Starter formula enriched in prebiotics and probiotics ensures normal growth of infants and promotes gut health: a randomized clinical trial.

This corrects the article DOI: 10.1038/pr.2016.270.

Starter formula enriched in prebiotics and probiotics ensures normal growth of infants and promotes gut health: a randomized clinical trial.

BACKGROUND: Prebiotics and probiotics exert beneficial effects by modulating gut microbiota and immune system. This study evaluates efficacy and safety of an infant formula containing bovine milk-derived oligosaccharides and Bifidobacterium animalis ssp lactis (B. lactis) (CNCM I-3446) on incidence of diarrhea and febrile infections during the first year of life (primary outcome). METHODS: Full-term infants receiving Test or Control (without bovine milk-derived oligosaccharide and B. lactis) formulae were enrolled in a multicenter, randomized, controlled, and double-blind trial with a reference breastfeeding group. . RESULTS: 413 infants were assigned between Test (n = 206) and Control (n = 207) formula. There was no significant difference for diarrhea and febrile infections incidence between groups at 6 (odds ratio (95% confidence interval) = 0.56 (0.26-1.15), P = 0.096) and 12 mo (odds ratio = 0.66 (0.38-1.14), P = 0.119). Test formula was well tolerated, anthropometrics parameters were not significantly different between groups and aligned with WHO growth standards up to 12 mo. Data from test group showed that gut microbiota pattern, fecal IgA and stool pH were brought to be closer to those of breastfed infants. CONCLUSION: An infant formula enriched with bovine milk-derived oligosaccharide and B. lactis supports normal infant growth, is well tolerated and improves intestinal health markers. No differences in diarrhea and febrile infection incidence were found in the population studied.

Catch-up growth in children born growth restricted to mothers with hypertensive disorders of pregnancy.

BACKGROUND: In preterm hypertensive disorders of pregnancy, fetal growth restriction (FGR) occurs frequently. The timing and severity of FGR impacts childhood growth and is associated with metabolic changes later in life. AIM: To examine growth and the impact of FGR in early childhood. DESIGN: Prospective cohort study. PARTICIPANTS: Children (n=135) born to mothers who were admitted before 34 weeks' gestational age with a severe hypertensive disorder of pregnancy. OUTCOME MEASURES: Height, weight, body mass index (BMI), head circumference (HC), SD scores (SDS) at 3 months, and 1 and 4.5 years of age, and complete catch-up growth (height SDS-target height SDS >-1.6). RESULTS: Growth scores were lower compared to Dutch growth curves, except for BMI at 3 months and girls' HC at all ages. Mean height SDS increased over time from -1.4 to -0.5 at 4.5 years, with 94% having complete catch-up growth. Mean BMI SDS decreased from -0.2 at 3 months to -1.0 at 1 year, and was -0.8 at age 4.5. Mean HC SDS was stable over time and -0.3 at 4.5 years. The customised birth weight ratio, as a measure of the degree of FGR, was related to all growth SDS at 4.5 years, while gestational age at birth was not. CONCLUSIONS: Although the majority of children born growth restricted had catch-up growth of height within the normal range at 4.5 years of age, they were smaller, but especially lighter compared to Dutch growth charts. The degree of FGR was associated with all growth outcomes.

Feeding preterm infants after hospital discharge: a commentary by the ESPGHAN Committee on Nutrition.

Survival of small premature infants has markedly improved during the last few decades. These infants are discharged from hospital care with body weight below the usual birth weight of healthy term infants. Early nutrition support of preterm infants influences long-term health outcomes. Therefore, the ESPGHAN Committee on Nutrition has reviewed available evidence on feeding preterm infants after hospital discharge. Close monitoring of growth during hospital stay and after discharge is recommended to enable the provision of adequate nutrition support. Measurements of length and head circumference, in addition to weight, must be used to identify those preterm infants with poor growth that may need additional nutrition support. Infants with an appropriate weight for postconceptional age at discharge should be breast-fed when possible. When formula-fed, such infants should be fed regular infant formula with provision of long-chain polyunsaturated fatty acids. Infants discharged with a subnormal weight for postconceptional age are at increased risk of long-term growth failure, and the human milk they consume should be supplemented, for example, with a human milk fortifier to provide an adequate nutrient supply. If formula-fed, such infants should receive special postdischarge formula with high contents of protein, minerals and trace elements as well as an long-chain polyunsaturated fatty acid supply, at least until a postconceptional age of 40 weeks, but possibly until about 52 weeks postconceptional age. Continued growth monitoring is required to adapt feeding choices to the needs of individual infants and to avoid underfeeding or overfeeding.

Simple and accurate assessment of energy expenditure in ventilated paediatric intensive care patients.

AIMS: To assess validity and reliability of energy expenditure measurements with a short Douglas bag protocol compared to the standard metabolic monitor in a paediatric intensive care setting. METHODS: 51 paired measurements were performed in 14 ventilated patients (age 0-18 years) with sepsis, trauma or following major surgery. Measured data were compared mutually and compared to Schofield equations using Bland-Altman analysis. RESULTS: Comparing Douglas bag (3.21 +/- 1.43 MJ/day) and metabolic monitor (3.15 +/- 1.49 MJ/day) we found bias in energy expenditure of -0.06 (equal to -2%, NS) with limits of agreement of -0.5 to 0.4 MJ/day (equal to -16% to +13%). Intra-measurement variability (coefficient of variation) was within 10% for both methods. Both the metabolic monitor and Douglas bag showed significant bias compared to Schofield equations (3.39 +/-1.64 MJ/day) of -7% (P < 0.01) and -5% (P < 0.05), respectively, with wide limits of agreement: metabolic monitor vs. Schofield: -37% to +22%, Douglas bag vs. Schofield: -37% to +26%. CONCLUSIONS: The Douglas bag method compared favourably to the metabolic monitor where Schofield equations failed to predict individual energy expenditure. Considering its low cost, this renders the short and simple Douglas bag method a robust measure and a routinely applicable instrument for tailored nutritional assessment in critically ill children.

Nutritional support in 111 pediatric intensive care units: a European survey.

OBJECTIVE: To study current strategies in nutritional management of pediatric intensive care units (PICUs) in Europe, focusing on energy requirements. DESIGN AND SETTING: Survey by a 35-item questionnaire sent to representatives of 242 PICUs in 28 countries. Addresses were obtained from national PICU associations and the members' list of the European Society of Pediatric and Neonatal Intensive Care. PARTICIPANTS: Staff members of 111 European PICUs (46%) from 24 countries. MEASUREMENTS AND RESULTS: Predominantly physicians were reported to be responsible for nutritional support. In 73% of PICUs a multidisciplinary nutritional team was available. In most PICUs daily energy requirements were estimated using weight, age, predictive equations and correction factors. In 17% of PICUs energy expenditure was regularly measured by indirect calorimetry. Nutritional status was mostly assessed by weight, physical examination, and a wide range of biochemical blood parameters. Approximately 70% of PICUs used dedicated software for nutritional support. A similar percentage of PICUs regarded "nutrition" as a research topic and part of the residents' training program. CONCLUSIONS: Most European PICUs regard nutritional support as an important aspect of patient care, as shown by the presence of nutritional teams, software, research, and education. However, energy requirements of pediatric intensive care patient were based predominantly on estimations rather than on measurements.

Nondigestible carbohydrates in the diets of infants and young children: a commentary by the ESPGHAN Committee on Nutrition.

The consumption of nondigestible carbohydrates is perceived as beneficial by health professionals and the general public, but the translation of this information into dietary practice, public health recommendations, and regulatory policy has proved difficult. Nondigestible carbohydrates are a heterogeneous entity, and their definition is problematic. Without a means to characterize the dietary components associated with particular health benefits, specific attributions of these cannot be made. Food labeling for "fiber" constituents can be given only in a general context, and the development of health policy, dietary advice, and education, and informed public understanding of nondigestible carbohydrates are limited. There have, however, been several important developments in our thinking about nondigestible carbohydrates during the past few years. The concept of fiber has expanded to include a range of nondigestible carbohydrates. Their fermentation, fate, and effects in the colon have become a defining characteristic; human milk, hitherto regarded as devoid of nondigestible carbohydrates, is now recognized as a source for infants, and the inclusion of nondigestible carbohydrates in the diet has been promoted for their "prebiotic" effects. Therefore, a review of the importance of nondigestible carbohydrates in the diets of infants and young children is timely. The aims of this commentary are to clarify the current definitions of nondigestible carbohydrates, to review published evidence for their biochemical, physiologic, nutritional, and clinical effects, and to discuss issues involved in defining dietary guidelines for infants and young children.

Maturity of the adrenal cortex in very preterm infants is related to gestational age.

To study the maturity of the adrenal cortex in preterms born before 33 wk of gestation, basal levels of cortisol and cortisone and the cortisol and 17-hydroxyprogesterone (17-OHP) response to 1 microg/kg adrenocorticotropic hormone stimulation were measured in 24 appropriate-for-gestational age preterm infants (26-33 wk; 690-1985 g). Gestational age influenced the response of cortisol, 17-OHP, and the ratio between cortisol/17-OHP in the studied infants. In preterms born <30 wk of gestation, levels of cortisol, and the ratio between cortisol/17-OHP were lower compared with preterms born between 30 and 33 wk. Levels of cortisone were higher in preterms born <30 wk, suggesting a lower activity of 11 beta-hydroxysteroid dehydrogenase that may be related to maturity as well. These findings indicate that the adrenal cortex function in preterm infants is closely related to the duration of gestation and may be important in neonatal morbidity.

Neuromotor function and school performance in 7-year-old children born as high-risk preterm infants.

Neuromotor behavior was studied in 63 children at a mean age of 7 years. They were born at a gestational age less than 32 weeks and/or birthweight under 1500 g and were categorized according to their medical history in conformance with the Neonatal Medical Index (from category I to V, from few to serious complications). We included only children considered at high risk as categorized in III to V. The neuromotor behavior study focuses on different subcategories, such as hand function, quality of walking, posture, passive muscle tone, coordination, and diadochokinesia. Hand preference and/or lateralization, the presence of associated movements, and/or asymmetry were noted, as was school performance. Then gender, gestational age, birthweight, and dysmaturity were investigated as confounding factors. The outcome at 7 years was correlated with the Neonatal Medical Index and the neonatal brain ultrasonography classification. None of the children scored 100% on the combined subcategories. Nineteen children (30%) had an overall score between 75 and 99%. Significant relationships between all different subcategories were found. Lack of hand preference, poor lateralization, and male gender were related to poor overall outcome. Poor motor control was correlated to special schooling and education below age level. The Neonatal Medical Index proved to have a significant influence on total outcome and the subcategories at the age of 7 years, with the worst outcome in children formerly classified in category V. Neuromotor behavior at 7 years of age was not related to birthweight, gestational age, dysmaturity, and neonatal brain ultrasonography classification only.

Muscle power development during the first year of life predicts neuromotor behaviour at 7 years in preterm born high-risk infants.

The aim of the study was to find if neurological function during the first year of life could predict neuromotor behaviour at 7 years of age in children born preterm with a high risk. A follow-up study of neuromotor behaviour in 52 children at a mean age of 3, 6, 12 months (corrected age) and 7 years was performed. All children were born with a gestational age less than 32 weeks and/or a birthweight under 1500 g and the infants were categorised according to their medical history in the three highest categories of the 'Neonatal Medical Index' (NMI, from category I to V, from few to serious complications). In addition, neonatal cerebral ultrasound abnormalities were used to divide the infants further into the different NMI categories. At 3 and 6 months, the relationship between active and passive muscle power was measured in shoulders, trunk and legs and (a)symmetry between right and left was noted. The results at 3 and 6 months were ranged from 1 for optimal to 5 for poor muscle power regulation. At 12 months of age, a neurological examination was done with special emphasis on the assessment of postural control, spontaneous motility, hand function and elicited infantile reactions with special attention to (a)symmetry. Outcome at 12 months was expressed as percentage of the optimal score on each subcategory. At 7 years, the motor behaviour study based on Touwen's examination for minor neurological dysfunction was performed. This investigation focuses on different functions, such as hand function, quality of walking, posture, passive muscle tone, coordination and diadochokinesis. The outcome was expressed as percentage of the optimal score on the combined subcategories. The best prediction of neuromotor behaviour at 7 years was assessed with stepwise linear multiple regression, using as potential predictors perinatal factors and outcome of motor behaviour at the corrected age of 3, 6 and 12 months. At 7 years none of the children scored 100% on the combined subcategories, 15 children (29%) scored between 75% and 99%, whereas 15 children scored less than 50%. Neuromotor behaviour at 7 years could be predicted by the NMI categorisation and gender with a sensitivity of 92% (specificity 47%; positive and negative predictive value 81% and 70%). No direct relation was found between neuromotor behaviour and cerebral ultrasound classification only, days on the ventilator and/or continuous positive airway pressure, birthweight, gestational age and dysmaturity. The best predictor of neuromotor behaviour at 7 years was the combination of outcome of muscle power in shoulders and legs at 3 months and postural control at 12 months, taking into account the gender of the child (sensitivity 95%; specificity 40%; positive predictive value 80%; negative predictive value 75%).

The corticotrophin-releasing hormone test in preterm infants.

OBJECTIVE: The developing hypothalamic--pituitary--adrenal axis (HPAA) may be immature and not yet fully functional in preterm infants. This may result in an inappropriate adrenal response to stress. Little is known about the pituitary--adrenal response to corticotrophin-releasing hormone (CRH) stimulation during the early neonatal period in preterm infants born before 32 weeks of gestation. Therefore, in a first study we investigated the pituitary--adrenal response to 1 microg/kg CRH i.v. in 13 preterm infants born less-than-or-equal 32 weeks of gestation. In addition, in a randomized placebo-controlled study we compared the pituitary--adrenal response of 1 microg/kg CRH to placebo and stimulation with 2 microg/kg CRH. RESULTS: In the first study, the level of ACTH increased from 6.9 +/-2.1 to 11.6 +/- 5.1 pmol/l (P < 0.01) and cortisol increased from 350 plus minus 115 to 582 +/- 201 nmol/l (P < 0.05). Thirty-eight percent of the studied infants showed a maximal level of ACTH < 9 pmol/l, and 15% showed a maximal level of cortisol < 360 nmol/l. In the randomized study, infants in the 1 microg/kg and in the 2 microg/kg CRH group, but not in the placebo group, showed a significant increase in cortisol and ACTH after stimulation (P < 0.01). Stimulated levels of ACTH and cortisol were significantly higher in the 2 microg/kg group compared with the placebo and the 1 microg/kg group. No differences were found for plasma ACTH and cortisol levels in the 1 microg/kg group compared with the placebo group. Basal levels of cortisol and ACTH obtained from the first and from the randomized study correlated significantly (n = 29; r = 0.42, P < 0.03). In addition, in infants stimulated with 1 microg/kg CRH a lower cortisol response correlated with a longer stay in hospital (n = 13; r = --0.57, P < 0.05). CONCLUSIONS: In this study we show that a 1 microg/kg CRH stimulation test in preterm infants results more often in an inappropriate adrenal response while stimulation with 2 microg/kg CRH gives rise to an appropriate response in all studied infants. Furthermore, stimulation with 2 microg/kg CRH results in higher levels of ACTH and cortisol compared to placebo and 1 microg/kg CRH. We conclude that in preterm infants the ability of the pituitary to respond adequately to CRH stimulation depends on the dose of CRH used and may also be dependent on the maturity of the pituitary--adrenal axis.