Age-related topographic map of magnetic resonance diffusion metrics in neonatal brains.

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.

The Impact of 2 Weight-Based Standard Parenteral Nutrition Formulations Compared With One Standard Formulation on the Incidence of Hyperglycemia and Hypernatremia in Low Birth-Weight Preterm Infants.

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.

Human milk fortification: the clinician and parent perspectives.

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.

Vitamin D in Toddlers, Preschool Children, and Adolescents.

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.

Investigation of a Common Clinical Approach to Poor Growth in Preterm Infants.

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.

The Importance of Interpolation in Computerized Growth Charting.

Computer growth charting is increasingly available for clinical and research applications. The LMS method is used to define the growth curves on the charts most commonly used in practice today. The data points for any given chart are at discrete points, and computer programs may simply round to the closest LMS data point when calculating growth centiles. We sought to determine whether applying an interpolation algorithm to the LMS data for commonly used growth charts may reduce the inherent errors which occur with rounding to the nearest data point. We developed a simple, easily implemented interpolation algorithm to use with LMS data. Using published growth charts, we compared predicted growth centiles using our interpolation algorithm versus a standard rounding approach. Using a test scenario of a patient at the 50th centile in weight, compared to using our interpolation algorithm, the method of simply rounding to the nearest data point resulted in maximal z-score errors in weight of the following: 2.02 standard deviations for the World Health Organization 0-to-23 month growth chart, 1.07 standard deviations for the Fenton preterm growth chart, 0.71 standard deviations for the Olsen preterm growth chart, and 0.11 standard deviations for the CDC 2-to-18 year growth chart. Failure to include an interpolation algorithm when designing computerizing growth charts can lead to large errors in centile and z-score calculations.

Randomized Clinical Trial of Preoperative Feeding to Evaluate Intestinal Barrier Function in Neonates Requiring Cardiac Surgery.

OBJECTIVES: To evaluate intestinal barrier function in neonates undergoing cardiac surgery using lactulose/mannitol (L/M) ratio measurements, and to determine correlations with early breast milk feeding. STUDY DESIGN: This was a single-center, prospective, randomized pilot study of 27 term-born neonates (≥ 37 weeks gestation) requiring cardiac surgery who were randomized to 1 of 2 preoperative feeding groups: nil per os (NPO) or trophic (10 mL/kg/day) breast milk feeds. At 3 time points (preoperative [preop], postoperative [postop] day 7, and postop day 14), subjects were administered an oral L/M solution, after which urine L/M ratios were measured using gas chromatography, with higher ratios indicative of increased intestinal permeability. Trends over time in the mean urine L/M ratios for each group were estimated using a general linear mixed model. RESULTS: There were no adverse events related to preoperative trophic feeding. In the NPO group (n = 13), the mean urine L/M ratio was 0.06 at preop, 0.12 at postop day 7, and 0.17 at postop day 14. In the trophic breast milk feeds group (n = 14), the mean urine L/M ratio was 0.09 at preop, 0.19 at postop day 7, and 0.15 at postop day 14. In both groups, L/M ratios were significantly higher at postop day 7 and postop day 14 compared with preop (P < .05). CONCLUSION: Neonates have increased intestinal permeability after cardiac surgery extending to at least postop day 14. This pilot study was not powered to detect differences in benefit or adverse events comparing the NPO and trophic breast milk feeds groups. Further studies to identify mechanisms of intestinal injury and therapeutic interventions are warranted. TRIAL REGISTRATION: Registered with ClinicalTrials.gov: NCT01475357.

Maternal stress and breastfeeding outcomes in the NICU couplet care experience: a prospective cohort study.

OBJECTIVE: Couplet care is an innovative approach to provide postpartum care in the neonatal intensive care unit (NICU) with little known about its impact on infant feeding outcomes and maternal stress. STUDY DESIGN: We compared breastfeeding outcomes and maternal NICU-related stress among mother-infant dyads based on exposure to couplet care in a prospective cohort study. RESULT: Among 19 couplet-care exposed (CCE) dyads and 19 traditional postpartum care dyads, CCE mothers had lower self-reported stress related to parent-infant relationship as compared to traditional care (P < 0.001). CCE infants received relatively more feeds at the breast (P < 0.001), more breastmilk feeds (P = 0.002), and fewer feeds by staff (P < 0.001). Adjusted for gestational age, marital status, and infant length of stay, couplet care was associated with being in a higher tertile of percent breastmilk feeds (aOR 7.29, 95% CI 1.45-36.65). CONCLUSION: NICU couplet care was associated with improved parental stress and breastfeeding outcomes during hospitalization.

Parent and grandparent neonatal intensive care unit visitation for preterm infants.

OBJECTIVE: Characterize family NICU visitation and examine associations with maternal health and social factors and infant health outcomes. STUDY DESIGN: Retrospective cohort study of 167 infants born ≤32 weeks at two urban NICUs 01/2019-03/2020. Average nurse-documented family member visitation and associations of visitation with maternal and infant factors and outcomes were compared. RESULTS: Mothers visited 4.4 days/week, fathers 2.6 days/week, and grandparents 0.4 days/week. Older maternal age, nulliparity, and non-English primary language were associated with more frequent family visitation. Mothers with depression or anxiety history visited less. Maternal depression and public insurance were associated with fewer father visits. Low parental visitation was associated with lower odds of feeding any maternal milk at discharge and low maternal visitation with 11.5% fewer completed infant subspecialty appointments in the year following discharge (95% CI -20.0%, -3.0%). CONCLUSION: Families with social disadvantage visited less often. Parental visitation was associated with infant feeding and follow-up.

Point-of-care human milk concentration by passive osmosis: comprehensive analysis of fresh human milk samples.

OBJECTIVE: Preterm infants need enrichment of human milk (HM) for optimal growth. This study evaluated a novel, point-of-care human milk concentration (HMC) process for water removal from fresh HM samples by passive osmotic concentration. STUDY DESIGN: Nineteen fresh HM samples were concentrated by incubation with the HMC devices for 3 h at 4 °C. Pre- and post-concentration HM samples were compared by HM properties for: pH, osmolality, macronutrients, enzyme activity, bioactive, and total cell viability. RESULTS: Passive osmotic concentration reduced HM volume by an average of 16.3% ± 3.8% without a significant effect on pH or cell viability. Ten of the 41 HM components did not differ significantly (p > 0.05) between pre- and post-concentration samples. Twenty-three increased within the expected range by volume reduction. Six increased more than expected, two less than expected, and none decreased significantly. CONCLUSION: Passive osmotic concentration of fresh HM can concentrate HM components by selective removal of water. HM osmolality and pH remained within neonatal feeding parameters.

Vitamin D status in neonates undergoing cardiac operations: relationship to cardiopulmonary bypass and association with outcomes.

OBJECTIVES: To determine the incidence of vitamin D deficiency in neonates with congenital heart disease and whether differences exist by race. In addition, we determined the effect of cardiopulmonary bypass on vitamin D levels and explored associations between 25-hydroxyvitamin D [25(OH)D] levels and postoperative outcomes. STUDY DESIGN: We performed a secondary analysis of a prospective randomized controlled trial in 70 neonates undergoing cardiac surgery. The neonates' 25(OH)D levels were measured in the operating room before skin incision (baseline), at the cessation of cardiopulmonary bypass, and at 24 hours postoperatively. Associations between these levels and clinical outcomes were explored. Vitamin D deficiency was defined as a 25(OH)D level <20 ng/mL. RESULTS: Vitamin D deficiency was present in 84% (59/70); concentrations in African Americans (n = 20) were significantly lower than those of Caucasian/other race/ethnicity (n = 50) (10.2 ± 4.2 vs 16.0 ± 5.6 ng/mL, P < .0001). The 24-hour postoperative 25(OH)D levels were not different from baseline and correlated with a reduced postoperative inotropic requirement (r = -0.316, P = .008). CONCLUSIONS: Vitamin D deficiency is prevalent in neonates with congenital cardiac defects, and lower postoperative 25(OH)D levels are associated with the need for increased inotropic support in neonates undergoing cardiac operations. These findings support that vitamin D deficiency may play a role in myocardial injury and postoperative recovery and warrants further investigation.

Dilemmas in initiation of very preterm infant enteral feeds-when, what, how?

With limited clinical evidence available to guide common nutritional decisions, significant variation exists in approaches to enteral feeding for very preterm infants, specifically when feedings are initiated, what is fed, and the method used for feedings. Preclinical studies have highlighted the benefits associated with avoiding nil per os and providing early-stage mother's own milk or colostrum. However, these recommended approaches are often mutually exclusive due to the delays in lactation associated with very preterm delivery, resulting in uncertainty regarding which approach should be prioritized. Few studies have evaluated feeding frequency in preterm infants, with limited generalizability to extremely preterm infants. Therefore, even evidence-based approaches to very preterm infant feed initiation can differ. Future research is needed to identify optimal strategies for enteral nutrition in very preterm infants, but, until then, evidence-informed approaches may vary depending on each neonatal intensive care unit's assessment of risk and benefit.

Nutrition Management of High-Risk Neonates After Discharge.

Nutrition management of the high-risk infant after hospital discharge is complicated by the infant's dysfunctional or immature oral feeding skills, nutritional deficits, and the family's feeding plan. Although evidence is limited, available studies point to developing an individualized nutritional plan, which accounts for these factors; protects and prioritizes the family's plan for breastfeeding; and promotes an acceptable growth pattern. Further research is needed to identify the type and duration of posthospital discharge nutrition to optimize high-risk infant neurodevelopment and body composition. Attention to infant growth, lactation support, and safe feed preparation practices are critical in the transition to home.

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.

No such thing as a free lunch: The direct marginal costs of breastfeeding.

Understanding costs associated with breastfeeding is critical to developing maximally effective policy to support breastfeeding by addressing financial barriers. Breastfeeding is not without cost; direct costs include those of equipment, modified nutritional intake, and time (opportunity cost). Breastfeeding need not require more equipment than formula feeding, though maternal equipment use varies by maternal preference. Meeting increased nutritional demands requires increased spending on food and potentially dietary supplementation, the marginal cost of which depends on a mother's baseline diet. The opportunity cost of the three to four hours per day breastfeeding demands may be prohibitively high, particularly to low-income workers. These costs are relatively highest for low-income individuals, a group disproportionately comprising racial and ethnic minorities, and who demonstrate lower rates of breastfeeding than their white and higher-income peers. Acknowledging and addressing these costs and their regressive nature represents a critical component of effective breastfeeding policy and promotion.

Self-Efficacy and Outcomes in Women with Diabetes: A Prospective Comparative Study.

Background: Breastfeeding is especially beneficial to women with diabetes and their infants, yet diabetic mothers frequently experience less favorable breastfeeding outcomes. Objectives: To identify facilitators and barriers to breastfeeding for women with diabetes by comparing cognitive and social factors, health and hospital-related factors, and breastfeeding outcomes between women with and without diabetes. Design/Methods: Women with any type of diabetes (n = 28) and without diabetes (n = 29) were recruited during pregnancy. Data were collected from the electronic medical record and maternal surveys at 24-37 weeks' gestation, birth hospitalization, and 4 weeks' postbirth. We compared differences in mother's regard for breastfeeding, breastfeeding intention, and birth hospital experience by diabetes status, and estimated odds ratios for exclusive breastfeeding (EBF) and unmet intention to breastfeed. Results: Women with and without diabetes had similar breastfeeding intentions, attitudes, and self-efficacy. Women with diabetes were less likely to EBF, and more likely to have unmet intentions to EBF at hospital discharge, compared to women without diabetes. At 4 weeks' postpartum, there was no difference in breastfeeding by diabetes status, although EBF at hospital discharge was strongly associated with EBF at 4 weeks. Infant neonatal intensive care unit (NICU) admission and hypoglycemia were significantly associated with diabetes status, reduced EBF rates, and unmet breastfeeding intentions. Conclusions: Despite having a strong intent to breastfeed, women with diabetes experienced less favorable early breastfeeding outcomes and were less likely to meet their own breastfeeding goals. These differences may be driven by neonatal complications, such as infant hypoglycemia and NICU admissions, rather than maternal cognitive and social factors.

Diabetes in Pregnancy, Neonatal Morbidities, and Early Growth in Moderate or Late Preterm Infants.

OBJECTIVES: To compare differences in short term morbidities and early growth among moderate and late preterm infants of mothers with and without diabetes (DM) in pregnancy. METHODS: In a longitudinal analysis using data from the Pediatrix Clinical Data Warehouse of preterm infants (born 32 0/7 to 36 6/7 weeks) discharged from neonatal intensive care units from 2008 to 2019, health characteristics were compared between DM exposure groups. Change in growth from birth to discharge were compared using linear mixed effects modeling. RESULTS: Among 301 499 moderate and late preterm infants in the analysis, 14% (N = 42 519) were exposed to DM in pregnancy. Incidence of congenital anomalies, hypoglycemia, and hyperbilirubinemia were higher in DM-group (P < .001), and DM-group was more likely to need respiratory support in the first postnatal days (P = .02). Percent weight change from birth differed by gestational age, such that 36-week DM-group infants remained on average 2% (95% confidence interval [CI]: 1.57 to 2.41) below birth weight on day 14, whereas 32-week DM-group infants were on average 2.1% (95% CI: 1.69 to 2.51) above birth weight on day 14. In the regression analysis, DM-group had faster weight loss in the first postnatal week when stratified by gestational age. The adjusted difference in weight velocity (g per day) from days 0 to 3 was -4.5 (95% CI: -5.1 to -3.9), -6.5 (95% CI: -7.4 to -5.7), and -7.2 (95% CI: -8.2 to -6.2) for infants born 34-, 35-, and 36-weeks, respectively. CONCLUSIONS: In moderate or late preterm infants, diabetes in pregnancy is associated with common neonatal morbidities. Examination of intensive care nutritional practices may identify reasons for observed differences in weight trajectories by gestational age and diabetes exposure.

A review and guide to nutritional care of the infant with established bronchopulmonary dysplasia.

Bronchopulmonary dysplasia (BPD) remains the most common long-term morbidity of premature birth, and the incidence of BPD is not declining despite medical advancements. Infants with BPD are at high risk for postnatal growth failure and are often treated with therapies that suppress growth. Additionally, these infants may display excess weight gain relative to linear growth. Optimal growth and nutrition are needed to promote lung growth and repair, improve long-term pulmonary function, and improve neurodevelopmental outcomes. Linear growth in particular has been associated with favorable outcomes yet can be difficult to achieve in these patients. While there has been a significant clinical and research focus regarding BPD prevention and early preterm nutrition, there is a lack of literature regarding nutritional care of the infant with established BPD. There is even less information regarding how nutritional needs change as BPD evolves from an acute to chronic disease. This article reviews the current literature regarding nutritional challenges, enteral nutrition management, and monitoring for patients with established BPD. Additionally, this article provides a practical framework for interdisciplinary nutritional care based on our clinical experience at the Comprehensive Center for Bronchopulmonary Dysplasia.

Pediatricians' Reports of Interaction with Infant Formula Companies.

Introduction: Seventy percent of countries follow the World Health Organization International Code of Marketing Breast Milk Substitutes that prohibits infant formula companies (IFC) from providing free products to health care facilities, providing gifts to health care staff, or sponsoring meetings. The United States rejects this code, which may impact breastfeeding rates in certain areas. Objective: We aimed at gathering exploratory data about interactions between IFC and pediatricians. Methods: We distributed an electronic survey to U.S. pediatricians asking about practice demographics, interactions with IFC, and breastfeeding practices. Using the zip code of the practice, we obtained additional information from the 2018 American Communities Survey, including median income, percent of mothers who had graduated college, percent of mothers working, and racial and ethnic identity. We compared demographic data for those pediatricians who had a formula company representative visit versus not and those who had a sponsored meal versus not. Results: Of 200 participants, the majority reported a formula company representative visit to their clinic (85.5%) and receiving free formula samples (90%). Representatives were more likely to visit areas with higher-income patients (median = $100K versus $60K, p < 0.001). They tended to visit and sponsor meals for pediatricians at private practices and in suburban areas. Most of the reported conferences attended (64%) were formula company-sponsored. Conclusion: Interactions between IFC and pediatricians are prevalent and occur in many forms. Future studies may reveal whether these interactions influence the advice of pediatricians or the behavior of mothers who had planned to exclusively breastfeed.

Brain injury patterns in hypoxic ischemic encephalopathy of term neonates.

BACKGROUND AND PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.