Olivier Claris

Body composition in appropriate and in small for gestational age infants

The body composition of 70 appropriate for gestational age newborn infants whose gestational age ranged from 32 to 41 weeks was determined by dual‐energy X‐ray absorptiometry during the first 48 h of life. The evolution of the bone mineral content, fat and lean mass was well correlated with gestational age (r= 0.66, r= 0.66 and r= 0.82. respectively) but even more closely with birthweight (r= 0.85, r= 0.91 and r= 0.97. respectively). The body composition of 20 symmetric small for gestational age infants (mean gestational age ± SD = 38.1 ± 1.2 weeks: mean birthweight ± SD = 2117 ± 183 g) was also studied. The total body fat, the lean mass and the bone mineral content of small for gestational age infants were decreased significantly in comparison with those of appropriate for gestational age infants with the same gestational age (p≤ 0.05, p≤ 0.0001 and p≤ 0.05) but was not significantly different from those observed in appropriate for gestational age infants of the same birthweight.

Aetiology, morphology and body composition of infants born small for gestational age.

Infants born small for gestational age (SGA) are a heterogeneous group. Both the timing and duration of the intrauterine insult determine the physical condition and body composition of the infant at birth. Infants with symmetrical intrauterine growth retardation (IUGR) have a similar body composition at birth to weight‐matched infants born appropriate for gestational age. However, these infants are more likely to remain shorter and lighter than normal infants. In contrast, infants with asymmetrical IUGR have reduced fat deposition but are more likely to exhibit catch‐up growth during the first few months of life. The low mortality and morbidity rates in infants born SGA observed in recent studies are linked to their appropriate perinatal management, including adequate early nutritional support. □ Body composition, dual‐energy X‐ray absorptiometry, aetiology, neonate, preterm, small for gestational age

Unlicensed and off‐label drug use in a neonatal unit in France

The lack of controlled clinical trials in the paediatric population and the subsequent paucity of trial-based data in children have forced clinicians to extrapolate the results of studies carried out in adults. Off-label and unlicensed prescriptions in the paediatric population and in neonatology are routine and well-documented. In a systematic review including 30 studies, off-label or unlicensed prescription rates in paediatric wards ranged from 16% to 62%, they were more common in hospital than in community settings and more frequent in neonatal (age range 0–183 days) than in paediatric wards (age range 1 days–20 years) (1). In another systematic review of 52 studies, Cuzzolin et al. (2) also showed that the extent of paediatric unlicensed or offlabel use was higher in neonatal wards than in paediatric wards. Conroy et al. (3) showed that up to 93% of neonates have received at least one unlicensed or off-label medicine during their hospital stay in an intensive care unit. Avenel et al. (4) reported that of the 55 drugs administrated to 40 newborns during a 1-month period in their Neonatal Intensive Care Unit (NICU) in France, 10% had no product licence, 62% were off-label for premature infants and 64% were for newborns. Little information on off-label or unlicensed use of drugs is available in neonatal units (neonatal wards receiving stable neonates >32 weeks GA, without intensive care). The objective of this study was to assess the extent and the type of unlicensed and off-label drug used in a neonatal unit at the university hospital in Lyon, France. The secondary objective was to determine the most frequent off-label or unlicensed drugs prescribed in the study unit. We performed a cross-sectional, prospective study assessing all drugs prescribed to newborns admitted to the Neonatal Unit of Lyon-Sud Hospital from 1 January to 30 April 2009. Information on date of birth, weight, gestational age and drugs prescribed was recorded using a case report form and checked independently by two health professionals. Prescriptions refer to each drug along with its respective indication, daily dose, number of doses per day, route of administration and treatment duration. Prescriptions for parenteral nutrition, standard crystalloid intravenous fluids, oxygen and drugs used in research studies were not included. The primary reference sources for determining licensed indications were the product characteristic summaries of marketing authorizations in the Vidal 2009 (French prescription products guide). Licensed drugs included medicines following the terms of the marketing authorization. We considered as unlicensed (i) the modified use of licensed drugs (such as crushing tablets to prepare a suspension), (ii) drugs that are licensed but the formulation is manufactured under a special licence (such as the liquid preparation of a drug that is licensed only in tablet form), (iii) use of chemicals as drugs when no pharmaceutical grade preparation is available, (iv) drugs used before a licence has been granted, (v) imported drugs (drugs imported from a country where they are licensed); and (vi) drugs without any product licence. Off-label use was defined as the use of a drug outside the scope of a drug’s approved label, i.e. at different doses or frequencies, in different clinical indications, in different age groups, administrated by an alternative route, or in a formulation not approved for use in children. Off-label analysis for age took the corrected, postnatal age in the preterm group into account. Physicians were aware of the study’s goal. All data were collected anonymously with regard to patient and physician identity. The study was approved by the Ethics Committee of Lyon. Data were entered and analysed using Epi-Info Acta Pædiatrica ISSN 0803–5253

Software and scan acquisition technique-related discrepancies in bone mineral assessment using dual-energy X-ray absorptiometry in neonates.

Aim: In adults, whole‐body mineralization assessment by dual‐energy X‐ray absorptiometry can be affected by the densitometer and/or the software used. As there are no published data on neonates, the aim of this study was to evaluate the magnitude of such effects in growing preterm infants. Methods: We analysed the absorptiometry results obtained from 44 preterm infants scanned at discharge and again 6 wk later using densitometers from the same manufacturer equipped with “Pediatric” (Group A, n= 24) or with “Infant” (Group B, n= 20) packages. Results of bone mineral content assessment were compared using an unpaired f‐test and a linear regression analysis. Results: At the time of the first absorptiometry (body weight = 2119 ± 144 g, n= 44), the bone mineral content was three times lower in Group A (10 ± 3 g) than in Group B (29 ± 4 g) (p < 0.001). Subsequently, on the second absorptiometry (body weight = 4037 ± 236 g, n= 44) such significant differences in bone mineral content (A: 65 ± 19 g, B: 66 ± 9 g, p= 0.85) were no longer in evidence. The differences in bone mineral content were related to differences in analysis algorithms between the two programs, which can lead to an overestimation of bone mineral content accretion when two successive measurements are made using the “Pediatric” package.

Unlicensed and off-label drug use: a prospective study in French NICU

1.Department of neonatal intensive care unit, Hospices Civils de Lyon, Hôpital Femme M ere Enfant, Lyon 1 University, Lyon, France 2.Laboratory of Biometrics and Evolutionary Biology, Department of biostatistics, Equipe Biostatistique-Sant e, Hospices Civils de Lyon, CNRS, UMR5558, Lyon 1 University, Lyon, France 3.Laboratory of Biometrics and Evolutionary Biology, INSERM CIC 1407, EPICIME, UMR 5558 CNRS, Hospices Civils de Lyon, Lyon 1 University, Lyon, France

Epidemiology of invasive Candida infection in a neonatal intensive care unit in France

Critically ill neonates possess a number of risk factors that predispose them to fungal colonization by Candida species. The extremely preterm infant has the combination of being immunocompromised (including immature skin and gastrointestinal tract), requiring prolonged intensive care (parenteral nutrition, mechanical ventilation, central venous access), being exposed to medications that promote fungal growth (H2 blocking agents, proton pump inhibiting agents, postnatal corticosteroids and broad-spectrum antibiotics), and predisposed to gastrointestinal dysmotility and disease (necrosing enterocolitis and focal bowel perforation) (1,2). Prevention of invasive Candida infections (ICIs) is critical, as there is significant mortality. Even with successful eradication, neurodevelopmental impairment occurs in 57% of survivors weighing <1000 g (3,4). Because of its success among immunocompromised patients, Fluconazole prophylaxis has been suggested as a possible approach for reducing the rates of both colonization and invasive fungal infections among at-risk neonates. To date, five prospective randomized controlled trials have examined fluconazole prophylaxis in neonates. Although fluconazole prophylaxis appears to reduce the rate of invasive fungal infections [RR 0.48 (95% CI 0.31, 0.73)], no trial was able to demonstrate a significant difference in long-term morbidity or mortality [RR 0.74 (95% CI 0.51, 1.09)] (5). Lack of standardized study designs and treatment regimens also limit widespread recommendation for the use of fluconazole prophylaxis in clinical practice (6). The epidemiology and prevention of ICIs depends largely on risk factors and the role they play in infection control and identifying high-risk patients for prevention. It is important to know local invasive fungal infection data in neonatal units, as the incidence in available literature varies from 1% (7) to 10% (4,8). Our aim was to evaluate the incidence of invasive fungal infection in our neonatal intensive care unit (NICU) in a university hospital centre in Lyon, France. The data from this study will help us consider an appropriate strategy of fluconazole prophylaxis. We conducted a laboratory-based surveillance study over a 3-year period to study trends in the rates of ICIs, the rate of candida colonization, demographic characteristics, Candida species, antifungal susceptibility and antifungal utilization in all neonates admitted between January 2007 and January 2010 in a NICU of a children’s hospital in Lyon, France. Our hospital has 52 neonatal beds and there is no established protocol for fluconazole prophylaxis in neonates. This study was reviewed and approved by the Ethics Committee of Lyon. We defined the ICIs as:

472 Unlicensed and Off-Label Drug Use in a Neonatal Unit in France

Aim: To determine the extent of unlicensed and off-label drugs prescribed in a neonatal unit at a University Hospital, Lyon, France. Methods: We conducted a prospective cohort study of newborns who were admitted to the neonatal unit in France during a 4 month-period (from January 1st to April 30th 2009). Using French primary reference source (Vidal 2009), all drug prescriptions were assessed to determine the extent of unlicensed or off-label use. Results: A total of 65 newborns, 55 preterm and 10 full-terms were admitted to the neonatal ward and received 265 prescriptions. Fifty four percent (143/265) of prescribed drugs were licensed, 16.6% (44/265) were off-label for paediatric use, 21% (56/265) for age, 2.4% (6/265) for dosage and 6% (16/265) for route of administration. Unlicensed drug utilisation has not been detected. Seventy one percent (46/65) of infants received at least one offlabel prescription. Conclusion: Prescriptions of off-label drugs in neonatal unit is common. Clinical trials assessing the benefit and harms of off-label or unlicensed drugs frequently prescribed should improve the lack of trial-based data for children.

Whole body bone mineral content (WbBMC) in very low birth weight (VLBW) infants fed a preterm formula (PTF) enriched with calcium and phosphorus

Whole body bone mineral content (WbBMC) in very low birth weight (VLBW) infants fed a preterm formula (PTF) enriched with calcium and phosphorus

Survival and incidence of hemorrhagic-ischemic cerebral lesions in premature infants of gestational age (GA) |[le]| 28 weeks

Survival and incidence of hemorrhagic-ischemic cerebral lesions in premature infants of gestational age (GA) ≤ 28 weeks

Dietary cholesterol does not affect vitamin D metabolism in preterm infants: preliminary results

Dietary cholesterol does not affect vitamin D metabolism in preterm infants: preliminary results