Neonatal Nutrition Research Articles

Feasibility of minimal enteral nutrition in neonates with perinatal asphyxia during therapeutic hypothermia: A randomized controlled trial.

Background: Therapeutic Hypothermia (TH) is a standard of care for neonates with birth asphyxia with moderate to severe hypoxic-ischemic encephalopathy. Despite lack of evidence, it is common practice to withhold feeds during TH due to risk of NEC. As there are no prior Indian studies and in view of limited evidence, this study was aimed to assess the feasibility of minimal enteral nutrition in our cohort of asphyxiated neonates during TH. Methods: This study was conducted in the Level III a NICU of Shri BM Patil Medical College Hospital and Research Centre, Vijayapura. Design: Open-label, parallel grouped, randomized controlled trial. 100 asphyxiated neonates undergoing therapeutic hypothermia were enrolled. Eligible newborns were randomized to receive either minimal enteral feeding or no feeding (50 newborns in each group) during therapeutic hypothermia. Results: Both groups were comparable in maternal and neonatal characteristics. Among 100 cooled neonates, 50 cooled neonates were randomized to MEN group and 50 cooled neonates to Control group. No statistically significant differences were observed among complications associated with therapeutic hypothermia between MEN group and Control group. Indicators of Sepsis and NEC such as Leucopenia/Neutropenia/Thrombocytopenia were observed in both groups which was not statistically significant (p>0.05). MEN neonates had a reduced length of hospital stay (mean 9 ± 2 days vs. 14 ± 3 days, p<0.05), and time to reach full oral feeds (7 ± 2 days vs. 12 ± 3 days, p<0.05). Conclusion: Minimal enteral feeding for neonates with moderate or severe HIE receiving therapeutic hypothermia is safe and feasible and associated with decreased time to reach full enteral feeding and reduced NICU stay and is not associated with significant complications like NEC.

Neonatal Total Parenteral Nutrition: Clinical Implications From Recent NICE Guidelines

Postnatal growth failure and its impact on the long term outcomes in preterm neonates is a long-standing problem. Optimal and aggressive nutrition strategies are required to ameliorate these concerns. Total parenteral nutrition (TPN) is widely practiced in management of preterm neonates. Recently published National Institute for Health and Care Excellence (NICE) guidelines provide recommendations for best practices for parenteral nutrition in neonates. However, healthcare associated sepsis, expertise as well as infrastructure of TPN, monitoring facilities and cost remain major constraints for widespread use of TPN in resource limited settings. Current update is aimed to summarize NICE and European society for Clinical Nutrition and Metabolism (ESPEN) guidelines to inform best practice for TPN for neonatologists in India.

Optimizing Neonatal Nutrition in Resource-Constrained Settings

Optimizing Neonatal Nutrition in Resource-Constrained Settings

148 Nutritional advances in fetal and neonatal development: Introduction to current knowledge

Abstract Processes associated with appropriate fetal and neonatal development from the periconceptual through the neonatal phases of life are critical for offspring health and productivity throughout life. The objectives are to provide a brief introduction to the current knowledge associated with nutritional advances in fetal and neonatal development. The concept of developmental or fetal programming is that inappropriate events during critical developmental stages can have lasting impacts on offspring outcomes. This idea has emerged over the past three decades to become a major research focus in both animal and human biomedical arenas. Perturbed maternal nutrition and/or nutrient supply from prebreeding through early neonatal life has long been known to shape reproductive efficiency and offspring outcomes. Nutrient supply to the conceptus varies during the time course of placental and fetal development. Uterine glandular secretions are major suppliers of nutrients during early placental and conceptus development. As the placenta develops and becomes fully functional, fetal nutrient supply becomes dependent on placental function. Research investigating changes in total maternal nutrient supply, including both an under and over abundance, has clearly demonstrated impacts on offspring outcomes. Investigations into supply of specific nutrients on development outcomes has increased rapidly in recent years with results demonstrating that in some cases, even small changes in supply can have developmental consequences. Specific amino acids, minerals, fatty acids, and nutrient supply interactions can influence developmental outcomes. Underlying mechanisms of developmental programming are associated with epigenetic events which are driven, at least in part, by methyl donors and one carbon metabolites. Emerging knowledge associated with how critical supply of specific nutrients influences offspring development and postnatal health, function, and productivity is shaping our understanding of parental, fetal, and neonatal nutrition and creating opportunities for enhanced livestock production through strategic nutrient supplementation.

406 Maternal nutrition during early gestation: Impacts on developmental outcomes

Abstract Changes in maternal nutrition that represent inadequacies or excesses in nutrient supply have been implicated in altered fetal development as well as offspring outcomes and have been termed fetal or developmental programming. Research in the area of developmental programming of livestock has greatly increased during the last two decades. For ruminants, most research efforts in developmental programming have focused on nutritional perturbations during the last two-thirds of gestation. Unfortunately, research investigating changes to maternal nutrient supply during early gestation or even periconceptually has been limited. The objectives of this invited review are to provide a summary of our current understanding of the impacts of inappropriate maternal nutrition during early gestation on embryo-fetal and offspring developmental outcomes. Nutrient supply to the conceptus varies during the time of early placental and conceptus development, and uterine glandular secretions, often called uterine milk or uterine histotroph, are major suppliers of nutrients during this time. Nutrients in histotroph are essential to conceptus development, and histotroph nutrient concentrations may be responsive to maternal nutrient supply. As the placenta develops and becomes fully functional, fetal nutrient supply becomes dependent on placental function. Research investigating changes in total maternal nutrient supply, even during early gestation, has clearly demonstrated impacts on offspring outcomes. Investigations into supply of specific nutrients and development outcomes have increased rapidly in recent years with results demonstrating that in some cases, even small changes in supply can have consequences on offspring development. Underlying mechanisms of developmental programming are associated with epigenetic events partially driven by methyl donors and cofactors. Emerging knowledge associated with the influence of periconceptual, fetal, and neonatal nutrition on offspring development, postnatal health, function, and productivity is creating opportunities for enhanced livestock production through strategic nutrient supplementation.

Do preterm girls need different nutrition to preterm boys? Sex-specific nutrition for the preterm infant.

Boys born preterm are recognised to be at higher risk of adverse outcomes than girls born preterm. Despite advances in neonatal intensive care and overall improvements in neonatal morbidity and mortality, boys born preterm continue to show worse short- and long-term outcomes than girls. Preterm birth presents a nutritional crisis during a critical developmental period, with postnatal undernutrition and growth-faltering common complications of neonatal intensive care. Furthermore, this preterm period corresponds to that of rapid in utero brain growth and development, and the developmental window relating to foetal programming of adult non-communicable diseases, the prevalence of which are associated both with preterm birth and sex. There is increasing evidence to show that from foetal life, boys and girls have different responses to maternal nutrition, that maternal breastmilk composition differs based on foetal sex and that early neonatal nutritional interventions affect boys and girls differently. This narrative review examines the evidence that sex is an important moderator of the outcomes of preterm nutrition intervention, and describes what further knowledge is required before providing nutrition intervention for infants born preterm based on their sex. IMPACT: This review examines the increasing evidence that boys and girls respond differently to nutritional stressors before birth, that maternal breastmilk composition differs by foetal sex and that nutritional interventions have different responses based on infant sex. Boys and girls born preterm are given standard nutritional support which does not take infant sex into account, and few studies of neonatal nutrition consider infant sex as a potential mediator of outcomes. By optimising early nutrition for boys and girls born preterm, we may improve outcomes for both sexes. We propose future studies of neonatal nutritional interventions should consider infant sex.

Lactoferrin Metal Saturation-Which Form Is the Best for Neonatal Nutrition?

We evaluated the impact of metal saturation of lactoferrin (with iron and manganese) on population numbers of pathogenic species relevant for neonatal sepsis that commonly originates from the gut due to bacterial translocation. Little attention has been paid to how metal ions bound to the protein affect its activity. Several reference and clinical strains as well as probiotic strains were incubated with different forms of lactoferrin: metal-depleted (apolactoferrin), iron-saturated (hololactoferrin) and manganese-saturated lactoferrin. We also attempted to confirm the observed effects of lactoferrin forms in vivo using rat pups. The observed decrease in population numbers of Gram-negative rods could not be confirmed by quantitative plating—lactoferrin may regulate these populations diversely (e.g., by anti-biofilm activity) and contribute to the inhibition of inflammatory response. We did not see any effect of lactoferrin forms on staphylococci and bifidobacteria. However, we have noted a significant increase of population numbers of Lactobacillus strains upon incubation with manganese-saturated lactoferrin. These results were confirmed in vivo in a rat model. Metal saturation is an underestimated factor regulating lactoferrin activity. Some forms are more potent in the inhibition of pathogenic species while others, such as manganese-saturated lactoferrin, could contribute to the restoration of gut homeostasis.

MODERN RECOMMENDATIONS FOR PARENTERAL NUTRITION OF NEWBORN

The problem of nutritional deficiency and the formation of postnatal body weight deficit in the first days after birth is characteristic mainly of premature babies. Newborns with very low birth weight have energy reserves that meet their needs only during the first 2-3 days of life. Even full-term babies quickly develop a catabolic type of metabolism if they do not get enough protein and calories. All preterm infants have an extremely low birth weight; there is a risk of early postnatal growth retardation associated with the formation of cumulative nutritional deficiencies and negative neurological consequences remotely. Therefore, an important result of quality medical care for newborns is the achievement of adequate (or as adequate as possible) nutrition, prevents or corrects nutritional deficiencies, and ensures the appropriate growth and development of the child. In the absence of full-fledged enteral feeding for medical reasons, parenteral nutrition is used. The purpose of the presented clinical recommendations is to improve the quality of medical care for significantly premature infants (gestational age less than 32 weeks), newborns with necrotizing enterocolitis, surgical pathology of the digestive tract, etc., by introducing modern approaches to effective and safe parenteral nutrition. The data presented are based on the ESPGHAN / ESPEN / ESPR Guidelines on Pediatric Parenteral Nutrition (2018) and NICE Neonatal Parenteral Nutrition (2020) and are intended for neonatologists, pediatric anesthesiologists, pediatricians, nurses, and other healthcare professionals involved in providing medical care to newborns for daily practice

Concentrating human milk: an innovative point-of-care device designed to increase human milk feeding options for preterm infants.

The purpose of this study was to determine whether a point-of-care osmotic device concentrates important human milk (HM) nutrients to support feeding neonates requiring high-nutrient, low-volume feedings. Raw and pasteurized HM samples were concentrated to determine the effects of time and temperature on concentration. Concentrated samples were compared with matched baseline samples to measure changes in selected nutrient concentrations. Furthermore, changes in concentration of certain bioactive components of raw milk samples were measured. The device significantly increased the concentrations of the majority of the measured nutrient and bioactive levels (p < 0.05). Increasing temperature of HM from 4 to 37 °C increased the concentration rate >30%. In all cases, the concentration rate of pasteurized HM was greater than that of raw HM. The osmotic concentration of HM is a promising option for neonatal nutrition. Further studies are needed to establish an evidence base for the practical applications of this point-of-care device.

Branched-chain amino acid supplementation for improving growth and development in term and preterm neonates.

Branched-chain amino acids (BCAAs) play a vital role in neonatal nutrition. Optimal BCAA supplementation might improve neonatal nutrient storage, leading to better physical and neurological development and other outcomes. To determine the effect of BCAA supplementation on physical growth and neurological development in term and preterm neonates. We planned to make the following comparisons: parenteral nutrition with and without BCAA supplementation; enteral BCAA supplementation versus no supplementation; and any type of supplementation including enteral, parenteral and both ways versus no supplementation. To investigate the supplementation effectiveness for different dosages assessed in the eligible trials. We conducted comprehensive searches using Cochrane Neonatal's standard search strategies: Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 6), MEDLINE, Embase and CINAHL (up to July 2016). We updated the search with CENTRAL (2019, Issue 8), MEDLINE, Embase and CINAHL (up to August 2019). We also searched clinical trials registries and reference lists of retrieved articles. We planned to include individual and cluster-randomised and quasi-randomised controlled trials comparing BCAA supplementation versus placebo or no supplementation in term and preterm neonates. We excluded trials presented only as abstracts and cross-over trials. Two review authors independently assessed the eligibility of all potential studies identified from the search strategy. We planned to extract data using a pilot-tested standard data extraction form and assess risk of bias of the included studies following the methods described in the Cochrane Handbook for Systematic Reviews of Interventions. We planned to analyse treatment effects and report their effect estimates as per dichotomous or continuous data with 95% confidence intervals. We planned to conduct subgroup analysis to investigate heterogeneity, and perform sensitivity analysis where possible. We planned to use fixed-effect meta-analysis to combine data wherever appropriate. We planned to assess evidence quality using the GRADE approach. We did not identify any potentially eligible studies that met the inclusion criteria in this review. We found no trial data to support or refute the idea that BCAA supplementation affects physical and neurological development and other outcomes in term and preterm neonates.

Iatrogenic Pleural Effusion Due to Extravasation of Parenteral Nutrition via an Epicutaneo Cava Catheter in Neonates: A Prospective Cohort Study.

Background: Although Epicutaneo cava catheters (ECCs) are being routinely used for intravenous access for long-term parenteral nutrition and prolonged medication administration in neonates, ECC use can be associated with rare but acute life-threatening events such as pleural effusion (PE). It is important to identify and maintain the ECC tip in a central location for preventing complications. Recently, intracavitary electrocardiogram (IC-ECG) has been developed for the real-time monitoring and verification of ECC tip position.Objective: To investigate the causes and preventive measures of ECC-related PE in neonates.Methods: This prospective cohort study was conducted between January 2013 and December 2017. We observed and analyzed the clinical characteristics and causes of ECC-related PE. From January to December 2017, all ECCs were guided by IC-ECG. The incidence of ECC-related PE and first-attempt success rates were analyzed before and after the introduction of IC-ECG. Additionally, the sensitivity and specificity of IC-ECG were evaluated.Results: ECC-related PE was identified in 14 infants. Catheters were malpositioned in three cases; in the other 11 cases, catheters were located centrally on insertion but had migrated to non-central locations at the time of PE. After the introduction of IC-ECG, the incidence of PE was zero (P < 0.05). The incidence of ECC-related PE was lower when veins of the lower extremities were selected as the insertion site (P < 0.05). The first-attempt success rate was significantly higher in the group with IC-ECG-guided ECC placement than in the group without (P < 0.05). The sensitivity and specificity of IC-ECG were 97.9 and 84.6%, respectively.Conclusion: ECC-related PE can be associated with either primary malposition or migration of the catheter tip. IC-ECG can help detect malposition and migration of catheter tips and improve the first-attempt success rate. Choosing a lower extremity insertion site may help decrease the rate of ECC-related PE. In neonates, IC-ECG is a reliable positioning method for ECCs with superior sensitivity and specificity.

Management and Nutrition of Neonates during the COVID-19 Pandemic: A Review of the Existing Guidelines and Recommendations.

We aimed at reviewing the currently available guidelines and scientific recommendations regarding the neonatal in-hospital management and feeding in the light of the coronavirus disease 2019 (COVID-19) pandemic. We systematically searched the guideline databases, Medline, Embase, and nationale/international neonatal societies websites as of June 19, 2020, for guidelines on neonatal management and feeding during the COVID-19 pandemic, at the same time assessing the methodological quality using the Appraisal of Guidelines for Research and Evaluation II tool. Eleven guidelines were included. The Chinese and American recommendations suggest separation of the mother and her neonate, whereas in French, Italian, UK, Canadian, and World Health Organization consensus documents the rooming-in is suggested, with Centers for Disease Control and Prevention guidelines suggesting to decide on a case-by-case basis. All the guidelines recommend breastfeeding or feeding with expressed maternal milk; the only exception is the Chinese recommendations, these last suggesting to avoid breastfeeding. This review may provide a useful tool for clinicians and organizers, highlighting differences and similarities of the existing guidelines on the management and feeding strategies in the light of the COVID-19 pandemic. · This study compares guidelines on management and nutrition of a newborn born to a mother with SARS-CoV-2 infection.. · Existing guidelines on neonatal management and nutrition during the SARS-CoV-2 pandemic show many differences.. · The majority of recommendations are mainly based on experts' opinion and are not evidence-based..

Early Protein Intake Influences Neonatal Brain Measurements in Preterms: An Observational Study.

Introduction: To limit extrauterine growth restriction, recent guidelines on nutrition of preterm neonates recommended high protein intake since the first day of life (DOL). The impact of this nutritional strategy on the brain is still controversial. We aimed to evaluate the effects of protein intake on early cerebral growth in very low birth weight newborns.Materials and Methods: We performed serial cranial ultrasound (cUS) scans at 3–7 DOL and at 28 DOL in very low birth weight newborns consecutively observed in the neonatal intensive care unit. We analyzed the relation between protein intake and cerebral measurements at 28 DOL performed by cUS.Results: We enrolled 100 newborns (gestational age 29 ± 2 weeks, birth weight 1,274 ± 363 g). A significant (p < 0.05) positive correlation between enteral protein intake and biparietal diameter (r = 0.490**), occipital–frontal diameter (r = 0.608**), corpus callosum (length r = 0.293*, genu r = 0.301*), caudate head (right r = 0.528**, left r = 0.364**), and cerebellum (transverse diameter r = 0.440**, vermis height r = 0.356**, vermis width r = 0.377**) was observed at 28 DOL. Conversely, we found a significant negative correlation of protein intake given by parenteral nutrition (PN) with biparietal diameter (r = −0.524**), occipital–frontal diameter (r = −0.568**), body of corpus callosum (r = −0.276*), caudate head (right r = −0.613**, left r = −0.444**), and cerebellum (transverse diameter r = −0.403**, vermis height r = −0.274*, vermis width r = −0.462**) at 28 DOL. Multivariate regression analysis showed that measurements of occipital–frontal diameter, caudate head, and cerebellar vermis at 28 DOL depend positively on protein enteral intake (r = 0.402*, r = 0.305*, and r = 0.271*) and negatively by protein parenteral intake (r = −0.278*, r = −0.488*, and r = −0.342*).Conclusion: Brain development in neonatal life depends on early protein intake. High protein intake affects cerebral structures' measurements of preterm newborn when administered by PN. Positive impact on brain development encourages the administration of recommended protein intake mainly by enteral nutrition.

P43 Concentrated standardised PN to optimise nutrition in preterm infants

BackgroundIn 2010, the NCEPOD1 report demonstrated a lack of good nutritional care for preterm infants. Since that time various approaches have evolved including standardisation of PN,2 concentrated standardised PN3 and publication of a national framework from BAPM.4 The delivery of nutrition to preterm infants on our unit has been continuously monitored, evaluated and adapted.AimsThe aim of this audit was to evaluate whether reformulating our PN recipes would improve nutritional intake and thus growth parameters over the first 14 days after birth.MethodsData was collected from our EPMA system and analysed retrospectively from all infants born at our unit &lt;28 weeks gestation or &lt;1Kg from 16/4/2016 to 15/4/2017 (audit 1) and from 1/6/2018 to 31/5/2019 (audit 2).ResultsData from a total of 33 patients was analysed using Excel™. The mean gestation and weight were similar for both audit cycles. Audit 1: gestation 26.5 weeks, weight 0.75 kg; audit 2: gestation 26.7 weeks, weight 0.74 kg. The average time from birth to PN was less in audit 2 (12 hrs 8 mins vs 13 hrs 12 mins), however the time from PN being prescribed to being administered took over 3 times longer (5 hrs 1 min vs 1 hr 30 mins). No patient received PN within 6 hours of birth in audit 2 compared to 20% in audit 1. The average nitrogen intake was higher in audit 2 than audit 1 (0.41 g/kg/day vs 0.36 g/kg/day) and the highest protein intake increased from 0.55 g/kg/day to 0.69 g/kg/day respectively; the average energy intake decreased from 73.5 kcal/kg/day in audit 1 to 68 kcal/kg/day in audit 2. The non-nitrogen energy to nitrogen ratio was lower in audit 2 versus audit 1 (165.3 kcal/g nitrogen vs 204.7 kcal/g nitrogen). There was no change in the percentage of patients requiring insulin: 40%. More patients had started receiving lipid infusion in the first 2 days after birth in audit 2 compared to audit 1 (94% compared to 33%). Both audits had 2 patients that had still not reached their birth weight by day 14, however the patients in audit 2 gained on average 9.12 g/kg/day compared to 4.96 g/kg/day in audit 1.ConclusionReformulating the PN resulted in higher nitrogen intakes and higher weight gain by day 14, although the full benefit may not have been achieved due to the lower kcal intake and non-nitrogen energy to nitrogen ratio. The time from birth to PN and the time taken to administer PN once prescribed were longer so work needs to be done on addressing these issues and reducing barriers to nutrition. The total nitrogen intake with PN and EN also needs to be reviewed to prevent excessive nitrogen intake which may result if enteral feeds increase and the rate of PN is maintained.ReferencesStewart JAD, Mason DG, Smith N, Protopapa K, Mason N, on behalf of CEPOD. 2010. A mixed bag; an enquiry into the care of hospital patients receiving parenteral. https://www.ncepod.org.uk/2010report1/downloads/PN_report.pdf Accessed 03/07/2019Paediatric Chief Pharmacists Group. Improving Practice and Reducing Risk in the Provision of Parenteral Nutrition for Neonates and Children. 2011Morgan C, Radbone L, Birch J. 2016 The Neonatal Parenteral Nutrition (PN) QIPP Toolkit https://www.networks.nhs.uk/nhs-networks/staffordshire-shropshire-and-black-country-newborn/documents/documents/national-toolkit-for-standardising-pn Accessed 03/07/2019British Association of Perinatal Medicine. The Provision of Parenteral Nutrition within Neonatal Services – A Framework for Practice. 2016. https://www.bapm.org/sites/default/files/files/Parenteral%20Nutrition%20April%202016.pdf Accessed 03/07/2019

P17 Introducing concentrated preterm stock parenteral nutrition and the impact on bespoke compounding

BackgroundIt is widely recommended that stock parenteral nutrition (PN) bags are used where possible to reduce the risks associated with bespoke PN compounding.1 A review was undertaken within a level three neonatal unit which identified that a large proportion of compounded bags were made due to the need to provide full nutrition in a smaller volume. A preterm concentrated aqueous PN bag was developed which, when run with stock lipid syringes, meets the nutritional requirements of preterm babies in a total volume of 100 ml/kg/day.2AimThe aim of this work is to evaluate the impact of the introduction of a preterm concentrated stock bag on the need for bespoke PN in preterm babies.MethodThe new concentrated PN bag was transitioned into use from November 2017. Data regarding the number of preterm patients admitted and the type of PN they received was collected from January to October 2017, (Group A), this was then repeated for all preterm patients admitted from August 2018 to May 19, (Group B), after the preterm concentrated bag was fully introduced. Preterm babies were classified as babies that were born &lt; 34 weeks gestation as the concentrated bag was formulated with these patients in mind.ResultsGroup A, (n=143), had 1045 bags supplied over the collection period. 47% of the PN bags supplied were bespoke PN bags, largely due to the need to provide PN in a smaller volume than the 130 ml/kg/day that the preterm stock bags available at that time. Group B, (n=118), had a total of 965 bags supplied, 16% of these bags were bespoke PN. The reasons behind requiring bespoke bags included the need for manganese free bags, requiring a reduction in glucose and a high electrolyte requirement in patients especially those with stomas. This has resulted in an overall reduction in spend on preterm PN of 34% and a reduction in compounded PN spend of 69%.ConclusionThis work has highlighted several benefits of introducing preterm concentrated PN bags. Firstly having concentrated preterm stock bags available on the ward has meant that a larger proportion of babies are maintained on stock PN without recourse to compounded PN. Secondly this has preserved the compounding capacity of our technical services unit so when a patient requires a bespoke bag that facility is available. Also, capacity for the compounding service has been preserved across the hospital minimising the need to outsource compounding. Finally the neonatal unit has seen a reduction in overall PN costs in this patient group. The introduction of this bag has been instrumental in reducing the need to outsource PN bags to commercial compounding units during periods of high demand, meeting national recommendations on the management of aseptic compounding capacity.3ReferencesA Report from the Paediatric Chief Pharmacists Group: Improving Practice and Reducing Risk in the Provision of Parenteral Nutrition for Neonates and Children. November 2011.British Association of Perinatal Medicine. The Provision of Parenteral Nutrition within Neonatal Services - A Framework for Practice. April 2016.Specialist Pharmacy Service/NHS England. National Pharmaceutical Supply Group (NPSG) Communication: Making best use of restricted aseptic compounding capacity. September 2018.

Type 2 Diabetes in Youth: the Role of Early Life Exposures.

This review examines the impact of early life exposures on glucose metabolism in the offspring and explores potential metabolic mechanisms leading to type 2 diabetes in childhood. One in five adolescents is diagnosed with prediabetes. Recent studies have elucidated the impact of early exposures such as maternal diabetes, but also hyperglycemia below the threshold of gestational diabetes, obesity, hyperlipidemia, and paternal obesity on the future metabolic health of the offspring. Mechanisms affecting the developmental programing of offspring toward type 2 diabetes include epigenetic modifications, alterations in stem cell differentiation, metabolome and microbiome variation, immune dysregulation, and neonatal nutrition. The risk of type 2 diabetes in offspring is increased not only by diabetes exposure in utero but also by exposure to a heterogeneous milieu of factors that accompany maternal obesity that provoke a vicious cycle of metabolic disease. The key period for intervention to prevent type 2 diabetes is within the first 1000days of life.

Neonatal parenteral nutrition affects the metabolic flow of glucose in newborn and adult male Hartley guinea pigs’ liver

Extremely premature birth is associated with a permanent disruption of energy metabolism. The underlying mechanisms are poorly understood. The oxidative stress induced by parenteral nutrition (PN) during the first week of life is suspected to reprogram energy metabolism in the liver. Full-term male Hartley guinea pigs (to isolate PN from prematurity) receiving PN enriched or not with glutathione (to isolate PN effects from PN-induced oxidative stress effects) or an Oral Nutrition (ON) during the first week of life were used. At 1 week (neonatal) and 16 weeks (adult), measurements of liver glutathione (GSH and GSSG) and activities of three key enzymes of energy metabolism (glucokinase (GCK), phosphofructokinase (PFK), and acetyl-CoA carboxylase (ACC)) were performed. Differences between groups were reported if p ≤ 0.05 (Analysis of Variance). At 1 week, compared to ON, PN induced higher GSSG (oxidative stress), higher GCK activity, and lower PFK and ACC activity, the glutathione supplement prevented all PN effects. At 16 weeks, early PN induced lower GSSG (reductive stress) and lower GCK activity, which was prevented by added glutathione, and higher ACC activity independent of glutathione supplement. ACC was negatively associated (r2 = 0.33) with GSSG. Increased nicotinamide adenine dinucleotide phosphate levels confirmed the glucose-6-phosphate accumulation at 1 week, whereas our protocol failed to document lipid accumulation at 16 weeks. In adult male guinea pigs, neonatal exposure to PN affected glutathione metabolism leading to reductive stress (lower GSSG) and an altered metabolic flow of glucose. Partial prevention with glutathione supplementation suggests that, in addition to peroxides, other factors of PN are involved.

Developmental programming of appetite and growth in male rats increases hypothalamic serotonin (5-HT)5A receptor expression and sensitivity.

Though it is well established that neonatal nutrition plays a major role in lifelong offspring health, the mechanisms underpinning this have not been well defined. Early postnatal accelerated growth resulting from maternal nutritional status is associated with increased appetite and body weight. Likewise, slow growth correlates with decreased appetite and body weight. Food consumption and food-seeking behaviour are directly modulated by central serotonergic (5-hydroxytryptamine, 5-HT) pathways. This study examined the effect of a rat maternal postnatal low protein (PLP) diet on 5-HT receptor mediated food intake in offspring. Microarray analyses, in situ hybridization or laser capture microdissection of the ARC followed by RT-PCR were used to identify genes up- or down-regulated in the arcuate nucleus of the hypothalamus (ARC) of 3-month-old male PLP rats. Third ventricle cannulation was used to identify altered sensitivity to serotonin receptor agonists and antagonists with respect to food intake. Male PLP offspring consumed less food and had lower growth rates up to 3 months of age compared with Control offspring from dams fed a normal diet. In total, 97 genes were upregulated including the 5-HT5A receptor (5-HT5AR) and 149 downregulated genes in PLP rats compared with Controls. The former obesity medication fenfluramine and the 5-HT receptor agonist 5-Carboxamidotryptamine (5-CT) significantly suppressed food intake in both groups, but the PLP offspring were more sensitive to d-fenfluramine and 5-CT compared with Controls. The effect of 5-CT was antagonized by the 5-HT5AR antagonist SB699551. 5-CT also reduced NPY-induced hyperphagia in both Control and PLP rats but was more effective in PLP offspring. Postnatal low protein programming of growth in rats enhances the central effects of serotonin on appetite by increasing hypothalamic 5-HT5AR expression and sensitivity. These findings provide insight into the possible mechanisms through which a maternal low protein diet during lactation programs reduced growth and appetite in offspring.

Characterization of a Swine Model of Birth Weight and Neonatal Nutrient Restriction

ABSTRACT Background Evidence indicates that birth weight and neonatal nutrition have lifelong effects. Animal models are required to improve our understanding of these factors. Objectives We aimed to develop and validate a swine model of birth weight and neonatal undernutrition. Methods At birth, a total of 112 piglets were identified as low (LBW; 1.22 ± 0.28 kg SEM) or normal birth weight (NBW; 1.70 ± 0.27 kg). From day 3 to weaning (day 28), piglets received normal nutrition (NN) or restricted nutrition (RN) via intermittent suckling, where piglets were isolated from the sow for 6 h/d. After weaning, pigs were fed a common diet for 28 d. Body weight (BW) was determined for the duration of the study. On days 28 and 56, empty carcass, viscera, and individual organ weights were determined in 8 pigs/treatment. Results LBW pigs remained smaller than NBW pigs, regardless of nutrient restriction (P &amp;lt; 0.05). Within birth weight category, RN reduced BW by day 7 after birth, which was maintained until weaning (P &amp;lt; 0.05); however, at 7 d postweaning there was no difference in BW due to RN (P &amp;gt; 0.05). At weaning, empty carcass, viscera, heart, liver, and lung weights were lower in LBW than in NBW pigs, whereas empty carcass, heart, small intestine, liver, kidneys, lung, and spleen weights were lower in RN than in NN pigs (P &amp;lt; 0.05). Brain weight was highest in NBW-NN and lowest in NBW-RN, with LBW intermediate, regardless of nutrient restriction (P &amp;lt; 0.05). Postweaning, LBW had lower empty carcass, viscera, heart, stomach, large intestine, liver, and kidney weights than NBW, whereas RN had a higher small intestine weight than NN (P &amp;lt; 0.05). Conclusions Intermittent suckling is an effective means of inducing nutrient restriction in a swine model.

NICE guidelines on neonatal parenteral nutrition: a step towards standardised care but evidence is scarce

NICE guidelines on neonatal parenteral nutrition: a step towards standardised care but evidence is scarce