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May 2, 2017 - MoMI CoRE Seminar 

time and location to be announced shortly
ALT-TEXT

Berthold Koletzko, MD

"Human milk lipids and their impact on child health and development”

Professor, Pediatrics, Ludwig-Maximilians-University Munich, Germany
Head, Division of Metabolic and Nutritional Medicine, Dr. Hauner Children's Hospital, University of Munich Medical Center, Germany
Immidiate Past-President, European Society for Pediatric Gastroenterology, Hepatology and Nutrition
Human milk lipids provide a major portion of the total energy intake in young infants, comprising a mean 44 % of the total energy supply. The average intake of human milk lipids in fully breastfed infants amounts to 21.42 g/day between birth and 6 months of age. This results in an impressive 3.9 kg of human lipid supplied during the first half year of life to fully breastfed infants, equivalent to some 35 000 kcal provided by human milk lipids alone during the first six months of life. While the mean lipid content in human milk is relatively stable during the course of the first months of lactation, there is very wide inter-individual and intra-individual variation of milk fat concentrations. In fact, among the macronutrients in milk, fat shows the most variable concen-tration. Milk lipids provide indispensable polyunsaturated fatty acids (PUFA) of both the omega-6 and the ome-ga-3 series that are important for infant growth, health and development. Maternal dietary PUFA intake affects milk contents. With increasing duration of lactation, linoleic acid (LA, C18:2,n-6) and α-linolenic acid (ALA, C18:3) increase, whereas the long-chain PUFA (LC-PUFA) arachidonic acid (ARA, C20:4, n-6; ≈15 mg/dL) and do-cosahexaenoic acid (DHA, C22:6, n-3; ≈7 mg/dL) remain fairly constant, reflecting greater metabolic control of milk LC-PUFA levels. Of interest, a review of human milk composition worldwide shows rather stable ARA levels of 0.4-0.6%, whereas DHA content is more variable and depends on maternal dietary DHA intake primarily from marine foods. The LC-PUFA supply with human milk modulates LC-PUFA incorporation into the develop-ing infant brain and visual, cognitive, motor and immune functions. The rate of conversion of LA and ALA to the LC-PUFA metabolites is generally low in humans and particularly low in those people who have less common variants of the genes for the fatty acid desaturating enzymes, FADS1 and FADS2. Breast milk fatty acid com-position depends on both the quality of maternal dietary fat supply and FADS gene polymorphisms which have a significant effect on ARA acid contents both in early lactation and at 6 months after birth. The human brain grows and develops very rapidly during the last part of pregnancy and the first two years after birth. At birth, the brain comprises as much as 13% of body weight, and at the age of 2 years it has already reached about 80% of its final adult weight. In addition to brain weight gain, pre- and postnally there is also critical development and differentiation, including dendrictic arborisation, synapse formation, and myelination, which depend on the adequate supply of energy and building blocks. Breastfeeding has been associated with a small but con-sistent advantage for later IQ development, with a benefit of about 3 IQ points in a meta-analysis of studies in term infants that adjusted for major confounding factors, and a greater benefit in VLBWI. However, it has been controversial whether this benefit is caused by the nutrient supply with breast milk, such as the content of DHA and other long-chain polyunsaturated fatty acids (LC-PUFA), or by residual confounding linked to better socioec-onomic status, education and health-consciousness in families that chose to breastfeed. Recent gene-nutrient interaction studies demonstrate that the benefit of breastfeeding providing LC-PUFA on IQ at school age is greater by more than 4 IQ points in those children who have a low ability to synthesize LC-PUFA endogenously due to their genotype. Similarly, we found a marked protective effect of prolonged breastfeeding providing LC-PUFA on doctor’s diagnosed asthma up to the age of 10 years in children with a genotype resulting in low LC-PUFA synthesis, whereas there was no significant effect in children homozygous for the major genetic allele. These studies support the conclusion that LC-PUFA status of infants is causally important for brain and immune development and health. A randomized clinical trial supplementing breastfeeding women during the first 4 months of lactation with 200 mg DHA/day or placebo also found a significant improvement in the psychomotor development at 2½ years of age and significantly improved sustained attention at the age of 5 years with im-proved early DHA supply. Using targeted lipidomics methodology, we found that the addition of DHA and ARA to infant formula modifies the molecular species of several plasma lysophosphatidylcholines, phospha-tidylcholines, and ether-linked phosphatidylcholines. Some recent studies also point to benefits of providing complex animal lipids from the milk fat globule membrane fraction to infants with regard to neurodevelopment and infection risk, which deserve further exploration. Providing dairy lipids with infant formula induced some changes in plasma phospholipid molecular species but could not overcome the marked differences in infant plasma glycerophospholipid profiles induced by breast-feeding induces compared with formula feeding. Based on the available evidence, it is recommended that breastfeeding women should consume preformed n-3 LC-PUFA providing an average intake of at least 200 mg DHA/day, which can be reached by eating 1-2 portions of sea fish per week including oily fish. Lactating women that do not consume fish, e.g. women follow-ing vegetarian or vegan diets, are advised to take supplements with DHA.