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Topographic patterns of brain injury in neonates can help with differentiation and prognostic categorization of hypoxic ischemic encephalopathy (HIE). In this study, we quantitatively and objectively characterized the location of hypoxic ischemic lesions in term neonates with varying severity of HIE.We analyzed term neonates (born ≥37 postmenstrual gestational weeks) with MRI diffusion-weighted imaging (DWI) and diagnoses of HIE. Neonates' HIE was categorized into mild, moderate, and severe. The hypoxic ischemic lesions were segmented on DWI series with attention to T1- and T2-weighted images and then co-registered onto standard brain space to generate summation maps for each severity category. Applying voxel-wise general linear models, we also identified cerebral regions more likely to infarct with increasing severity of HIE, after correction for lesion volume and time-to-scan as covariates.We included 33 neonates: 20 with mild, eight with moderate, and five with severe HIE. Infarct volumes (p = .00052) and Appearance, Pulse, Grimace, Activity, and Respiration scores at 1 minute (p = .032) differed between HIE severity categories. Hypoxic ischemic lesions in neonates with mild and moderate HIE were predominant in subcortical and deep white matter along the border zones of arterial supply territories, while severe HIE also involved basal ganglia, hippocampus, and thalamus. In voxel-wise analysis, higher severity of HIE was associated with the presence of lesions in hippocampus, thalamus, and lentiform nucleus.In term neonates, mild/moderate HIE is associated with infarctions of arterial territory watershed zones, whereas severe HIE distinctively involves basal ganglia, thalami, and hippocampi.

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.

Human milk (HM) with appropriate fortification is the recommended nutrition for very low birth weight (VLBW) infants. Fortification provides additional nutrients, vitamins, and minerals to support the growing preterm infant during critical periods of development. This article discusses the variability of HM including differences between maternal and pasteurized donor human milk (DHM), fortification of HM through the use of single- and multi-nutrient fortifiers, and clinical controversies including the timing of fortification, volume of feedings, and future innovations in HM fortification.

Background: Racial disparities in breastfeeding rates persist in the United States with Black women having the lowest rates of initiation and continuation. A literature review attributes this to ma...

Background Standardized parenteral nutrition (PN) formulations are used in at-risk neonates to provide nutrition immediately following birth. However, evidence for the optimal formulation(s) to maximize growth while reducing the risks of glucose and electrolyte abnormalities is limited. Purpose The purpose of this study was to compare the rates of hypernatremia and hyperglycemia with 2 weight-based standardized PN formulations versus one standard PN in low birth-weight preterm neonates. Methods This was a single-center observational study of infants less than 1800 g birth weight and less than 37 weeks' gestation who received standardized PN in the first 48 hours of life. Patients in the weight-based PN group were compared with a historical group of patients receiving single standard PN. Rates of hypernatremia and hyperglycemia were compared by χ2 analysis. Results There was a nonsignificant (P = .147) reduction in hypernatremia in the weight-based PN group (9 of 87; 10.3%) compared with the single PN group (16 of 89; 18.0%). However, hyperglycemia was significantly more frequent in the weight-based group than in the single PN group (24.1% vs 12.4%, P = .035). Implications for practice The 2 weight-based PN standardized formulations studied did not significantly decrease the incidence of hypernatremia or hyperglycemia. Implications for research Future studies to determine optimal standardized PN to provide early nutrition in high-risk neonates are warranted.

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 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.

This study reports on the human milk fortification session at the 2019 NEC Society Symposium, which included clinicians and parents discussing the evidence comparing fortification options such as efficacy, safety, cost effectiveness, and the need for parents to be informed about fortifier choice. With the current literature available and the varying standard of care practices for human milk fortification, further studies are needed to determine the most complete diet for preterm infants. The optimal diet would not only provide key nutrients and energy for growth and development, but also improve short- and long-term outcomes. Parents, as advocates and providers for their infant, should be informed, educated, and included in the discussion and decisions regarding fortification of human milk for their infant.

ImportanceAside from widely known cardiovascular implications, higher weight in children may have negative associations with brain microstructure and neurodevelopment.ObjectiveTo evaluate the association of body mass index (BMI) and waist circumference with imaging metrics that approximate brain health.Design, Setting, and ParticipantsThis cross-sectional study used data from the Adolescent Brain Cognitive Development (ABCD) study to examine the association of BMI and waist circumference with multimodal neuroimaging metrics of brain health in cross-sectional and longitudinal analyses over 2 years. From 2016 to 2018, the multicenter ABCD study recruited more than 11 000 demographically representative children aged 9 to 10 years in the US. Children without any history of neurodevelopmental or psychiatric disorders were included in this study, and a subsample of children who completed 2-year follow-up (34%) was included for longitudinal analysis.ExposuresChildren’s weight, height, waist circumference, age, sex, race and ethnicity, socioeconomic status, handedness, puberty status, and magnetic resonance imaging scanner device were retrieved and included in the analysis.Main Outcomes and MeasuresAssociation of preadolescents’ BMI z scores and waist circumference with neuroimaging indicators of brain health: cortical morphometry, resting-state functional connectivity, and white matter microstructure and cytostructure.ResultsA total of 4576 children (2208 [48.3%] female) at a mean (SD) age of 10.0 years (7.6 months) were included in the baseline cross-sectional analysis. There were 609 (13.3%) Black, 925 (20.2%) Hispanic, and 2565 (56.1%) White participants. Of those, 1567 had complete 2-year clinical and imaging information at a mean (SD) age of 12.0 years (7.7 months). In cross-sectional analyses at both time points, higher BMI and waist circumference were associated with lower microstructural integrity and neurite density, most pronounced in the corpus callosum (fractional anisotropy for BMI and waist circumference at baseline and second year: P P P = .09; neurite density for BMI at second year: P = .002; neurite density for waist circumference at second year: P = .05), reduced functional connectivity in reward- and control-related networks (eg, within the salience network for BMI and waist circumference at baseline and second year: P P P = .003) and microstructure and cytostructure of the corpus callosum (fractional anisotropy: P = .01; neurite density: P = .02).Conclusions and RelevanceIn this cross-sectional study, higher BMI and waist circumference among children aged 9 to 10 years were associated with imaging metrics of poorer brain structure and connectivity as well as hindered interval development. Future follow-up data from the ABCD study can reveal long-term neurocognitive implications of excess childhood weight. Imaging metrics that had the strongest association with BMI and waist circumference in this population-level analysis may serve as target biomarkers of brain integrity in future treatment trials of childhood obesity.

Accelerated maturation of brain parenchyma close to term-equivalent age leads to rapid changes in diffusion-weighted imaging (DWI) and diffusion tensor imaging (DTI) metrics of neonatal brains, which can complicate the evaluation and interpretation of these scans. In this study, we characterized the topography of age-related evolution of diffusion metrics in neonatal brains. We included 565 neonates who had MRI between 0 and 3 months of age, with no structural or signal abnormality-including 162 who had DTI scans. We analyzed the age-related changes of apparent diffusion coefficient (ADC) values throughout brain and DTI metrics (fractional anisotropy [FA] and mean diffusivity [MD]) along white matter (WM) tracts. Rate of change in ADC, FA, and MD values across 5 mm cubic voxels was calculated. There was significant reduction of ADC and MD values and increase of FA with increasing gestational age (GA) throughout neonates' brain, with the highest temporal rates in subcortical WM, corticospinal tract, cerebellar WM, and vermis. GA at birth had significant effect on ADC values in convexity cortex and corpus callosum as well as FA/MD values in corpus callosum, after correcting for GA at scan. We developed online interactive atlases depicting age-specific normative values of ADC (ages 34-46 weeks), and FA/MD (35-41 weeks). Our results show a rapid decrease in diffusivity metrics of cerebral/cerebellar WM and vermis in the first few weeks of neonatal age, likely attributable to myelination. In addition, prematurity and low GA at birth may result in lasting delay in corpus callosum myelination and cerebral cortex cellularity.

Despite abundant research comparing postdischarge hospital diets for preterm infants, the ideal clinical approach has not been determined. Dilemmas persist because randomized controlled trials of preterm versus term infant formula have yielded equivocal results and because the predominant postdischarge diet for preterm infants has shifted from formula-based to a combination that includes maternal milk and increasingly includes a plan for breastfeeding. As the investigation of the influence of the post–hospital discharge diet on preterm infant outcomes evolves, factors to consider include the infant’s oral feeding ability and the maternal lactation goal. The maturation of the preterm infant’s oral feeding skills may at least partially explain why increased nutrient density appears to most benefit growth outcomes when given during the first 3 to 4 months after hospital discharge. At some point in maturation, the preterm infant may develop the ability to vary intake as needed to obtain sufficient nutrition no matter the density of the diet. In addition, attention to the maternal lactation goal is critical as intake of maternal milk likely influences neurodevelopmental outcomes as much or even to a greater extent than growth trajectory.

Background: Vitamin D supplementation is known to both prevent and treat rickets, a disease of hypomineralized bone. Childhood is a period of great bone development and, therefore, attention to the vitamin D needed to optimize bone health in childhood is imperative. Summary: Observational studies have pointed to a vitamin D status, as indicated by a 25-hydroxyvitamin D concentration, of 50 nmol/L to ensure avoidance of rickets and of 75 nmol/L to optimize health. However, the benefits of achieving these levels of vitamin D status are less evident when pediatric randomized, controlled trials are performed. In fact, no specific pediatric vitamin D supplementation has been established by the existing evidence. Yet, study of vitamin D physiology continues to uncover further potential benefits to vitamin D sufficiency. This disconnection between vitamin D function and trials of supplementation has led to new paths of investigation, including establishment of the best method to measure vitamin D status, examination of genetic variation in vitamin D metabolism, and consideration that vitamin D status is a marker of another variable, such as physical activity, and its association with bone health. Nevertheless, vitamin D supplementation in the range of 10–50 μg/day appears to be safe for children and remains a promising intervention that may yet be supported by clinical trials as a method to optimize pediatric health. Key Message: Pediatric vitamin D status is associated with avoidance of rickets. Randomized, controlled trials of vitamin D supplementation for pediatric bone health are limited and equivocal in their results. Beyond bone, decreased risk for autoimmune, infectious, and allergic diseases has been associated with higher vitamin D status. The specific vitamin D supplementation to optimize toddler, child, and adolescent outcomes is unknown, but doses 10–50 μg/day are safe and may be beneficial.

Objective This study aimed to determine the effect of elevated energy intake with medium-chain triglyceride (MCT) oil or formula powder on growth velocity and weight z-score in very low birth weight infants receiving human milk and human milk fortifier. Study Design This was a cohort study of infants exposed to MCT oil or formula powder for at least 7 days. Mean 7-day change in growth velocity and weight z-scores were compared pre- and postintervention. Results Forty-three infants received increased energy with either MCT oil or formula powder. Infants receiving MCT oil were more preterm and had a lower birth weight. When evaluating 7-day changes pre- and postintervention, growth velocity increased from 10.0 g/kg/day to 19.8 g/kg/day, and change in weight Z-score increased from –0.24 to 0.05. Conclusion This clinical approach using MCT oil or formula powder for additional energy was associated with improved, at least short-term, growth velocity and weight z-score trajectory.

Background: The safety of higher dose vitamin D (vitD) supplementation in women who change from exclusive or full breastfeeding to combination feeding or who continue supplementation after cessation of breastfeeding is unknown. Objective: Compare vitD supplementation safety of 6,400 to 400 IU/day and 2,400 IU/day using specific laboratory parameters in postpartum women and their infants through 7 months postpartum by feeding type. Design: In this randomized controlled trial, mothers (exclusively breastfeeding or formula-feeding) were randomized at 4–6 weeks' postpartum to 400, 2,400, or 6,400 IU vitD(3) (cholecalciferol)/day for 6 months. Breastfeeding infants in 400 IU group received oral 400 IU vitD(3)/day; infants in 2,400 and 6,400 IU groups received placebo. Maternal safety parameters (serum vitD, 25-hydroxy-vitamin D [25(OH)D; calcidiol], calcium, phosphorus, intact PTH; urinary calcium/creatinine ratios; and feeding type/changes) were measured monthly; infant parameters were measured at months 1, 4, and 7. Sufficiency was defined as 25(OH)D >50 nmol/L. Feeding type was defined as exclusive/full, combination, or formula-feeding. Data were analyzed using SAS 9.4. Results: Four hundred nineteen mother-infant pairs were randomized into the three treatment groups and followed: 346 breastfeeding and 73 formula-feeding pairs. A dose of 6400 IU/day safely and significantly increased maternal vitD and 25(OH)D from baseline in all mothers regardless of feeding type (p

The American Academy of Pediatrics recommends donor human milk (DHM) as the preferred feeding strategy for preterm infants when the milk of the mother is unavailable, based on conclusive evidence of lower rates of necrotizing enterocolitis with DHM feedings compared with preterm infant formula. The nutritional composition of DHM may differ from maternal milk for many reasons including differences in maternal characteristics, milk collection methods, and the impact of donor milk banking practices. The purpose of this systematic review is to examine the literature regarding research on the fat, protein, carbohydrate, vitamin, and mineral composition of DHM obtained through nonprofit milk banks or commercial entities. PubMed, CINAHL, and Scopus databases were searched for articles published between 1985 and 30 April, 2019. In total, 164 abstracts were screened independently by 2 investigators, and 14 studies met all inclusion criteria. Studies were predominantly small (

In designing longitudinal lactation research studies, certain factors must be taken into account that are necessary for the generation of meaningful data. Perhaps more like longitudinal childhood research studies in terms of ongoing changes that occur during childhood that challenge study design, longitudinal lactation research studies encompass a period of tremendous change in both the mother and her breastfeeding infant that affect study design, implementation, and analysis. Given this changing dynamic, studies should be designed to accommodate a whole host of factors, such as changes in maternal and infant health; coexisting conditions during the lactation period; the stage of lactation; diurnal variations; the frequency and exclusivity of breastfeeding; maternal diet and any complementary/supplementary foods given to the infant; geography; socioeconomic factors; body mass index; physical activity; and any changes in milk composition that occur across longer periods of lactation. The study of human milk composition itself has lacked rigor and any standardization of methods, and has only recently been revisited with more sophisticated laboratory techniques that have allowed a more meaningful understanding of milk structure and biology, with a greater global approach. In this Research Column, we review some of the issues and challenges in conducting longitudinal lactation research, and provide several references that will aid in the development of meaningful study designs and the interpretation of data.

Critically ill neonates who require extracorporeal life support have particular nutrition needs. These infants require prescription of aggressive, early nutrition support by knowledge providers. Understanding the unique metabolic demands and nutrition requirements of these fragile patients is paramount, particularly if additional therapies such as aggressive diuretic regimens or continuous renal replacement therapy are used concurrently. Although the American Society for Parenteral and Enteral Nutrition has published guidelines for this population, a review of each nutrition component is warranted because few studies exist specific to this population. Long-term complications in survivors of neonatal extracorporeal life support, particularly in patients with select diagnoses such as congenital diaphragmatic hernia, can be significant and must be recognized and anticipated. This review focuses on recognizing the nutrition needs of neonatal patients requiring extracorporeal life support, appraising the available data to guide selection of an appropriate mode of nutrition delivery, and describing the anticipated long-term nutrition implications of extracorporeal life support provision during the neonatal period.

A central goal of The Academy of Breastfeeding Medicine is the development of clinical protocols, free from commercial interest or influence, for managing common medical problems that may impact breastfeeding success. These protocols serve only as guidelines for the care of breastfeeding mothers and infants and do not delineate an exclusive course of treatment or serve as standards of medical care. Variations in treatment may be appropriate according to the needs of an individual patient.

Adequate protein intake by very-low-birth-weight preterm infants (≤1,500 g at birth) is essential to optimize growth and development. The estimated needs for this population are the highest of all humans, however, the recommended intake has varied greatly over the past several years. A literature search was conducted in PubMed, Embase, CINAHL (Cumulative Index to Nursing and Allied Health Literature), and Cochrane Central databases to identify randomized controlled trials evaluating the effect of prescribed protein intake and identified outcomes. Articles were screened by 2 reviewers, risk of bias was assessed, data were synthesized quantitatively and narratively, and each outcome was separately graded for certainty of evidence. The literature search retrieved 25,384 articles and 2 trials were included in final analysis. No trials were identified that evaluated effect of protein amount on morbidities or mortality. Moderate certainty evidence found a significant difference in weight gain when protein intake of greater than 3.5 g/kg/day from preterm infant formula was compared with lower intakes. Low-certainty evidence found no evidence of effect of protein intake of 2.6 vs 3.1 vs 3.8 g/kg/day on length, head circumference, skinfold measurements, or mid-arm circumference. Low-certainty evidence found some improvement in development measures when higher protein intake of 3.8 vs 3.1 vs 2.6 g/kg/day were compared. Low-certainty evidence found no significant difference in bone mineral content when these protein intakes were compared. No studies were identified that compared protein intake greater than 4.0 g/kg/day. This systematic review found that protein intake between 3.5 and 4.0 g/kg/day promotes weight gain and improved development.

The mechanism through which developmental programming of offspring overweight/obesity following in utero exposure to maternal overweight/obesity operates is unknown but may operate through biologic pathways involving offspring anthropometry at birth. Thus, we sought to examine to what extent the association between in utero exposure to maternal overweight/obesity and childhood overweight/obesity is mediated by birth anthropometry. Analyses were conducted on a retrospective cohort with data obtained from one hospital system. A natural effects model framework was used to estimate the natural direct effect and natural indirect effect of birth anthropometry (weight, length, head circumference, ponderal index, and small-for-gestational age [SGA] or large-for-gestational age [LGA]) for the association between pre-pregnancy maternal body mass index (BMI) category (overweight/obese vs normal weight) and offspring overweight/obesity in childhood. Models were adjusted for maternal and child socio-demographics. Three thousand nine hundred and fifty mother–child dyads were included in analyses (1467 [57.8%] of mothers and 913 [34.4%] of children were overweight/obese). Results suggest that a small percentage of the effect of maternal pre-pregnancy BMI overweight/obesity on offspring overweight/obesity operated through offspring anthropometry at birth (weight: 15.5%, length: 5.2%, head circumference: 8.5%, ponderal index: 2.2%, SGA: 2.9%, and LGA: 4.2%). There was a small increase in the percentage mediated when gestational diabetes or hypertensive disorders were added to the models. Our study suggests that some measures of birth anthropometry mediate the association between maternal pre-pregnancy overweight/obesity and offspring overweight/obesity in childhood and that the size of this mediated effect is small.

Growth and nutrition in preterm infants have long-term implications for neurodevelopmental and cardiometabolic outcomes. Many infants are discharged from the neonatal intensive care unit (NICU) with growth restriction, but often without a specialized team to monitor postdischarge growth. At our institution, we addressed our ongoing concerns for the health and growth of these infants post-discharge by creating a Nutrition NICU Graduate Clinic. This clinic serves infants discharged from our NICU who were born with very low birth weight, had difficulty growing or feeding while inpatient, had a gastrostomy tube placed during hospitalization, or were deemed high risk for other reasons by our neonatal team, with the first clinic visit within 5 weeks of discharge. Data from our first 227 patients at time of discharge, first clinic visit, and any available second clinic visits are described. Anthropometrics show a high rate of extrauterine growth restriction at time of discharge with continued growth restriction at follow-up. Feeding regimens prescribed at discharge and variations from the prescribed regimen at time of follow-up are described. At time of first clinic visit, most patients (92.2%) required a medical or dietary intervention by our team. Our findings illustrate the need for early and specialized nutrition follow-up in this patient population to improve growth trajectory post-discharge.

In the critical care of preterm infants, feeding is complex and potentially harmful to an immature gastrointestinal system. Parents have expressed the desire to be fully informed about what is being fed to their child, as this places them in the best position to nurture their child&rsquo, s health. In the parent-engaged setting of the Necrotizing Enterocolitis Symposium, NICU parents expressed concern and confusion about how cow&rsquo, s milk product and donor human milk product both carry the label &ldquo, Human Milk Fortifier&rdquo, (HMF). Accordingly, two online surveys were developed to characterize how the label HMF is used and interpreted in the NICU by parents and providers. Of 774 United States participants, only 21.9% of providers reported consistently describing the source of HMF to parents, and only 20.6% of parents whose child received an HMF product report knowing the source. Parents expressed that they were &ldquo, not given information&rdquo, regarding HMF, while both parents and healthcare providers expressed that &ldquo, the label (HMF) is misleading&rdquo, This study documents the ambiguity around the label HMF as well as the need for more specific language and clearer communication.