6%). Neonatal mortality was compared among these three groups using bi- (according to gestational age and to anaesthetic technique) and multivariate analyses. Results: Neonatal mortality was 10.1% with general anaesthesia, 12.2% with spinal anaesthesia and 7.7% with epidural anaesthesia. After adjustment for gestational age and characteristics of pregnancy, delivery and neonate, spinal anaesthesia was associated with a higher risk of neonatal death than general anaesthesia (adjusted odds ratio, 1.7; 95% confidence interval 1.1 to 2.6). Conclusion: In this population-based study, spinal anaesthesia was associated with an increased risk of neonatal mortality in very preterm infants compared to general anaesthesia (and epidural anaesthesia), independently from gestational age and characteristics of the pregnancies, deliveries and neonates. Although this multivariate analysis does not prove a causal relationship, the results suggest it could exist, particularly if maternal haemodynamics are poorly controlled. With recent significant change in the conduct of spinal anaesthesia, further studies are needed to investigate potential harmful effects of anaesthesia on very preterm infants delivered by caesarean section. [Copyright &y& Elsevier]

Objective: Synchronous bilateral breast carcinoma (SBBC) is not uncommon. Women with unilateral breast carcinoma are at increased risk for developing contralateral disease. The purpose of this study was to evaluate risk factors, diagnostic circumstances, histological characteristics and therapeutic methods for SBBC. Patients and methods: Between July 1992 and May 2006, 62 patients with SBBC were treated at Tenon hospital (Paris, France). Population was divided into two sub-groups corresponding with two successive periods. Epidemiological characteristics, diagnostic circumstances, therapeutic methods and histological characteristics were analysed. Results: Global incidence of SBBC during this period was 2.6%. The patients presenting a CSBS had a family antecedent of breast cancer in 23.7% of the cases. The most frequent situation associated a palpable tumour and an infraclinic contralateral lesion (43.5%). MRI made diagnosis possible in seven tumours. Among the patients 38.7% had a bilateral mastectomy and 33.9% profited from the technique of the ganglion sentinel. The proportions of invasive lobular carcinomas and the multifocal tumours were 17.7%. The tumours had the same histological type in 78.3% of the cases and the expression of oestrogen receptors was identical in 91.4% of the cases. Discussion and conclusion: The principal risk factors of CSBS are a family history of breast cancer, the histological type lobular invasive and the multifocal character of the first tumour. A conservative surgery is possible as well as the use of the technique of the ganglion sentinel. The CSBS have histological similarities, probably due to environmental factors. [Copyright &y& Elsevier]

Summary: The immature brain is highly susceptible to the consequences of very preterm birth with a high rate of long-term neurodisabilities in survivors and high use of specific outpatient services to limit the functional effects of the disabilities. To assess the economic burden for the social and health care system, it is necessary to inventory the community supports and need for special education or rehabilitation used by preterm children. Such studies are few and were done only in extremely low-birthweight or extremely preterm newborns in the United States. Objective: To study the rates of specific outpatient services and special education at 5 years of age and between 5 and 8 years of age in a geographically-defined population of children born very preterm. Design, Setting and Patients: 2901 liveborn children before 33 weeks’gestation (WG) and one control group of 666 liveborn children at 39-40WG were included in nine regions of France in 1997 corresponding to more than one third of all births. At five years, these children had a medical examination and were evaluated by a psychologist at local centres organised for the study in every region. Cognitive function was assessed by the mental processing composite scale (PMC) of the Kauffmann Assessement Battery for Children test, which is considered to be equivalent to intelligence quotient and behavioral difficulties using the Strength and Difficulties questionnaire completed by the parents. Data for dependence or compensatory aids, i.e. occupational therapy or physical therapy, speech therapy, psychologist or psychiatrist visits, orthoptic therapy, wearing glasses, wearing hearing aid, specific equipment to walk (walker, wheelchair…), orthopaedic treatment or anti-epileptic treatment were collected from parents. At eight years, a postal questionnaire was sent to the parents to collect data on specific outpatient services and special treatments at home and school. Stata software was used (version 9.0). Main outcome measures. Parent Questionnaire for identifying children with chronic conditions and specific health care needs at 5 and 8 years and categorization of developmental neurodisabilities based on examination of children and psychometric evaluation at 5 years. Results: At 5 years data were obtained for respectively 1817 and 396 children born before 33WG or at 39-40WG, which represent 80% of the very preterm children and 71% of the at term children. At 8 years we obtained data for 63% of the very preterm children and 59% of the at term children. At 5 years, care in a rehabilitation center and/or specific outpatient services were required for 41% of children born between 24 and 28WG, 32% of children born between 24 and 32WG and 15% of those born at 39-40WG. Between 5 and 8 years, these figures were respectively 61%, 50% and 36%. In the very preterm group, rates of specific outpatient services were higher than 80% if the child had a motor and/or a neurosensory deficit. In case of cognitive deficiencies (PMC < 85), rates of specific outpatient services were low at 37% at 5 years and increases at 63% between 5 and 8 years. Conclusion: Compared to the children born at term, the very preterm children have considerable educational needs, which are inversely related to gestational age at birth and to age of the children at the time of reporting. Despite economic burden, efforts to improve access to services are necessary, in particular in case of cognitive impairment. [Copyright &y& Elsevier]

Abstract: Objectives: To describe the characteristics of the children of parents who did not respond to a follow-up questionnaire in a cohort of very preterm infants (EPIPAGE study) and to explore the reasons why they did not complete the questionnaires. Methods: The non-respondents (N =176) were the parents who did not return the questionnaires at 1 and 2 years. Contacts were organised by telephone calls and at home visits. Results: The families of the non-respondents presented more socioeconomic difficulties and their children were born more preterm than those followed up without difficulties. The efforts made to contact the non-respondents revealed that their families were often confronted with major adverse socioeconomic difficulties, had severe illnesses and psychological troubles. Half of the children of the non-respondents were finally examined at the 5-year assessment. They showed lower performances at the cognitive development test and a poorer health status than the children of the respondents. Conclusion: When the follow-up does not include the initial population in its totality, the socioeconomic difficulties are underestimated and probably also the rate of sequelae associated with very preterm delivery. [Copyright &y& Elsevier]

Background Several countries, including France, have restricted the indications for monoclonal antibodies directed against respiratory syncytial virus (RSV) compared to the marketing authorization (MA). No new data concerning use of palivizumab on a national scale have been published since the 2007 update of the national guidelines. Objectives To describe palivizumab administration for RSV prophylaxis during the first RSV season in infants born prematurely in France in 2011. Methods Infants from the national population-based cohort EPIPAGE-2 born at ≤ 34 weeks’ gestation, discharged home before 31 March 2012 and followed-up at 1 year were included. The RSV season ran from 1 October 2011 to 31 March 2012. Prophylaxis was deemed “initiated” if the infant had received at least one dose of palivizumab during this period and “complete” if it had received at least five doses or as many doses as the number of exposed months. The reference documents were the MA and French Transparency Committee guidelines (TC). Results Prophylaxis was indicated in 3586 of 3608 infants (99.7%) according to the MA and 1315 of 3608 (16.7%) according to the TC. A total of 1906 infants (26.6%) received at least one dose of palivizumab. The overall rate of conformity with TC indications was 85%, but was lower for infants born at 27–32 weeks’ gestation. The rate of complete prophylaxis was 77.2%. The factors associated with prophylaxis initiation were low gestational age, low birthweight, high maternal educational level, type of neonatal unit, and date at discharge. Factors associated with complete prophylaxis were respiratory impairment, high educational level, and characteristics related to living conditions (absence of siblings at home, type of childcare). Conclusions Palivizumab administration in France generally conformed with TC guidelines, but could be further improved for infants born at 27–32 weeks’ gestation without bronchopulmonary dysplasia. [ABSTRACT FROM AUTHOR]

Résumé La prématurité est une priorité de santé publique dans le monde où un enfant sur dix naît avant 37 semaines d’aménorrhée (SA). La survie sans morbidité néonatale majeure augmente dans les pays développés pour les enfants de petit terme, notamment entre 25 et 30 SA. Les taux de séquelles sévères de type paralysie cérébrale diminuent très probablement mais les difficultés cognitives spécifiques, le plus souvent associées dans de multiples domaines, sont encore très fréquentes, gênant le développement normal des acquisitions scolaires et l’intégration sociétale et expliquant les besoins élevés en rééducation à l’âge scolaire voire préscolaire. La prévalence des séquelles augmente quand le terme de naissance diminue, d’autant plus élevée que le milieu socioculturel est bas. Mais, le nombre absolu d’enfants présentant des difficultés cognitives ou comportementales en cas de naissance prématurée modérée ou tardive est équivalent à celui des enfants nés grands prématurés du fait de leur nombre plus élevé à la naissance. Un meilleur recensement à l’âge de 3–4 ans de l’ensemble des caractéristiques développementales précoces de la population des enfants nés prématurés est indispensable pour pouvoir faire un dépistage plus précoce des difficultés cognitives spécifiques (mémoire de travail, planification, inhibition, langage en expression et réception, attention, motricité fine) ou comportementales. Des essais de remédiation (mémoire de travail, langage, motricité fine, thérapie comportementale et cognitive) et de prise en charge précoce pourront être évalués pour améliorer les performances scolaires. Summary Preterm birth remains a public health priority given that one child out of ten is born before 37 weeks of gestation. Survival without major neonatal morbidity has increased in high-income countries, in particular in France and in cases of extreme preterm birth before 27 weeks of gestation. Rate of severe handicaps, such as cerebral palsy, is probably decreasing, but specific cognitive disabilities in a variety of domains remain frequent, interfering with normal learning abilities at school and explaining the high rate of special education needs. Prevalence of sequelae increases when gestational age at birth decreases. However, because there are more moderate to late preterm children compared to very preterm children, the absolute number of children with specific cognitive or neurological disabilities is equivalent in these two groups. Better characterization of the development in a recent cohort of very preterm children is necessary to improve the early detection of variations in normal neurodevelopment and to propose trials with remediation actions targeting working memory and language for example. These protocols could decrease the rates of learning disabilities at school. [ABSTRACT FROM AUTHOR]

Summary: With improving neonatal survival for very premature babies, the challenge for neonatalogists is to ameliorate outcome of surviving babies. Several pharmacological molecules have been shown to have protective effects in different types of in vitro or in vivo animal models of acquired cerebral brain damages. However translational research and conduction of therapeutic trials in human remain difficult due to failure to recognize start of deleterious cascade leading to cerebral damage and additional toxic effect of potential protective molecules. This review concentrates on best evidence emerging in recent years on prevention on brain damage by early drug administration. It has been shown in two randomised trials that prenatal low-dose of magnesium sulphate does not increase paediatric mortality in very-preterm infants and has non significant neuroprotective effects on occurrence of motor dysfunction (with a 0.62 odds ratio in the French trial Premag and 0.71 relative risk in the Australian trial ACTOMgSO4), justifying that magnesium sulphate should be discussed as a stand-alone treatment or as part of a combination treatment, at least in the context of clinical trials. Antenatal corticosteroid therapy increases the survival of very-preterm infants, including the most immature. Moreover in an observational recent study of the Epipage cohort, it has been observed a significant decrease in white matter injury in the 28-32 weeks’ gestation group but no effect on long term outcome and behaviour. Conversely in the most immature of the 24-27 weeks’ gestation group, no effect has been detected either in white matter injury incidence or in long term outcome rates. Caffeine has a protective effect since a decrease in cerebral palsy has been noted in the caffeine group in a randomised trial studying caffeine versus placebo. For what concern other widely used potential protective molecules during the perinatal period, there is no evidence of cerebral protection with indometacine, nitric oxide, eythropoietin, phenobarbital, and etamsylate. Due to their specific properties, a careful evaluation of aspirin, anaesthetic drugs and tocolytics should be done in the next months. [Copyright &y& Elsevier]