6q24 Transient Neonatal Diabetes - How to Manage while Waiting for Genetic Results.

Diabetes, rare in the neonatal period, should be evoked in every newborn presenting with unexplained intrauterine and early postnatal growth retardation. This case report illustrates the clinical course and therapeutic approach of a newborn diagnosed with transient diabetes. The baby was born at 37 weeks of gestation with a severe intrauterine growth restriction. Except a mild macroglossia and signs of growth restriction, physical examination was normal. On the fifth day of life, hyperglycemia (180 mg/dl) was noted, and the next day, the diagnosis of diabetes was confirmed (high blood sugar, glucosuria, undetectable levels of insulin and C-peptide). Insulin infusion, initially intravenously and then subcutaneously, was started, tailored to assure the growth catch-up and normalize the blood sugar levels. At the age of 4 weeks, the baby returned at home under pump. At 8 weeks, the clinical impression of evolution to a transient diabetes (decreasing needs of insulin with very satisfactory weight gain) was genetically confirmed (paternal uniparental disomy of chromosome 6). There is no screening for neonatal diabetes, but the clinical suspicion avoids the metabolic decompensation and allows early initiation of insulin therapy. The genetic approach (for disease itself and its associated features) relies on timely clinical updates

Variability in human milk composition: benefit of individualized fortification in very-low-birth-weight infants.

BACKGROUND: Preterm infants fed fortified human milk (HM) grow more slowly than those fed preterm formulas. These differences could be related to the variability in the macronutrient composition of expressed HM, resulting in inadequate nutrient intake in relation to the estimated needs of the preterm infants. OBJECTIVES: The aim of this article was to show the variability in HM composition from an infant's own mother's milk (OMM) or pooled HM from the milk bank. The second objective was to evaluate the advantages of individual fortification on nutritional intakes over standard fortification. DESIGN: The macronutrient composition of 428 OMM, 138 HM pools from single donors, 224 pools from multiple donors, and 14 pools from colostral milk was determined by using a mid-infrared analyzer. Individualized fortification was performed after analysis of the milk samples in 2 steps: adjustment of fat content up to 4 g/dL, followed by the addition of an HM fortifier to provide 4.3 g . kg(-1) . d(-1) according to the daily prescribed volume of feeding. Nutritional intakes resulting from the individualized fortification were compared with calculated intakes resulting from standard fortification (HM fortifier: 4 packets/dL). RESULTS: The variability in contents of fat, protein, and energy was high for all types of HM samples. Compared with standard fortification, individual fortification significantly reduced the variability in nutritional intakes, allowing the maintenance of protein intake and the protein:energy ratio in the range of the nutritional recommendations. CONCLUSIONS: The variability in expressed HM with respect to its protein and energy content is high. This variability persists after standard fortification, possibly resulting in under- or overnutrition. Because both over- and undernutrition confer risks in later development, individualized fortification optimizes protein and energy intake

Contribution à l'utilisation du lait maternel en néonatologie

In preterm infants, Human milk (HM) feeding is associated with significant benefits on health and development. The mother’s own milk (OMM) is recommended as the first nutritional choice . When OMM is unavailable, the use of donor milk (DM) should be the second alternative. However, HM use in neonatal intensive care units may raise some concerns. The purpose of this work is to evaluate them and to find appropriate solutions in order to promote the HM use for preterm infants. HM despite anti-infective properties is not sterile, and additional contaminations may occur during handling and processing for use in neonatology. We confirmed that expressed HM may harbor skin flora, as well as less frequent pathogenic bacteria with potential infectious risk for vulnerable preterm infants (chapter 2) . It therefore requires careful monitoring and eventual processing to eradicate pathogens while preserving its immune function. Holder Pasteurization is the method currently used in HM banks and should also be considered for OMM in the most immature preterm infants although, unfortunately, it alters some HM components, especially among those with immune function. It was suggested that raw OMM is superior to pasteurized OMM in protective effects against infections and other morbidities, but clinical evidence is still lacking. We also demonstrated that colostrum is less contaminated than mature milk and therefore could be used raw. The results of our study on bacterial contamination of HM and the literature review of the postnatal cytomegalovirus (CMV) infections from OMM of CMV positive mothers suggest that pasteurization of OMM remains worthwhile in very preterm infants (<32 weeks GA) fed OMM heavily contaminated with pathogenic bacteria as well as in extremely preterm infants (<28 weeks GA) of CMV positive mothers . Nutritional requirements of preterm infants are high, explaining the risks of nutritional deficits and extrauterine growth restriction. Exclusive HM feeding with both OMM and DM cannot meet their nutritional needs without being fortified. However, despite standard fortification, growth of HM fed preterm infants remains suboptimal and lower than those of fed preterm formula. These differences could be related to large variations in the macronutrients content of expressed HM, that is frequently lower than their assumed concentration. Additional explanations include lower HM metabolizable protein and energy availability for new tissue synthesis and negative impact of pasteurization. Therefore, optimization of HM fortification is required. Both improving the quality of the fortifiers, including by increasing the protein content, and individualization of the fortification have been suggested. In a controlled, multicenter, double-blind study, we demonstrated an improved weight gain during the study period (+1.18 g/kg/d; p=0.013) in infants fed HM supplemented with a new HM fortifier providing similar energy but higher protein intakes (4.5 vs 3.8 g/kg/d) (chapter 3) . However, in this study, nutrients intakes were not measured and were probably overestimated in both groups. This study suggests that nutritional requirements of preterm infants fed human milk could be higher that of preterm infants fed formula and that separate nutritional recommendations should be published for preterm fed HM. Devices using infrared technology allow rapid analysis of macronutrients concentrations but require a careful validation before their use for HM. We evaluated several infrared analyzers (Milkoscan® minor and three generation of Miris®) and demonstrated that after individual adjustments, infrared analyzers provide precise and accurate determination of protein and lipid concentration (chapter 4) . However, as validation techniques are time consuming and request several chemical analyses not available in most NICUs, their use needs to be reserved for research pending the availability of dedicated validation kits. Using the Milkoscan®, we confirmed the high variability of HM contents and the appeal of individualized HM fortification to optimize the fortified OMM or DM nutritional compositions up to the nutritional needs of preterm infants (chapter 5) . In clinical settings, applying our individualized fortification protocol allowed us to provide daily remarkably similar controlled nutritional intakes to a group of 101 VLBW infants fed fortified OMM or DM (chapter 6) . Therefore, independently from protein and energy intakes, it was possible for the first time to demonstrate that fortified( OMM promoted growth of premature infants with increased weight gain velocity of 1.6 g/kg/d (p=0.002) and length gain of 0,18 cm/week (p=0.02), relative to fortified DM. This result could be partially explained by the pasteurization of DM as the weight gain differences between raw and pasteurized OMM were in the same range. This suggests that pasteurization impaired the bioavailability of nutrient intakes. According to our results, we speculate that energy requirements could be higher in preterm infants fed pasteurized DM or OMM versus those fed raw OMM. In view of these results, we also suggested that nutritional recommendations need to take into consideration the types of HM: OMM or DM, raw or pasteurized.Le lait maternel (LM) présente de nombreux avantages pour la santé et le développement du nouveau-né prématuré. Le lait maternel de la propre mère constitue ainsi le premier et meilleur choix d’alimentation. Si le lait maternel de la propre mère n’est pas disponible, le lait humain de don représente la meilleure alternative . Cependant, l’utilisation du lait maternel dans les unités néonatales peut soulever certaines questions. Le sujet de ce travail est d’évaluer ces problèmes et de tenter de trouver des solutions appropriées afin de promouvoir l’usage du lait maternel pour l’alimentation du nouveau-né prématuré. Le lait maternel, malgré ses propriétés anti-infectieuses, n’est pas stérile et peut être contaminé durant les manipulations nécessaires à son usage en néonatologie. Nos études bactériologiques des laits tirés amenés par les mères en néonatologie confirment la présence de bactéries de la flore cutanée mais aussi de bactéries pathogènes avec un risque potentiel d’infection chez le grand prématuré (chapitre 2) . Par conséquent, il parait prudent de réaliser une surveillance bactériologique attentive ainsi qu’un traitement des laits contaminés, éliminant virus ou bactéries pathogènes tout en préservant au maximum les propriétés immunologiques du LM. La pasteurisation de Holder, malgré ses effets délétères sur certains composants, surtout immunitaires du LM est la méthode actuellement utilisée dans les banques de lait et peut être considérée pour traiter le LM de la propre mère des enfants prématurés très immatures et vulnérables. Le LM de la propre mère cru est généralement considéré comme supérieur au LM pasteurisé dans son rôle de protection contre les infections et autres morbidités mais des données cliniques probantes manquent. Nous avons également démontré que le colostrum est moins contaminé que le lait mature et pourrait être utilisé cru. Notre étude sur la contamination bactérienne du LM et la revue de littérature concernant le risque d’infection postnatale au cytomégalovirus (CMV) via le LM de mères séropositives pour le CMV suggère que la pasteurisation demeure préférable chez les prématurés extrêmes de moins de 28 semaines à la naissance, nés de mères séropositives pour le CMV ainsi qu’en cas de contamination significative du LM avec des bactéries pathogènes chez ceux nés avant 32 semaines. Les besoins nutritionnels de l’enfant prématuré sont très élevés avec un risque de déficit nutritionnel et de retard de croissance extra-utérin. L’alimentation exclusive au LM de la propre mère ou au lait de don ne peut satisfaire ces besoins nutritionnels. Le LM doit donc être fortifié. Cependant, malgré la fortification, la croissance des enfants prématurés alimentés au LM fortifié reste inférieure à celle de ceux alimentés avec une formule destinée aux prématurés. Ces différences pourraient être expliquées par la grande variabilité nutritionnelle du LM tiré avec un contenu nutritionnel réel plus faible que présumé mais aussi par la moindre disponibilité en protéines et énergie métabolisables du LM pour la synthèse de nouveaux tissus, auxquelles s’ajoute l’impact négatif d’une éventuelle pasteurisation. Une optimisation de la fortification du LM est donc requise. L’amélioration de la qualité des fortifiants en augmentant le contenu en protéines et l’individualisation de la fortification ont été des pistes suggérées. Dans une étude multicentrique contrôlée en double-aveugle, nous avons montré une amélioration du gain pondéral (+1,18 g/kg/j; p=0,013) chez les enfants alimentés au LM enrichi avec un nouveau fortifiant apportant plus de protéines (4,5 vs 3,8 g/kg/j) pour un apport similaire en énergie (chapitre 3). Cependant, dans cette étude, les apports nutritionnels étaient non directement mesurés et probablement surestimés dans les deux groupes. Cette étude suggère des besoins nutritionnels plus élevés chez les enfants prématurés alimentés au LM fortifié par rapport à ceux alimentés avec une formule ainsi que la nécessité d’élaborer et de publier des recommandations nutritionnelles spécifiques pour l’enfant alimenté au LM fortifié. Des appareils utilisant la technologie infra-rouge permettent une détermination rapide de la composition en macronutriments du lait de vache mais nécessitent une validation minutieuse avant utilisation pour l’analyse du LM. Nous avons évalué plusieurs analyseurs (le Milkoscan® minor et trois générations de Miris®) et démontré, qu’après ajustement individuel, ces analyseurs à infra-rouge permettent une détermination exacte et précise de la concentration en lipides et en protéines du LM (chapitre 4) . Cependant, la validation est laborieuse et demande des analyses chimiques de référence non disponibles dans la majorité des services de néonatologie. Leur usage devrait donc être réservé à la recherche tant que des kits de validation adéquatement certifiés ne sont pas disponibles. En utilisant le Milkoscan®, nous avons confirmé la grande variabilité de composition du LM et démontré l’intérêt d’une fortification individualisée du LM, de la propre mère ou de don, pour en optimiser sa composition nutritionnelle et permettre ainsi de rencontrer les besoins nutritionnels élevés des enfants prématurés (chapitre 5) . En appliquant notre protocole de fortification individualisée en clinique, nous avons pu fournir des apports nutritionnels contrôlés et similaires dans un groupe de 101 enfants grands prématurés alimentés au LM fortifié de la propre mère ou de don (chapitre 6) . Pour la première fois, nous avons pu démontrer que, de façon indépendante des apports en macronutriments, le LM de la propre mère favorisait la croissance par comparaison au lait de don avec un bénéfice de gain pondéral de 1,6 g/kg/j (p=0,002) et statural de 0,18 cm/sem (p= 0,02). Cette différence pourrait être partiellement expliquée par la pasteurisation du lait de don car nous avons aussi observé une différence de gain pondéral similaire entre le LM de la propre mère cru et pasteurisé, suggérant que la pasteurisation altérait la biodisponibilité des apports nutritionnels du LM. Tenant compte de nos résultats, nous spéculons que les besoins en énergie pourraient être plus élevés chez les enfants alimentés au LM pasteurisé par rapport à ceux alimentés au LM de la propre mère cru. Nous suggérons également que les recommandations nutritionnelles prennent en considération le type de LM utilisé : LM de la propre mère ou de don, cru ou pasteurisé.3. Good health and well-bein

Respiratory Syncytial Immunoprophylaxis with Palivizumab

peer reviewedRespiratory syncytial virus (RSV) is a serious pathogen causing significant morbidity, especially in premature infants and infants with chronic lung disease or significant congenital heart disease. There is no specific treatment for RSV infection and the therapy is essentially supportive. Therefore, prophylaxis is the best strategy against RSV disease. Passive immunization with monoclonal antibodies (palivizumab) provides protection against severe RSV infection and significantly reduces hospitalizations in high-risk childrens. However, palizumab is an expensive drug and its use should be reserved for children at the highest risk of severe RSV disease

The use of human milk in the neonatal intensive care unit: Practices in Belgium and Luxembourg

Background: Human milk remains the preferred feeding for all infants, including premature and sick newborns. However, mother's milk is not sterile, and expressed milk can be a source of commensal and pathogenic microorganisms. Microbiological quality standards for the use of expressed human milk in hospitals are not available, unlike for donor or formula milk. Methods: To document current practices for the use of human milk in the neonatal intensive care units (NICU) in Belgium and Luxembourg, both for mother's own milk and donor milk, a questionnaire was sent to all 20 neonatal units. Results: Of the 19 units that completed the survey, 47% perform bacteriological testing of expressed milk. Applied bacterial count limits for the acceptable level of contamination differ among units, for both commensals and pathogens. Only six units have a device for pasteurizing milk at their disposal. Storage time in the refrigerator for fresh milk varies between 24 hours to 7 days before use. Access to donor milk is limited. Conclusions: Routines for handling of human milk differ widely among NICUs in Belgium and Luxembourg. An assessment of current issues through a structured survey is a useful tool in the development of best practice guidelines. © 2012, Mary Ann Liebert, Inc.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

The use of human milk in the neonatal intensive care unit: practices in Belgium and Luxembourg

Human milk remains the preferred feeding for all infants, including premature and sick newborns. However, mother's milk is not sterile, and expressed milk can be a source of commensal and pathogenic microorganisms. Microbiological quality standards for the use of expressed human milk in hospitals are not available, unlike for donor or formula milk.status: publishe

Surprising causes of C5-carnitine false positive results in newborn screening.

During an 18-month period, we noticed an alarming increase of newborn screening false positivity rate in identifying isovaleric acidemia. In 50 of 50 newborns presenting elevated C5-carnitine, we confirmed the presence of pivaloylcarnitine. Exogenous pivalate administration had been previously identified as the causal agent of this concern. No pivalic-ester prodrug is commercially available in Belgium, but pivalic derivates are also used in the cosmetic industry as emollient under the term "neopentanoate". We have identified neopentanoate-esters in a nipple-fissure unguent that was provided to young mothers. Ceasing distribution of this product hugely reduced the C5-carnitine false positivity rate