Introduction Aggressive nutritional strategy, particularly enhancing early provision of energy and protein, has appeared to reduce postnatal growth failure and improve later developmental outcomes. But the amount of macronutrients required remains unclear. The aim of this study was to investigate the impact of protein and energy intakes during the first two weeks after birth on neurodevelopmental outcomes. Methods This retrospective cohort study of very low birth weight infants born between January 2012 and December 2015 was conducted at one tertiary neonatal intensive care unit. The primary outcome was a neurodevelopmental impairment (NDI) at 2 years corrected age defined by a cerebral palsy or a 24 month Ages and Stages Questionnaires score on any of the five domains lower than 2 standard deviation below the mean score. Multivariable logistic regression analysis was used to adjust for perinatal and postnatal confounders. Results Among 245 (73%) infants discharged home alive, 159 (65%) had follow-up at 2 years. Infants with NDI (55/159, 35%) were more likely male gender (67.3% versus 46.2%, P = 0.02) and experienced more patent ductus arteriosus (PDA) ligation (20% versus 5.8%, P = 0.01) than control. After adjusting for confounders, first-week protein intake (OR: 2.27 [CI: 1.07–5.14]; P < 0.05), second-week non-protein energy intake (OR: 1.03 [CI: 1.01–1.05]; P < 0.01) and PDA ligation (OR: 6.81 [1.80–28.46]; P < 0.01) had significant independent association with higher likelihood of NDI at 2 years. Conclusion Providing nutrition above the optimal level may not be beneficial and may even be harmful. These results confirm the recent recommendation to decrease amino acid intakes published in the latest ESPGHAN guidelines.
L‘objectif principal de ce travail a ete d‘analyser la dispersion des couts pharmaceutiques de deux protocoles de prise en charge des cancers colorectaux (CCR) en seconde ligne de traitement : Folfiri et Folfox 4, dans 9 centres hospitaliers (6 CHU, 2 CAC, 1 CHG). Les donnees de cout : cout d‘acquisition, cout de preparation et cout d‘administration (representant le cout d‘usage du medicament) ont ete saisies a partir d‘un site internet (REES France) interactif developpe en vue de cette analyse. Pour le protocole Folfiri, la dispersion des couts intercentres est de 12 % en valeur du cout d‘usage du medicament. Pour le protocole Folfox 4, cette dispersion des couts atteint 24,2 %. Le cout d‘acquisition des produits represente 90 % du cout d‘usage du protocole Folfox 4 et 91 % de Folfiri. Il apparait ainsi licite de transformer a partir d‘un microcosting realise sur un centre les donnees de cout de preparation en couts standards dans un essai multicentrique. En revanche, l‘attribution classique d‘un pourcentage de variation arbitraire (± 10 %) des couts d‘acquisition en vue de documenter une analyse de sensibilite sur les couts apparait au travers de cette etude hasardeuse. L‘analyse de sensibilite necessite d‘apres nos resultats un recueil preliminaire multicentrique des donnees de couts compte tenu des variations de couts constatees entre etablissements.
-Objectives and study: Human milk is the ideal food for neonatal nutrition and optimal growth.
When the mother's own milk is unavailable or limited, pasteurized human milk from milk banks is
preferentially administered instead of infant formula, especially for preterm hospitalized neonates.
Holder pasteurization (62.5 °C, 30 min) is applied for sanitary reasons but alters human milk
components such as enzymes and immunoglobulins. In vitro studies have also shown that
pasteurization of human milk impacts its hydrolysis and disintegration in term newborns (De Oliveira
et al., 2016). Our study aimed at investigating the impact of pasteurization of human milk on its
gastric digestion in preterm infants.
-Methods: In vivo study was conducted at Rennes Hospital on preterm infants (n=12) fed by a
feeding nasogastric tube each three hours (NCT02112331). Over a six-day sequence, gastric aspirates
were collected twice a day, before and after administration of raw or pasteurized human milk.
Samples were collected at 35, 60 or 90 min after meal ingestion. Gastric volume and pH were
measured. Structural changes of the digesta were evaluated by confocal microscopy and laser light
scattering. In digesta, residual intact proteins left were followed by gel electrophoresis (SDS-PAGE)
submitted to densitometry, and lipolysis degree was evaluated by gas and thin layer chromatography
fitted to flame ionization detector.
-Results: On average (±SD), infants were 27.5 ± 12.3 days old at the first day of the study. Birth
weight was 1.4 ± 0.3 kg and gestational age 29.6 ± 1.0 weeks. Digestive kinetics presented high inter
and intra-individual variabilities. Regarding proteins, results showed a rapid disappearance of intact
caseins and lactoferrin, but a resistance of alpha-lactalbumin. The contribution of meal gastric
emptying or hydrolysis in protein disappearance depended on the protein. Some pre-lipolysis was
determined in milk before digestion and it was in overall significantly lower in pasteurized than in
raw milk, likely due to the heat-denaturation of endogenous lipases. During gastric digestion the
kinetics of lipolysis were not affected by pasteurization (p > 0.05). The lipolysis degree ranged from 6
to 20% at 90 min. This relatively limited extent of gastric lipolysis was observed for both raw and
pasteurized human milk, and was illustrated by the microscopic observations: some native milk fat
globule structure (hydrophobic core enveloped by an amphiphilic membrane) persisted through the
gastric digestion for both raw and pasteurized human milk. Regarding the structure, pasteurization
led to heat-induced protein aggregates in the soluble phase and at the interface of the human milk
fat globule membrane, and also impacted the protein aggregation and emulsion disintegration
during gastric digestion.
-Conclusion: This study represents a unique and important dataset on the behavior of pasteurized
versus raw human milk. The gastric digestion is a key step which can further modulate nutrient
absorption and infant nutrition. Digestive hydrolysis may also impact on gut microbiota, a major
contributor to the development of the intestinal and systemic immune systems in the neonatal
period. Physiologic and metabolic consequences remain to be investigated.
Ensuring adequate growth of preterm newborns remains a challenge. When breastfeeding is not possible, pasteurized human milk (PHM) from milk banks is preferentially administered to hospitalized newborns. Holder pasteurization (62.5°; 30 min) is applied for sanitary reasons but may reduce fat absorption through the inactivation of milk endogenous lipases. It has been suggested that homogenization of Holder-pasteurized human milk (PHM) could improve fat absorption and weight gain. The objective of the present work was to determine the impact of pasteurization and homogenization on gastric digestion in preterm infants.
In a randomized controlled trial (NCT02112331), hospitalized tube-fed preterm infants were their own control to compare the gastric digestion of either i) raw (RHM) and pasteurized human milk (PHM), or ii) pasteurized (PHM) and homogenized PHM (PHHM). Over a six-day sequence, gastric aspirates were collected twice a day, before and 35, 60 or 90 min after the start of milk ingestion. The impact of homogenization on PHM digestive kinetics, lipolytic activity and disintegration was monitored.
Pasteurization and homogenization affected milk initial structure, with the formation of protein aggregates at the interface of the milk fat globules in PHM and a six-fold increase of the specific surface (P<0.01) of lipid droplets in PHHM. Treatments also affected gastric aggregation. Despite inactivation of bile salt stimulated lipase, pasteurization did not impact gastric lipolysis level averaging 12.6 ± 4.7% at 90 min. Conversely, homogenization increased this level (P<0.01). Homogenization also reduced meal emptying rate (P<0.001). Pre-lipolysis occurred prior to pasteurization in all milks ranging between 2.2-4.0%. The global gastric lipolytic activity detected in fasted state averaged 17.5±2.9 U/mL/kg at pH 4.5. Postprandial lipolytic activity increased with time and was higher after administration of RHM compared to PHM (n=5) whereas it was not different after administration of PHM vs. PHHM (n=4).
Overall, in vivo data gathered here are crucial for a better understanding of milk neonatal digestion and help supporting the nutritional management of preterm infants.
L‘objectif principal de ce travail a ete d‘analyser la dispersion des couts pharmaceutiques de deux protocoles de prise en charge des cancers colorectaux (CCR) en seconde ligne de traitement : Folfiri et Folfox 4, dans 9 centres hospitaliers (6 CHU, 2 CAC, 1 CHG). Les donnees de cout : cout d‘acquisition, cout de preparation et cout d‘administration (representant le cout d‘usage du medicament) ont ete saisies a partir d‘un site internet (REES France) interactif developpe en vue de cette analyse. Pour le protocole Folfiri, la dispersion des couts intercentres est de 12 % en valeur du cout d‘usage du medicament. Pour le protocole Folfox 4, cette dispersion des couts atteint 24,2 %. Le cout d‘acquisition des produits represente 90 % du cout d‘usage du protocole Folfox 4 et 91 % de Folfiri. Il apparait ainsi licite de transformer a partir d‘un microcosting realise sur un centre les donnees de cout de preparation en couts standards dans un essai multicentrique. En revanche, l‘attribution classique d‘un pourcentage de variation arbitraire (± 10 %) des couts d‘acquisition en vue de documenter une analyse de sensibilite sur les couts apparait au travers de cette etude hasardeuse. L‘analyse de sensibilite necessite d‘apres nos resultats un recueil preliminaire multicentrique des donnees de couts compte tenu des variations de couts constatees entre etablissements.
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