Infant Milk Formula with Large, Milk Phospholipid-coated Lipid Droplets Enriched in Dairy Lipids Affects Body Mass Index Trajectories and Blood Pressure at School Age: Follow-up of a Randomized Controlled Trial.

BACKGROUND: Human milk comprises large fat globules enveloped by a native phospholipid membrane, whereas infant formulas contain small, protein-coated lipid droplets. Previous experimental studies indicated that mimicking the architecture of human milk lipid droplets in infant milk formula (IMF) alters lipid metabolism with lasting beneficial impact on later metabolic health. OBJECTIVES: To evaluate in a follow-up (FU) study of a randomized, controlled trial whether a Concept IMF with large, milk phospholipid-coated lipid droplets enriched with dairy lipids beneficially impacts long-term body mass index (BMI in kg/m2) trajectories and blood pressure at school age. METHODS: Fully formula-fed infants were randomly assigned to Concept IMF (n = 115) or Control IMF with conventional, small lipid droplets containing vegetable oils (n = 108) for the first 4 mo of age. A group of 88 breastfed infants served as a reference. During FU, anthropometrics were collected at 1, 3, 4, and 5 y of age, and blood pressure only at the last visit. RESULTS: Compared to Control, Concept group children had consistently lower mean BMI values during FU, with the most marked difference at 1 y of age (difference in means -0.71 kg/m2, 95% confidence interval (CI): -1.13, -0.29; P = 0.001); mean values were close to the breastfed group (P > 0.05). Contrary, the mean BMI values of the Control group were higher compared with the breastfed group during FU from 1 to 5 y of age (differences in means from 0.59 to 0.96 kg/m2, respectively; P < 0.02). At 5 y of age, the Concept group had a lower mean diastolic and arterial blood pressure compared with the Control group; -4.3mm Hg (95% CI: -7.3, -1.3; P = 0.005) and -3.7 mm Hg (95% CI: -6.5, -0.9; P = 0.01), respectively. CONCLUSIONS: Early life feeding of an innovative IMF with large, milk phospholipid-coated lipid droplets enriched with dairy lipids results in a BMI trajectory closer to breastfed infants and a lower blood pressure at school age. This trial was registered at the Dutch Trial Register as NTR3683 and NTR5538.

Infant formula containing large, milk phospholipid-coated lipid droplets and dairy lipids affects cognitive performance at school age.

Background: Breastfeeding has been positively associated with infant and child neurocognitive development and function. Contributing to this effect may be differences between human milk and infant formula in the milk lipid composition and milk fat globule structure. Objective: To evaluate the effects of an infant formula mimicking human milk lipid composition and milk fat globule structure on childhood cognitive performance. Methods: In a randomized, controlled trial, healthy term infants received until 4 months of age either a Standard infant formula (n = 108) or a Concept infant formula (n = 115) with large, milk phospholipid coated lipid droplets and containing dairy lipids. A breastfed reference group (n = 88) was included. Erythrocyte fatty acid composition was determined at 3 months of age. Neurocognitive function was assessed as exploratory follow-up outcome at 3, 4, and 5 years of age using the Flanker test, Dimensional Change Card Sort (DCCS) test and Picture Sequence Memory test from the National Institutes of Health Toolbox Cognition Battery. Mann-Whitney U test and Fisher exact test were used to compare groups. Results: Erythrocyte omega-6 to -3 long-chain polyunsaturated fatty acid ratio appeared to be lower in the Concept compared to the Standard group (P = 0.025). At age 5, only the Concept group was comparable to the Breastfed group in the highest reached levels on the Flanker test, and the DCCS computed score was higher in the Concept compared to the Standard group (P = 0.021). Conclusion: These outcomes suggest that exposure to an infant formula mimicking human milk lipid composition and milk fat globule structure positively affects child neurocognitive development. Underlying mechanisms may include a different omega-3 fatty acid status during the first months of life. Clinical trial registration: https://onderzoekmetmensen.nl/en/trial/28614, identifier NTR3683 and NTR5538.

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.

Partially Hydrolysed Whey-Based Formulae with Reduced Protein Content Support Adequate Infant Growth and Are Well Tolerated: Results of a Randomised Controlled Trial in Healthy Term Infants.

The current study aimed to investigate growth, safety and tolerance of partially hydrolysed infant formulae in healthy full-term infants. Fully formula-fed infants were randomised ≤14 days of age to receive a partially hydrolysed whey formula with 2.27 g protein/100 kcal (pHF2.27) or the same formula with 1.8 g or 2.0 g protein/100 kcal (pHF1.8 and pHF2.0) until 4 months of age. The primary outcome was equivalence in daily weight gain within margins of ± 3 g/day; comparison with WHO Child Growth Standards; gastrointestinal tolerance parameters and number of (serious) adverse events were secondary outcomes. A total of 207 infants were randomised, and 61 (pHF1.8), 46 (pHF2.0) and 48 (pHF2.27) infants completed the study per protocol. Equivalence in daily weight gain was demonstrated for the comparison of pHF1.8 and pHF2.27, i.e., the estimated difference was -1.12 g/day (90% CI: [-2.72; 0.47]) but was inconclusive for the comparisons of pHF2.0 and pHF2.27 with a difference of -2.52 g/day (90% CI: [-4.23; -0.81]). All groups showed adequate infant growth in comparison with the World Health Organization (WHO) Child Growth Standards. To conclude, the evaluated partially hydrolysed formulae varying in protein content support adequate growth and are safe and well tolerated in healthy infants.

An infant formula with large, milk phospholipid-coated lipid droplets containing a mixture of dairy and vegetable lipids supports adequate growth and is well tolerated in healthy, term infants.

BACKGROUND: Lipid droplets in human milk have a mode diameter of ∼4 µm and are surrounded by a native phospholipid-rich membrane. Current infant milk formulas (IMFs) contain small lipid droplets (mode diameter ∼0.5 µm) primarily coated by proteins. A concept IMF was developed mimicking more closely the structure and composition of human milk lipid droplets. OBJECTIVES: This randomized, controlled, double-blind equivalence trial evaluates the safety and tolerance of a concept IMF with large, milk phospholipid-coated lipid droplets (mode diameter 3-5 µm) containing vegetable and dairy lipids in healthy, term infants. METHODS: Fully formula-fed infants were enrolled up to 35 d of age and randomly assigned to 1 of 2 formulas until 17 wk of age: 1) Control IMF with small lipid droplets containing vegetable oils (n = 108); or 2) Concept IMF with large, milk phospholipid-coated lipid droplets comprised of 48% dairy lipids (n = 115). A group of 88 breastfed infants served as reference. Primary outcome was daily weight gain during intervention. Additionally, number and type of adverse events, growth, and tolerance parameters were monitored. RESULTS: Equivalence of daily weight gain was demonstrated (Concept compared with Control IMF: -1.37 g/d; 90% CI: -2.71, -0.02; equivalence margin ± 3 g/d). No relevant group differences were observed in growth, tolerance and number, severity, or relatedness of adverse events. We did observe a higher prevalence of watery stools in the Concept than in the Control IMF group between 5 and 12 wk of age (P < 0.001), closer to the stool characteristics observed in the breastfed group. CONCLUSIONS: An infant formula with large, milk phospholipid-coated lipid droplets containing dairy lipids is safe, well tolerated, and supports an adequate growth in healthy infants. This trial was registered in the Dutch Trial Register (www.trialregister.nl) as NTR3683.

Diet Quality during Infancy and Early Childhood in Children with and without Risk of Type 1 Diabetes: A DEDIPAC Study.

Previous studies have indicated that mothers of children at increased risk of type 1 diabetes (T1D) may modify their child's diet following risk notification. Our aim was to investigate the diet quality after notified of T1D risk in at-risk children compared to not-at-risk children. The quality of nutrient intake (PANDiet score) and food intake (analyzed by a newly developed score and the HuSKY score) were assessed using three-day dietary records collected for at-risk children (BABYDIET study, n = 109) and a matched sample of not-at-risk children (DONALD study, n = 205) at nine and 24 months of age. Nutrient and food intake quality were lower at nine months of age and food intake quality was lower at 24 months of age in at-risk than in not-at-risk children (p = 0.01 and p < 0.0001, respectively). The amount of added sugar was higher in at-risk children at both ages (p < 0.0001). In at-risk children, dietary quality was similar between children who were first exposed to gluten at six or 12 months of age. Despite being notified about their child's risk of T1D, the child's mother did not switch to healthier diets compared with not-at-risk mothers.

Differences in Postprandial Lipid Response to Breast- or Formula-feeding in 8-Week-Old Infants.

OBJECTIVE: Lipids play important roles in infant growth and development. In this exploratory observational single-center study, we investigated postmeal responses of infants to dietary lipids and differences between breast-feeding (BF) and formula-feeding (FF). METHODS: Two capillary blood samples were collected from each subject, before and randomly assigned at either 30, 60, 90, 120, 180, or 240 minutes after their respective feeding, followed by measurement of lipid-related plasma parameter concentrations using enzyme-linked immunosorbent assay-based or combined enzymatic and colorimetric methods. RESULTS: The intermeal interval before testing was shorter in the BF (182.91 ±â€Š22.85 minutes, n = 33) versus FF group (214.1 ±â€Š30.76 minutes, n = 34); BF subjects fed 5 minutes longer (BF 20.27 ±â€Š7.7 minutes; FF 14.82 ±â€Š3.57 minutes). Composite postmeal concentration profiles were generated from 59 plasma sample pairs with sufficient volume (BF = 30): triglyceride (TG) baselines were not different. A TG difference was indicated for BF over FF subjects at 30 minutes, for FF over BF subjects at 60 minutes when corrected for baseline. TG responses in both groups appeared and seemed to clear much faster than those reported for adults. The TG:apolipoprotein B48 (ApoB48) ratio suggests that chylomicrons in BF subjects may carry a higher fat load (P < 0.05), compensated by a higher chylomicron number in FF subjects (P < 0.05). Cholesterol in BF subjects was higher and showed an increase after feeding when corrected for baseline. CONCLUSIONS: Our results indicate that lipids from either BF or FF may be handled differently in young healthy infants.

Food composition database harmonization for between-country comparisons of nutrient data in the TEDDY Study.

The Environmental Determinants of Diabetes in the Young Study (TEDDY) aims at examining the associations between islet autoimmunity and various environmental exposures, (e.g. diet) in Finland, Germany, Sweden and the United States (US). In order to produce comparable results from dietary assessments, the national food composition databases (FCDB) must contain mutually comparable food composition data. Systematic comparison (definition, unit of measurement, and method of analysis) of energy, protein, fats, carbohydrates, cholesterol, fiber, 13 vitamins, and 8 minerals was carried out among the FCDB of the four countries. Total fat, cholesterol, vitamin A: retinol equivalents and beta-carotene, thiamin, riboflavin, pyridoxine, vitamin B(12), calcium, phosphorus, potassium, magnesium, iron, and zinc are comparable across all four databases. Carbohydrates, fiber, sugars, fatty acids, vitamin D, vitamin E: alpha-tocopherol, vitamin K, vitamin C, pantothenic acid, niacin, manganese, and copper are comparable or can be converted comparable at least across three of the databases. Vitamin E: alpha-tocopherol equivalents, will be comparable across all databases after Finland and Germany subtract tocotrienols from their values. Nitrogen values were added to the Swedish and US databases. After recalculation of protein from nitrogen (Sweden and US), and subtraction of fiber from the total carbohydrate (Finland) followed by recalculations of energy, these values will be comparable across the countries. Starch and folate are not comparable.

Validation of energy requirement equations for estimation of breast milk consumption in infants.

OBJECTIVE: To test equations for calculating infants' energy requirements as a simple and reliable instrument for estimating the amount of breast milk consumed in epidemiological studies where test-weighing is not possible. DESIGN: Infants' energy requirements were calculated using three different equations based on reference data and compared with actual energy intakes assessed using the 3 d weighed dietary records of breast-fed infants from the DOrtmund Nutritional and Anthropometric Longitudinally Designed (DONALD) Study. SETTING: A sub-sample of 323 infants from the German DONALD Study who were predominantly breast-fed for at least the first four months of life, and who had 3 d weighed dietary records and repeated body weight measurements within the first year of life. SUBJECTS: Healthy, term infants breast-fed for at least 4 months, 0-12 months of age. RESULTS: The overall differences between measured energy intake and calculated energy requirements were quite small, never more than 10 % of total energy intake, and smaller than the mean variance of energy intake between the three days of recording. The equation of best fit incorporated body weight and recent growth, while the worst fit was found for the equation not considering body weight. CONCLUSIONS: Breast milk consumption in fully and partially breast-fed infants can be reasonably quantified by calculating the infants' individual energy requirements via simple equations. This provides a feasible approach for estimating infant energy intake in epidemiological studies where test-weighing of breast milk is not possible.

Breastfeeding duration in families with type 1 diabetes compared to non-affected families: results from BABYDIAB and DONALD studies in Germany.

BACKGROUND: There are only a few small studies that compare breastfeeding rates in mothers with and without type 1 diabetes (T1D). STUDY DESIGN: We studied breastfeeding duration in 665 German infants whose mother and/or father had T1D from the BABYDIAB Study (data collected between 1992 and 2000) and compared it with data from 268 German infants of unaffected parents from the DONALD Study. RESULTS: Infants with a parent who had T1D were less likely to be breastfed and breastfed for shorter lengths of time than infants from unaffected families. Mothers with T1D showed a positive long-term breastfeeding time trend, but did not reach the rates of the DONALD Study. CONCLUSIONS: This study identified minor secular trends influencing the differences in breastfeeding initiation and duration between families affected with T1D and those without.