Risk factors associated with preoperative fecal carriage of extended-spectrum ß-lactamase-producing Enterobacteriaceae in liver transplant recipients.

OBJECTIVE: The aim of the study was to identify risk factors associated with pre-transplant fecal carriage of extended-spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae in liver transplant recipients. PATIENTS AND METHODS: Over a 3-year period (January 2009-December 2011), 317 patients who underwent liver transplantation were screened preoperatively for fecal carriage of ESBL-producing Enterobacteriaceae. Risk factors for fecal carriage were investigated by univariate analysis and stepwise logistic regression. RESULTS: Of the 317 patients screened, 50 (15.7%) harbored an ESBL-producing isolate. Previous infection with an ESBL-producing organism had developed during the last 6 months in 20% of fecal carriers versus in none of the non-carriers. Other variables associated with fecal carriage were a model for end-stage liver disease score ≥25, pre-transplant stay in the intensive care unit ≥48 h, hospital stay ≥10 days in the last 6 months, a history of spontaneous bacterial peritonitis (SBP), exposure to a ß-lactam agent in the last month, and prophylaxis with norfloxacin. Independent predictors of fecal carriage in the multivariate logistic regression model were exposure to a ß-lactam agent in the month preceding transplantation (odds ratio [OR] = 7.8, confidence interval [CI] = 4-15.5, P < 0.001), and a history of SBP (OR = 2.4, CI = 1.1-4.9, P = 0.02). CONCLUSIONS: Previous infection with an ESBL-producing isolate, recent exposure to a ß-lactam agent, and a history of SBP are risk factors for preoperative fecal carriage of ESBL-producing Enterobacteriaceae in liver transplant recipients. Patients at risk of fecal carriage should receive intraoperative prophylaxis and, when necessary, empiric postoperative antimicrobial treatment that includes coverage for these organisms.

Prevalence and characteristics of children with mild intellectual disability in a French county.

BACKGROUND: Studies conducted on mild intellectual disability (MID) in children are infrequent and the prevalence rates vary widely. This study aimed to estimate the prevalence of MID in children in a French county (Isère), to describe the clinical signs and associated comorbidities, and to specify the aetiologies of this disability. METHODS: The target population was comprised of the 15 100 children born in 1997 residing in Isère County, France, in 2008. Our goal was to find the children in this group with MID diagnosed between 9 and 13 years of age. MID was defined as an overall IQ score of between 50 and 69 [International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10)]; this definition was adjusted for the study by integrating confidence intervals so that the risk of IQ measurement relativity and possible discrepancy of scores could be taken into account. Children were identified through an administrative data source designed to assist disabled persons that contains health information, and an educational data source. Parents who agreed to let their children participate responded to an in-depth questionnaire on their child's medical and academic history. A genetic investigation was proposed for those children whose MID had an unknown aetiology. RESULTS: The preliminary selection included 267 children, resulting in a prevalence rate of 18 per 1000 (CI [15.6; 19.9]), within the expected mean. Of these 267 cases, 181 families agreed to participate in the study (68%). MID more often affected boys [male gender ratio = 1.4 (CI [1.2; 1.6])], low socioeconomic groups, and families with a history of intellectual disability. The clinical signs and comorbidities associated with MID were very frequent, with 54% spoken language disorders and 10% pervasive developmental disorder. Only 9% of the children had undergone a genetic investigation before the study. The known aetiology rate for MID was 19% among all the children who had had genetic tests performed. CONCLUSION: MID is an important public health issue based on its prevalence. The associated clinical signs and comorbidities may be warning signs of MID in case of learning difficulties. This study may help decision-makers to develop and organise screening and care for MID.

Lower risk of atopic dermatitis among infants born extremely preterm compared with higher gestational age.

BACKGROUND: It is not yet known whether the risk of developing atopic dermatitis (AD) is influenced by preterm birth. Moreover, AD risk has not been assessed in a large sample of extremely preterm infants (< 29 weeks' gestation). OBJECTIVES: To determine whether the risk of AD is influenced by preterm birth. METHODS: We investigated the relationship between gestational age (GA) and AD using data from two independent population-based cohorts, including a total of 2329 preterm infants, of whom 479 were born extremely preterm. RESULTS: There was a lower percentage of children with AD in the extremely preterm group compared with those born at a greater GA (Epipage cohort, 2-year outcome: 13·3% for 24-28 weeks, 17·6% for 29-32 weeks, 21·8% for 33-34 weeks, P = 0·02; LIFT cohort, 5-year outcome: 11% for 24-28 weeks, 21·5% for 29-32 weeks, 19·6% for 33-34 weeks, P = 0·11). After adjusting for confounding variables, a lower GA (< 29 weeks) was significantly associated with decreased risk of AD in the Epipage cohort [adjusted odds ratio (aOR) 0·57, 95% confidence interval (CI) 0·37-0·87; P = 0·009] and the LIFT cohort (aOR 0·41, 95% CI 0·18-0·90; P = 0·03). CONCLUSIONS: Very low GA (< 29 weeks) was associated with a lower risk of AD compared with higher GA (29-34 weeks) and full-term birth.

Pregnancy in women with portal vein thrombosis: results of a multicentric European study on maternal and fetal management and outcome.

BACKGROUND & AIMS: Women of childbearing age account for approximately 25% of patients with non-cirrhotic portal vein thrombosis (PVT). We aimed at assessing maternal and fetal outcome in pregnant women with known PVT. METHODS: We performed a retrospective analysis of the files of women with chronic PVT in three European referral centers between 1986 and 2010. RESULTS: Forty-five pregnancies, 28 (62%) treated with low molecular weight heparin, occurred in 24 women. Nine (20%) were lost before gestation week 20. Preterm birth occurred in 38% of deliveries: there were 3 births at week 24-25, 7 at week 32-36, and 26 after week 37. A term birth with a healthy infant occurred in 58% of pregnancies. Cesarean section was used in 53% of deliveries. Two women developed HELLP syndrome. A favorable outcome happened in 64% of pregnancies. Pregnancies with an unfavorable outcome were associated with a higher platelet count at diagnosis. Bleeding from esophageal varices occurred in 3 patients during pregnancy, all without adequate primary prophylaxis. Genital or parietal bleeding occurred postpartum in 4 patients, only one being on anticoagulation therapy. Thrombotic events occurred in 2 patients, none related to lower limbs or mesenteric veins. There were no maternal deaths. CONCLUSIONS: In pregnant PVT patients treated with anticoagulation on an individual basis, the rate of miscarriage and preterm birth appears to be increased. However, fetal and maternal outcomes are favorable for most pregnancies reaching gestation week 20. High platelet counts appear to increase the risk for unfavorable outcome. Pregnancy should not be contraindicated in stable PVT patients.

Impact of the use of antenatal corticosteroids on mortality, cerebral lesions and 5-year neurodevelopmental outcomes of very preterm infants: the EPIPAGE cohort study.

OBJECTIVE: To assess the impact of antenatal corticosteroids (ACS) on neonatal mortality, cerebral lesions and 5-year neurodevelopmental outcome of infants born at 24-27 and 28-32 weeks of gestational age (GA). DESIGN: Observational population-based study including all births at GAs between 22 and 32 weeks in 1997 in nine regions of France. Survivors were assessed at the age of 5 years. SAMPLE AND METHODS: The population enrolled in the follow up comprised 2323 infants; there were 23 deaths before age 5 years and outcome at 5 years was available for up to 1781 subjects. Two GA subgroups (24-27 and 28-32 weeks of GA) were analysed separately. Propensity scores were used to reduce bias in the estimation of the association between ACS treatment and outcomes. MAIN OUTCOME MEASURES: Neonatal death, neonatal white matter injury, cerebral palsy, mental processing composite (MPC) of the Kaufman Assessment Battery for Children test and behavioural difficulties at 5 years. RESULTS: In the 28- to 32-week GA subgroup, there was a significant association between ACS and a decreased risk of both neonatal death (OR = 0.61 [0.41-0.91]) and white matter injury (OR = 0.60 [0.46-0.79]) but only a nonsignificant trend for improved 5-year outcome (cerebral palsy, MPC < 70). In the 24- to 27-week GA subgroup, ACS was associated with a significant decrease risk of neonatal death (OR = 0.43 [0.27-0.68]) but there was only a trend for a lower risk of white matter injury and no beneficial impact on outcome at 5 years. Limiting the analysis to only those who received complete courses of ACS did not modify the results. CONCLUSION: The study shows that ACS therapy greatly increases the survival of very preterm infants, including the most immature, but there is little evidence that ACS affects long-term neurodevelopmental and behavioural outcome in 28- to 32-week survivors, and none in <28-week survivors.

[Is it possible to protect the preterm infant brain and to decrease later neurodevelopmental disabilities?]. / Est-il possible de protéger le cerveau de l'enfant né prématuré et de diminuer le taux de séquelles neuro-développementales ?

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.

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.

Maternal tobacco smoking in pregnancy and children's socio-emotional development at age 5: The EDEN mother-child birth cohort study.

BACKGROUND: There is debate as to whether maternal tobacco use in pregnancy is related to offspring behaviour later on. We tested this association examining multiple aspects of children's behaviour at age 5 and accounting for parental smoking outside of pregnancy, as well as child and family characteristics. METHODS: Data come from a prospective community based birth cohort study (EDEN; n=1113 families in France followed since pregnancy in 2003-2005 until the child's 5th birthday). Maternal tobacco use in pregnancy was self-reported. Children's socio-emotional development (emotional symptoms, conduct problems, symptoms of hyperactivity/inattention, peer relationship problems, prosocial behaviour) was assessed by mothers using the Strengths and Difficulties Questionnaire (SDQ) at age 5 years. Logistic regression analyses controlled for Inverse Probability Weights (IPW) of maternal tobacco use calculated based on study center, children's characteristics (sex, premature birth, low birth weight, breastfeeding), maternal characteristics (age at the child's birth, psychological difficulties and alcohol use in pregnancy, post-pregnancy depression, and smoking), paternal smoking in and post-pregnancy, parental educational attainment, family income, parental separation, and maternal negative life events. RESULTS: Maternal smoking in pregnancy only predicted children's high symptoms of hyperactivity/inattention (sex and study center-adjusted ORs: maternal smoking in the 1st trimester: 1.95, 95%CI: 1.13-3.38; maternal smoking throughout pregnancy: OR=2.11, 95%CI: 1.36-3.27). In IPW-controlled regression models, only children of mothers who smoked throughout pregnancy had significantly elevated levels of hyperactivity/inattention (OR=2.20, 95%CI: 1.21-4.00). CONCLUSIONS: Maternal tobacco smoking in pregnancy may contribute directly or through epigenetic mechanisms to children's symptoms of hyperactivity/inattention.

Alcohol and the fetus.

The teratogenic effects of alcohol have been recognized in the fetal alcohol syndrome. The syndrome is associated with very high levels of maternal consumption. Studies of the relation between much lower levels of consumption and pregnancy outcome seem to indicate consistently lower birthweight among children born to mothers drinking more than 140 g absolute alcohol per week, or about two drinks a day.

Survival of very preterm infants: Epipage, a population based cohort study.

OBJECTIVE: To evaluate the outcome for all infants born before 33 weeks gestation until discharge from hospital. DESIGN: A prospective observational population based study. SETTING: Nine regions of France in 1997. PATIENTS: All births or late terminations of pregnancy for fetal or maternal reasons between 22 and 32 weeks gestation. MAIN OUTCOME MEASURE: Life status: stillbirth, live birth, death in delivery room, death in intensive care, decision to limit intensive care, survival to discharge. RESULTS: A total of 722 late terminations, 772 stillbirths, and 2901 live births were recorded. The incidence of very preterm births was 1.3 per 100 live births and stillbirths. The survival rate for births between 22 and 32 weeks was 67% of all births (including stillbirths), 85% of live births, and 89% of infants admitted to neonatal intensive care units. Survival increased with gestational age: 31% of all infants born alive at 24 weeks survived to discharge, 78% at 28 weeks, and 97% at 32 weeks. Survival among live births was lower for small for gestational age infants, multiple births, and boys. Overall, 50% of deaths after birth followed decisions to withhold or withdraw intensive care: 66% of deaths in the delivery room, decreasing with increasing gestational age; 44% of deaths in the neonatal intensive care unit, with little variation with gestational age. CONCLUSION: Among very preterm babies, chances of survival varies greatly according to the length of gestation. At all gestational ages, a large proportion of deaths are associated with a decision to limit intensive care.

Folate status during pregnancy: relationship with alcohol consumption, other maternal risk factors and pregnancy outcome.

This study was designed to identify the factors affecting folate status in pregnant women and to explore the relationship between folate status and alcohol consumption during pregnancy. For this purpose, 347 French women were recruited during 1985-1986 on their first visit to the antenatal clinic at Roubaix Hospital (northern France). Alcohol consumption was ascertained by a standardized interview. Folate status assessment was available for 246 pregnant women who were not given folate supplementation. Average folate levels during pregnancy were lower among young women and smokers. Serum folate values diminished with the educational level, and red cell folate values increased with high parity. Unexpectedly, high red cell folate values were strongly related with high alcohol consumption after adjustment for the maternal risk factors associated with alcohol consumption and folate status. This was probably because in the Roubaix region where the study was conducted women consume mostly beer, which contains folates. Pregnancy outcome was not related to folate levels; birthweight was negatively associated with alcohol consumption during the first trimester of pregnancy.

[Space-time clustering of sudden infant death in France from 1981 to 1986]. / Agrégation temporospatiale de mort subite du nourrisson en France de 1981 à 1986.

In tempered countries, higher sudden infant death rates are observed during winters, which is in favor of an infectious factor in the etiology. According to the geographic regions, the rates of SIDS are showing a downward gradient from the north of France to the south. In an attempt to assess the infectious hypothesis, we carried out a research about space-time clusters of Sudden infant deaths. The Knox's méthode was used with data of the medical causes of death registered in France from 1981-82 to 1985-86, by areas. Clusters were found in several regions, but they are moving from one year to another. The interpretation of these findings remains difficult because of the large number of tests.

[Infant temperament at 6-9 months old: validation of the French version of the Infant Characteristics Questionnaire and factors associated with measurement]. / Tempérament des nourrissons âgés de 6 à 9 mois: validation de la version française de l'Infant Characteristics Questionnaire et facteurs associés à la mesure.

BACKGROUND: The aim of the study was to assess the validity of the French version of the Infant Characteristics Questionnaire (ICQ), which was developed by Bates in 1979 to investigate the parental perceptions of infant temperament at 6 months of age. METHODS: The French version was established after translation/back-translation, and tested on a sample of 794 mothers, who gave birth in 1995 in four French Departments and who returned the questionnaire which was mailed 6 months after the birth. RESULTS: The non-response rate of each item was very low (< 2%). Factor analysis resulted in the same four factors as in the American data: fussy/difficult, unadaptable, unpredictable, dull. However, some of the items did not have similar factor loadings. Thus new factor scores were defined for the French version of the ICQ. Internal consistency, as measured by the Cronbach coefficient, was satisfactory (> 0.7) for the factors fussy/difficult and unadaptable. It was lower, but acceptable (> 0.6) for the two other factors. The infant's temperament was not related to birth parameters. In contrast, some factor scores were significantly associated with parity, mother's education, as well as her health and the infant's health after leaving the maternity ward. CONCLUSIONS: The French version of the ICQ is well accepted and has a good validity. This scale provides a useful instrument for research, especially for epidemiological studies on infant health and development, as well as their determinants.

[Use of medical services by very preterm children during the first year of life in the Epipage cohort]. / Utilisation des services médicaux par les grands prématurés pendant la première année de vie dans la cohorte Epipage.

OBJECTIVES: To compare the use of health and social services between children born before 33 weeks (very preterm), children born at 33 or 34 weeks (moderately preterm) and children born at 39 or 40 weeks (full term). POPULATION AND METHODS: All very preterm children born in 1997 in nine French regions and a representative sample of the two other groups were followed up since birth. Data on the use of services between discharge from initial neonatal hospitalisation and the 9 months after birth were obtained by mail questionnaire filled in by parents. RESULTS: 38.2% of very preterm children, 24.3% of moderately preterm children and 10.3% of full term children were admitted to hospital at least once. Respiratory tract disorder was the main reason for rehospitalisation of very preterm children. The total number of visits, visits to specialists, and chest therapy were more frequent among very preterm children than among the two other groups. CONCLUSION: Medical care of very preterm children is intensive after discharge from initial neonatal hospitalisation. Need of services are also substantial for moderately preterm children.

[Developmental problems of very premature children at school age. Review of the literature]. / Les troubles du développement des enfants grands prématurés mesurés à l'âge scolaire. Revue de la littérature.

Advances in perinatal care have lead to the survival of an increasing number of children born very premature. The purpose of this review is to discuss findings in the literature regarding long term developmental outcome of infants born prematurely especially for studies with children at least 5 years old, born in the 80's or after, in a context of care with increased use of antenatal corticoids, in utero transfer, and surfactant therapy. Developmental sequelae, which are seen in children older than those presenting severe deficiencies, concerns a greater number of very premature children. They have poorer outcomes than term children or normal birth weight controls for cognitive-neuropsychological skills, school performances and behavior. Long term follow up of these children shows that consequences are still present for adolescents or young adults. There is a gradient of developmental sequelae in children that is inversely related to decreasing gestational age or birth weight. Developmental sequelae are related to neonatal medical complications and social risks factors. Research should be conducted in order to better understand etiology and neuropathological basis of sequelae, and the long term developmental implication of being born very premature and the type of care or intervention which could improve their development. An early and regular follow up by a team specialized in child development should be proposed in order to detect developmental sequelae and propose early intervention.

[Prenatal exposure to tobacco smoke and cognitive development: epidemiology studies]. / Exposition prénatale au tabac et développement cognitif: études épidémiologiques.

Studies concerning smoking during pregnancy and cognitive development of the child were reviewed. Some studies tend to support the existence of an association between smoking during pregnancy and a less optimal cognitive development of the child. The meaning of these relationships remains obscure, since it cannot be assumed that they are due to maternal cigarette smoking: they could be due to different characteristics of smokers or non-smokers. In the older studies, potential confounding factors were not adequately taken into account and in some recent studies, the observed difference was no longer significant after taking into account the maternal educational level and the family stimulation of the child. Behavior problems are associated with smoking during pregnancy in nearly all studies but the same problem of confounding factors remains. It is thus difficult to conclude presently from these studies if there is a causal relationship between prenatal exposure to tobacco smoke and cognitive development.

[Epipage study: mortality of very premature infants and state of progress at follow up]. / Etude Epipage: mortalité des enfants grands prématurés et état d'avancement du suivi.

OBJECTIVE: To study perinatal and neonatal mortality of very preterm infants and to assess the association with birth weight and multiple births. METHODS: Infants enrolled in the Epipage study born between 22 and 32 weeks gestational age in 9 French regions in 1997 were included in this study. The main outcome measure was stillbirth and death before discharge from hospital. RESULTS: During the study period, 4397 births and therapeutic abortions meeting the inclusion criteria were recorded (including 16% therapeutic abortions and 18% stillbirths). Survival rate for babies born between 22 and 32 weeks was 67% of all births (stillborn + liveborn) and 85% among livebirths. Survival rose with increasing gestational age: survival (livebirths) was 50% at 25 weeks gestation, 78% at 28 weeks and 97% at 32 weeks. Survival was lower for infants with a birthweight below the 10th percentile and for multiple-pregnancy infants. The different stages of the follow-up planned up to 5 years are presented together with the response rate to the postal follow-up questionnaire. CONCLUSION: This cohort provides mortality data on very premature infants during pregnancy, at birth, during hospitalization before discharge. Survival of liveborn infants was stratified by gestational age and was consistent with other geographically based studies of very preterm infants born in the 1990s.

Height at 2 and 5 years of age in children born very preterm: the EPIPAGE study.

OBJECTIVES: To evaluate growth for children born very preterm with particular focus on those born small-for-gestational age (SGA) or with ex utero growth restraint (GR), and to identify risk factors for short stature at 5 years of age. STUDY DESIGN: Population-based study of children born at less than 33 completed weeks of gestation (Étude Epidémiologique sur les Petits Ages Gestationnels (EPIPAGE)). Short stature was defined as height <-2SD on WHO growth curves. Ex utero GR was considered to have occurred in children with appropriate size for gestational age at birth and with a height and/or weight below -2SD at 2 years of corrected age. Logistic regression models were used to test associations between risk factors and short stature. RESULTS: The authors measured height at 5 years of age for 1,597 of 2,193 children (73%), 5.6% (95% CI 4.6 to 6.9) of whom were diagnosed as having a short stature. Height was measured at 2 and 5 years of age in 1417 children. Among these, 24% of those born SGA and 36% of those with ex utero GR (p=0.002) had a short stature at 5 years. Predictors of short stature were SGA or birth length <-2SD, maternal height ≤ 160 cm, gestational age <29 weeks and systemic corticosteroids. Breastfeeding at discharge decreased the risk of short stature. CONCLUSIONS: Short stature at 5 years of age is common in children born preterm. The highest incidence was observed in the group with ex utero GR. Systemic steroids have a long-term impact on growth and should be used with caution. Breastfeeding at discharge appeared to be protective.