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Fetuses affected by intrauterine growth restriction have an increased risk of developing heart disease and failure in adulthood. Compared with controls, late gestation intrauterine growth‐restricted (IUGR) fetal sheep have fewer binucleated cardiomyocytes, reflecting a more immature heart, which may reduce mitochondrial capacity to oxidize substrates. We hypothesized that the late gestation IUGR fetal heart has a lower capacity for mitochondrial oxidative phosphorylation. Left (LV) and right (RV) ventricles from IUGR and control (CON) fetal sheep at 90% gestation were harvested. Mitochondrial respiration (states 1–3, LeakOmy, and maximal respiration) in response to carbohydrates and lipids, citrate synthase (CS) activity, protein expression levels of mitochondrial oxidative phosphorylation complexes (CI–CV), and mRNA expression levels of mitochondrial biosynthesis regulators were measured. The carbohydrate and lipid state 3 respiration rates were lower in IUGR than CON, and CS activity was lower in IUGR LV than CON LV. However, relative CII and CV protein levels were higher in IUGR than CON; CV expression level was higher in IUGR than CON. Genes involved in lipid metabolism had lower expression in IUGR than CON. In addition, the LV and RV demonstrated distinct differences in oxygen flux and gene expression levels, which were independent from CON and IUGR status. Low mitochondrial respiration and CS activity in the IUGR heart compared with CON are consistent with delayed cardiomyocyte maturation, and CII and CV protein expression levels may be upregulated to support ATP production. These insights will provide a better understanding of fetal heart development in an adverse in utero environment. Key points: Growth‐restricted fetuses have a higher risk of developing and dying from cardiovascular diseases in adulthood.Mitochondria are the main supplier of energy for the heart. As the heart matures, the substrate preference of the mitochondria switches from carbohydrates to lipids.We used a sheep model of intrauterine growth restriction to study the capacity of the mitochondria in the heart to produce energy using either carbohydrate or lipid substrates by measuring how much oxygen was consumed.Our data show that the mitochondria respiration levels in the growth‐restricted fetal heart were lower than in the normally growing fetuses, and the expression levels of genes involved in lipid metabolism were also lower. Differences between the right and left ventricles that are independent of the fetal growth restriction condition were identified.These results indicate an impaired metabolic maturation of the growth‐restricted fetal heart associated with a decreased capacity to oxidize lipids postnatally. [ABSTRACT FROM AUTHOR]

This article discusses a randomized trial that aimed to assess routine nutritional interventions for moderate-to-late preterm infants. The study examined three interventions and assessed body fat percentage and time to full enteral feeding. The study found no significant differences in these outcomes. The authors conclude that routine nutritional interventions do not affect time to full enteral feeds or body composition at 4 months corrected age. The study also adds to the growing literature on the addition of smell and taste during tube feedings, finding minimal adverse effects but little identified benefit. [Extracted from the article]

Key points: Fetuses with intrauterine growth restriction (IUGR) have reduced muscle mass that persists postnatally, which may contribute to their increased risk for adult onset metabolic diseases, such as diabetes and obesity.Amino acid transporter‐mediated histidine uptake and system L amino acid transporter activity were similar in sarcolemmal membranes isolated from control and IUGR hindlimb skeletal muscle.Activity of Na+K+‐ATPase, which is responsible for establishing the sodium gradient necessary for system A and N amino acid transporter function, was significantly reduced in IUGR skeletal muscle sarcolemma compared to control.ATP content was lower in IUGR skeletal muscle.Expression and phosphorylation of proteins in the mechanistic target of rapamycin pathway were similar in control and IUGR skeletal muscle homogenate.Our data suggest that lower Na+K+‐ATPase activity, which reduces the driving force for active amino acid transport, and lower ATP availability contribute to reduced amino acid uptake and protein synthesis in IUGR fetal skeletal muscle. Fetuses with intrauterine growth restriction (IUGR) have lower muscle mass that persists postnatally. Using a sheep model of placental insufficiency and IUGR, we have previously demonstrated lower net total uptake of amino acids by the fetal hindlimb and lower skeletal muscle protein synthesis rates. To investigate the mechanisms underlying these changes, we tested the hypothesis that ex vivo amino acid transporter and Na+K+‐ATPase activity is reduced, and ex vivo ATP levels are lower in hindlimb skeletal muscle of the IUGR fetus. We developed a novel protocol to measure transporter‐mediated histidine uptake, system L amino acid transporter activity and Na+K+‐ATPase activity using sarcolemmal membranes isolated from hindlimb muscle of control (CON, n = 11‐12) and IUGR (n = 12) late gestation fetal sheep. We also determined ATP content and the activity of insulin and mechanistic target of rapamycin (mTOR) signalling, which are involved in regulating cellular amino acid uptake and protein synthesis, by measuring the expression and phosphorylation of AKT, 4E‐BP1, eIF2α, AMPKα, p70 S6 kinase and rpS6 in muscle homogenates. Transporter‐mediated histidine uptake and system L activity were similar in control and IUGR sarcolemma, although ex vivo Na+K+‐ATPase activity was lower by 64% (P = 0.019) in IUGR sarcolemma. ATP content was lower by 25% (P = 0.007) in IUGR muscle. Insulin, AMPK, and mTOR signalling activity was similar in control and IUGR muscle. We speculate that reduced muscle sarcolemmal Na+K+‐ATPase activity and lower ATP content diminishes the sodium gradient in vivo, resulting in a reduced driving force for sodium‐dependent transporters and subsequently lower muscle amino acid uptake. Key points: Fetuses with intrauterine growth restriction (IUGR) have reduced muscle mass that persists postnatally, which may contribute to their increased risk for adult onset metabolic diseases, such as diabetes and obesity.Amino acid transporter‐mediated histidine uptake and system L amino acid transporter activity were similar in sarcolemmal membranes isolated from control and IUGR hindlimb skeletal muscle.Activity of Na+K+‐ATPase, which is responsible for establishing the sodium gradient necessary for system A and N amino acid transporter function, was significantly reduced in IUGR skeletal muscle sarcolemma compared to control.ATP content was lower in IUGR skeletal muscle.Expression and phosphorylation of proteins in the mechanistic target of rapamycin pathway were similar in control and IUGR skeletal muscle homogenate.Our data suggest that lower Na+K+‐ATPase activity, which reduces the driving force for active amino acid transport, and lower ATP availability contribute to reduced amino acid uptake and protein synthesis in IUGR fetal skeletal muscle. [ABSTRACT FROM AUTHOR]

Growth and neurodevelopmental outcomes of early, high-dose parenteral amino acid intake in very low birth weight infants: a randomized controlled trial. Preterm infants require nutritional support immediately after birth to prevent catabolism and support normal growth, often in the setting of increased energy requirements due to postnatal environmental conditions and critical illness. Relationship between amino acid and energy intake and long-term growth and neurodevelopmental outcomes in very low birth weight infants. [Extracted from the article]