Evaluation of an Infant Formula with Large, Milk-Phospholipid Coated Lipid Droplets on Long-Term Growth and Development of Singaporean Infants:Randomized Controlled Trial Protocol

A concept infant formula (IF) was developed with physical properties of lipid droplets mimicking more closely those in human milk. This paper describes the unique design of a randomised controlled trial evaluating the impact of the concept IF on infant growth and body composition development whilst applying a cohort-like recruitment approach that fully supports breastfeeding practices of the study population. Subjects entered the study between birth and 1 months of age, and whenever parents decided to introduce formula were randomised to one of three study formulas; the concept IF comprising large lipid droplets coated by milk phospholipids and containing a specific mixture of prebiotics, a standard IF with the specific prebiotic mixture or a standard IF without the prebiotic mixture. The primary objective was to evaluate the impact of the concept IF on growth and body composition outcomes during the first year of life with a follow-up at 2, 3, 4 and 5 years of age. In addition, stool, saliva and buccal smear samples and parameters assessing safety, gastrointestinal tolerance and cognitive outcomes were collected. The applied cohort-like enrolment approach is distinctly different from standard clinical safety or efficacy studies and may provide valuable insights on trial design for the evaluation of IF while carefully considering breastfeeding practices

An Infant Formula with Large, Milk Phospholipid-Coated Lipid Droplets Supports Adequate Growth and Is Well-Tolerated in Healthy, Term Asian Infants:A Randomized, Controlled Double-Blind Clinical Trial

Lipids are essential for healthy infant growth and development. The structural complexity of lipids in human milk is not present in infant milk formula (IF). A concept IF was developed mimicking more closely the structure and composition of human milk fat globules. The current study evaluates whether a concept IF with large, milk phospholipid-coated lipid droplets (mode diameter 3 to 5 μm) is equivalent to standard IF with regard to growth adequacy and safety in healthy, term Asian infants. In this randomized, double-blind, controlled trial, infants were randomized after parents decided to introduce formula. Infants received a standard IF with (Control) or without the specific prebiotic mixture scGOS/lcFOS (9:1 ratio; Control w/o prebiotics), or a Concept IF with large, milk phospholipid-coated lipid droplets and the prebiotic mixture. A group of 67 breastfed infants served as a reference. As a priori defined, only those infants who were fully intervention formula-fed ≤28 days of age were included in the equivalence analysis (Control n = 29; Control w/o prebiotics n = 28; Concept n = 35, per-protocol population). Primary outcome was daily weight gain during the first four months of life, with the difference between the Concept and Control as the key comparison of interest. Additionally, adverse events, growth and tolerance parameters were evaluated. Equivalence of daily weight gain was demonstrated between the Concept and Control group after additional correction for ethnicity and birthweight (difference in estimated means of 0.1 g/d, 90%CI [−2.30, 2.47]; equivalence margin +/− 3 g/d). No clinically relevant group differences were observed in secondary growth outcomes, tolerance outcomes or number, severity or relatedness of adverse events. This study corroborates that an infant formula with large, milk phospholipid-coated lipid droplets supports adequate growth and is well tolerated and safe for use in healthy infants

Long-term effects of a modified, low-protein infant formula on growth and body composition:Follow-up of a randomized, double-blind, equivalence trial

Background & aim: High protein intake in early life is associated with an increased risk of childhood obesity. Feeding a modified lower-protein (mLP) infant formula (1.7 g protein/100 kcal) until the age of 6 months is safe and supports adequate growth. The aim of the present study is to assess longer-term anthropometry with BMI at 1 and 2 years as primary outcome parameter and body composition in children fed mLP formula. Methods: Healthy term-born infants received mLP or control formula (CTRL) (2.1 g protein/100 kcal) until 6 months of age in a double-blinded RCT. A breast-fed (BF) group served as a reference. Anthropometry data were obtained at 1 and 2 years of age. At the age of 2 years, body composition was measured with air-displacement plethysmography. Groups were compared using linear mixed model analysis. Results: At 1 and 2 years of age, anthropometry, including BMI, and body composition did not differ between the formula groups (n = 74 mLP; n = 69 CTRL). Compared to the BF group (n = 51), both formula-fed groups had higher z scores for weight for age, length for age, waist circumference for age, and mid-upper arm circumference for age at 1 year of age, but not at 2 years of age (except for z score of weight for age in the mLP group). In comparison to the BF group, only the mLP group had higher fat mass, fat-free mass, and fat mass index. However, % body fat did not differ between feeding groups. Conclusions: In this follow-up study, no significant differences in anthropometry or body composition were observed until 2 years of age between infants fed mLP and CTRL formula, despite the significantly lower protein intake in the mLP group during the intervention period. The observed differences in growth and body composition between the mLP group and the BF reference group makes it necessary to execute new trials evaluating infant formulas with improved protein quality together with further reductions in protein content. Clinical Trial Registry: This trial was registered in the Dutch Trial Register (Study ID number NTR4829, trial number NL4677). https://www.trialregister.nl/trial/4677

Early-Life Metabolic and Hormonal Markers in Blood and Growth until Age 2 Years:Results from a Randomized Controlled Trial in Healthy Infants Fed a Modified Low-Protein Infant Formula

Background: High protein intake in early life is associated with an increased risk of childhood obesity. Dietary protein intake may be a key mechanistic modulator through alterations in endocrine and metabolic responses. Objective: We aimed to determine the impact of different protein intake of infants on blood metabolic and hormonal markers at the age of four months. We further aimed to investigate the association between these markers and anthropometric parameters and body composition until the age of two years. Design: Term infants received a modified low-protein formula (mLP) (1.7 g protein/100 kcal) or a specifically designed control formula (CTRL) (2.1 g protein/100 kcal) until 6 months of age in a double blinded RCT. The outcomes were compared with a breast-fed (BF) group. Glucose, insulin, leptin, IGF-1, IGF-BP1, -BP2, and -BP3 levels were measured at the age of 4 months. Anthropometric parameters and body composition were assessed until the age of 2 years. Groups were compared using linear regression analysis. Results: No significant differences were observed in any of the blood parameters between the formula groups (n = 53 mLP; n = 44 CTRL) despite a significant difference in protein intake. Insulin and HOMA-IR were higher in both formula groups compared to the BF group (n = 36) (p < 0.001). IGF-BP1 was lower in both formula groups compared to the BF group (p < 0.01). We found a lower IGF-BP2 level in the CTRL group compared to the BF group (p < 0.01) and a higher IGF-BP3 level in the mLP group compared to the BF group (p = 0.03). There were no significant differences in glucose, leptin, and IGF-1 between the three feeding groups. We found specific associations of all early-life metabolic and hormonal blood parameters with long-term growth and body composition except for IGF-1. Conclusions: Reducing protein intake by 20% did not result in a different metabolic profile in formula-fed infants at 4 months of age. Formula-fed infants had a lower insulin sensitivity compared to breast-fed infants. We found associations between all metabolic and hormonal markers (except for IGF-1) determined at age 4 months and growth and body composition up to two years of age

Early detection of childhood obesity through extended routine growth monitoring of children below two years of age in Asia Pacific region

Introduction: Increased body fat deposition during early life predisposes to higher obesity and metabolicdisorder risks in later life. This is particularly relevant in the Asia Pacific region where historically prevalentunder-nutrition is now been paralleled or even overruled by over-nutrition over the last few decades. Thisoverview aims to evaluate the potential of early detection of obesity (risk) among experts through additionof specific growth monitoring assessments in children during the first two years of life.Methods: A discussionamong experts from Malaysia, Singapore, Sri Lanka and Australia on infant growth and a qualitativeevaluation of current practice highlighted the need to measure body composition to assess the quality ofgrowth. Current tools are mainly directed towards simple anthropometric measures such as body weight,length and head circumference which do not adequately reflect concurrent changes in body composition todetect early life adiposity development. Recent findings have shown benefits of measurement such as thesum of four skinfold thickness (S4SFT) during the first two years of life for risk assessment of lateroverweight/obesity. We recommend this assessment for routine practice as a proxy for fat deposition inyoung children. Further studies to understand implementation hurdles and cost-effectiveness of S4SFT andhealth outcomes in young children in the Asia Pacific region are necessary.Conclusion: Inclusion of fourskinfold thickness measurements as part of routine growth monitoring assessment, in addition to weight andheight, could be recommended to assess adiposity development in early life allowing identification of infantsat risk for obesity

Environmental enrichment improves the performance and behavior of piglets in the nursery phase

In modern pig farming, the search for systems that promote environmental quality and welfare is an important issue. In this sense, the present study evaluated the effects of environmental enrichment on the performance and behavior of piglets. In a completely randomized block design, 32 piglets (7.43kg mean weight), weaned at 28 days of age, were distributed into four treatments (control without enrichment, environmental enrichment with wood shavings as bedding; environmental enrichment with hanging toys and environmental enrichment with wood shavings + hanging toys). Four repetitions were performed for each treatment, with two animals per experimental unit. The instant scan sampling technique was used to record the behavior of each piglet for 20h. Animals receiving environmental enrichment with wood shavings + hanging toys were heavier at 70 days (P=0.02), exhibited higher total and daily weight gain (P=0.04 and P=0.02, respectively) and better feed conversion (P=0.02). Environmental enrichment increased the interaction of animals with the environment, allowing them to exhibit natural behaviors

Intermittent suckling during an extended lactation period: Effects on piglet behavior

The objectives of the current study were to determine how intermittent suckling (IS) affects nursing behavior, litter activity, and general behavioral patterns during lactation, and whether IS during an extended lactation period results in behavioral patterns associated with piglet distress. Intermittent suckling was applied either with 6-h separation intervals (IS6) or with 12-h separation intervals (IS12) and was compared with the conventional treatment (CT). In the CT (n = 17 litters), sows were continuously present until weaning (d 21, d 0 = farrowing). In both IS6 and IS12, sows were separated from their litter for 12 h/d, beginning at d 14 and lasting until weaning (d 43 +/- 1 d). In IS6, litters (n = 14) and sows were separated from 0800 to 1400 and from 2000 to 0200; in IS12 litters (n = 14) and sows were separated between 0800 and 2000. In IS litters, the activity pattern over the 24-h cycle was markedly changed by IS; litter activity was lower (P <0.001) during sow absence and greater (P <0.001) during sow presence compared with the unweaned CT litters. Moreover, both total nursing frequency (P <0.00 1) and the percentage (P <0.002) of successful nursings were reduced by IS. Although total nursing frequency was greater in IS6 compared with IS12 (on d 21 and 28), no differences in the frequency of successful nursings existed between IS6 and IS12 from d 14 onward. Eating behavior was increased shortly after the onset of IS (d 17) in both IS6 (P = 0.059) and IS12 (P <0.001) compared with the unweaned CT litters. The IS12 litters showed more eating behavior compared with IS6 and their exploratory behavior increased in time (P <0.001), whereas IS6 showed more nursing behavior. Aggressive or manipulative behavior of both IS treatments was similar compared with the unweaned CT, and remained relatively unaltered with time in IS12 and IS6. Weaning in the CT resulted in more manipulative (P <0.001) and aggressive (P = 0.004) behavior compared with pre-weaning values. Intermittent suckling may contribute to adaptation to the postweaning state by stimulating eating behavior, without causing obvious behavioral distress

Postweaning growth check in pigs is markedly reduced by intermittent suckling and extended lactation

The objective of this study was to determine whether intermittent suckling (IS) combined with an extended lactation can reduce postweaning growth check in pigs. Three weaning regimens [ conventional weaning (CW), IS with 6-h separation intervals (IS6), and IS with 12-h separation intervals (IS12)] were compared. In CW (n = 17 litters), litters had continuous access to the sow until weaning (d 21, d 0 = farrowing). In IS6 and IS12, litters were separated from the sow for 12 h/d, beginning at d 14 and lasting until weaning (d 41 to 45). Litters were with the sow from 1400 to 2000 and from 0200 to 0800 (IS6, n = 14) or between 2000 and 0800 (IS12, n = 14). Litter size was standardized within 2 d after farrowing by crossfostering, resulting in an average litter size of 10.9 +/- 1.8 piglets. Piglets had ad libitum access to creep feed from d 7 onward. One week after the onset of IS (d 20), creep feed intake was increased in litters from both IS groups compared with CW litters (P <0.05). Both IS groups consumed considerable amounts of creep feed before weaning (d 41 to 45). Total feed intake before weaning was greater (P = 0.004) in IS12 (3,808 +/- 469 g/ piglet) than in IS6 (2,717 +/- 404 g/ piglet). In comparison, CW litters consumed 18 +/- 9 g/ piglet before weaning (d 21). Irrespective of weaning regimen, total feed intake of litters before weaning was highly correlated with postweaning feed intake (P <0.001). Furthermore, in all treatment groups, total preweaning feed intake was correlated with postweaning growth (P <0.10). Irrespective of treatment, piglets suckling anterior teats grew faster than piglets suckling middle or posterior teats during the first 2 wk of lactation. Body weights at the end of the experiment (d 55) were similar among weaning regimens. Onset of IS induced a growth check in both IS groups (34% for IS12 and 22% for IS6). Only a mild growth check was observed after weaning of IS litters (14% for both IS groups). However, a serious growth check (98%) was observed after weaning of CW litters. Results of the current study indicate that IS stimulated feed intake during lactation, providing a more gradual transition to weaning. Because the IS6 regimen did not prevent the growth check after the onset of IS and is rather laborious, we suggest that IS12 might be preferable for a practical implementation of IS