NNIW89 - Recent Research in Nutrition & Growth

Editor(s): N. Wagemans, M. Lampl, E.B. Huniker, M. Fiorotto, P. Arner, T. Clemens, K. Michaelsen, V. Grote, R. Black, Z. Bhutta, S. Carlson, J. Colombo, S. Deoni, P. Willatts, M. Black. 89

It is now well understood around the world that good nutrition plays a major role in the health of individuals, at all stages of development and life.

In recent years, detailed clinical research into the effects of nutrition on growth has brought a wealth of new data that is giving fresh understanding to this key area of development particularly in the first 1,000 days of life: appropriate nutrition at this time can program and prepare the body for long-term health status. Poor nutrition can contribute to obesity or stunting and can also have an adverse effect on brain development and cognition.


Metabolic Regulation of Pre- and Postnatal Growth

Author(s): B. Koletzko, F. F. Kirchberg, C. Hellmuth, M. Weber, V. Grote, H. Demmelmair, M. Standl, J. Heinrich, E. Thiering, and O. Uhl

Growth characteristics during periods of early developmental plasticity are linked with later health outcomes and with disease risks. Infant growth is modulated by genetic and exogenous factors including nutrition. We try to explore their underlying mechanisms us- ing targeted metabolomic profiling of small molecules in biological samples using high- performance liquid chromatography (LC) coupled to tandem mass spectrometry (MS/MS) to quantify hundreds of molecules in small biosamples, e.g., 50 μL plasma. In the large German LISA birth cohort study, cord blood lysophosphatidylcholines and fatty acids were closely associated with infant birth weight, with a nonsignificant trend towards an association with infant weight gain and later BMI. Studies in infants randomized to different protein intakes in the European CHOP Study show conventional high protein intakes to markedly increase plasma-indispensable amino acids (AA), particularly branched-chain AA (BCAA), while exceeding the infant’s capacity of BCAA breakdown, and an increase in the dispensable AA tyrosine previously associated with insulin resistance. In a path mod- el analysis of the relationship of infant plasma AA, growth factors, and infant growth, AA were generally found to induce a stronger response of insulin than IGF-I although effects of individual AA were very different. We conclude that targeted improvement in nutrient supply in pregnancy and infancy may offer large opportunities for promoting desirable child growth patterns and long-term health.

Causes of Stunting and Preventive Dietary Interventions in Pregnancy and Early Childhood

Author(s): R. E. Black and R. Heidkamp

Stunting of linear growth, a highly prevalent problem in children of low- and middle-in- come countries, is the result of the exposure of the fetus and/or young child to nutritional deficiencies and infectious diseases. Maternal undernutrition results in fetal growth restriction, and infectious diseases in pregnancy can result in preterm delivery. Both of these conditions are important contributors to stunting in early childhood, albeit their relative contribution varies by world region. After birth, growth faltering may begin at 3–5 months of life and becomes more prominent from 6 to 18 months. During this time, the young child is exposed to many infectious diseases, such as diarrhea, that have an adverse effect on growth. There is also increasing evidence that frequent ingestion of microorganisms results in damage to the small intestine. The resulting condition, referred to as environmental enteric dysfunction, even without clinical symptoms, may cause growth faltering. The complementary foods that the child receives in addition to breast milk are often inadequate in nutrients and energy, negatively affecting growth. Harmful exposure during pregnancy and the first 2 years of life, a critical period for growth and development, has led to a programmatic focus on this “1,000 days” in the life cycle. Dietary interventions, including nutrition education and for undernourished women provision of food supplements during pregnancy, result in improvements in fetal growth that position the newborn for healthier growth. Interventions in the first 2 years of life include promotion of exclusive breastfeeding for the first 6 months of life and continued breastfeeding for at least the first 2 years, nutritional counseling to assure adequate complementary feeding, and, if necessary in food insecure areas, the provision of supplemental food to be given to the child. Evidence shows that each of the interventions has a beneficial effect on the growth of the young child, yet that the effect is modest in relation to the degree of stunting observed in these underprivileged populations. Nevertheless, in recent years, reductions in the prevalence of stunting in some low-income countries show that substantial improvements are possible as a result of socioeconomic changes along with specific infection control and dietary interventions.

Breastfeeding, Breast Milk Composition, and Growth Outcomes

Author(s): M. Vendelbo Lind, A. Larnkjær, C. Mølgaard, and K. Fleischer Michaelsen

Breastfed infants have a growth pattern that is different from formula-fed infants, which is regarded as the optimal growth pattern. Breastfed infants increase more in weight, length, and BMI during the first 2–3 months of life and then have a slower growth velocity up to 12 months. They also have a higher accumulation of fat during early infancy. Breastfed infants have lower levels of circulating IGF-I and insulin, which could be part of the explanation of their growth pattern. Many studies and meta-analyses have examined the association between breastfeeding and later obesity. Most find a moderate reduction in the risk of later obesity, but it has been argued that this could be biased due to residual confounding and reverse causation. From studies in low- and middle-income countries randomizing women to breastfeeding promotion, there was only little effect on early growth. Recent studies have found associations between breast milk composition (total fat, protein, human milk oligosaccharides, adiponectin, leptin, and insulin) and growth. However, the studies are few, and the results are inconsistent. More studies, including studies of maternal factors influencing breast milk composition, are needed to better understand how breastfeeding influences current and later growth and thereby short- and long-term health. 

Complementary Feeding, Infant Growth, and Obesity Risk: Timing, Composition and Mode of Feeding

Author(s): V. Grote, M. Theurich, V. Luque, D. Gruszfeld, E. Verducci, A. Xhonneux, and B. Koletzko

The complementary feeding period is a short transitional period from breastfeeding and formula feeding to family foods. Timing, quantity, and quality are implied to impact growth and obesity risk. We summarized the literature and analyzed data of monthly 3-day food diaries of >1,000 children from 5 European countries in the first 2 years of life, which were collected as part of the prospective European Childhood Obesity Project (CHOP Study). Formula-fed children started complementary food approximately 2 weeks earlier than breastfed children, and almost 40% of them at or before 4 months of age. While in- troduction of solids between 4 and 6 months or after 6 months does not seem to impact growth and later obesity risk, solids before 4 months of age increased the risk. There are indications that this is especially problematic for formula-fed children. During the comple- mentary feeding period, fat intake decreases, and protein and carbohydrate intakes in- crease. Protein intake often exceeds European recommendations from 9 months onwards. However, the role of macronutrients during complementary feeding in growth and me- tabolism needs further clarification. Findings on the role of responsive feeding or baby-led feeding during complementary feeding in growth are not conclusive. In summary, while introduction of complementary foods before 4 months of age should be avoided, the im- pact of the quality of complementary food on short-term growth and later obesity risk has to be elucidated further.

Critical Windows for the Programming Effects of Early-Life Nutrition on Skeletal Muscle Mass

Author(s): M. L. Fiorotto and T. A. Davis

Skeletal myogenesis begins in the embryo with proliferation and differentiation of muscle progenitor cells that ultimately fuse to form multinucleated myofibers. After midgestation, muscle growth occurs through hypertrophy of these myofibers. The most rapid growth phase occurs in the perinatal period, resulting in the expansion of muscle mass from 25% of lean mass at birth to 40–45% at maturity. These 2 phases of muscle growth are regulated by distinct molecular mechanisms engaged by extracellular cues and intracellular signaling pathways and regulatory networks they activate. Nutrients influence muscle growth by both providing the necessary substrates and eliciting extracellular cues which regulate the signal transduction pathways that control the anabolic processes of the fibers. The uniquely large capacity of immature myofibers for hypertrophy is enabled by a heightened capacity and sensitivity of protein synthesis to feeding-induced changes in plasma insulin and amino acids, and the ability to expand their myonuclear population through proliferation of muscle precursor cells (satellite cells). With maturation, satellite cells become quiescent, limiting myonuclear accretion, and the capacity of the muscles for protein anabolism progressively diminishes. Therefore, the early developmental phases represent critical windows for muscle growth which, if disrupted, result in muscle mass deficits that are unlikely to be entirely recoverable.

Micronutrients and Child Growth: Current Evidence and Progress

Author(s): R. Sharma, T. Vaivada, and Z. A. Bhutta