Claude Billeaud

Safety and Tolerance Evaluation of Milk Fat Globule Membrane-Enriched Infant Formulas: A Randomized Controlled Multicenter Non-Inferiority Trial in Healthy Term Infants

Objective This multicenter non-inferiority study evaluated the safety of infant formulas enriched with bovine milk fat globule membrane (MFGM) fractions. Methods Healthy, full-term infants (n = 119) age ≤14 days were randomized to standard infant formula (control), standard formula enriched with a lipid-rich MFGM fraction (MFGM-L), or standard formula enriched with a protein-rich MFGM fraction (MFGM-P). Primary outcome was mean weight gain per day from enrollment to age 4 months (non-inferiority margin: –3.0 g/day). Secondary (length, head circumference, tolerability, morbidity, adverse events) and exploratory (phospholipids, metabolic markers, immune markers) outcomes were also evaluated. Results Weight gain was non-inferior in the MFGM-L and MFGM-P groups compared with the control group. Among secondary and exploratory outcomes, few between-group differences were observed. Formula tolerance rates were high (>94%) in all groups. Adverse event and morbidity rates were similar across groups except for a higher rate of eczema in the MFGM-P group (13.9% vs control [3.5%], MFGM-L [1.4%]). Conclusion Both MFGM-enriched formulas met the primary safety endpoint of non-inferiority in weight gain and were generally well tolerated, although a higher rate of eczema was observed in the MFGM-P group.

Relationships between Red Blood Cell Vitamin E and Polyunsaturated Fatty Acid in the Premature Infant

Low-birth-weight infants were fed breast milk (BM, n = 25) for 1 of 2 formulas containing 0.5 (PG, n = 32) or 1.7% fatty acids as alpha-linolenic acid (ALA)(ALA-PG, n = 31). Polyunsaturated fatty acids (PUFA) and alpha-tocopherol (alpha T) of RBC membrane phospholipids were measured at days 2 (D2) and 15 (D15) of enteral feeding, and at term. PUFA concentrations did not differ significantly between the 3 groups from D2 to term. The membrane integrity assessed by the alpha T/phospholipids ratio neither changed with time nor differed between formula groups. A metabolic relationship between alpha T and long-chain PUFA in RBC membranes was suggested by multiple regression analysis: alpha T showed a significant positive correlation with docosahexaenoic acid at D15 and term and with arachidonic acid at D15; the correlation with arachidonic acid tended toward significantly (p = 0.06) at term.

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 · kg−1 · day−1 (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.

Growth of Infant Fed Starter Formula Containing Milk Fat Globule Membranes

Objective: To assess growth of infants fed starter formula supplemented with milk fat globule membranes (MFGM).Methods: Healthy, full term newborns (n= 199, ITT population) were enrolled the 14th day of their childs life and randomly assigned between 3 exclusively formula fed groups: one control group (commercial starter IF) and 2 experimental groups i.e. starter IF supplemented with 2 different MFGM fractions. Growth was assessed by body weight gain, length and head circumference measurements during the 4-month intervention period. Incidence of morbidity was appraised.Results: After 4-month intervention treatment, no significant effect in infant body weight gain was observed when comparing each experimental groups versus the control and all z-scores both for male and females stayed between the interval of +/− 1 during the whole interventional period. In addition, no statistical difference was observed between groups on the other anthropometric measurements (head circumference and length) during the intervention period. In summary, non inferiority in growth was established between each experimental groups versus the control at the end of the 4 months intervention period (Non-inferiority margin was pre-defined as Δ=-3 g/day). On the other hand, no statistically significant difference of adverse events was detected between all three groups.Conclusion: Growth of newborns receiving IF containing MFGM was non inferior to the growth observed in controls and within the limits defined by WHO growth reference curves.

Effects on Fatty Acid Metabolism of a New Powdered Human Milk Fortifier Containing Medium-Chain Triacylglycerols and Docosahexaenoic Acid in Preterm Infants

Preterm infants require fortification of human milk (HM) with essential fatty acids (FA) to ensure adequate post-natal development. As part of a larger randomized controlled study, we investigated FA metabolism in a subset of 47 clinically stable preterm infants (birth weight ≤1500 g or gestational age ≤32 weeks). Infants were randomized to receive HM supplemented with either a new HM fortifier (nHMF; n = 26) containing 12.5 g medium-chain FA (MCFA), 958 mg linoleic acid (LA), 417 mg α-linolenic acid (ALA), and 157 mg docosahexaenoic acid (DHA) per 100 g of powder (in compliance with the latest guidelines) or a fat-free HMF (cHMF; n = 21). Plasma phospholipid (PL) and triacylglycerol (TAG), and red blood cell phosphatidylcholine (RBC-PC) and phosphatidylethanolamine (RBC-PE) FA profiles were assessed before and after 21 days of feeding. In the nHMF group, significantly increased levels of n-9 monounsaturated fatty acids were observed, formed most likely by elongation and desaturation of dietary saturated fatty acids present in HM. ALA fortification increased ALA assimilation into plasma TAG. Similarly, DHA fortification enriched the DHA content in RBC-PE, which, in this compartment, was not associated with lower arachidonic acid levels as observed in plasma TAG and phospholipids. RBC-PE, a reliable indicator of FA metabolism and accretion, was the most sensitive compartment in this study.

Transfatty Acids (TFAs) in Cord Blood and Cord Tissue, in France

Background: Recent studies suggest that dietary transfatty acids (TFAs) at relative high levels (i) increase the risk of coronary heart disease, (ii) inhibit the metabolism of linoleic acid and consequently increase requirement for essential fatty acids (EFAs). The aim of this prospective study was to estimate TFAs the placental transfer of TFAs to the foetus cord blood and cord tissues in France. Material: TFAs consumption was measured in 59 mother-foetus couples. TFAs transferring across the placenta were estimated by comparative measurement (Capillary Gaz Chromatography) of TFAs in mother’s blood lipids (n = 59), cord blood lipids and cord tissue plasma lipids (n = 25) cord red blood tissue (n = 25) and umbilical vessels (n = 15). Results-Discussion: TFA deposition in cord blood is 0.58% slightly lower than mother level. TFAs incorporation in total lips of cord show selectivity of transfer with lower 18:1 t in cord blood and preferential transfer of diene 18:2 tc in cord blood. There is competition between the 18:2 tc in cholesterol esters (CE) with the linolenic acid and a negative correlation in PLT of arterial tissues with the 18:2 tc and C20:4 n-6 or arachidonic acid (AA), then there is the same competition in PE of venous tissue. But there is no effect on growth in our population of term newborn. Conclusions: Our results confirm the placental TFAs transfer, a better incorporation in the fetus CE; we demonstrated a selective transfer for the 18:2 9 trans 12 cis (18:2 tc) and a negative correlation (r = -0.76) with the linoleic acid and AA (r = 0.98). This competition, and the presence of these TFAs in cord tissues, even at a low TFAs consumption, remind us to be a potential risk for the fetus concerning EFA metabolism and growth.