Early Postnatal Nutrition Research Articles

Early post-natal nutrition and renal consequences in preterm infants.

Early post-natal nutrition and renal consequences in preterm infants.

Early postnatal nutrition and renal consequences in preterm infants.

Perinatal nutritional factors may lead to decreased nephron endowment, decreased kidney function, and long-term development of chronic kidney disease and non-communicable diseases. At the same time, optimal postnatal nutrition and catch-up growth are associated with better neurodevelopmental outcomes in preterm infants. Therefore, nutritional management of preterm infants is a major challenge for neonatologists. In this context, the Section of Nutrition, Gastroenterology and Metabolism reviewed the current knowledge on nutritional issues related to kidney function. This narrative review discusses the clinical impact of early postnatal nutrition on long-term kidney function. In preterm infants, data are largely lacking to determine the extent to which early nutrition contributes to nephrogenesis and nephron endowment. However, some nutritional principles may help clinicians better protect the developing kidney in preterm infants. IMPACT: Clinical data show that preterm infants are an emerging population at high risk for chronic kidney disease. Both undernutrition and overnutrition can alter long-term kidney function. In preterm infants, data are largely lacking to determine the extent to which early postnatal nutrition contributes to nephrogenesis, nephron endowment and increased risk for chronic kidney disease. Some nutritional principles may help clinicians better protect the developing kidney in preterm infants: avoiding extrauterine growth restriction; providing adequate protein and caloric intakes; limiting exposure to high and prolonged hyperglycaemia; avoiding micronutrient deficiencies and maintaining acid-base and electrolyte balance.

Gene co-expression network analysis reveals perirenal adipose tissue as an important target of prenatal malnutrition in sheep.

We have previously demonstrated that pre- and early postnatal malnutrition in sheep induced depot- and sex-specific changes in adipose morphological features, metabolic outcomes, and transcriptome in adulthood, with perirenal (PER) as the major target followed by subcutaneous (SUB) adipose tissue. We aimed to identify co-expressed and hub genes in SUB and PER to identify the underlying molecular mechanisms contributing to the early nutritional programming of adipose-related phenotypic outcomes. Transcriptomes of SUB and PER of male and female adult sheep with different pre- and early postnatal nutrition histories were used to construct networks of co-expressed genes likely to be functionally associated with pre-and early postnatal nutrition histories, and phenotypic traits using Weighted Gene Co-expression Network Analysis. The modules from PER showed enrichment of cell cycle regulation, gene expression, transmembrane transport, and metabolic processes associated with both sexes' prenatal nutrition. In SUB (only males), a module of enriched adenosine diphosphate metabolism and development correlated with prenatal nutrition. Sex-specific module enrichments were found in PER, such as chromatin modification in the male network, but histone modification and mitochondria- and oxidative phosphorylation-related functions in the female network. These sex-specific modules correlated with prenatal nutrition and adipocyte size distribution patterns. Our results point to PER as a primary target of prenatal malnutrition compared to SUB, which played only a minor role. The prenatal programming of gene expression and cell cycle, potentially through epigenetic modifications, might be underlying mechanisms responsible for observed changes in PER expandability and adipocyte-size distribution patterns in adulthood in both sexes.

Combined Effect of Prenatal Mosquito Coil Smoke Exposure and Early Postnatal Nutritional Status on Obesity among Preschoolers

Informed by the theory of developmental origins of health and disease, we conducted a survey among 66,854 mother–preschooler dyads in all kindergartens within the Longhua District of Shenzhen in China for exploring the combined effect of prenatal mosquito coil smoke (MCS) exposure and early postnatal nutritional status on obesity in preschoolers. A self-administered questionnaire was completed by mothers to collect parents’ and children’s socio-demographic characteristics, prenatal MCS exposure, child nutritional status at 1–3 years, etc., and children’s heights and weights were measured at the same time. After controlling for potential confounders, a series of logistic regression models and cross-over analyses were used to examine the independent and combination effects of prenatal MCS exposure and postnatal nutritional status on preschoolers’ obesity. We found that prenatal MCS exposure significantly increased the risk of preschoolers’ obesity (AOR = 1.14, 95%CI = 1.08–1.21). Additionally, early postnatal well-nourished nutritional status also increased the risk of preschoolers’ obesity (AOR = 1.56, 95%CI = 1.47–1.66). The cross-over analysis showed that the combination of prenatal MCS exposure with early general postnatal nutrition status (AOR = 1.22, 95%CI = 1.10–1.36) and early postnatal well-nourished nutrition status (AOR = 1.81, 95%CI = 1.65–1.97), respectively, increased the risk of preschoolers’ obesity. Our results indicated that prenatal MCS exposure and early postnatal nutritional status can independently and jointly increase the risk of preschoolers’ obesity.

The influence of nutrition on white matter development in preterm infants: a scoping review.

White matter (WM) injury is the most common type of brain injury in preterm infants and is associated with impaired neurodevelopmental outcome (NDO). Currently, there are no treatments for WM injury, but optimal nutrition during early preterm life may support WM development. The main aim of this scoping review was to assess the influence of early postnatal nutrition on WM development in preterm infants. Searches were performed in PubMed, EMBASE, and COCHRANE on September 2022. Inclusion criteria were assessment of preterm infants, nutritional intake before 1 month corrected age, and WM outcome. Methods were congruent with the PRISMA-ScR checklist. Thirty-two articles were included. Negative associations were found between longer parenteral feeding duration and WM development, although likely confounded by illness. Positive associations between macronutrient, energy, and human milk intake and WM development were common, especially when fed enterally. Results on fatty acid and glutamine supplementation remained inconclusive. Significant associations were most often detected at the microstructural level using diffusion magnetic resonance imaging. Optimizing postnatal nutrition can positively influence WM development and subsequent NDO in preterm infants, but more controlled intervention studies using quantitative neuroimaging are needed. IMPACT: White matter brain injury is common in preterm infants and associated with impaired neurodevelopmental outcome. Optimizing postnatal nutrition can positively influence white matter development and subsequent neurodevelopmental outcome in preterm infants. More studies are needed, using quantitative neuroimaging techniques and interventional designs controlling for confounders, to define optimal nutritional intakes in preterm infants.

Circulating progranulin in human infants: relation to prenatal growth and early postnatal nutrition.

Progranulin (PGRN) displays pleiotropic biological functions and has been proposed as a biomarker for metabolic diseases. We longitudinally assessed PGRN concentrations in infants born appropriate (AGA) or small for gestational age (SGA), the latter being at risk for obesity and type 2 diabetes, especially if they experience an excessive postnatal catch-up in weight and are formula-fed (FF). The study population consisted of 183 infants who were exclusively breast-fed [(BF), AGA, n = 66; SGA, n = 40], or FF (AGA, n = 31; SGA, n = 46) over the first 4 months. Assessments included auxology, fasting glucose, insulin, IGF-1, high-molecular-weight adiponectin, PGRN and body composition (by DXA), at birth, and at age 4 and 12 months. PGRN levels were low at birth and unaffected by prenatal growth. PGRN increased at 4 and 12 months, although to a lesser extent in SGA infants, and was unrelated to the mode of feeding. PGRN correlated with markers of adiposity, inflammation and insulin resistance in both AGA and SGA infants, especially in those FF. The attenuated increase of PGRN levels in SGA infants over the first year of life, along with the association to markers of unhealthy metabolic profile, might point to a role of PGRN in future disease risks. Progranulin (PGRN) displays pleiotropic biological functions and has been proposed as a biomarker for metabolic diseases. In healthy infants, PGRN concentrations are low at birth and experience a significant and progressive increase up to age 12 months, which is less marked in infants born small for gestational age (SGA) and is unrelated to the mode of feeding. Circulating PGRN is related to markers of adiposity, inflammation, and insulin sensitivity, especially in formula-fed SGA infants. PGRN may play a role in the metabolic adaptations of SGA infants during early life, potentially contributing to the risk for obesity and type 2 diabetes in this population.

Establishing Postnatal Growth Monitoring Curves of Preterm Infants in China: Allowing for Continuous Use from 24 Weeks of Preterm Birth to 50 Weeks.

Background: Early postnatal growth monitoring and nutrition assessment for preterm infants is a public health and clinical concern. We aimed to establish a set of postnatal growth monitoring curves of preterm infants to better help clinicians make in-hospital and post-discharge nutrition plan of these vulnerable infants. Methods: We collected weight, length and head circumference data from a nationwide survey in China between 2015 and 2018. Polynomial regression and the modified LMS methods were employed to construct the smoothed weight, length and head circumference growth curves. Results: We established the P3, P10, P25, P50, P75, P90, P97 reference curves of weight, length and head circumference that allowed for continuous use from 24 weeks of preterm birth to 50 weeks and developed a set of user-friendly growth monitoring charts. We estimated approximate ranges of weight gain per day and length and head circumference gains per week. Conclusions: Our established growth monitoring curves, which can be used continuously without correcting gestational age from 24 weeks of preterm birth to 50 weeks, may be useful for assessment of postnatal growth trajectories, definition of intrauterine growth retardation at birth, and classification of early nutrition status for preterm infants.

Social-Cognitive Network Connectivity in Preterm Children and Relations With Early Nutrition and Developmental Outcomes.

Infants born very low birth weight (VLBW, < 1,500 g) are at a heightened risk for structural brain abnormalities and social-cognitive deficits, which can impair behavioural functioning. Resting-state fMRI, reflecting a baseline level of brain activity and underlying social-cognitive processes, has also been reported to be altered in children born VLBW. Yet very little is known about the functional networks underlying social cognition using magnetoencephalography (MEG) and how it relates to neonatal factors and developmental outcomes. Thus, we investigated functional connectivity at rest in VLBW children and the associations with early nutrition and IQ and behavioural problems. We collected resting-state MEG recordings and measures of IQ and social-cognitive behaviour, as well as macronutrient/energy intakes during initial hospitalisation in 5-year-old children born VLBW (n = 37) compared to full-term (FT; n = 27) controls. We examined resting-state network differences controlling for sex and age at scan. Functional connectivity was estimated using the weighted phase lag index. Associations between functional connectivity with outcome measures and postnatal nutrition were also assessed using regression analyses. We found increased resting-state functional connectivity in VLBW compared to FT children in the gamma frequency band (65–80 Hz). This hyper-connected network was primarily anchored in frontal regions known to underlie social-cognitive functions such as emotional processing. In VLBW children, increased functional connectivity was related to higher IQ scores, while reduced connectivity was related to increased behavioural problems at 5 years of age. These within-group associations were found in the slower frequency bands of theta (4–7 Hz) and alpha (8–12 Hz), frequently linked to higher-order cognitive functions. We also found significant associations between macronutrient (protein and lipid) and energy intakes during the first postnatal month with functional connectivity at preschool-age, highlighting the long-term impacts of postnatal nutrition on preterm brain development. Our findings demonstrate that at preschool-age, VLBW children show altered resting-state connectivity despite IQ and behaviour being in the average range, possibly reflecting functional reorganisation of networks to support social-cognitive and behavioural functioning. Further, our results highlight an important role of early postnatal nutrition in the development of resting-state networks, which in turn may improve neurodevelopmental outcomes in this vulnerable population.

Transcriptomics analysis of differentially expressed genes in subcutaneous and perirenal adipose tissue of sheep as affected by their pre- and early postnatal malnutrition histories

BackgroundEarly life malnutrition is known to target adipose tissue with varying impact depending on timing of the insult. This study aimed to identify differentially expressed genes in subcutaneous (SUB) and perirenal (PER) adipose tissue of 2.5-years old sheep to elucidate the biology underlying differential impacts of late gestation versus early postnatal malnutrition on functional development of adipose tissues. Adipose tissues were obtained from 37 adult sheep born as twins to dams fed either NORM (fulfilling energy and protein requirements), LOW (50% of NORM) or HIGH (110% of protein and 150% of energy requirements) diets in the last 6-weeks of gestation. From day 3 to 6 months of age, lambs were fed high-carbohydrate-high-fat (HCHF) or moderate low-fat (CONV) diets, and thereafter the same moderate low-fat diet.ResultsThe gene expression profile of SUB in the adult sheep was not affected by the pre- or early postnatal nutrition history. In PER, 993 and 186 differentially expressed genes (DEGs) were identified in LOW versus HIGH and NORM, respectively, but no DEG was found between HIGH and NORM. DEGs identified in the mismatched pre- and postnatal nutrition groups LOW-HCHF (101) and HIGH-HCHF (192) were largely downregulated compared to NORM-CONV. Out of 831 DEGs, 595 and 236 were up- and downregulated in HCHF versus CONV, respectively. The functional enrichment analyses revealed that transmembrane (ion) transport activities, motor activities related to cytoskeletal and spermatozoa function (microtubules and the cytoskeletal motor protein, dynein), and responsiveness to the (micro) environmental extracellular conditions, including endocrine and nervous stimuli were enriched in the DEGs of LOW versus HIGH and NORM. We confirmed that mismatched pre- and postnatal feeding was associated with long-term programming of adipose tissue remodeling and immunity-related pathways. In agreement with phenotypic measurements, early postnatal HCHF feeding targeted pathways involved in kidney cell differentiation, and mismatched LOW-HCHF sheep had specific impairments in cholesterol metabolism pathways.ConclusionsBoth pre- and postnatal malnutrition differentially programmed (patho-) physiological pathways with implications for adipose functional development associated with metabolic dysfunctions, and PER was a major target.

Early nutrition and white matter microstructure in children born very low birth weight.

Infants born at very low birth weight (<1500 g) are vulnerable to nutritional deficits during their first postnatal month, which are associated with poor neurodevelopmental outcomes. Despite this knowledge, the impact of early postnatal nutrition on white matter microstructure in children born with very low birth weight has not been investigated. In this prospective cohort study, we employed a whole-brain approach to investigate associations between precise estimates of nutrient intake within the first postnatal month with white matter microstructure at 5 years of age. Detailed information about breastmilk, macronutrient and energy intakes during this period were prospectively recorded for all participants. Multi-shell diffusion and T1-weighted MRIs were acquired in 41 children (21 males; mean scan age: 5.75 ± 0.22 years; mean birth weight: 1028.6 ± 256.8 g). The diffusion tensor imaging and neurite orientation dispersion and density imaging models were used to obtain maps of fractional anisotropy, radial diffusivity, orientation dispersion and neurite density indices. Tract-based spatial statistics was used to test associations between metrics of white matter microstructure with breastmilk, macronutrient (protein, lipids and carbohydrate) and energy intake. Associations between white matter microstructure and cognitive outcomes were also examined. Compared to children who did not meet enteral feeding recommendations, those who achieved enteral protein, lipid and energy recommendations during the first postnatal month showed improved white matter maturation at 5 years. Among the macronutrients, greater protein intake contributed most to the beneficial effect of nutrition, showing widespread increases in fractional anisotropy and reductions in radial diffusivity. No significant associations were found between white matter metrics with breastmilk or carbohydrate intake. Voxel-wise analyses with cognitive outcomes revealed significant associations between higher fractional anisotropy and neurite density index with higher processing speed scores. Lower radial diffusivity and orientation dispersion index were also associated with improved processing speed. Our findings support the long-term impacts of early nutrition on white matter microstructure, which in turn is related to cognitive outcomes. These results provide strong support for early postnatal nutritional intervention as a promising strategy to improve long-term cognitive outcomes of infants born at very low birth weight.

39 Early Higher Parenteral Lipid Intake Decreases Extra-Uterine Growth Restriction in Very Low Birth weight Infants: A Randomized Controlled Trial

Abstract Background Approximately 43-65% of very low birth weight (VLBW) infants develop extra-uterine growth restriction (EUGR). EUGR is associated with a significant increase in the risk of neurodevelopmental impairment. Inadequate early postnatal nutrition results in excessive weight loss that cannot be explained by the physiologic contraction of body water alone. EUGR and postnatal growth failure are usually associated with negative early energy and nitrogen balance in the first week of life. Growth trajectories after initial weight loss have similar slopes regardless of gestational age, which indicates that the early excessive weight loss is a lead cause for EUGR. Objectives To study whether an early and higher parenteral lipid intake in the first week after birth would decrease the percentage of weight loss and subsequently the incidence of EUGR. Design/Methods This was a randomized, open-label, control trial of appropriate-for-gestational age VLBW infants admitted to our level III NICU. Lipid intake in the control group started at 0.5-1 g/kg/day and was increased daily by 0.5-1 g/kg/day until 3 g/kg/day was reached. The intervention group was started on 2 g/kg/day then increased to 3 g/kg/day the following day. Triglyceride levels were measured the day after the start and after each increase in lipid intake. Results Among the 176 infants assessed for eligibility, eighty-three were included in the trial. There were no significant differences between the control and the intervention group in mean gestational age (27.3 ± 2.4 vs. 27.1 ± 2.3 weeks respectively) or birth weight (1011 ± 250 vs. 1019 ± 271 g respectively). Infants in the intervention group were started on lipid earlier (13.8±7.8 vs. 17.5±7.8 h; p=0.03) and had higher cumulative lipid intake in the first 7 days of age (13.5±4.2 vs. 10.9±3.5 g/kg; p=0.004) that led to a protein to energy ratio; closer to the recommended values. Total fluid intake was similar between the two groups. Infants in the intervention group had a lower percentage of weight loss (10.4±3.6 vs. 12.7±4.6; p=0.02). The mean triglyceride level was higher in the intervention group (1.91± 0.79 vs. 1.49±0.54 mmol/L; p= 0.01), however, hypertriglyceridemia was similar between the two groups at 2 and 3 g/kg/day of lipid intake. Enteral energy and protein intake calculated weekly between the time of parenteral nutrition discontinuation and 36 weeks corrected gestational age (CGA) were similar between the 2 groups. EUGR at 36 weeks CGA was significantly lower in the intervention group (38.6% vs. 67.6%; p=0.01). Conclusion In VLBW infants, the provision of an early and higher dose of parenteral lipid in the first week of life results in less weight loss and lower incidence of EUGR.

Epigenetics: Linking Early Postnatal Nutrition to Obesity Programming?

Despite constant research and public policy efforts, the obesity epidemic continues to be a major public health threat, and new approaches are urgently needed. It has been shown that nutrient imbalance in early life, from conception to infancy, influences later obesity risk, suggesting that obesity could result from “developmental programming”. In this review, we evaluate the possibility that early postnatal nutrition programs obesity risk via epigenetic mechanisms, especially DNA methylation, focusing on four main topics: (1) the dynamics of epigenetic processes in key metabolic organs during the early postnatal period; (2) the epigenetic effects of alterations in early postnatal nutrition in animal models or breastfeeding in humans; (3) current limitations and remaining outstanding questions in the field of epigenetic programming; (4) candidate pathways by which early postnatal nutrition could epigenetically program adult body weight set point. A particular focus will be given to the potential roles of breast milk fatty acids, neonatal metabolic and hormonal milieu, and gut microbiota. Understanding the mechanisms by which early postnatal nutrition can promote lifelong metabolic modifications is essential to design adequate recommendations and interventions to “de-program” the obesity epidemic.

Nutrition, epigenetics and health

Nutrition, epigenetics and health

Maternal high-fat diet during suckling programs visceral adiposity and epigenetic regulation of adipose tissue stearoyl-CoA desaturase-1 in offspring.

The lactation-suckling period is critical for white adipose tissue (WAT) development. Early postnatal nutrition influences later obesity risk but underlying mechanisms remain elusive. Here, we tested whether altered postnatal nutrition specifically during suckling impacts epigenetic regulation of key metabolic genes in WAT and alter long-term adiposity set point. We analyzed the effects of maternal high-fat (HF) feeding in rats exclusively during lactation-suckling on breast milk composition and its impact on male offspring visceral epidydimal (eWAT) and subcutaneous inguinal (iWAT) depots during suckling and in adulthood. Maternal HF feeding during lactation had no effect on mothers' body weight (BW) or global breast milk composition, but induced qualitative changes in breast milk fatty acid (FA) composition (high n-6/n-3 polyunsaturated FA ratio and low medium-chain FA content). During suckling, HF neonates showed increased BW and mass of both eWAT and iWAT depot but only eWAT displayed an enhanced adipogenic transcriptional signature. In adulthood, HF offspring were predisposed to weight gain and showed increased hyperplastic growth only in eWAT. This specific eWAT expansion was associated with increased expression and activity of stearoyl-CoA desaturase-1 (SCD1), a key enzyme of FA metabolism. SCD1 converts saturated FAs, e.g. palmitate and stearate, to monounsaturated FAs, palmitoleate and oleate, which are the predominant substrates for triglyceride synthesis. Scd1 upregulation in eWAT was associated with reduced DNA methylation in Scd1 promoter surrounding a PPARγ-binding region. Conversely, changes in SCD1 levels and methylation were not observed in iWAT, coherent with a depot-specific programming. Our data reveal that maternal HF feeding during suckling programs long-term eWAT expansion in part by SCD1 epigenetic reprogramming. This programming events occurred with drastic changes in breast milk FA composition, suggesting that dietary FAs are key metabolic programming factors in the early postnatal period.

Early postnatal nutrition after preterm birth and cardiometabolic risk factors in young adulthood.

ObjectivesAdults born preterm at very low birthweight (VLBW; <1500 g) have a non-optimal cardiometabolic risk factor profile. Since higher protein intake during the first weeks of life predicted a healthier body composition in adulthood in our previous studies, we hypothesized that it would also predict a favorable cardiometabolic profile.Study designThe Helsinki Study of VLBW Adults includes 166 VLBW and preterm infants born between 1978 and 1985. We collected postnatal nutrition data among 125 unimpaired subjects, who attended two study visits at the mean ages of 22.5 and 25.1 years. We evaluated the effects of energy and macronutrient intakes during the first three 3-week periods of life on key cardiometabolic risk factors with multiple linear regression models. We also report results adjusted for prenatal, postnatal and adult characteristics.ResultsMacronutrient and energy intakes were not associated with blood pressure, heart rate, or lipid levels in adulthood. Intakes were neither associated with fasting glucose or most other markers of glucose metabolism. An exception was that the first-three-weeks-of-life intakes predicted higher fasting insulin levels: 1 g/kg/day higher protein intake by 37.6% (95% CI: 8.0%, 75.2%), and 10 kcal/kg/day higher energy intake by 8.6% (2.6%, 14.9%), when adjusted for sex and age. These early intakes similarly predicted the adult homeostasis model assessment index. Further adjustments strengthened these findings.ConclusionsAmong VLBW infants with relatively low early energy intake, early macronutrient and energy intakes were unrelated to blood pressure, lipid levels and intravenous glucose tolerance test results. Contrary to our hypothesis, a higher macronutrient intake during the first three weeks of life predicted higher fasting insulin concentration in young adulthood.

Liver transcriptomic and proteomic profiles of preweaning lambs are modified by milk replacer restriction

Prenatal and early postnatal nutrition may promote long-term effects on both feed efficiency and health of animals. Therefore, moderated milk replacer restriction during the artificial rearing period might negatively affect feed efficiency during the postweaning phases in dairy ewes. The aim of this work was to identify differentially expressed (DE) genes by RNA sequencing and differentially accumulated proteins using MALDI-TOF mass spectrometry in the liver of artificially reared Assaf lambs to identify modified metabolic pathways as a consequence of milk replacer restriction in order to find possible solutions to correct any detrimental effect caused by this factor. Forty female Assaf lambs were used in this experiment. The animals were penned individually and assigned randomly to 1 of 2 treatments groups (n = 20 per treatment). The first group of lambs was fed ad libitum (AL), whereas the second (restricted, RES) only received approximately 62.5% of the level of intake measured in the AL group. Eight 35-d-old lambs from each group (16 lambs in total) were harvested and a piece of liver of 8 lambs (4 AL and 4 RES lambs) was excised for transcriptomic and proteomic analysis. Differential gene expression analysis identified 386 DE genes [198 of them being annotated genes in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway], with 176 downregulated and 210 upregulated in the early feed-restricted group relative to the AL group. A total of 26 spots were also differentially accumulated proteins in the liver of the 2 groups of lambs, 10 of them being down-accumulated whereas the other 16 evolved in the opposite way in the liver of RES relative to AL lambs. Collectively, both the transcriptomic and proteomic approaches revealed an upregulation of genes participating in oxidation of fatty acids in the early feed-restricted lambs. The expression of many genes involved in the degradation of several AA (e.g. alanine, valine, isoleucine, tyrosine) was also modified in the RES lambs, probably to render substrates for gluconeogenesis. Moreover, other genes involved in apoptosis, inflammation, or hepatic oxidative pathways were upregulated in these lambs. Finally, the expression of genes implicated in oxidative phosphorylation was modified in RES animals. Altogether all these modifications suggest that the partitioning and utilization of nutrients in the early feed-restricted lambs might have been modified, being partially responsible for changes during the replacement phase later in life.

Nerve Growth Factor Levels in Term Human Infants: Relationship to Prenatal Growth and Early Postnatal Feeding.

Background Nerve growth factor (NGF) plays a key role in neuroprotection and developmental maturity. We assessed longitudinally the circulating concentrations of NGF in term healthy human newborns and infants as well as their association with prenatal growth and early postnatal feeding patterns. Methods Circulating NGF and anthropometric measures (weight, length, body mass index, and ponderal index) were assessed longitudinally—at birth and at age 4 months—in 86 term infants born appropriate (AGA), small (SGA), or large for gestational age (LGA). Results Cord blood NGF levels in SGA newborns were higher than those in AGA newborns (1.41 ± 0.2 pg/mL vs. 0.66 ± 0.1 pg/mL; p = 0.02) and not different from those in LGA neonates (0.79 ± 0.2 pg/mL). At age 4 months, SGA-breastfed infants showed the highest NGF concentrations (p = 0.02 and p = 0.01 vs. AGA and SGA-formula-fed infants, respectively), while LGA infants depicted a marginal increase. NGF levels in cord blood correlated negatively with the ponderal index at birth (r = −0.36; p = 0.0008). Conclusions Circulating NGF is related to both prenatal growth and early postnatal nutrition. The maintenance of increased NGF concentrations in SGA-breastfed infants at age 4 months might be a potential mechanism to counterbalance potential risks for developing cognitive and psychomotor disadvantages.

43 Effect of early life nutrition on endometrial gland development and endometrial gene expression in heifers

In cattle, uterine gland development (adenogenesis) occurs postnatally, beginning immediately after birth, and is normally complete by approximately 2 months of age. Normal development of uterine glands is essential for subsequent fertility. Early life plane of nutrition can impact age at puberty, but the impact of early postnatal nutrition on adenogenesis is unclear. The aim of this study was to examine the effect of enhanced nutrition during the first 21 weeks of life on heifer reproductive organ growth, endometrial gland development, and endometrial gene expression. To this end, Angus×Holstein-Friesian heifer calves with a mean (±s.d.) age and body weight of 19 (±5) days and 51.2 (±7.8) kg, respectively, were assigned to either a high (HIGH; n=16; targeted average daily gain, ADG, 1.2 kg/d) or a moderate plane of nutrition (MOD; n=16; targeted ADG 0.5 kg/d). Calves were slaughtered at five months of age, and their reproductive tracts were collected and dissected for analysis. To assess endometrial gland number, a cross-section of the midpoint of one horn (n=8 per group) was fixed in 10% neutral buffered formalin, embedded, and processed for histology. Slides were stained with haematoxylin-eosin. Five pictures were randomly taken on each slide using a stereomicroscope at 40× magnification and the number of glands was counted using ImageJ (https://imagej.nih.gov/ij/) software. In addition, endometrial tissue samples were collected and snap frozen for subsequent quantitative RT-PCR analysis. At the time of slaughter, calves on the HIGH and MOD diets presented a body weight of 189.6 and 110.2kg, respectively (P&amp;lt;0.001), indicating an ADG of 1.18 kg/d for the HIGH group and 0.50 kg/d for the MOD group (P&amp;lt;0.001). Calves in the HIGH group had a greater (P&amp;lt;0.001) total reproductive tract (mean±s.d.; 114.01±35.56g v. 52.67±14.29g), isolated cervix (33.17±9.35g v. 16.14±5.27g), uterus (59.35±25.78g v. 27.46±10.61g), and ovarian (14.80±11.38g v. 5.40±1.94g) tissue weights compared with those in the MOD group. This difference was also present when organ weight was expressed on a per unit of body weight basis (P&amp;lt;0.05). However, no differences were found in the number of endometrial glands between groups (HIGH: 453.50±94.18v. MOD: 482.38±124.69). In accordance with this result, transcript abundance of six paracrine mediators of gland development (ESR1, IGF1, IGFBP1, WNT5A, WNT7A, and FGF10) was not affected by diet. In conclusion, enhanced early-life plane of nutrition increased the size of the reproductive tract in heifer calves but did not affect endometrial gland development. Future studies will compare the global endometrial transcriptome between groups to explore other putative effects of diet on uterine development. Research was supported by EU, Horizon 2020 Marie Sklodowska-Curie, REPBIOTECH 675526, Science Foundation Ireland 13/IA/1983, and São Paulo Research Foundation (FAPESP) 2017/21415-5.

Impact of a high-protein diet during lactation on milk composition and offspring in a pig model.

Early postnatal nutrition not only holds relevance to infant growth, but also determines the risk of developing obesity and chronic diseases such as diabetes type 2 and cardiovascular diseases in adulthood. It is suggested that a high-protein (HP) diet in early childhood can predispose children to obesity. However, data concerning possible alterations in milk composition and the development of the offspring in response to a maternal HP diet are currently not available. To address this question, we conducted a study using pigs as a model organism. At parturition, sows were assigned to two experimental groups. During lactation, the control group received a diet with a protein content of 16%, whereas the diet of the HP group contained 30% protein. After 28 days of lactation, samples were taken from sows and piglets for the quantification of free amino acids and other metabolites and for histology. Serum and milk urea showed the most marked differences between the two groups of sows, whereas serum urea concentration in piglets did not differ. Here, we found that the intake of an HP diet changed a series of metabolites in sows, but had only small effects on milk composition and virtually no effects on growth in the offspring. Interestingly, maternal protein intake during lactation shapes the microbiome of the offspring. From our current study, we conclude that even a very high maternal protein intake throughout lactation has no impact on growth and health parameters of the offspring.

Effect of early postnatal nutrition on chronic kidney disease and arterial hypertension in adulthood: a narrative review.

Intrauterine growth restriction (IUGR) has been identified as a risk factor for adult chronic kidney disease (CKD), including hypertension (HTN). Accelerated postnatal catch-up growth superimposed to IUGR has been shown to further increase the risk of CKD and HTN. Although the impact of excessive postnatal growth without previous IUGR is less clear, excessive postnatal overfeeding in experimental animals shows a strong impact on the risk of CKD and HTN in adulthood. On the other hand, food restriction in the postnatal period seems to have a protective effect on CKD programming. All these effects are mediated at least partially by the activation of the renin-angiotensin system, leptin and neuropeptide Y (NPY) signaling and profibrotic pathways. Early nutrition, especially in the postnatal period has a significant impact on the risk of CKD and HTN at adulthood and should receive specific attention in the prevention of CKD and HTN.