Early Postnatal Nutrition Research Articles

Environmental Influences on Epigenetic Gene Regulation

Substantial evidence in human epidemiologic and animal model data reveals that epigenetics plays crucial roles in normal development by governing proper gene expression of critical developmental genes. However, during this critical period of prenatal and early postnatal development, nutrition and other environmental stimuli can influence these developmental pathways to induce epigenetic changes of these critical genes. Such changes are often necessary to ensure survival of the developing organism. The opposite effect is that the altered gene expression profile may be maladaptive as the individual ages and may even set up the individual for increased lifelong risk for certain diseases. Our current task of trying to dissect how epigenetic variation arises during development is vital if we are to understand which epigenetic code predicts future disease risk. More importantly, future therapeutic interventions to ameliorate disease risk cannot be accomplished without understanding the molecular underpinnings of such epigenetic change.

Role of maternal nutrition in programming adiposity in the offspring: potential implications of glucocorticoids.

The epidemiological studies initially indicated that maternal undernutrition leading to a low birth weight may predispose to the long-lasting energy balance disorders. A high birth weight due to maternal obesity or diabetes, inappropriate early postnatal nutrition, and rapid catch-up growth, may also sensitize to an increased risk of obesity. As stated by the developmental origin of health and disease concept, the perinatal perturbation of the fetus/neonate nutrient supply might be a crucial determinant of the individual programming of the body weight set point. The adipose tissue is considered as the main fuel storage unit involved in the maintenance of the energy homeostasis. Several models have demonstrated that this tissue is a prime target of the developmental programming in a gender- and depot-specific manner. In the rodents, the perinatal period of life corresponds largely to the period of adipogenesis. In contrast, this phenomenon essentially takes place before birth in bigger mammals. Despite these different developmental time windows, the altricial and precocial species share several common offspring programming mechanisms. Thus, the adipose tissue of the offspring from malnourished dams exhibited impaired glucose uptake and leptin/insulin resistance with increased proinflammatory markers. It also displayed a modified sympathetic activity, circadian rhythm, fatty acid composition, and thermogenesis. This might lead to the reprogrammed metabolism and distribution of the adipose tissue with enhanced adipogenesis and fat accumulation predisposing to adiposity. The inappropriate glucocorticoid (GC) levels and modified tissue sensitivity might be key actors of perinatal programming and long-lasting altered adipose tissue activity in the offspring. Following maternal malnutrition, the epigenetic mechanisms might also be responsible for the adipose tissue programming.

Long term effects of pre- and early postnatal nutrition and environment on the gut1

The Developmental Origins of Health and Disease hypothesis formulated in the early 1990 s has stimulated research on long-term effects of early nutrition and environment over the last decades. Long-term is understood in this review as physiologically relevant periods such as after weaning, around sexual maturity, and in adulthood, as opposed to early developmental periods. The small and large intestines as targets for the study of long-term effects have received little attention until recent years and the stomach has been considered very rarely. Data have accumulated for laboratory animal models but they are still scarce in the swine species. Following the epidemics of metabolic diseases and obesity in western countries, experimental evidence has been published showing that nutritional factors, including energy, fat and fatty acids, protein, and micronutrients impact various facets of gut function. These include alterations in intestinal digestive, absorptive, secretory, barrier, and defense systems, often in a way potentially detrimental to the host. Environmental factors with long-term influence include stress (e.g., maternal deprivation, neonatal gut irritation), chemical pollutants (e.g., bisphenol A), and gut microbiota disturbances (e.g., by antibiotics). Examples of such long-term effects on the gut are provided in both laboratory animals and pigs together with underlying physiological mechanisms whenever available. Experimental evidence for the involvement of underlying epigenetic modifications (e.g., genomic DNA methylation) in long-term studies has just started to emerge with regard to the gastrointestinal tract. Also, interactions between the microbiota and the host are being considered pivotal in the early programming of gut functions. Finally, suggestions for future research are provided in order to better understand and then control early programming as an attempt to optimize vital functions of the gastrointestinal tract throughout adult life.

The hypothalamus–adipose axis is a key target of developmental programming by maternal nutritional manipulation

Epidemiological studies initially demonstrated that maternal undernutrition leading to low birth weight may predispose for energy balance disorders throughout life. High birth weight due to maternal obesity or diabetes, inappropriate early post-natal nutrition and rapid catch-up growth may also sensitise to increased risk of obesity. As stated by the Developmental Origin of Health and Disease concept, the perinatal perturbation of foetus/neonate nutrient supply might be a crucial determinant of individual programming of body weight set point. The hypothalamus-adipose axis plays a pivotal role in the maintenance of energy homoeostasis controlling the nutritional status and energy storage level. The perinatal period largely corresponds to the period of brain maturation, neuronal differentiation and active adipogenesis in rodents. Numerous dams and/or foetus/neonate dietary manipulation models were developed to investigate the mechanisms underlying perinatal programming in rodents. These models showed several common offspring hypothalamic consequences such as impaired neurogenesis, neuronal functionality, nuclei structural organisation and feeding circuitry hardwiring. These alterations led to a persistent reprogrammed appetite system that favoured the orexigenic pathways, leptin/insulin resistance and hyperphagia. Impaired hypothalamic sympathetic outflow to adipose tissue and/or reduced innervation may also account for modified fat cell metabolism. Thus, enhanced adipogenesis and/or lipogenesis capacities may predispose the offspring to fat accumulation. Abnormal hypothalamus-adipose axis circadian rhythms were also evidenced. This review mainly focuses on studies in rodents. It highlights hormonal and epigenetic mechanisms responsible for long-lasting programming of energy balance in the offspring. Dietary supplementation may provide a therapeutic option using a specific regimen for reversing adverse programming outcomes in humans.

1400 Body Fat in VLBW is Influenced by Duration of Total Parenteral Nutrition (TPN)

BackgroundAdequate postnatal nutrition and growth are essential for optimal neurodevelopment in VLBW infants. In an effort to optimize nutrition, early TPN implementation is recommended while enteral nutrition is achieved. However,...

OR01-1 Early postnatal nutrition programs the somatotropic axis through epigenetic mechanism

OR01-1 Early postnatal nutrition programs the somatotropic axis through epigenetic mechanism

Early postnatal low-protein nutrition, metabolic programming and the autonomic nervous system in adult life

Protein restriction during lactation has been used as a rat model of metabolic programming to study the impact of perinatal malnutrition on adult metabolism. In contrast to protein restriction during fetal life, protein restriction during lactation did not appear to cause either obesity or the hallmarks of metabolic syndrome, such as hyperinsulinemia, when individuals reached adulthood. However, protein restriction provokes body underweight and hypoinsulinemia. This review is focused on the regulation of insulin secretion and the influence of the autonomic nervous system (ANS) in adult rats that were protein-malnourished during lactation. The data available on the topic suggest that the perinatal phase of lactation, when insulted by protein deficit, imprints the adult metabolism and thereby alters the glycemic control. Although hypoinsulinemia programs adult rats to maintain normoglycemia, pancreatic β-cells are less sensitive to secretion stimuli, such as glucose and cholinergic agents. These pancreatic dysfunctions may be attributed to an imbalance of ANS activity recorded in adult rats that experienced maternal protein restriction.

Maternal malnutrition programs the endocrine pancreas in progeny

Type 2 diabetes arises when the endocrine pancreas fails to secrete sufficient insulin to cope with metabolic demands resulting from β cell secretory dysfunction, decreased β cell mass, or both. Epidemiologic studies have shown strong relations between poor fetal and early postnatal nutrition and susceptibility to diabetes later in life. Animal models have been established, and studies have shown that a reduction in the availability of nutrients during fetal development programs the endocrine pancreas and insulin-sensitive tissues. We investigated several modes of early malnutrition in rats. Regardless of the type of diet investigated, whether there was a deficit in calories or protein in food or even in the presence of a high-fat diet, malnourished pups were born with a defect in their β cell population, with fewer β cells that did not secrete enough insulin and that were more vulnerable to oxidative stress; such populations of β cells will never completely recover. Despite the similar endpoint, the cellular and physiologic mechanisms that contribute to alterations in β cell mass differ depending on the nature of the nutritional insult. Hormones that are operative during fetal life, such as insulin, insulin-like growth factors, and glucocorticoids; specific molecules, such as taurine; and islet vascularization have been implicated as possible factors in amplifying this defect. The molecular mechanisms responsible for intrauterine programming of β cells are still elusive, but among them the programming of mitochondria may be a strong central candidate.

Epigenetic mechanisms elicited by nutrition in early life

A growing number of studies focusing on the developmental origin of health and disease hypothesis have identified links among early nutrition, epigenetic processes and diseases also in later life. Different epigenetic mechanisms are elicited by dietary factors in early critical developmental ages that are able to affect the susceptibility to several diseases in adulthood. The studies here reviewed suggest that maternal and neonatal diet may have long-lasting effects in the development of non-communicable chronic adulthood diseases, in particular the components of the so-called metabolic syndrome, such as insulin resistance, type 2 diabetes, obesity, dyslipidaemia, hypertension, and CVD. Both maternal under- and over-nutrition may regulate the expression of genes involved in lipid and carbohydrate metabolism. Early postnatal nutrition may also represent a vital determinant of adult health by making an impact on the development and function of gut microbiota. An inadequate gut microbiota composition and function in early life seems to account for the deviant programming of later immunity and overall health status. In this regard probiotics, which have the potential to restore the intestinal microbiota balance, may be effective in preventing the development of chronic immune-mediated diseases. More recently, the epigenetic mechanisms elicited by probiotics through the production of SCFA are hypothesised to be the key to understand how they mediate their numerous health-promoting effects from the gut to the peripheral tissues.

The protein level of isoenergetic formulae does not modulate postprandial insulin secretion in piglets and has no consequences on later glucose tolerance

Early postnatal nutrition is involved in metabolic programming, an excess of protein being suspected to enhance early growth and the propensity to later develop insulin resistance and type 2 diabetes mellitus. The aim of the present study was to test the hypothesis that excessive protein intake during the suckling period would overstimulate the endocrine pancreas in the short term and alter durably its maturation, contributing to the later disruption of glucose homeostasis. Normal-birth-weight and low-birth-weight piglets were fed isoenergetic formulae providing an adequate-protein (AP, equivalent to sow milk) or a high-protein (HP, +48 %) supply between 7 and 28 d of age and were fed a standard diet until 70 d of age. During the formula-feeding period, the HP formula did not modify postprandial insulin secretion but transiently increased fasting insulin and the homeostasis model assessment-insulin resistance index (HOMA-IR, P < 0·05). Fasting insulin and HOMA-IR were restored to AP piglets' values 1 month after weaning. The structure of the endocrine pancreas was not affected by the protein content of the formula. The weight at birth had no major effect on the studied parameters. We concluded that a high-protein supply during the suckling period does not interfere with insulin secretion and endocrine pancreas maturation in the short term. It has no consequences either on glucose tolerance 1 month after weaning. The present study demonstrated that up-regulation of postprandial insulin secretion is not involved in higher growth observed in piglets fed a HP formula.

RUMINANT NUTRITION SYMPOSIUM: OPTIMIZING PERFORMANCE OF THE OFFSPRING: Nourishing and managing the dam and postnatal calf for optimal lactation, reproduction, and immunity1,2

For several mammalian species, it has been shown that fetal and early postnatal nutrition has a role in long-term lipid and glucose metabolism of the offspring, and it thus also may have consequences on milk yield in the dairy cow. For instance, high-energy diets during the last weeks of pregnancy may result in increased glycemia, which in turn, may alter fetal adipose tissue development. However, most research efforts on management and nutrition of dry cows have focused on minimizing metabolic disorders of the postpartum cow without devoting much attention to potential consequences for the offspring. Similarly, nutritional needs for proper placental development and early fetal growth have received little attention, despite the fact that alterations in placental and fetal development may alter expression of genes participating in homeorhesis of the offspring. Therefore, nutrition of the pregnant cow, both while lactating and dry, should also consider aspects of placental and fetal development that may affect health and performance of the progeny. Similarly, newborn calves and young heifers are fed to ensure a particular growth target without compromising mammary development, although data linking postnatal growth targets with future milk yield are scarce. However, milk yield not only depends on mammary development, but also on nutrient partitioning, which is regulated by the endocrine milieu. There are some periods of time during development where nutrition may have long-lasting effects on metabolic function and milk production. For instance, the first months of postnatal life seem to be critical because recent data from both retrospective and controlled studies indicate that increased growth rate or plane of nutrition during this phase is positively associated with future milk production. Postnatal growth rate depends on nutrition (a necessary but not sufficient condition) and management (i.e., grouping strategies and housing systems), and thus optimal rearing programs should be designed considering long-term consequences on milk yield.

A nutritional program to improve outcome of very low birth weight infants

The growth of very low birth weight infants does not match intrauterine trajectories, likely due to inappropriate caloric intake. We therefore investigated whether modification of the standard nutritional schedule can impact postnatal growth. We introduced a set of evidence-based strategies in a study group of infants (n=123): 1)higher maximum intake of intravenous amino acids and lipids; 2) prioritisation of earlier enteral feeding; 3) faster attainment of full enteral feeds; 4) daily adjustment of enteral feeds according to growth trajectory; and 5) utilisation of an electronic pre-structured prescription ordering system that tracks individual growth and energy intake. These infants were compared with a control group (n=115) in a pre/post retrospective cohort study. The study group achieved a higher caloric intake, attained full enteral feeds 5 days earlier, and returned to their birth weight more rapidly than the control group. At 36 weeks postmenstrual age, infants who had been born at <30 weeks were heavier (Δ260g) but had a similar percentage fat mass. Those born at <28 weeks had a larger head circumference (Δ1.4cm) and lower sepsis rate (7.8%). Optimization of early postnatal nutrition and daily adjustment of milk intake according to weight gain improved growth, without any unfavourable outcomes for body composition and neurodevelopmental follow-up.

Fish Oil Supplementation During Late Pregnancy Does Not Influence Plasma Lipids or Lipoprotein Levels in Young Adult Offspring

Nutritional influences on cardiovascular disease operate throughout life. Studies in both experimental animals and humans have suggested that changes in the peri- and early post-natal nutrition can affect the development of the various components of the metabolic syndrome in adult life. This has lead to the hypothesis that n-3 fatty acid supplementation in pregnancy may have a beneficial effect on lipid profile in the offspring. The aim of the present study was to investigate the effect of supplementation with n-3 fatty acids during the third trimester of pregnancy on lipids and lipoproteins in the 19-year-old offspring. The study was based on the follow-up of a randomized controlled trial from 1990 where 533 pregnant women were randomized to fish oil (n = 266), olive oil (n = 136) or no oil (n = 131). In 2009, the offspring were invited to a physical examination including blood sampling. A total of 243 of the offspring participated. Lipid values did not differ between the fish oil and olive oil groups. The relative adjusted difference (95% confidence intervals) in lipid concentrations was −3% (−11; 7) for LDL cholesterol, 3% (−3; 10) for HDL cholesterol, −1% (−6; 5) for total cholesterol,−4% (−16; 10) for TAG concentrations, 2%(−2; 7) for apolipoprotein A1, −1% (−9; 7) for apolipoprotein B and 3% (−7; 15) in relative abundance of small dense LDL. In conclusion, there was no effect of fish oil supplementation during the third trimester of pregnancy on offspring plasma lipids and lipoproteins in adolescence.

Early postnatal nutrition and programming of the preterm neonate

Early postnatal nutrition is a vital determinant of adult health; this is particularly true for the infant born prematurely and cared for in a hospital setting such as the neonatal intensive care unit. Human and animal studies support the contribution of postnatal dietary composition and the rate of extrauterine growth to long-term metabolic outcomes. One mechanism by which postnatal nutrition affects long-term outcome is via developmental programming. Programming, or the modulation of gene expression to impart a short-term advantage accompanied by a long-term cost, may be achieved by epigenetic modifications to chromatin. This review summarizes the details of postnatal nutritional content and rate of growth on the development of metabolic disease. The role of epigenetics in developmental programming of the preterm infant is also discussed, with an emphasis on animal models of dietary manipulation and directions in which the field must move in order to formulate effective feeding strategies for the preterm infant.

Diet and gender influences on processing and discrimination of speech sounds in 3‐ and 6‐month‐old infants: a developmental ERP study

Early post-natal nutrition influences later development, but there are no studies comparing brain function in healthy infants as a function of dietary intake even though the major infant diets differ significantly in nutrient composition. We studied brain responses (event-related potentials; ERPs) to speech sounds for infants who were fed either breast milk (BF), milk-based formula (MF), or soy formula (SF) during the first 6 months of life. Two syllables presented in an oddball paradigm elicited a late positive wave (P350) from temporal and frontal brain regions involved in language processes. All groups showed significantly greater response amplitudes to the infrequent syllable across sites at 3 months and frontally at 6 months, but significant discrimination at temporal sites was only observed at 6 months in BF infants. Decreases in response amplitudes from 3 to 6 months were greater for the frequently presented syllable, most prominent in BF infants, and greater in females than males. The results indicate greater syllable discrimination in BF than formula-fed infants, but whether this can be attributed to dietary influences alone remains unclear. Feeding method and background factor differences between breastfed and formula-fed infants may also contribute to the observed differences. The general absence of differences between formula-fed groups is notable and suggests that milk-based formula and soy formula equally support brain development and function during the first post-natal 6 months. Finally, the results indicate gender differences in the development of neural and temporal processes involved in sensory discrimination, and suggest that at 6 months these processes are better developed in females.

The influence of early postnatal nutrition on retinopathy of prematurity in extremely low birth weight infants

Background Retinopathy of prematurity(ROP) is the most common serious ophthalmic disease in preterm infants. Human milk may provide a protective effect for ROP; however, beneficial effects of human milk preclude randomized trials. Therefore, we conducted a retrospective analysis comparing early postnatal nutrition with ROP development. Objective Evaluate relationship between early postnatal nutriture and ROP surgery. Design/methods Nutrition data was collected for inborn AGA infants, BW 700–1000 g. ROP surgery was the primary outcome variable. A single pediatric ophthalmologist supervised examinations. All infants received triweekly IM vitamin A as chronic lung disease prophylaxis (Tyson: NEJM, 1999). Results BW and gestational age were 867 ± 85 g and 26.3 ± 1.2 weeks ( n = 77, mean ± 1SD). ROP surgery infants( n = 11) received more parenteral nutrition, 1648 mL, and less human milk, 13.8 mL/kg-day, and vitamin E, 1.4 mg/kg-day, during the second postnatal week. Human milk was a negative predictor for ROP surgery, odds ratio = 0.94. Both groups met vitamin A recommendations; however, 74% was administered via IM injections. Neither group met vitamin E recommendations. Conclusions Human milk feeding, parenteral nutrition volume and vitamin E intake were predictors for ROP surgery. IM vitamin A injections provided the majority of vitamin A; vitamin E administration was insufficient. Improving human milk feeding rates and vitamin dosing options may affect ROP surgery rates.

Metabolic imprinting effects in grass‐fed Wagyu (Japanese Black) beef production

We aim at producing a high‐quality safe beef product while maximising the use of domestic grass resources. Alterations in foetal and early postnatal nutrition and endocrine status may result in developmental adaptations that permanently change the structure, physiology, and metabolism in the adult life of rats, mice, domestic species and humans. This phenomenon is referred to as “metabolic imprinting” based on the concept of “the developmental origins of health and disease (DOHaD)”. In this study, we investigate whether the metabolic imprinting effect of differences in feeding during an early growth influences on the meat quality of Japanese Black (Wagyu) steers or not. The high energy group (HE: n=12) underwent intense nursing till 3 months of age and was fed a high‐concentrate diet for 4 to 10 months of age. On the contrary, the Roughage group (R: n=11) underwent normal nursing and was fed only roughage ad libitum from 3 to 10 months of age. Both groups were fed only roughage ad libitum and grazed from 10 to 30 months of age. Samples of tissues from the longissimus muscles in all animals were collected and biopsied at 3, 10, 14, 20 and 30 months of age. Gene expressions related to adipogenesis, fatty acid synthase etc. in muscle were measured by real‐time PCR. We also investigated meat quality after slaughter. We could show the metabolic imprinting effects on meat quality and quantity of grass‐fed Wagyu.

Further evidence for the dependence of diabetes prevalence on nutrition in perinatal life.

In order to investigate the possible influence of pre- and/or early postnatal nutrition on the development of diabetes mellitus in later life, diabetes prevalences were ascertained in subjects of similar ages who were born in different periods with or without shortage of food supply. Between 1974 and 1982 the total prevalence of diabetes mellitus increased in Berlin/GDR by 26%. A significantly higher increase of diabetes prevalence (approximately 90%) was found between 1974 and 1982 for subjects at 26-33 years of age, whose years of birth changed from a "hypocaloric war and post-war period (1941-1948)" to a "relatively hypercaloric peace period (1949-1956)". By contrast, there was not found any significant increase of diabetes prevalence between 1974 and 1982 for subjects at 34-41 years of age, whose years of birth changed from a "relatively hypercaloric period (1933-1940)" to a "hypocaloric period (1941-1948)". These findings give further evidence for the dependence of diabetes prevalence in later life on nutrition in perinatal life.

Long-term effects of early postnatal nutrition on subsequently body weight gain, emotionally and learning behaviour in male rats.

Male rats have been reared as litters of 2 pups (group A) or 12 pups (group B) during the first 3 weeks of life. Males of group A exhibited higher body weights from day 10 to day 430, reached puberty at earlier age and showed lower emotionality as well as diminished learning capability and decreased memory capacity in adulthood as compared to males of group B. Furthermore, adult males of group A developed an increased ratio of insulin to glucose serum concentration at 90 minutes after glucose administration.

Early Postnatal Nutrition Determines Somatotropic Function in Mice

Increasing evidence suggests a developmental origin for a number of human diseases, notably after intrauterine or postnatal nutrient deprivation. Nutritional changes readily translate into alterations of somatic growth. However, whereas intrauterine growth retardation often shows postnatal catch-up growth, recovery from food restriction immediately after birth is limited. Therefore, we investigated whether early postnatal nutrition (undernutrition and overfeeding) modifies plasticity of growth through developmental control of the somatotropic hormone axis. We used cross-fostering in mice to induce changes in early nutrition, and examined endocrine growth regulation and the development of specific disease phenotypes in adults. We showed that underfeeding during the early postnatal period delayed growth, whereas overfeeding accelerated it. In both cases, final body size was permanently altered. We found coordinated alterations in pituitary GH, plasma IGF-I and acid labile subunit, and gene expression of hypothalamic GHRH during postnatal development. These changes were consistent with the observed phenotypes. Alterations in the somatotropic axis persisted throughout adulthood. Although limited to the early postnatal period, both underfeeding and overfeeding led to reduced glucose tolerance later in life. These metabolic abnormalities were in line with defective insulin secretion in restricted mice and insulin resistance in overfed mice. Moreover, both restricted and overfed mice had increased arterial blood pressure, suggestive of vascular impairment. Our findings indicate a significant link between early postnatal diet, somatotropic development, and specific late onset diseases in mice. We suggest that, together with other hormones like leptin, IGF-I may play a role in modulating hypothalamic stimulation of the developing somatotropic function.