Targeting optimal protein delivery in parenteral and enteral nutrition for preterm infants: a review of randomized, controlled trials.

Close attention to nutritional management is essential for optimizing growth and neurodevelopment of the preterm infant. Protein intake and the protein to energy ratio are the main determinants of growth and body composition. Yet large, multi-center, randomized controlled trials are lacking to guide protein delivery for the preterm infant. Until these studies are pursued, smaller trials must be used to inform clinical practice. This review summarizes the randomized controlled trials that have been performed to test the impact of higher vs. lower protein delivery to the preterm infant. We consider the trials that varied protein delivery rates during parenteral and enteral phases of nutrition. Considerable heterogeneity exists across study designs. Still, cumulative evidence from these trials provides a framework for current recommendations for protein intake in the preterm infant.

Guidelines for parenteral nutrition in preterm infants: The American Society for Parenteral and Enteral Nutrition.

BACKGROUND: Parenteral nutrition (PN) is prescribed for preterm infants until nutrition needs are met via the enteral route, but unanswered questions remain regarding PN best practices in this population. METHODS: An interdisciplinary committee was assembled to answer 12 questions concerning the provision of PN to preterm infants. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) process was used. Questions addressed parenteral macronutrient doses, lipid injectable emulsion (ILE) composition, and clinically relevant outcomes, including PNALD, early childhood growth, and neurodevelopment. Preterm infants with congenital gastrointestinal disorders or infants already diagnosed with necrotizing enterocolitis or PN-associated liver disease (PNALD) at study entry were excluded. RESULTS: The committee reviewed 2460 citations published between 2001 and 2023 and evaluated 57 clinical trials. For most questions, quality of evidence was very low. Most analyses yielded no significant differences between comparison groups. A multicomponent oil ILE was associated with a reduction in stage 3 or higher retinopathy of prematurity (ROP) compared to an ILE containing 100% soybean oil. For all other questions, expert opinion was provided. CONCLUSION: Most clinical outcomes were not significantly different between comparison groups when evaluating timing of PN initiation, amino acid dose, and ILE composition. Future clinical trials should standardize outcome definitions to permit statistical conflation of data, thereby permitting more evidence based recommendations in future guidelines. This guideline has been approved by the ASPEN 2022-2023 Board of Directors.

Administering Parenteral Nutrition in the Neonatal Intensive Care Unit: Logistics, Existing Challenges, and a Few Conundrums.

Use of parenteral nutrition (PN) in the neonatal intensive care unit (NICU) requires evaluating the need for central venous catheters, potential drug incompatibilities, unintentional exposures, and suboptimal energy and nutrient intake during the transition to full enteral nutrition. Risks of photooxidation reactions in PN components, refeeding syndrome, and excess early amino acid intake should prompt the reevaluation of routine practices. The goal of this paper is to review the practicalities, challenges, and conundrums of administering PN in the NICU.

The Role of Work as a Social Determinant of Health in Mother's Own Milk Feeding Decisions for Preterm Infants: A State of the Science Review.

In the United States, 10% of infants are born preterm (PT; <37 weeks gestational age) each year and are at higher risk of complications compared to full term infants. The burden of PT birth is borne disproportionately by Black versus non-Black families, with Black mothers significantly more likely to give birth to a PT infant. One proven strategy to improve short- and long-term health outcomes in PT infants is to feed mother's own milk (MOM; breast milk from the mother). However, mothers must make decisions about work and MOM provision following PT birth, and more time spent in paid work may reduce time spent in unpaid activities, including MOM provision. Non-Black PT infants are substantially more likely than Black PT infants to receive MOM during the birth hospitalization, and this disparity is likely to be influenced by the complex decisions mothers of PT infants make about allocating their time between paid and unpaid work. Work is a social determinant of health that provides a source of income and health insurance coverage, and at the same time, has been shown to create disparities through poorer job quality, lower earnings, and more precarious employment in racial and ethnic minority populations. However, little is known about the relationship between work and disparities in MOM provision by mothers of PT infants. This State of the Science review synthesizes the literature on paid and unpaid work and MOM provision, including: (1) the complex decisions that mothers of PT infants make about returning to work, (2) racial and ethnic disparities in paid and unpaid workloads of mothers, and (3) the relationship between components of job quality and duration of MOM provision. Important gaps in the literature and opportunities for future research are summarized, including the generalizability of findings to other countries.

Preterm infant nutrition: considerations for infants at risk of refeeding syndrome.

Refeeding syndrome (RS) in preterm infants is a scenario of fetal malnutrition, primarily resulting from placental insufficiency, followed by a postnatal physiologic adaptation and response to an imbalance of nutrients provided parenterally. Growth restriction and small gestational age status are common findings in infants at risk of developing RS. Adverse clinical outcomes associated with RS may be severe and life-threatening. The biochemical abnormalities that occur in RS may be mitigated through careful monitoring and adaptation of the clinical management of parenteral and enteral nutrition. This perspective reviews the physiology and metabolism in infants with RS and provides suggested approaches to their clinical monitoring and nutritional management.

Body composition measurement for the preterm neonate: using a clinical utility framework to translate research tools into clinical care.

Body composition analysis to distinguish between fat mass and fat-free mass is an established research approach to assess nutritional status. Within neonatal medicine, preterm infant body composition is linked with later health outcomes including neurodevelopment and cardiometabolic health. Mounting evidence establishing fat-free mass as an indicator of nutritional status, coupled with the availability of testing approaches that are feasible to use in preterm infants, have enhanced interest in measuring body composition in the neonatal intensive care unit (NICU) setting. In this paper, we use the concept of clinical utility-the added value of a new methodology over current standard care-as a framework for assessing several existing body composition methodologies with potential for clinical application to preterm neonates. We also use this framework to identify remaining knowledge gaps and prioritize efforts to advance our understanding of clinically-oriented body composition testing in the NICU.

Hypertriglyceridemia in Preterm Infants.

Preterm and critically ill infants are at risk for hypertriglyceridemia (HTG). Common risk factors for HTG include prematurity, intravenous lipid emulsion dose and oil composition, reduced lipoprotein lipase activity, fetal growth restriction, sepsis, and renal failure. Despite these risk factors, clinicians lack a universally agreed upon definition for HTG and evidence-based approach to HTG management. This review provides a detailed overview of triglyceride and intravenous lipid emulsion metabolism and how this relates to specific HTG risk factors, along with some practical considerations for managing HTG in the neonatal population.

Early Growth and Cognitive Development in Children Born Preterm: Relevance of Maternal Body Mass Index.

OBJECTIVE: Maternal prepregnancy body mass index (BMI) represents a surrogate marker of fetal exposures to the maternal metabolism during pregnancy. Yet, it remains poorly understood whether this marker indicates risk of altered trajectories in postnatal growth and development in children born preterm. This study aimed to determine whether maternal prepregnancy BMI is associated with altered growth and development in children born preterm. STUDY DESIGN: A retrospective cohort study evaluated prepregnancy BMI as the exposure for childhood outcomes using linear regression and mixed effects models. The 38 children included in this follow-up evaluation originally participated in a prospective, observational cohort study to determine longitudinal levels of lipid species in preterm human milk expressed by women who delivered prior to 32 weeks. Childhood outcomes in this study were anthropometric measures during hospitalization (n = 38), after discharge through 36 months (n = 34) and Bayley-III developmental scores through 18 months corrected age (n = 26). RESULTS: In 38 children born prior to 32 weeks, higher maternal prepregnancy BMI was independently associated with higher preterm infant growth velocity during hospitalization, but not associated with in-hospital change in length or head circumference and/or postdischarge growth. In univariate linear regression models, higher maternal BMI was associated with lower cognitive scores at 18 months corrected age. This significant association remained in an adjusted model accounting for relevant influences on early childhood development. CONCLUSION: Increasing maternal prepregnancy BMI may reflect risk of altered growth and cognitive development in children born preterm. KEY POINTS: · Maternal BMI was associated with early preterm infant weight gain.. · Maternal BMI was not associated with postdischarge growth.. · Increased maternal BMI may be associated with lower cognitive function scores in offspring..

Providing Breastfeeding Support During COVID-19: A Survey of Staff Experiences.

BACKGROUND: The COVID-19 pandemic presents unique challenges to maternity settings. Its influence on providing in-hospital lactation support has not been well described. RESEARCH AIM: To describe the experiences of healthcare workers as they provided in-hospital lactation support during the pandemic. METHODS: A prospective, cross-sectional, online survey evaluated healthcare providers working with postpartum women and newborns affected by COVID-19 at an academic center during March-June 2020. Providers were queried regarding the influence of COVID-19 and COVID-19-specific policies on providing lactation support. Questions assessed guidance received, perceived stress, difficulty providing care, and solicited qualitative responses. The constant comparative method was used to analyze qualitative data. RESULTS: Of 108 providers, 70 (65%) completed the survey. Of 57 providing direct lactation support to women affected by COVID-19, most (n = 39, 67%) reported increased stress. Participants reported lower stress scores when receiving guidance through shift meetings or email compared to those not receiving this guidance [stress score with shift meeting guidance (M [SD]): 3.10 (0.88); score without guidance: 3.83 (0.66); n = 39, p = .009; score with email guidance: 3.79 (0.58); score without guidance: 4.50 (0.58); n = 18, p = .045). Qualitative responses (n = 67; 96%) identified three themes: visitor restrictions allowed less distraction during lactation support; physical separation disrupted maternal/infant bonding; workflow challenges resulted from policy changes and supply access. CONCLUSIONS: Most participating staff providing lactation support to participants affected by COVID-19 reported increased stress. Ensuring written or verbal guidance may reduce staff's experiences of stress. Efforts to optimize lactation support during COVID-19 should consider reducing distractions, physical separation, and logistic challenges.

Human Milk Growth Factors and Their Role in NEC Prevention: A Narrative Review.

Growing evidence demonstrates human milk's protective effect against necrotizing enterocolitis (NEC). Human milk derives these properties from biologically active compounds that influence intestinal growth, barrier function, microvascular development, and immunological maturation. Among these protective compounds are growth factors that are secreted into milk with relatively high concentrations during the early postnatal period, when newborns are most susceptible to NEC. This paper reviews the current knowledge on human milk growth factors and their mechanisms of action relevant to NEC prevention. It will also discuss the stability of these growth factors with human milk pasteurization and their potential for use as supplements to infant formulas with the goal of preventing NEC.

Recommendations for photoprotection of parenteral nutrition for premature infants: An ASPEN position paper.

Although crucial in improving health outcomes in the preterm infants, parenteral nutrition (PN) is not without risk, especially if handled improperly. A growing body of evidence suggests that components of PN admixtures, including lipid injectable emulsions (ILEs), are susceptible to degradation, including oxidation when exposed to light (ie, photo-oxidation), resulting in the production of reactive oxygen species. Infants, especially those born preterm, are considered more susceptible to consequences of oxidative stress than children and adults. Oxidative stress is associated with bronchopulmonary dysplasia, retinopathy of prematurity, necrotizing enterocolitis, and intestinal failure-associated liver disease. The American Society for Parenteral and Enteral Nutrition (ASPEN) assembled a working group to provide recommendations on clinical practice surrounding photoprotection of PN.This Position Paper reviews the scientific literature on the formation of quantifiable peroxides and other degradation products when PN admixtures and ILEs are exposed to light and reports adverse clinical outcomes in premature infants exposed to PN. Recommendations for photoprotection of PN admixtures and ILEs are provided, as well as the challenges in achieving complete photoprotection with the equipment, supplies, and materials currently available in the US. ASPEN and the authors understand that the full implementation of complete photoprotection may not currently be feasible given current product availability; recommendations provided in this paper serve to represent the goal to which to strive as well as to highlight the importance of product availability to achieve these practices. This paper has been approved by the ASPEN Board of Directors.

Dietary Fat and Fatty Acid Intake in Nulliparous Women: Associations with Preterm Birth and Distinctions by Maternal BMI.

BACKGROUND: Evidence documenting whether diet quality, particularly dietary fatty acids, is associated with preterm birth (PTB) is limited. OBJECTIVE: The aim was to measure associations between dietary fatty acid intake prior to pregnancy, specifically n-3 (É·-3) PUFAs and odds of PTB in US women and determine if associations differed by prepregnancy BMI. METHODS: We designed a secondary analysis of dietary intake in nulliparous women enrolled in a longitudinal cohort (NCT01322529). Participants completed an FFQ, modified to assess detailed PUFA intake, during the 3 mo preceding pregnancy. Inclusion in this analytic cohort required total energy intake within 2 SDs of the group mean. Prepregnancy BMI was categorized as underweight, normal, overweight, or obese. The primary exposure was estimated intake of EPA and DHA (combined EPA+DHA), in the context of a recommended intake of 250 mg. The primary outcome was PTB (<37 wk). Adjusted regression models controlled for maternal factors relevant to PTB and evaluated associations with PUFAs. Interaction terms estimated effect modification of BMI. A false discovery rate (FDR) correction accounted for multiple comparisons. RESULTS: Median daily intake of combined EPA+DHA in 7365 women was 70 mg (IQR: 32, 145 mg). A significant interaction term indicated the effects of EPA+DHA on odds of PTB were different for different BMI categories (P < 0.01). Specifically, higher intake of combined EPA+DHA was nominally associated with reduced odds of PTB in women with underweight (OR: 0.67; 95% CI: 0.46-0.98) and normal BMI (OR: 0.87; 95% CI: 0.78-0.96), yet was associated with increased odds of overweight BMI (OR: 1.21; 95% CI: 1.02-1.44). Associations remained significant after FDR correction. CONCLUSIONS: Based on a cohort of US women designed to identify predictors of adverse pregnancy outcomes, dietary intake of combined EPA+DHA was considerably lower than recommended. Associations between intake of these recommended n-3 fatty acids and risk of PTB differ by maternal BMI.

Randomized Controlled Trial of Early Docosahexaenoic Acid and Arachidonic Acid Enteral Supplementation in Very Low Birth Weight Infants.

OBJECTIVE: To determine feasibility of providing a concentrated emulsified long-chain polyunsaturated fatty acids (LCPUFA) supplement to very low birth weight infants, and to evaluate blood LCPUFA concentrations at 2 and 8 weeks of study supplementation. STUDY DESIGN: This prospective, randomized, double-blind, placebo-controlled trial randomized infants to receive (1) LCPUFA-120 (a supplement of 40 mg/kg/day docosahexaenoic acid [DHA] and 80 mg/kg/day arachidonic acid [ARA]; DHA:ARA at 1:2 ratio), (2) LCPUFA-360 (a supplement of 120 mg/kg/day DHA and 240 mg/kg/day ARA), or (3) sunflower oil (placebo control). Infants received supplement daily for 8 weeks or until discharge, whichever came first. Whole blood LCPUFA levels (wt%; g/100 g) were measured at baseline, 2 weeks, and 8 weeks. RESULTS: Infants were 28 weeks of gestation (IQR, 27-30 weeks of gestation) and weighed 1040 g (IQR, 910-1245 g). At 2 weeks, the change in blood DHA (wt%) from baseline differed significantly among groups (sunflower oil, n = 6; -0.63 [IQR, -0.96 to -0.55]; LCPUFA-120: n = 12; -0.14 [IQR, -0.72 to -0.26]; LCPUFA-360, n = 12; 0.46 [IQR, 0.17-0.81]; P = .002 across groups). Change in blood ARA (wt%) also differed by group (sunflower oil: -2.2 [IQR, -3.9 to -1.7]; LCPUFA-120: 0.1 [IQR, -2.1 to 1.1] vs LCPUFA-360: 2.9 IQR, 1.5 to 4.5]; P = .0002). Change from baseline to 8 weeks significantly differed between groups for DHA (P = .02) and ARA (P = .003). CONCLUSIONS: Enteral LCPUFA supplementation supported higher blood DHA by 2 weeks. LCPUFA supplementation at 360 mg of combined DHA and ARA is likely necessary to reduce declines as well as allow increases in whole blood concentrations in the first 8 weeks of life. TRIAL REGISTRATION: Clinicaltrials.gov: NCT03192839.

Preterm human milk at lactation weeks 1 and 4 categorized by maternal pre-pregnancy body mass index: Metabolomics and lipidomics datasets.

Human milk samples were prospectively obtained from women who delivered prior to the 32nd week of gestation [1]. The 36 preterm human milk samples analysed in this dataset were collected at week 1 and week 4 of lactation. Samples were categorized as being from women with normal pre-pregnancy body mass index (BMI 18-24.9 kg/m2) versus overweight/obese (BMI ≥25). Whole milk samples were frozen at -80 Celsius without prior processing and shipped for analysis on dry ice. Untargeted metabolomic and lipidomic platforms using UPLC-MS/MS and infusion-MS analysis for select lipids were performed by Metabolon. Lipidomic analysis included detection of complex lipids found in the milk fat globule membrane. Data were categorized by maternal BMI, week of lactation as well as gestational age at delivery. Data sheets are separated based on whether they report metabolomics versus lipidomics, as well as whether they report output from samples collected at week 1 versus week 4 of lactation. These data allow calculating relationships between clinical variables and human milk components. As an illustrative example, correlations between pre-pregnancy BMI and total milk fatty acids were calculated for this report using the Spearman correlation. These data will inform scientists of variability in milk composition attributable to maternal pre-pregnancy BMI as well as changes in milk composition as milk matures during lactation from week 1 to week 4. These data may best be used for generating hypotheses and justification of future work investigating whether maternal pre-pregnancy body mass index impacts preterm human milk composition.

Implications of continuity of care on infant caloric intake in the neonatal intensive care unit.

OBJECTIVE: To estimate the association of continuity of neonatologist care with caloric intake and growth velocity (GV) in very low birth weight (VLBW) infants. STUDY DESIGN: We created a daily continuity index (DCI) defined as the number of days the neonatologist worked in the previous week. We estimated the independent associations between this index and infants' daily caloric intake (kcal/kg/day) and GV (g/kg/day) through the first 6 weeks of life using regression analyses. RESULTS: Twenty-eight neonatologists cared for 115 infants over 4643 patient-days. The DCI was independently associated with increased caloric intake (ß = 1.27 kcal/kg/day per each day of continuity, p < 10-4); this effect was magnified (ß = 3.33, p < 10-4) in the first 2 weeks. No association was observed between the index and GV. CONCLUSIONS: Neonatologist continuity may contribute to caloric intake in VLBW infants. Quality metrics focused on this area of health care delivery warrant further discovery.

Intravenous Lipid Emulsions in the NICU.

The clinical goals of intravenous lipid emulsions (ILEs) have changed since their initial development. In the past, 100% soybean oil was used to provide energy and prevent an essential fatty acid deficiency. Now, different oil sources are used with the goal of improving nutritional status and preventing common neonatal comorbidities. We now have a better understanding of specific ILE constituents, namely, fatty acids, vitamin E, and phytosterols, and how these components contribute to complications such as intestinal failure-associated liver disease. This review addresses the development and composition of different ILEs and summarizes how individual ILE ingredients affect infant metabolism and health.