A Partly Fermented Infant Formula with Postbiotics Including 3'-GL, Specific Oligosaccharides, 2'-FL, and Milk Fat Supports Adequate Growth, Is Safe and Well-Tolerated in Healthy Term Infants: A Double-Blind, Randomised, Controlled, Multi-Country Trial.

This study investigated growth, safety, and tolerance in healthy infants consuming a partly fermented infant formula (IF) with postbiotics, 2'-linked fucosyllactose (2'-FL), a specific prebiotic mixture of short-chain galacto-oligosaccharides (scGOS) and long-chain fructo-oligosaccharides (lcFOS), and milk fat. This double-blind, controlled trial randomised 215 fully IF-fed infants ≤ 14 days of age to either: Test Group (IF) containing 26% fermented formula with postbiotics derived from Lactofidus fermentation process (including 3'-Galactosyllactose; 3'-GL), 0.8 g/100 mL scGOS/lcFOS (9:1), 0.1 g/100 mL 2'-FL, and milk fat), or Control group (IF with 0.8 g/100 mL scGOS/lcFOS (9:1)) until 17 weeks of age. Fully breastfed infants were included as a reference. Anthropometric measures, gastrointestinal symptoms, and safety were assessed monthly. Equivalence in weight gain (primary outcome) between the Test and Control groups was confirmed (difference in means -0.08 g/day; 90% CI (-1.47;1.31)) with estimated mean weight gain (SE) of 31.00 (0.59) g/day and 31.08 (0.60) g/day, respectively, (PP population, n = 196). Equivalence in length and head circumference gain between the randomised groups was also confirmed. No statistically significant differences were observed in adverse events or gastrointestinal tolerance between randomised IF groups. A partly fermented IF with postbiotics, specific oligosaccharides, 2'-FL, and milk fat supports adequate infant growth and is safe and well-tolerated in healthy term infants.

Growth Benefits of Own Mother's Milk in Preterm Infants Fed Daily Individualized Fortified Human Milk.

The influence of types of human milk (HM)-raw own mother's milk (OMM), pasteurized OMM, and donor milk (DM)-was evaluated for growth in premature infants fed exclusively HM with controlled nutritional intakes using daily individualized HM fortification (IHMF). Growth and nutritional intakes were prospectively collected in preterm infants (<32 weeks) fed IHMF and compared in infants fed predominantly (≥75%) OMM and DM. The influence of HM types (raw OMM, pasteurized OMM, and DM) on growth were also evaluated in the whole population. One-hundred and one preterm infants (birth weight 970 ± 255 g, gestational age 27.8 ± 1.9 weeks) were included. Energy (143 ± 8 vs. 141 ± 6 kcal/kg/day; p = 0.15) and protein intakes (4.17 ± 0.15 vs. 4.15 ± 0.14 g/kg/day; p = 0.51) were similar in both groups. Infants receiving predominantly OMM (n = 37), gained significantly more weight (19.8 ± 2.0 vs. 18.2 ± 2.2 g/kg/day; p = 0.002) and length (1.17 ± 0.26 vs. 0.99 ± 0.36 cm/week; p = 0.020) than those fed predominantly DM (n = 33). Stepwise multivariate analysis (n = 101) suggests that raw OMM was the major determinant of growth, contributing 22.7% of weight gain. Length gain was also related to OMM (raw + pasteurized) intakes, explaining 4.0% of length gain. In conclusion, at daily controlled similar protein and energy intakes, OMM had significant beneficial effects on weight and length versus DM in VLBW infants. This difference could be partially explained by the use of raw OMM.

Growth and Nutritional Biomarkers of Preterm Infants Fed a New Powdered Human Milk Fortifier: A Randomized Trial.

OBJECTIVES: The aim of this study was to assess growth and nutritional biomarkers of preterm infants fed human milk (HM) supplemented with a new powdered HM fortifier (nHMF) or a control HM fortifier (cHMF). The nHMF provides similar energy content, 16% more protein (partially hydrolyzed whey), and higher micronutrient levels than the cHMF, along with medium-chain triglycerides and docosahexaenoic acid. METHODS: In this controlled, multicenter, double-blind study, a sample of preterm infants ≤32 weeks or ≤1500 g were randomized to receive nHMF (n = 77) or cHMF (n = 76) for a minimum of 21 days. Weight gain was evaluated for noninferiority (margin = -1 g/day) and superiority (margin = 0 g/day). Nutritional status and gut inflammation were assessed by blood, urine, and fecal biochemistries. Adverse events were monitored. RESULTS: Adjusted mean weight gain (analysis of covariance) was 2.3 g/day greater in nHMF versus cHMF; the lower limit of the 95% CI (0.4 g/day) exceeded both noninferiority (P < 0.001) and superiority margins (P = 0.01). Weight gain rate (unadjusted) was 18.3 (nHMF) and 16.8 g ·â€Škg ·â€Šday (cHMF) between study days 1 and 21 (D1-D21). Length and head circumference (HC) gains between D1 and D21 were not different. Adjusted weight-for-age z score at D21 and HC-for-age z score at week 40 corrected age were greater in nHMF versus cHMF (P = 0.013, P = 0.003 respectively). nHMF had higher serum blood urea nitrogen, pre-albumin, alkaline phosphatase, and calcium (all within normal ranges; all P ≤ 0.019) at D21 versus cHMF. Both HMFs were well tolerated with similar incidence of gastrointestinal adverse events. CONCLUSIONS: nHMF providing more protein and fat compared to a control fortifier is safe, well-tolerated, and improves the weight gain of preterm infants.

Use of donor milk in the neonatal intensive care unit.

Own mother's milk is the first choice in feeding preterm infants and provides multiple short- and long-term benefits. When it is unavailable, donor human milk is recommended as the first alternative. Donor milk undergoes processing (i.e. pasteurization) to reduce bacteriological and viral contaminants but influences its bioactive properties with potentially fewer benefits than raw milk. However, there is no clinical evidence of health benefit of raw compared to pasteurized human milk, and donor milk maintains documented advantages compared to formula. Nutrient content of donor and own mother's milk fails to meet the requirements of preterm infants. Adequate fortification is necessary to provide optimal growth. There are significant challenges in providing donor milk for premature infants; therefore, specific clinical guidelines for human milk banks and donor milk use in the neonatal intensive care unit should be applied and research should focus on innovative solutions to process human milk while preserving its immunological and nutritional components. In addition, milk banks are not the only instrument to collect, process and store donor milk but represent an excellent tool for breastfeeding promotion.

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.

Electrolyte and Mineral Homeostasis After Optimizing Early Macronutrient Intakes in VLBW Infants on Parenteral Nutrition.

OBJECTIVES: The aim of the present study was to evaluate electrolyte and mineral homeostasis in very-low-birth-weight (VLBW) infants who received high protein and energy intakes with a unique standardized parenteral nutrition solution containing electrolytes and minerals from birth onward. METHODS: Prospective cohort study in 102 infants with birth weight <1250 g. The evolution of plasma biochemical parameters was described during the first 2 weeks of life. RESULTS: During the first 3 days of life, mean parenteral intakes were 51 ±â€Š8 kcal · kg · day with 2.7 ±â€Š0.4 g · kg · day of protein, 1.1 ±â€Š0.2 mmol · kg · day of sodium and potassium, and 1.3 ±â€Š0.2 mmol · kg · day of calcium and phosphorus. Afterwards, most nutritional intakes (parenteral and enteral) met growth requirements. No infant developed a hyperkalemia >7 mmol/L, and a hypernatremia >150 mmol/L occurred only in 15.7% of the infants. In contrast, hyponatremia <130 mmol/L and hypokalemia <3 mmol/L occurred in 30.4% and 8.8% of the infants, respectively. The initial neonatal metabolic acidosis rapidly resolved in most infants and only 2.0% developed a base deficit >10 mmol/L after day 3 of life. Early hypocalcemia <1.8 mmol/L occurred in 13.7% of the infants. In contrast, hypophosphatemia <1.6 mmol/L occurred in 37.3% and hypercalcemia >2.8 mmol/L occurred in 12.7% of the infants. CONCLUSIONS: Increasing early protein and energy intakes in VLBW infants in the first week of life improves electrolyte homeostasis. It also increases the phosphorus requirements with a calcium-to-phosphorus ratio ≤1.0 (mmol/mmol) and the potassium and sodium requirements to avoid the development of a refeeding-like syndrome. These data suggest that the parenteral nutrition guidelines for VLBW infants for the first week of life need to be revised.

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.

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.

Neonatal liver cirrhosis without iron overload caused by gestational alloimmune liver disease.

Gestational alloimmune liver disease has emerged as the major cause of antenatal liver injury and failure. It usually manifests as neonatal liver failure with hepatic and extrahepatic iron overload, a clinical presentation called neonatal hemochromatosis. We report on a newborn in whom fetal hepatomegaly was detected during pregnancy and who presented at birth with liver cirrhosis and mild liver dysfunction. Liver biopsy showed the absence of iron overload but strong immunostaining of hepatocytes for the C5b-9 complex, the terminal complement cascade neoantigen occurring specifically during complement activation by the immunoglobulin G-mediated classic pathway, which established the alloimmune nature of the hepatocyte injury. The infant survived with no specific therapy, and follow-up until 36 months showed progressive normalization of all liver parameters. This case report expands the recognized clinical spectrum of congenital alloimmune liver disease to include neonatal liver disease and cirrhosis, even in the absence of siderosis. Such a diagnosis is of utmost importance regarding the necessity for immunotherapy in further pregnancies to avoid recurrence of alloimmune injury.

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.

The effect of blood transfusion on the hemoglobin oxygen dissociation curve of very early preterm infants during the first week of life.

A study was conducted during the first week of life to determine the changes in P50 (PO2 required to achieve a saturation of 50% at pH 7.4 and 37 degrees C) and the proportions of fetal hemoglobin (HbF) and adult hemoglobin (HbA) prior to and after transfusion in very early preterm infants. Eleven infants with a gestational age < or = 27 weeks have been included in study. The hemoglobin dissociation curve and the P50 was determined by Hemox-analyser. Liquid chromatography was also performed to determine the proportions of HbF and HbA. The mean gestational age of the 11 infants was 25.1 weeks (+/- 1 weeks) and their mean birth weight was 736 g (+/- 125 g). They received 26.9 mL/kg of packed red cells. The mean P50 prior and after transfusion was 18.5 +/- 0.8 and 21.0 +/- 1 mm Hg (P = .0003) while the mean percentage of HbF was 92.9 +/- 1.1 and 42.6 +/- 5.7%, respectively. The data of this study show a decrease of hemoglobin oxygen affinity as a result of blood transfusion in very early preterm infants prone to O2 toxicity. The shift in HbO2 curve after transfusion should be taken into consideration when oxygen therapy is being regulated for these infants.