Impact of Donor Milk on Short- and Long-Term Growth of Very Low Birth Weight Infants

Mother’s own milk (MOM) reduces the risk of morbidities in very low birth weight (VLBW) infants. When MOM is unavailable, donor breastmilk (DM) is used, with unclear impact on short- and long-term growth. This retrospective analysis compared anthropometric data at six time points from birth to 20–24 months corrected age in VLBW infants who received MOM supplements of preterm formula (n = 160) versus fortified DM (n = 161) during neonatal intensive care unit (NICU) hospitalization. The cohort was 46% female; mean birth weight and gestational age (GA) were 998 g and 27.3 weeks. Multilevel linear growth models assessed changes in growth z-scores short-term (to NICU discharge) and long-term (post-discharge), controlling for amount of DM or formula received in first 28 days of life, NICU length of stay (LOS), birth GA, and sex. Z-scores for weight and length decreased during hospitalization but increased for all parameters including head circumference post-discharge. Short-term growth was positively associated with LOS and birth GA. A higher preterm formula proportion, but not DM proportion, was associated with slower rates of decline in short-term growth trajectories, but feeding type was unrelated to long-term growth. In conclusion, controlling for total human milk fed, DM did not affect short- or long-term growth

Breastfeeding and the origins of health: Interdisciplinary perspectives and priorities

Breastfeeding and human milk (HM) are critically important to maternal, infant and population health. This paper summarizes the proceedings of a workshop that convened a multidisciplinary panel of researchers to identify key priorities and anticipated breakthroughs in breastfeeding and HM research, discuss perceived barriers and challenges to achieving these breakthroughs and propose a constructive action plan to maximize the impact of future research in this field. Priority research areas identified were as follows: (1) addressing low breastfeeding rates and inequities using mixed methods, community partnerships and implementation science approaches; (2) improving awareness of evidence-based benefits, challenges and complexities of breastfeeding and HM among health practitioners and the public; (3) identifying differential impacts of alternative modes of HM feeding including expressed/pumped milk, donor milk and shared milk; and (4) developing a mechanistic understanding of the health effects of breastfeeding and the contributors to HM composition and variability. Key barriers and challenges included (1) overcoming methodological limitations of epidemiological breastfeeding research and mechanistic HM research; (2) counteracting ‘breastfeeding denialism’ arising from negative personal breastfeeding experiences; (3) distinguishing and aligning research and advocacy efforts; and (4) managing real and perceived conflicts of interest. To advance research on breastfeeding and HM and maximize the reach and impact of this research, larger investments are needed, interdisciplinary collaboration is essential, and the scientific community must engage families and other stakeholders in research planning and knowledge translation

Time to full enteral feeding for very low-birth-weight infants varies markedly among hospitals worldwide but may not be associated with incidence of necrotizing enterocolitis:The NEOMUNE-NeoNutriNet Cohort Study

Background: Transition to enteral feeding is difficult for very low-birth-weight (VLBW; ≤1500 g) infants, and optimal nutrition is important for clinical outcomes. Method: Data on feeding practices and short-term clinical outcomes (growth, necrotizing enterocolitis [NEC], mortality) in VLBW infants were collected from 13 neonatal intensive care units (NICUs) in 5 continents (n = 2947). Specifically, 5 NICUs in Guangdong province in China (GD), mainly using formula feeding and slow feeding advancement (n = 1366), were compared with the remaining NICUs (non-GD, n = 1581, Oceania, Europe, United States, Taiwan, Africa) using mainly human milk with faster advancement rates. Results: Across NICUs, large differences were observed for time to reach full enteral feeding (TFF; 8–33 days), weight gain (5.0–14.6 g/kg/day), ∆z-scores (−0.54 to −1.64), incidence of NEC (1%–13%), and mortality (1%–18%). Adjusted for gestational age, GD units had longer TFF (26 vs 11 days), lower weight gain (8.7 vs 10.9 g/kg/day), and more days on antibiotics (17 vs 11 days; all P <.001) than non-GD units, but NEC incidence and mortality were similar. Conclusion: Feeding practices for VLBW infants vary markedly around the world. Use of formula and long TFF in South China was associated with more use of antibiotics and slower weight gain, but apparently not with more NEC or higher mortality. Both infant- and hospital-related factors influence feeding practices for preterm infants. Multicenter, randomized controlled trials are required to identify the optimal feeding strategy during the first weeks of life

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Digested Early Preterm Human Milk Suppresses Tumor Necrosis Factor-induced Inflammation and Cytotoxicity in Intestinal Epithelial Cells

OBJECTIVES: The aim of this study was to determine the effect of digested whole human milk (HM; first sample available after birth from mothers of premature infants) on inflammation, oxidative stress, and cytotoxicity in Caco-2 human intestinal epithelial cells stimulated with lipopolysaccharides or tumor necrosis factor (TNF) to mimic the potential in vivo insults facing the premature infant's gastrointestinal tract. METHODS: Fully differentiated Caco-2 cells were exposed to digested HM (n = 10; samples from 10 different individuals) before stimulation with lipopolysaccharides, TNF, or no stimulation overnight. Inflammation was determined by production of interleukin-8, oxidative stress by levels of F2-isoprostane, and cytotoxicity by released lactate dehydrogenase. RESULTS: HM significantly suppressed interleukin-8 production and cytotoxicity in TNF-stimulated cells, while also suppressing cell death under baseline conditions. Individual HM samples differed widely in their ability to modulate cellular responses. CONCLUSIONS: Results from this study provide evidence that digested HM can reduce both an exaggerated inflammatory response and intestinal damage that contribute to the pathogenesis of necrotizing enterocolitis

High-Dose Human Milk Feedings Decrease Oxidative Stress in Premature Infant

Background: Premature infants are susceptible to oxidative stress, increasing the risk of serious morbidities. High-dose human milk (HM) feedings decrease morbidity risks and may reduce oxidative stress in this population. The purpose of this study was to compare oxidative stress using serial urinary F2-isoprostane concentrations in predominantly HM and preterm formula (PF) fed premature infants over the first 21 days of life (DOL), while controlling for perinatal oxidative stress exposures including bovine-based human milk fortifier (HMF) or PF introduction to predominantly HM-fed infants. Methods: This was a quasi-experimental design that categorized 22 premature infants into mutually-exclusive comparison groups based on exposure to HM and PF. Serial urine samples (pre- and post-first feeding, and DOL 7, 14, and 21) were used to determine urine F2-isoprostane concentrations measured by ELISA. We analyzed data using Mann Whitney U, Wilcoxon rank test and multilevel models. Results: Comparing the predominantly HM-fed and predominantly PF-fed groups over time, median F2-isoprostane concentrations decreased significantly in the predominantly HM group (p = 0.003) and increased significantly in the predominantly PF group (p=0.01). Perinatal oxidant exposures and the introduction of HMF did not affect results. Conclusion: Our results demonstrate that predominantly HM feedings were associated with decreased oxidative stress while PF feedings increased oxidative stress in premature infants, even after controlling for perinatal oxidant exposures of HMF or PF introduction

Barriers to Human Milk Feeding at Discharge of Very Low–Birthweight Infants: Evaluation of Neighborhood Structural Factors

BackgroundAlthough 98% of mothers in our cohort initiated human milk (HM) provision for their very low-birthweight (VLBW) infants, fewer black infants received HM at neonatal intensive care unit (NICU) discharge than non-black infants. This study examined neighborhood structural factors associated with HM feeding at discharge to identify potential barriers.Materials and methodsSociodemographic and HM data were prospectively collected for 410 VLBW infants and mothers. Geocoded addresses were linked to neighborhood structural factors. Bivariate and multivariate logistic regression analyses were conducted for the entire cohort and racial/ethnic subgroups.ResultsHM feeding at discharge was positively correlated with further distance from Women, Infants, and Children (WIC) office, less violent crime, less poverty, greater maternal education, older maternal age, greater infant gestational age, and shorter NICU hospitalization. Multivariate analysis demonstrated that only maternal race/ethnicity, WIC eligibility, and length of NICU hospitalization predicted HM feeding at discharge for the entire cohort. The interaction between access to a car and race/ethnicity significantly differed between black and white/Asian mothers, although the predicted probability of HM feeding at discharge was not significantly affected by access to a car for any racial/ethnic subgroup.ConclusionsNeighborhood structural factors did not significantly impact HM feeding at discharge. However, lack of access to a car may be a factor for black mothers, potentially representing restricted HM delivery to the NICU or limited social support, and warrants further study

Barriers to Human Milk Feeding at Discharge of Very-Low-Birth-Weight Infants: Maternal Goal Setting as a Key Social Factor

BackgroundWhile black mothers initiate human milk (HM) provision at lower rates than non-black mothers in the United States, some neonatal intensive care units (NICUs) report similar initiation rates regardless of race/ethnicity for mothers of very-low-birth-weight (VLBW) infants. However, racial disparity frequently becomes evident in the proportion of black infants who continue to receive HM feedings at NICU discharge. Since social factors have been associated with differences in HM provision for term infants, we sought to identify differences in social factors associated with HM feeding at discharge based on race/ethnicity.Materials and methodsA prospective cohort study of racially diverse mothers of VLBW infants measured social factors including maternal education, breastfeeding support, return to work/school, HM feeding goal, previous breastfeeding, or formula experience. Multivariate logistic regression modeling was applied to social factors to predict HM feeding at discharge. Additional regression models were created for racial/ethnic subgroups to identify differences.ResultsFor all 362 mothers, WIC (Special Supplemental Nutrition Program for Women, Infants, and Children) eligibility and maternal goal near time of discharge of providing any HM negatively and positively predicted HM feeding at discharge, respectively. Perceived breastfeeding support from the infant's maternal grandmother negatively predicted HM feeding at discharge for black mothers.ConclusionsFuture interventions to increase duration of HM provision in VLBW infants should focus on the establishment and maintenance of maternal HM feeding goals. Further studies of the familial support system of black mothers are warranted to determine multigenerational impact and potential interventions

Barriers to Human Milk Feeding at Discharge of Very Low–Birthweight Infants: Evaluation of Neighborhood Structural Factors

Background: Although 98% of mothers in our cohort initiated human milk (HM) provision for their very low–birthweight (VLBW) infants, fewer black infants received HM at neonatal intensive care unit (NICU) discharge than non-black infants. This study examined neighborhood structural factors associated with HM feeding at discharge to identify potential barriers. Materials and Methods: Sociodemographic and HM data were prospectively collected for 410 VLBW infants and mothers. Geocoded addresses were linked to neighborhood structural factors. Bivariate and multivariate logistic regression analyses were conducted for the entire cohort and racial/ethnic subgroups. Results: HM feeding at discharge was positively correlated with further distance from Women, Infants, and Children (WIC) office, less violent crime, less poverty, greater maternal education, older maternal age, greater infant gestational age, and shorter NICU hospitalization. Multivariate analysis demonstrated that only maternal race/ethnicity, WIC eligibility, and length of NICU hospitalization predicted HM feeding at discharge for the entire cohort. The interaction between access to a car and race/ethnicity significantly differed between black and white/Asian mothers, although the predicted probability of HM feeding at discharge was not significantly affected by access to a car for any racial/ethnic subgroup. Conclusions: Neighborhood structural factors did not significantly impact HM feeding at discharge. However, lack of access to a car may be a factor for black mothers, potentially representing restricted HM delivery to the NICU or limited social support, and warrants further study

Transforming Growth Gactor-β\u3csub\u3e2\u3c/sub\u3e is Sequestered in Preterm Human Milk by Chondroitin Sulfate Proteoglycans

Human milk contains biologically important amounts of transforming growth factor-β2 isoform (TGF-β2), which is presumed to protect against inflammatory gut mucosal injury in the neonate. In preclinical models, enterally administered TGF-β2 can protect against experimental necrotizing enterocolitis, an inflammatory bowel necrosis of premature infants. In this study, we investigated whether TGF-β bioactivity in human preterm milk could be enhanced for therapeutic purposes by adding recombinant TGF-β2 (rTGF-β2) to milk prior to feeding. Milk-borne TGF-β bioactivity was measured by established luciferase reporter assays. Molecular interactions of TGF-β2 were investigated by nondenaturing gel electrophoresis and immunoblots, computational molecular modeling, and affinity capillary electrophoresis. Addition of rTGF-β2 (20–40 nM) to human preterm milk samples failed to increase TGF-β bioactivity in milk. Milk-borne TGF-β2 was bound to chondroitin sulfate (CS) containing proteoglycan(s) such as biglycan, which are expressed in high concentrations in milk. Chondroitinase treatment of milk increased the bioactivity of both endogenous and rTGF-β2, and consequently, enhanced the ability of preterm milk to suppress LPS-induced NF-κB activation in macrophages. These findings provide a mechanism for the normally low bioavailability of milk-borne TGF-β2 and identify chondroitinase digestion of milk as a potential therapeutic strategy to enhance the anti-inflammatory effects of preterm milk