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To characterize the rapid weight gain (RWG) phenotype associated with the onset of childhood narcolepsy and to determine whether it could constitute a marker of severity of the disease.RWG was defined using the BMI z-score slope reported to one year (0.67 SD) from symptom onset to disease diagnosis. We compared the clinical, metabolic, and sleep characteristics between patients with or without RWG at diagnosis. Pharmacological management, anthropometric, and clinical progression were also evaluated during the follow-up.A total of 84 de novo narcoleptic pediatric patients were included; their median age at diagnosis was 12.0 years; 59.5% boys, 90.5% cataplexy, and 98.7% HLA-DQB1*06:02, 57% had RWG profile. RWG patients were younger at diagnosis than non-RWG patients, despite a shorter diagnostic delay. They had a higher BMI z-score and a higher prevalence of obesity at diagnosis, but not at symptom onset, and higher adapted Epworth Sleepiness Scale and Insomnia Severity Index scores than non-RWG patients. No differences on nocturnal polysomnography and multiple sleep latency tests were found between groups at disease diagnosis. After a median follow-up of 5 years, RWG patients still had a higher BMI z-score and a higher prevalence of obesity despite benefiting from the same therapeutic management and displaying improvement in sleepiness and school difficulties.Narcoleptic RWG patients were younger, sleepier, and the prevalence of obesity was higher at diagnosis despite a shorter diagnostic delay than that of non-RWG patients. These patients had also a higher risk of developing a long-term obesity, despite a positive progression of their narcoleptic symptoms. RGW could then represent a maker of a more severe phenotype of childhood narcolepsy, which should inspire a prompt and more offensive management to prevent obesity and its complications.

Study objectives To determine the prevalence of metabolic syndrome (MS) in children with narcolepsy and to evaluate their clinical and sleep characteristics according to the different components of MS. Methods This retrospective study consisted of 58 de novo children with narcolepsy (median age: 12.7 years, 48.3% of boys). The recently published MS criteria in a French population of children were used. Clinical and sleep characteristics were compared between groups with different components of MS. Results MS was present in 17.2% of children with narcolepsy, among whom 79.3% presented with high homeostasis model assessment for insulin resistance (HOMA-IR), 25.9% with high body mass index, 24.1% with low high-density lipoprotein cholesterol (HDL-C), and 12.1% with high triglycerides. Patients with at least two MS components had more night eating behaviors and tended to have lower percentage of slow-wave sleep and more fragmented sleep. On multiple sleep latency test, they had shorter mean sleep latencies to rapid eye movement (REM), non-REM sleep and tended to have more sleep onset REM periods (SOREMPs) than those with less than two MS components. Conclusions Insulin resistance was found to be the core metabolic disturbance in obese as well as in nonobese children with narcolepsy. Children with narcolepsy with at least two MS components presented a more severe daytime sleepiness and a higher prevalence of night-eating behaviors than those with less than two MS components. Such children might benefit from early evaluation and management in order to prevent future complications.

Introduction Sleep troubles have been associated with respiratory and allergic health problems in children, however the time line of their association is overlooked. The current study examined the associations between: (1) sleep patterns at age 1 year and respiratory and allergic multi-trajectories between 1 and 5.5 years; (2) respiratory and allergic multi-trajectories between 1 and 5.5 years and sleep patterns at age 5.5 years in a French birth cohort. Methods Clusters of sleep characteristics at age 1 year (nocturnal sleep duration (NSD), day sleep duration (DSD), sleep onset difficulties (SOD), night awakenings (NA)) and at age 5.5 years (NSD, SOD, NA) and respiratory and allergic symptoms multi-trajectory groups between 1 and 5.5 years (wheezing, asthma medication, eczema, allergic conjunctivitis) were identified using unsupervised methods. Associations between sleep clusters at each age and multi-trajectory groups were assessed using multinomial regressions adjusted for potential confounding factors among 9,577 children. Results Two sleep clusters were identified at both age 1 and 5.5 years: C1a (79.9%, age 1 year) and C1b (83.1%, age 5.5 years) characterized by adequate sleep duration and good sleep quality; C2a (20.1%, age 1 year) and C2b (16.9%, age 5.5 years) characterized by shorter sleep duration and poorer sleep quality. Four multi-trajectory groups were also identified: G1 (no/few symptoms, 44.4%), G2 (persistent non-respiratory allergic symptoms, 23.1%), G3 (transient early respiratory symptoms, 25.2%), G4 (persistent respiratory and allergic symptoms, 7.3%). Belonging to cluster C2a was associated with an increased odds of belonging to G3 (adjusted odds ratio [95% interval confidence]; 1.14 [0.99-1.31]) and G4 (1.29 [1.05-1.59]). After accounting for sleep clusters at age 1 year, belonging to G4 was associated with an increased odds of belonging to cluster C2b (1.21 [0.98-1.5]). Conclusion Sleep disturbances at 1 year were associated with poorer respiratory and allergic health between 1 and 5.5 years and respiratory and allergic problems between age 1 and 5.5 years were associated with sleep troubles at 5.5 years suggesting bidirectionality. Further research is needed to explore potential coevolution of sleep and allergic and respiratory troubles during early childhood. Support (if any) ANR-21-CE36-0001-01

Resume Le sommeil et le systeme immunitaire interagissent notamment via les cytokines. Chez l’adulte, il a ete montre que le manque de sommeil chronique conduisait a une activation des marqueurs de l’inflammation (comme l’IL-6 et la CRP, les plus etudies), constituant une inflammation chronique de bas grade, avec cependant des differences selon le sexe. Seulement 3 etudes ont ete realisees chez des enfants d’âge scolaire en dehors de toute pathologie. Elles montrent que la variabilite du temps de sommeil est associee a une augmentation de la CRP, mais uniquement chez les filles. Aucune etude n’a ete realisee chez les enfants d’âge prescolaire, alors les problemes de sommeil presents dans la petite enfance peuvent perdurer jusqu’a l’âge adulte. Nous proposons une etude longitudinale, chez 687 enfants d’âge prescolaire de la cohorte francaise EDEN, visant a mettre en relation les trajectoires de sommeil entre 2 et 5 ans et les dosages seriques de biomarqueurs immunitaires (cytokines) a 5 ans.

Obstructive sleep apnea syndrome (OSAS) treatment has been shown to improve cardiac behavioral and cognitive functions in typically developing children. Early OSAS diagnosis in children with Down syndrome (DS) would be important to prevent its complications, especially cognitive ones, but remains overlooked. The main objective of our study was to assess the cognitive function of children with DS, with and without OSAS. The second objective was to determine the impact of the therapeutic intervention on the cognitive function of children with OSAS. This study included 41 children with DS who underwent polysomnography for OSAS diagnosis and a cognitive evaluation. They were aged between 3.4 and 17.3 years and 24 (59%) were boys. Their median OAHI was 2.6 (0-31)/h of sleep, 30 (73%) were diagnosed with OSAS (15 had mild OSAS, and 15 had moderate/severe OSAS). Some scores of the Raven's colored progressive matrices were negatively correlated with the respiratory arousal index, OAHI tended to be positively correlated with Reiss behavioral problems. 24 (59%) patients received a treatment. Even if we were unable to demonstrate this formally due that only 16 children (39%) accepted a follow-up visit, some displayed improvement in their neuropsychological scores, especially those with moderate/severe OSAS after treatment. Children with DS have low intellectual abilities and more risk of developing OSAS compared to the general population, which may lead to further neurocognitive impairment. Early screening and management are important in this population to prevent any further neurocognitive delay in their development.

Introduction Parents reported degraded sleep outcomes up to several years after child birth. Most published studies were cross-sectional, in early post-partum and focusing on maternal-child dyads. We aimed at identifying sleep multi-trajectories (SMT) including night (NSD) and daytime (DSD) sleep duration and subjective sleep loss (SSL) between 3 and 36 months postpartum in couples from the SEPAGES cohort. Methods From 484 mothers and 410 fathers included in the SEPAGES cohort, sleep information was collected by self-reports at 3, 18, 24 and 36 months postpartum. Couple SMT were modelled using Group-Based Trajectory Modelling method. Each couple was assigned to the group of SMT with the highest probability of belonging to. Multinomial logistic regression assessed sociodemographic, parental and child covariates associated SMT Results Three groups SMT were identified in couple who reported sleep data at least 2 times across the 4 time-points (N=188). In G1 (29.3%), couples had 8-9hr of mean NSD and a stable and relatively short mean maternal and paternal DSD (≈10min and ≈5min, respectively) while SSL was decreasing for mother (58% to 31%) but stable for father (≈30%) between 3 and 36 months postpartum. In G2 (27.7%), they had a stable but relatively short mean NSD (7-8hr), a maternal DSD decreasing by 20min between 3 and 18 months then being stable at 23min, a stable paternal DSD (≈10min) and high but decreasing SSL from 90% to 86% for mothers and 76% to 61% for fathers. In G3 (43.0%), couples had a stable mean NSD (8-9hr), a relatively long mean DSD, decreasing from 54 to 41min for mothers but increasing from 28 to 39min for fathers, and a stable but relatively high SSL (≈70% for mothers and ≈55% for fathers). From logistic regression, belated paternal chronotype increased odds for belonging to G2 while having a first child and born in autumn decreased odds to belong to G2 compared to G1. Conclusion We identified 3 different SMT between 3 and 36 months postpartum for the first time. We found several factors associated with each SMT. Studies are still warranted to investigate further interrelation with the child sleep patterns. Support (if any)

Background Integrated patterns of energy balance-related behaviours of preschool children in Asia are sparse, with few comparative analyses. Purpose Using cohorts in Singapore (GUSTO) and France (EDEN), we characterized lifestyle patterns of children and investigated their associations with family-focused contextual factors. Methods Ten behavioural variables related to child’s diet, walking, outdoor play and screen time were ascertained by parental questionnaires at age 5–6 years. Using principal component analysis, sex-specific lifestyle patterns were derived independently for 630 GUSTO and 989 EDEN children. Contextual variables were organised into distal (family socio-economics, demographics), intermediate (parental health, lifestyle habits) and proximal (parent-child interaction factors) levels of influence and analysed with hierarchical linear regression. Results Three broadly similar lifestyle patterns were identified in both cohorts: “discretionary consumption and high screen time”, “fruit, vegetables, and low screen time” and “high outdoor playtime and walking”. The latter two patterns showed small differences between cohorts and sexes. The “discretionary consumption and high screen time” pattern was consistently similar in both cohorts; distal associated factors were lower maternal education (EDEN boys), no younger siblings (GUSTO boys) and Malay/Indian ethnicity (GUSTO), while intermediate and proximal associated factors in both cohorts and sexes were poor maternal diets during pregnancy, parents allowing high child control over food intake, snacking between meals and having television on while eating. Conclusions Three similar lifestyle patterns were observed among preschool children in Singapore and France. There were more common associated proximal factors than distal ones. Cohort specific family-focused contextual factors likely reflect differences in social and cultural settings. Findings will aid development of strategies to improve child health.

The objective of this study was to compare the maturation of spontaneous arousals during day and night sleep in preterm and term infants. From the Autonomic Baby Evaluation study, the sleep and arousal characteristics of 12 preterm (35.1 ± 2.1 weeks’ gestational age, GA) and 21 term (39.8 ± 0.8 weeks GA) newborns were compared between diurnal and nocturnal sleep periods at birth (M0) and 6 months (M6) of age. Models were adjusted for time (night/day), maturation (M0/M6), prematurity (yes/no). We found that preterm infants had less active sleep (AS)% than term infants with maturation during both day and night sleep, which may reflect accelerated brain maturation secondary to stress or environmental exposure after birth. Moreover, there was a difference in arousal maturation during day and night sleep in the preterm infants, as shown previously for term infants, which suggests the emergence of a circadian rhythm during the earliest postnatal period. We also showed that compared to term infants, these moderate preterm infants had fewer total arousals and, more specifically, fewer arousals in AS during day and night sleep, exposing them to a higher risk of sudden infant death syndrome.

ObjectiveA defect of the waking systems could constitute a factor of vulnerability for sudden infant death syndrome (SIDS). A decrease in orexin levels, which promotes wakefulness and activates histaminergic neurons (another hypothalamic wake-promoting system) has already been demonstrated between 2 and 6 months. This work aims to study the levels of histamine (HA), tele-methylhistamine (t-MeHA), its direct metabolite, and t-MeHA/HA ratio in the cerebrospinal fluid (CSF) of healthy children, to evaluate the maturation of the histaminergic system and its possible involvement in SIDS.MethodsSeventy Eight French children between 0 and 20 years (48.7% boys) were included, all of whom had a clinical indication for lumbar puncture, but subsequently found to be normal. Measurements of HA and t-MeHA in CSF were performed by reverse phase liquid chromatography coupled to mass spectrometry detection. Statistical analyses were performed using Spearman correlations and Non-parametric pairwise ranking tests.ResultsA negative correlation was found between age and CSF HA (r = −0.44, p < 10−4) and t-MeHA (r = −0.70, p < 10−4) levels. In pairwise comparisons, no difference in CSF HA and t-MeHA levels was observed between youngest age groups (i.e., 0–2 mo vs. 3–6 mo), but CSF HA and t-MeHA levels were significantly lower in older children (i.e., >6 mo vs. 0–6 mo). The CSF HA decrease with age was only observed in boys, who also presented global lower CSF HA levels than girls.ConclusionCSF HA and t-MeHA levels decrease with age in boys, and global levels are lower in boys than in girls. These results reveal changes in histaminergic transmission and metabolism during maturation. Whether lower CSF histamine values in boys compared to girls could contribute to their higher risk of SIDS warrants further research.

Introduction There has been little focus on sleep and its relation to behavior and cognition in preschool-aged children. We aimed to investigate the association between sleep duration in early preschoolers (» 3.5 years of age) and later behavioral and cognitive outcomes (» 5 years of age) in European children. Methods We used harmonized data from five cohorts from the EU Child Cohort Network, established by the LifeCycle Project (n=16.444 children): ALSPAC and SWS from UK, EDEN and ELFE from France and INMA from Spain. Within all cohorts, total sleep duration per day and behavioral and cognitive information were reported by parents. Internalizing and externalizing behaviors were measured with the Strengths and Difficulties Questionnaire and treated as percentile scores. Verbal and non-verbal intelligence were assessed by the Wechsler Preschool and Primary Scale of Intelligence or with the McCarthy Scales of Children’s Abilities depending on the cohort and treated as standardized scores. All scores were cohort specific. Associations between sleep duration during early preschool age and later behavior and/or cognition were estimated using linear regression and pooled with two-stage individual participant data meta-analysis adjusted for child, maternal and household information. Analyses were done in DataSHIELD. Results Global mean sleep duration was 11h54 ± 1h00 per day at mean age 3.5 years but differed by country, with children from France showing longer sleep duration than children from the UK or Spain. In multivariate meta-analysis, 1 hour of additional sleep duration per day at mean age 3.5 years was associated with reduced internalizing and externalizing behavior percentile scores at mean age 5.1 years (internalizing behavior: badjusted= -1.05, 95%-CI [-1.93, -0.18], I2: 30.3%; externalizing behavior: badjusted= -2.12, 95%-CI [-2.78, -1.47], I2: 0.0%). No association was observed between sleep duration and subsequent verbal or non-verbal intelligence Conclusion Longer sleep duration in early preschool age (» 3.5 years of age) was associated with subsequent lower internalizing and externalizing behavior scores (» 5 years of age), but not with verbal or non-verbal intelligence. Adequate sleep duration at an early age is important for children’s later mental health. Support (If Any) KG was granted a LifeCycle fellowship.

International audience; Objective: 25-hydroxyvitamin D (25OHD) deficiency has been associated with sleep disorders in adults. Only three cross-sectional studies were performed in children and showed an association between 25OHD deficiency and both obstructive sleep apnea syndrome and primary snoring. No longitudinal study has been performed in children from the general population. We analyzed the association between cord-blood vitamin D level at birth and night-sleep duration trajectories for children between 2 and 5-6 years old in a non-clinical cohort.Method: We included 264 children from the French EDEN mother-child birth-cohort with both cord-blood 25OHD level determined by radio-immunoassay at birth, and night-sleep trajectories for children between 2 and 5-6 years old obtained by the group-based trajectory modeling method. Associations between 25OHD and sleep trajectories were assessed by multinomial logistic regression adjusted for maternal and child characteristics.Results: The trajectories short sleep (

Introduction Sleepiness is associated with a decrease in cognitive abilities with effects comparable to those of alcohol. It remains one of the main causes of fatal road accidents. Various tools are available to assess sleepiness subjectively and objectively, such as questionnaires and multiple sleep latency test. However, the former are subject to intra- and inter-individual variability, and the latter is only feasible in a sleep laboratory. The main objective of this study was to explore new potential markers (biological, neurocognitive) to assess sleepiness in drivers. In this perspective, the easy-to-use BLAST attention test allows the evaluation of micro-fluctuations in vigilance. In addition, salivary markers are good physiological markers, easily accessible and non-invasive to collect. Recent studies have suggested that salivary a-amylase and oxalate may be biomarkers of sleep pressure. Methods 185 drivers (median age 44 years, 72% male, 15% obese) were included during a break at a highway service area, in the morning, while on the road for vacation. Questionnaires on sleepiness, sleep the day before departure, an attention test and two salivary samples (alpha-amylase and oxalate) were taken. Associations between subjective and objective measures of sleepiness, sleep characteristics and salivary concentrations were tested using regression models adjusted for confounding factors. Results The night before departure, 57% of drivers reduced their sleep time and more than ¼ slept 5 hours or less. The higher the number of miles to drive, the shorter the sleep time. 16% of the drivers complained of poor sleep quality and difficulty falling asleep. At the time of the test, 46% of the drivers felt drowsy. Poor sleep quality or difficulty falling asleep the night before departure was associated with increased sleepiness as assessed by the Stanford Sleepiness Scale and decreased attentional ability as assessed by the BLAST. No association between salivary samples and sleepiness was observed. Conclusion Sleep characteristics on the day before departure were associated with sleepiness and attentional performance. The Stanford Sleepiness Scale and the BLAST could be used by individual drivers in a self-evaluation context. Support (If Any) This study was funded by the Vinci Foundation.

Sleep is essential for optimal child development and health during the life course. However, sleep disturbances are common in early childhood and increase the risk of cognitive, metabolic and inflammatory disorders throughout life. Sleep and immunity are mutually linked, and cytokines secreted by immune cells could mediate this interaction. The sleep modulation of cytokines has been studied mostly in adults and adolescents; few studies have focused on school-aged children and none on preschoolers. We hypothesized that night sleep duration affects cytokine levels in preschoolers. In a sample of 687 children from the EDEN French birth cohort, we studied the associations between night sleep duration trajectories from age to 2-5 years old and serum concentrations of four cytokines (Tumor necrosis factor α [TNF-α], Interleukin 6 [IL-6], IL-10, Interferon γ [IFN)-γ] at age 5, adjusting for relevant covariates. As compared with the reference trajectory (≈11h30/night sleep, 37.4% of children), a shorter sleep duration trajectory (10 ​h/night, 4.5% of children), and changing sleep duration trajectory (≥11h30/night then 10h30/night, 5.6% of children) were associated with higher serum levels of IL-6 and TNF-α, respectively at age 5. We found no associations between sleep duration trajectories and IL-10 or IFN-γ levels. This first longitudinal study among children aged 2-5 years old suggests an impact of sleep duration on immune activity in early childhood. Our study warrants replication studies in larger cohorts to further explore whether and how immune activity interacts with sleep trajectories to enhance susceptibility to adverse health conditions.

This work was conducted in the framework of the French network for Nutrition And Cancer Research (NACRe network), www.inra.fr/nacre.; International audience; Circadian disruption has been classified as probably carcinogenic to humans by the World Health Organization's International Agency for Research on Cancer. The circadian clock is subject to environmental factors, particularly light exposure and food intake rhythms. However, the association between nutritional circadian behaviours and cancer is not well understood. We investigated the longitudinal associations between number of eating episodes, night-time fasting duration, time of first and last eating episodes, as well as nutritional quality of last eating episode, respectively, with breast and prostate cancer risks, the two main cancer locations in women and men respectively. This prospective study included 41,389 day-working adults in the French NutriNet-Santé cohort (2009-2016) who completed at least three 24 h dietary records during the first 2 years of follow-up. Multivariable Cox models were computed. 1,732 first primary incident cancer cases were diagnosed during the follow-up, among which 428 breast and 179 prostate cancers. After adjustment for covariates including sleep duration, late eaters (last eating episode after 9:30 pm) had an increased risk of breast (Hazard ratio [HR] = 1.48 [1.02-2.17], p = 0.03) and prostate (HR = 2.20 [1.28-3.78], p = 0.004) cancers. However, no association was observed between cancer risk and number of eating episodes, night-time fasting duration, time of first eating episode or macronutrient composition of the last eating episode. This large cohort study suggests that circadian perturbations resulting from late time of last food intake may be involved in carcinogenesis at different locations. Beyond nutritional quality of food intake, nutritional circadian regulation should be further investigated in the context of cancer prevention.

Background. Few studies on the relations between sleep quantity and/or quality and cognition were conducted among pre-schoolers from healthy general population. We aimed at identifying, among 3 years old children, early factors associated with intelligence quotient estimated through Weschler Preschool and Primary Scale Intelligence-III test and its indicators: full-scale-, verbal- and performance-intelligence quotients and their sub-scale scores. Methods. We included 194 children from the French birth-cohort AuBE with both available Weschler Preschool and Primary Scale Intelligence-III scores at 3y and sleep data. Information was collected through self-questionnaires at birth, 6, 12, 18 and 24 months. A day/night sleep ratio was calculated. Results. Mean scores were in normal ranges for verbal-, performance- and full-scale-intelligence quotients. In multivariate models, being a $\ge$3 born-child and watching television $\ge$1 hour/day at 24 months were negatively associated with all intelligence quotient scores while collective care arrangement was positively associated. Night waking at 6 and frequent snoring at 18 months were negatively associated with performance intelligence quotient, some subscales and full-scale-intelligence quotient contrary to day/night sleep ratio at 12 months. No association was observed between early sleep characteristics and verbal intelligence quotient. Conclusion. We showed that early features including infant sleep characteristics influence intelligence quotient scores at 3 years old. Some of these may be accessible to prevention.

Objective Infant sleep plays a critical role in normal development. Sleep problems, including sleep onset difficulties (SODs) and night waking (NW), range from 20% to 30% in infants and young children and can be persistent over time up to adulthood. Young French children seem to have longer sleep durations and less sleep troubles than their counterparts worldwide. Here, we aimed at describing infant sleep characteristics (total sleep time (TST)/24 h, NW, and SODs) and associated sleep habits in infants at age one year from the French nationwide birth cohort Etude Longitudinale Francaise depuis l’Enfance (ELFE). Methods This study included 11,783 infants with information on both sleep characteristics and sleep habits (parental presence when falling asleep, eating to fall asleep, sucking a pacifier or finger to sleep and sleep arrangement and location). Associations were studied by multinomial logistic regression analyses adjusted for familial and infant characteristics. Results Mean TST was 13 h36 min including 2 h54 min of naps; 20% of the infants had TST ≤12 h/24 h. About 46% did not present SOD or NW, 16% had frequent SODs and 22% had NW > 1 night in 2. Parental presence, feeding to fall asleep and infant sleep arrangements were frequent in infants with short sleep duration (≤12 h/24 h), NW and SODs. Non-nutritive sucking was associated with risk of NW, SOD and TST >14 h/24 h. Parental room sharing was associated with NW. Conclusion This work provides new information on infant sleep arrangements and non-nutritive sucking that should be accounted for when considering sleep behaviors. In addition, most identified sleep habits associated with poor sleep characteristics may be amenable to change.

International audience; Objective. Sleep duration may vary inter-individually and intra-individually over time. We aimed at both identifying night-sleep duration (NSD) trajectories among preschoolers and studying associated factors. Methods. NSD were collected within the French birth-cohort study EDEN at ages 2, 3 and 5-6 years through parental questionnaires, and were used to model NSD trajectories among 1205 children. Familial socioeconomic factors, maternal sociodemographic, health and lifestyle characteristics as well as child health, lifestyle, and sleep characteristics at birth and/or at age 2 years were investigated in association with NSD using multinomial logistic regressions. Results. Five distinct NSD trajectories were identified: short (SS

Introduction Refractive errors are very common, in particular in children and adolescents, leading to global health issues, academic implications and economic costs. The process of emmetropization in child development is a multifactorial and active mechanism, and is yet to be fully understood. Light exposure and endogenous circadian rhythmicity are thought to have an important role in this process. They are also known to be both cause and consequence of various sleep habits. The study aims at investigating the role of sleep duration and timing in refractive error development of preschoolers. Methods Sleep duration and timing were assessed at age 2 and 5 years, and vision problems at age 5 through parental auto-questionnaires in 1,130 children from the EDEN birth-cohort. We performed both cross-sectional and longitudinal analyses using logistic regression models, before and after adjusting for age, sex, socio-economic status, nap duration, time spent outdoors and daily screen-time. We conducted multiple imputations to deal with missing data on covariates. The shape of the association was considered by splitting sleep duration into tertiles. Results At age 5 years, 20.4% of the children were prescribed glasses (2% for myopia, 11.9% for hyperopia and 6.8% for unknow reason). Children slept on average (SD) 11h05 (30 min) per night at age 2 and 10h49 (48 min) at age 5. Average bedtime and midsleep were 8.36 pm (30 min), 2.06 am (36 min), and 8.54 pm (30 min), 2.06 am (24 min) at age 2 and 5, respectively. In the raw longitudinal analysis, a U-shaped association was observed between nocturnal sleep duration at age 2 and eyeglass prescription at age 5: 2-years-old children sleeping 11h30 had a higher risk to have an eyeglass prescription by the age of 5. Later midsleep and bedtime at age 2 were associated with an increased risk of eyeglass prescription at age 5. All associations, except the one concerning bedtime, were barely changed after adjustment while becoming borderline significant. Conclusion Duration and timing of sleep at age 2 were associated with subsequent onset of refractive errors in preschoolers from a general population. Sleep and light hygiene might be targets for prevention. Support (if any)

Objectif Les troubles de la refraction sont tres courants. Le sommeil et les rythmes circadiens pourraient etre impliques dans leur developpement. Methodes L’etude inclus 1133 enfants d’une cohorte de naissance ayant des donnees sur le sommeil a 2 ans et les troubles de la refraction a 5 ans (myopie, hypermetropie et prescription de lunettes). La duree de sommeil a ete categorisee en tertiles ( 11h30) pour etudier une possible relation non lineaire suggeree par la litterature. Les associations longitudinales ont ete estimees par regression logistique ajustee sur des facteurs de confusion (dont âge, sexe, statut socio-economique, duree de sieste, activite exterieure, temps d’ecrans). Resultats A 5 ans, 2 % des enfants presentaient une myopie, 12 % une hypermetropie et 20 % ont eu une prescription de lunettes. En moyenne, les enfants dormaient 11h05 (± 30 min)/nuit a 2 ans, se couchaient a 20h54 (± 30 min) et avaient un milieu de nuit a 2h06 (± 36 min). Une relation en U a ete observee entre duree de sommeil a 2 ans et prescription de lunettes a 5 ans, le risque etant accru de 45 % pour les plus courts et plus longs dormeurs. Les enfants avec un milieu de nuit plus tardif a 2 ans avaient un risque accru de prescription de lunettes a 5 ans de 30 %/heure. Les associations persistaient apres ajustement bien qu’a la limite de la significativite. Conclusion La duree du sommeil et son timing a 2 ans sont associees a l’apparition ulterieure de troubles de refraction chez les enfants d’âge prescolaire en population generale. Ces resultats doivent etre confirmes dans des cohortes de plus grande taille.

Objectif Le sommeil et le systeme immunitaire interagissent y compris hors contexte pathologique. Les relations entre durees de sommeil et niveaux seriques de cytokines inflammatoires ont ete essentiellement etudiees chez les adultes, tres peu chez les enfants et jamais chez les enfants d’âge prescolaire. Methodes L’etude inclus 687 enfants d’une cohorte de naissance ayant des donnees sur les durees de sommeil entre 2 et 5 ans et un dosage serique de cytokines inflammatoires (IL-6, IL-10, TNF-alpha et IFN-gamma) a 5 ans. Les associations longitudinales entre sommeil et niveaux seriques de cytokines ont ete evaluees par des regressions lineaires brutes et ajustees sur les facteurs de confusion. Resultats Apres ajustement, les enfants avec une courte duree de sommeil entre 2 et 5 ans ( 11h30/nuit (4, 9 %) entre 2 et 5 ans tendaient a avoir un taux augmente d’IL-10 a 5 ans (p = 0, 09) et les enfants modifiant leur duree de sommeil (> 11h30 puis 10h30/nuit, 4, 7 %) avaient un taux augmente de TNF-alpha a 5 ans (p = 0.02). Conclusion Nos resultats suggerent la mise en place d’une inflammation de bas grade selon certaines evolutions de duree de sommeil et ce des l’âge prescolaire. Or, de courtes et longues durees de sommeil d’une part et la presence d’une inflammation de bas grade d’autre part ont ete associees a la survenue de pathologies chroniques y compris chez l’enfant.

Objectif Explorer les relations entre l’exposition fœtale a certains phenols et phtalates et le sommeil de l’enfant a 2 ans. Methodes Au total, 4456 dyades mere–fils d’une cohorte de naissance avec des dosages de metabolites urinaires maternels de 9 phenols et 11 phtalates et des donnees sur le sommeil de 2 ans (duree de sommeil, reveils nocturnes frequents [> 1 nuit sur 2]) ont ete incluses. Les relations entre les expositions considerees en tertiles et les caracteristiques du sommeil a 2 ans ont ete etudiees par des modeles de regression lineaire ou logistique ajustes sur les facteurs de confusion. Resultats Les concentrations urinaires etaient parmi les plus elevees pour le triclosan (TCS, biocide, cosmetiques), le methylparaben (MP, conservateur, cosmetiques), le mono-n-butyle phthalte (MBP, parfum, cosmetiques), et parmi les plus faibles pour bisphenol A (BPA, plastifiant, contenants) et le monocarboxyisononyl phthalate (MCNP, plastifiant, contenants). Le TCS etait associe a une moindre frequence des reveils nocturnes a 2 ans tandis que le MP etait associe avec une duree de sommeil plus longue. Le MBP etait associe a une moindre frequence des reveils nocturnes tandis que le MCNP etait associe a une moindre duree de sommeil a 2 ans. Aucune association n’etait observee avec les autres metabolites dont le BPA. Conclusion Nous montrons l’existence d’associations entre exposition prenatale a certains perturbateurs endocriniens et sommeil. La confirmation de ces resultats est necessaire par des etudes toxicologiques chez l’animal et des etudes epidemiologiques dans des populations plus larges.

Objectif Identifier les pratiques alimentaires associees a la duree totale de sommeil (DTS), aux reveils nocturnes (RN) et aux difficultes d’endormissement (DE) a 1 an. Methodes Au total, 8340 enfants avec des donnees disponibles sur le sommeil (DTS, RN, DE) et les pratiques alimentaires ont ete incluses. Les pratiques alimentaires etudiees etaient la duree d’allaitement et 5 trajectoires d’utilisation des cereales infantiles entre 2 et 10 mois : jamais, utilisation intermittente, introduction avant 4 mois, introduction vers 5 mois, introduction vers 7 mois. Les associations ont ete etudiees par regressions logistiques multinomiales tenant compte des facteurs de confusion dont les RN a 2 mois et les pratiques de sommeil (lieu d’endormissement/reveil, presence parentale). Resultats Une duree d’allaitement longue (≥ 6 mois) et une introduction precoce des cereales infantiles (≤ 5 mois) etaient associees a un risque accru de DTS courte (≤ 12 h/24 h), de RN frequents (> 2 nuits) et de DE (souvent). L’ajustement sur les RN a 2 mois ne change pas les resultats. En revanche, la prise en compte des pratiques de sommeil a 1 an fait disparaitre les associations entre duree d’allaitement et DTS courte et DE, et attenue celle entre duree d’allaitement et RN. Conclusion Les troubles du sommeil des enfants allaites longtemps sont expliques, pour tout ou partie, par des pratiques parentales. Ces dernieres sont modifiables et sont des pistes d’interventions a evaluer. L’ajout precoce de cereales, si utilise pour ameliorer le sommeil, ne semble pas etre une strategie efficace.

Objectif Les enfants a haut potentiel intellectuel (HPI) representent 2,3 % de la population pediatrique generale et presentent frequemment des troubles de l’humeur, du comportement et/ou du sommeil. L’objectif etait de comparer l’architecture du sommeil de 33 enfants HPI a celle de 25 enfants controles apparies pour l’âge (M = 10,5 ans) et le sexe (m = 64 %). L’objectif secondaire etait de determiner si le profil cognitif pouvait etre implique dans les troubles de l’humeur ou du comportement. Methodes Les enfants ont beneficie d’une polysomnographie (PSG), d’une evaluation psychometrique (WISC-IV) et d’une evaluation de l’humeur et du comportement. Resultats Les enfants HPI avaient davantage de QI heterogenes (dissociation de plus de 15 points entre l’Indice de Comprehension Verbale et l’Indice de Raisonnement Perceptif), de plaintes d’insomnie et d’hyperactivite que les controles. Les enfants HPI faisaient plus de sommeil paradoxal et moins de sommeil lent de stade 1 (en duree et en pourcentage de temps de sommeil total) que les controles. Le QI etait correle positivement avec le pourcentage de sommeil paradoxal. Les enfants HPI avec un QI heterogene avaient des scores d’anxiete et de depression plus eleves et davantage de symptomes d’impulsivite-hyperactivite que les enfants HPI avec un QI homogene. Conclusion Le sommeil paradoxal est correle au QI: les enfants HPI font davantage de sommeil paradoxal que les controles. Parmi ces enfants, ceux ayant un QI heterogene sont plus a risque d’anxiete et de depression.

Objective The aim was to study, with a developmental approach, the longitudinal association between night-waking from age 2 to 5–6 years and behavior at age 5–6 years. Methods Within the French birth cohort study Etude sur les Determinants pre et post natals du developpement et de la sante de l'ENfant (EDEN), repeated measures of children's night-waking were collected at age 2, 3 and 5–6 through parental questionnaires and were used to model night-waking trajectories. Behavior was assessed with the “Strengths and Difficulties Questionnaire,” which provides five subscales measuring a child's conduct problems, emotional symptoms, peer relation problems, antisocial behavior, and hyperactivity/attention problems. The behavioral subscales were dichotomized at the tenth percentile. Multivariable logistic regressions, adjusted for parents' socio-economic factors, parental characteristics, and children's characteristics and sleep habits allowed us to study, in 1143 children, the association between night-waking trajectories from 2 to 5–6 years and behavior at age 5–6 years. Results The “2 to 5–6 rare night-waking” trajectory represented 78% of the included population (n = 896), and the “2 to 5–6 common night-waking” 22% (n = 247%). Children belonging to the “2 to 5–6 common night-waking trajectory” had, at age 5–6, increased risk of presenting emotional symptoms (odds ratio [OR] = 2.17, 95% CI = 1.27–3.70, p = 0.004), conduct problems (OR = 1.63, 95% CI = 1.00–2.65, p = 0.050), and hyperactivity/attention problems (OR = 1.61, 95% CI = 1.00–2.57, p = 0.049). After adjusting for baseline behavior at age two years, only the association with emotional symptoms remained significant (OR = 2.02, 95% CI = 1.15–3.55, p = 0.015). Results did not differ according to sex. Conclusion Results suggest that the persistence of night-waking difficulties in early years is positively associated with emotional symptoms, hyperactivity/inattention, and conduct problems.

Objectif Peu d’etudes rapportent le lien entre la quantite et/ou la qualite du sommeil et la cognition chez l’enfant pre-scolaire. Le but etait donc d’etudier les relations entre le sommeil des premiers mois de vie et les caracteristiques neurocognitives a 3 ans. Methodes Les enfants inclus dans cette etude faisaient partie de la cohorte AuBE. Ces enfants ont beneficie d’une polysomnographie a terme (M0) et a 6 mois (M6) ainsi que d’un bilan neuropsychologique a 3 ans (WIPPSI-III). Les caracteristiques du sommeil ont ete determinees pour la nuit et le jour et les differents sous-scores du WIPPSI-III ont ete calcules : le score total (FISQ), la composante verbale (VIQ), la composante de performance (PIQ). Les relations entre les scores de QI et les variables du sommeil ont ete etudiees en utilisant des modeles avec l’enfant comme variable repetee avec ajustement pour la periode de sommeil (jour/nuit), la maturation (M0/M6), l’exposition au tabac, le score de depression, l’âge de la mere, la duree d’allaitement et le genre. Resultats Les resultats de 118 polysomnographies realisees chez 78 enfants ont ete analyses. Les scores moyens obtenus pour le VIQ, PIQ et FISQ etaient dans les normes. Plus les micro-eveils pendant le sommeil de nuit etaient frequents, plus le VIQ etait diminue. D’autre part, la duree de sommeil et l’efficacite du sommeil en journee etaient negativement associees a tous les scores de QI. Conclusion En conclusion, des caracteristiques de sommeil precoces telles que la fragmentation du sommeil ou la duree des siestes pourraient influencer les fonctions cognitives a 3 ans.

Objectif Afin de determiner si l’histamine cerebrale (HA) est impliquee dans la narcolepsie, nous avons quantifie les niveaux d’HA et de son metabolite direct (tele-methylhistamine, t-MeHA) dans le liquide cephalorachidien (LCR) chez l’enfant narcoleptique de type1 (NT1). Methodes L’etude inclut 24 enfants NT1 et 21 temoins apparies en sexe et âge. L’HA et la t-MeHA ont ete mesurees dans le LCR utilisant un dosage de grande sensibilite par des essais de chromatographie liquide-electrospray/spectrometrie. Resultats Compares aux temoins, les enfants NT1 presentaient des taux LCR d’HA plus eleves (771 vs 234 pM, p Conclusion Les enfants NT1 presentent un taux d’HA dans le LCR plus eleve avec un taux de t-MeHA diminue, conduisant a une diminution significative des ratios t-MeHA/HA. Ces resultats suggerent un turnover d’HA diminue et une neurotransmission histaminergique ralentie chez l’enfant narcoleptique et donc ils sont en faveur de la prise en charge de la narcolepsie par une therapie histaminergique.

International audience; Night waking in preschoolers has been associated with adverse health outcomes in cross-sectional studies, but has rarely been analyzed in a longitudinal setting. Therefore, little is known about the evolution of night waking in early childhood. The objectives of the present study were: to identify night-waking trajectories in preschoolers, and to examine the risk factors associated with those trajectories. Analyses were based on the French birth-cohort study EDEN, which recruited 2002 pregnant women between 2003 and 2006. Data on a child's night waking at the ages of two, three, and five, six years, and potential confounders, were collected through parental self-reported questionnaires. Night-waking trajectories were computerized using group-based trajectory modeling on 1346 children. Two distinct developmental patterns were identified: the "2-5 rare night-waking" (77% of the children) and the "2-5 common night-waking" pattern. Logistic regressions were performed to identify the factors associated with the trajectories. Risk factors for belonging to the "2-5 common night-waking" trajectory were: exposure to passive smoking at home, daycare in a collective setting, watching television for extended periods, bottle feeding at night, high emotionality, and low shyness. This approach allowed identification of risk factors associated with night waking during a critical age window, and laid the groundwork for identifying children at higher risk of deleterious sleep patterns. Those risk factors were mainly living habits, which indicated that prevention and intervention programs could be highly beneficial in this population.

In the course of primary infection with herpes simplex virus 1 (HSV-1), children with inborn errors of toll-like receptor 3 (TLR3) immunity are prone to HSV-1 encephalitis (HSE) 1–3 .W e tested the hypothesis that the pathogenesis of HSE involves nonhaematopoietic CNS-resident cells. We derived induced pluripotent stem cells (iPSCs) from the dermal fibroblasts of TLR3- and UNC-93B-deficient patients and from controls. These iPSCs were differentiated into highly purified populations of neural stem cells (NSCs), neurons, astrocytes and oligodendrocytes. The induction of interferon-b (IFN-b) and/or IFN-l1 in response to stimulation by the dsRNA analogue polyinosinic:polycytidylic acid (poly(I:C)) was dependent on TLR3 and UNC-93B in all cells tested. However, the induction of IFN-b and IFN-l1 in response to HSV-1 infection was impaired selectively in UNC-93B-deficient neurons and oligodendrocytes. These cells were also much more susceptible to HSV-1 infection than control cells, whereas UNC-93B-deficient NSCs and astrocytes were not. TLR3-deficient neurons were also found to be susceptible to HSV-1 infection. The rescue of UNC-93B- and TLR3deficient cells with the corresponding wild-type allele showed that the genetic defect was the cause of the poly(I:C) and HSV-1 phenotypes. The viral infection phenotype was rescued further by treatment with exogenous IFN-a or IFN-b ( IFN-a/b) but not IFN-l1. Thus, impaired TLR3- and UNC-93B-dependent IFN-a/b intrinsic immunity to HSV-1 in the CNS, in neurons and oligodendrocytes in particular, may underlie the pathogenesis of HSE in children with TLR3-pathway deficiencies. Childhood HSE is a rare, life-threatening, central nervous system (CNS)-restricted complication of primary infection with HSV-1, an almost ubiquitous virus that is typically innocuous 4 . Children with HSE are not unusually susceptible to other infectious agents, including viruses, or even to HSV-1-related diseases affecting sites other than the CNS 4,5 . HSV-1 reaches the CNS from the oral and nasal epithelium, via the cranial nerves 4 . We identified autosomal recessive UNC-93B deficiency as the first genetic aetiology of childhood HSE 1 . UNC-93B is required for TLR3, TLR7, TLR8 and TLR9 responses 1,6 . We then identified autosomal-recessive or autosomal-dominant deficiencies of TLR3 (refs 2 and 3), TRAF3 (ref. 7), TRIF 8 and TBK1 (ref. 9), revealing

Human T-cell leukemia virus (HTLV) indeterminate Western blot (WB) serological patterns are frequently observed in plasma/serum from persons living in intertropical areas. In the framework of ongoing projects on HTLV-1/2 and related viruses in Central Africa, we systematically analyzed plasma from villagers living in South Cameroon by WB. The group included 1,968 individuals (mean age, 44 years; age range, 5 to 90 years; 978 women/990 men), both Bantus (1,165) and Pygmies (803). Plasma samples were tested by WB analysis (MPD HTLV Blot 2.4) and interpreted according to the manufacturer's instructions. Only clear bands were considered in the analysis. Among the 1,968 plasma samples, 38 (1.93%) were HTLV-1, 13 (0.66%) were HTLV-2, and 6 (0.3%) were HTLV WB seropositive. Furthermore, 1,292 (65.65%) samples were WB sero-indeterminate, including 104 (5.28%) with an HTLV-1 Gag-indeterminate pattern (HGIP) and 68 (3.45%) with a peculiar yet unreported pattern exhibiting mostly a strong shifted GD21 and a p28. The other 619 (31.45%) samples were either WB negative or exhibited other patterns, mostly with unique p19 or p24 bands. DNA, extracted from peripheral blood buffy coat, was subjected to PCR using several primer pairs known to detect HTLV-1/2/3/4. Most DNAs from HTLV-1- and HTLV-seropositive individuals were PCR positive. In contrast, all the others, from persons with HTLV-2, HGIP, new WB, and other indeterminate patterns, were PCR negative. Epidemiological determinant analysis of the persons with this new peculiar WB pattern revealed that seroprevalence was independent from age, sex, or ethnicity, thus resembling the indeterminate profile HGIP rather than HTLV-1. Moreover, this new pattern persists over time.

Objectif Etudier les trajectoires de developpement jointes de reveils nocturnes et des difficultes d’attention (DA) chez l’enfant de 2 et 5 ans. Methodes Des mesures repetees de reveils nocturnes ainsi que de DA ont ete collectees chez 1342 enfants de la cohorte EDEN a 2, 3 et 5 ans. Les reveils nocturnes ont ete definis comme frequents si, selon les parents, ils avaient lieu une nuit sur deux ou plus. Les DA des enfants ont ete evaluees a partir du « Strength and Difficulty Questionnaire » et transformees en z-score (ZA). Un ZA positif traduit de plus grande difficultes d’attention par rapport a la moyenne du meme echantillon. Les trajectoires de developpement jointes de reveils nocturnes et de ZA ont ete modelisees par la methode du « group based trajectory modeling ». Resultats Deux trajectoires de reveils nocturnes ont ete identifiees dans la cohorte. Une groupant les enfants se reveillant tres peu tout au long du suivi (80 % de la population) et l’autre ceux se reveillant plus frequemment. Trois trajectoires de ZA ont ete identifiees : DA− pour les enfants avec un ZA inferieur a la moyenne sur l’ensemble du suivi (–1,6, 47 %), DA0 pour ceux avec un ZA autour de la moyenne (+0,3, 40 %), et DA+, pour ceux avec un ZA au-dessus de la moyenne (+1,3, 13 %), sans aucun recoupement entre les trajectoires. Par rapport aux enfants DA−, les enfants DA+, avaient 4,6 fois plus de risques d’appartenir a la trajectoire de reveils nocturnes frequents (valeur de p Conclusion Les trajectoires developpementales de reveils nocturnes et de difficultes d’attention evoluent conjointement chez l’enfant d’âge prescolaire.

Background Only a minority of patients with chronic hepatitis C virus (HCV) infection develops severe liver fibrosis, a process that may be controlled by human genetic factors. Objective To investigate the role of 384 single nucleotide polymorphisms (SNPs) located in 36 candidate genes related to the fibrogenesis/fibrolysis process. Methods Patients with chronic HCV infection were gathered from two French cohorts (prospectively and retrospectively). The overall sample consisted of 393 HCV-infected subjects without known risk factors for fibrosis progression, including 134 patients with severe liver fibrosis and 259 without severe fibrosis. Results Only two SNPs in strong linkage disequilibrium (LD) in the interferon γ receptor 2 gene ( IFNGR2 ) were significantly associated with liver fibrosis in both the prospective and the retrospective samples. The strongest association (p=8×10 −5 ) was observed with the G/A SNP rs9976971 with an OR of severe fibrosis for AA versus AG or GG subjects at 2.95 (95% CI 1.70 to 5.11). This effect was higher (p=9×10 −7 ) when taking into account the time of follow-up, and the hazard ratio of progression towards severe fibrosis for AA patients was 2.62 (1.76 to 3.91). Refined sequencing and analysis of the IFNGR2 region identified two additional variants in strong LD with rs9976971. No haplotypes derived from this cluster of four variants provided stronger evidence for association than rs9976971 alone. Conclusions This identification of a cluster of four IFNGR2 variants strongly associated with fibrosis progression in chronic HCV infection underlines the role of IFNγ in the development of liver fibrosis that may pave the way for new treatments.

Objectif Etudier les relations entre pratiques alimentaires de la naissance a 8 mois et trajectoires de sommeil (difficultes d’endormissement [DE], reveils nocturnes [RN] et duree du sommeil nocturne [DSN]) entre 2 et 5–6 ans dans la cohorte EDEN. Methodes Les analyses concernent 1034 enfants avec des donnees completes collectees par questionnaires et enregistrements alimentaires. Les pratiques alimentaires etudiees sont la duree d’allaitement, l’âge de diversification alimentaire, l’alimentation nocturne. Des trajectoires de DE, RN et DSN entre 2 et 5–6 ans ont ete identifiees par « group based trajectory modeling » puis mises en relation avec l’alimentation precoce par des regressions logistiques multiples incluant les principaux facteurs familiaux, maternels et de l’enfant. Resultats Deux trajectoires ont ete identifiees pour les RN et les DE (1. rares, 2. persistants), 5 pour la DSN (1. courte, 2. moyenne bas et 3. haut, 4. longue et 5. modifiee, c.-a-d. 4 puis 2). Nos analyses indiquent qu’un allaitement maternel predominant > 4 mois est associe a la trajectoire de DE persistants (OR = 0,6 [0,3 ; 1,0]). Une alimentation nocturne entre 4 et 8 mois ou a 2 ans est associee a la trajectoire de DE persistants (OR = 2,0 [1,3 ; 3,0] et OR = 1,6 [1,1 ; 2,2]). Une alimentation nocturne a 2 ans est aussi associee a la trajectoire de DSN modifiee (OR = 2,4 [1,3 ; 4,3]). Aucune association n’a ete observee avec les trajectoires de RN. Conclusion Nous montrons que l’alimentation nocturne est la principale pratique associee aux troubles persistants du sommeil chez les enfants d’âge prescolaire. Ces pratiques sont accessibles a la prevention.

International audience; Infection by human herpesvirus 8 (HHV-8) in childhood is common in the Mediterranean basin; however, classic Kaposi sarcoma (KS) is exceedingly rare in children not infected with HIV and not receiving immunosuppression, with only 30 cases having been reported since 1960. We recently reported 2 children with autosomal and X-linked recessive primary immunodeficiencies underlying KS in a context of multiple clinical manifestations. These reports suggested that classic KS in otherwise healthy children might also result from inborn errors of immunity more specific to HHV-8. In this article, we describe 3 unrelated Turkish children with classic KS born to first-cousin parents. The first patient, a girl, developed KS at 2 years of age with disseminated cutaneous and mucosal lesions. The clinical course progressed rapidly, and the patient died within 3 months despite treatment with vincristine. The other 2 children developed a milder form of KS at the age of 9 years, with multiple cutaneous lesions. A boy treated with interferon alpha therapy for 12 months is now in full remission at the age of 14, 2 years after treatment. The second girl is currently stabilized with etoposide, which was begun 4 months ago. None of the 3 children had any relevant familial history or other clinical features. The occurrence of classic KS in 3 unrelated Turkish children, each born to consanguineous parents, strongly suggests that autosomal recessive predisposition may drive the rare occurrence of HHV-8-associated classic KS in children.

Hepatitis C virus (HCV), infecting 170 million people worldwide, is a major public health problem. In developing countries, unsafe injections and blood transfusions are thought to be the major routes of transmission. However, our previous work in a population from Egypt, endemic for HCV, revealed highly significant familial correlations, strongly suggesting the existence of both familial transmission of the virus and genetic predisposition to HCV infection. We investigated the hypothesis of genetic predisposition by carrying out a segregation analysis of HCV infection in the same population. We used a logistic regression model simultaneously taking into account a major gene effect, familial correlations and relevant risk factors. We analyzed 312 pedigrees (3,703 subjects). Overall HCV seroprevalence was 11.8% and increased with age. The main associated risk factors were previous parenteral treatment for schistosomiasis and blood transfusions. We found strong evidence for a dominant major gene conferring a predisposition to HCV infection. The frequency of the predisposing allele was 0.013, reflecting a strong predisposition to HCV infection in 2.6% of the subjects, particularly those under the age of 20. This study provides evidence for the involvement of host genetic factors in susceptibility/resistance to HCV infection in endemic conditions.