Antimicrobial Protein and Peptide Concentrations and Activity in Human Breast Milk Consumed by Preterm Infants at Risk of Late-Onset Neonatal Sepsis

IntroductionThe mortality rate of extremely low gestational age (ELGA) (born <gestational week 28+0) infants remains high, and severe infections and necrotising enterocolitis (NEC) are common causes of death. Preterm infants receiving human milk have lower incidence of sepsis and NEC than those fed a bovine milk-based preterm formula. Despite this, fully human milk fed ELGA infants most often have a significant intake of cow’s milk protein from bovine-based protein fortifier. The aim of this study is to evaluate whether the supplementation of human milk-based, as compared with bovine-based, nutrient fortifier reduces the prevalence of NEC, sepsis and mortality in ELGA infants exclusively fed with human milk.Methods and analysisA randomised-controlled multicentre trial comparing the effect of a human breast milk-based fortifier with a standard bovine protein-based fortifier in 222–322 ELGA infants fed human breast milk (mother’s own milk and/or donor milk). The infants will be randomised to either fortifier before reaching 100 mL/kg/day in oral feeds. The intervention, stratified by centre, will continue until the target postmenstrual week 34+0. The primary outcome is a composite of NEC, sepsis or death. Infants are characterised with comprehensive clinical and nutritional data collected prospectively from birth until hospital discharge. Stool, urine, blood and breast milk samples are collected for analyses in order to study underlying mechanisms. A follow-up focusing on neurological development and growth will be performed at 2 and 5.5 years of age. Health economic analyses will be made.Ethics and disseminationThe study is conducted according to ICH/GCP guidelines and is approved by the regional ethical review board in Linköping Sweden (Dnr 2018/193-31, Dnr 2018/384-32). Results will be presented at scientific meetings and published in peer-reviewed publications.Trial registration numberThe study was registered with ClinicalTrials.gov NCT03797157, 9 January 2019.

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Human breast milk exosomes may protect against necrotizing enterocolitis in preterm infants

Pediatric Research ◽

10.1038/s41390-021-01580-w ◽

2021 ◽

Author(s):

Jessica W. Madden

Keyword(s):

Breast Milk ◽

Preterm Infants ◽

Necrotizing Enterocolitis ◽

Human Breast Milk ◽

Human Breast

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Analysis of Susceptibility to the Antimicrobial and Anti-Biofilm Activity of Human Milk Lactoferrin in Clinical Strains of Streptococcus agalactiae With Diverse Capsular and Sequence Types

Frontiers in Cellular and Infection Microbiology ◽

10.3389/fcimb.2021.740872 ◽

2021 ◽

Vol 11 ◽

Author(s):

Jacky Lu ◽

Miriam A. Guevara ◽

Jamisha D. Francis ◽

Sabrina K. Spicer ◽

Rebecca E. Moore ◽

...

Keyword(s):

Breast Milk ◽

Bacterial Growth ◽

Neonatal Sepsis ◽

Biofilm Formation ◽

Late Pregnancy ◽

Human Breast Milk ◽

Human Breast ◽

Wide Range ◽

Group B ◽

Sequence Types

Group B Streptococcus (GBS) is one of the leading infection-related causes of adverse maternal and neonatal outcomes. This includes chorioamnionitis, which leads to preterm ruptures of membranes and can ultimately result in preterm or stillbirth. Infection can also lead to maternal and neonatal sepsis that may contribute to mortality. Currently, treatment for GBS infection include a bolus of intrapartum antibiotic prophylaxis to mothers testing positive for GBS colonization during late pregnancy. Lactoferrin is an antimicrobial peptide expressed in human breast milk, mucosal epithelia, and secondary granules of neutrophils. We previously demonstrated that lactoferrin possesses antimicrobial and antibiofilm properties against several strains of GBS. This is largely due to the ability of lactoferrin to bind and sequester iron. We expanded upon that study by assessing the effects of purified human breast milk lactoferrin against a panel of phenotypically and genetically diverse isolates of GBS. Of the 25 GBS isolates screened, lactoferrin reduced bacterial growth in 14 and biofilm formation in 21 strains. Stratifying the data, we observed that colonizing strains were more susceptible to the growth inhibition activity of lactoferrin than invasive isolates at lactoferrin concentrations between 250-750 µg/mL. Treatment with 750 µg/mL of lactoferrin resulted in differences in bacterial growth and biofilm formation between discrete sequence types. Differences in bacterial growth were also observed between capsular serotypes 1a and III. Maternally isolated strains were more susceptible to lactoferrin with respect to bacterial growth, but not biofilm formation, compared to neonatal sepsis isolates. Finally, high biofilm forming GBS strains were more impacted by lactoferrin across all isolates tested. Taken together, this study demonstrates that lactoferrin possesses antimicrobial and antibiofilm properties against a wide range of GBS isolates, with maternally isolated colonizing strains being the most susceptible.

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Macronutrient analysis of preterm human milk using mid-infrared spectrophotometry

Journal of Perinatal Medicine ◽

10.1515/jpm-2019-0105 ◽

2019 ◽

Vol 47 (7) ◽

pp. 785-791 ◽

Cited By ~ 2

Author(s):

Özgül Bulut ◽

Asuman Çoban ◽

Zeynep İnce

Keyword(s):

Breast Milk ◽

Human Milk ◽

Preterm Infants ◽

High Body Mass Index ◽

Income Level ◽

Human Breast Milk ◽

Human Breast ◽

Mid Infrared ◽

Macronutrient Content ◽

Nutritional Needs

Abstract Background Human milk is the optimal source of nutrition for preterm infants. However, breast milk alone is often not sufficient to satisfy the high nutritional needs for growth and development in preterm infants. Fortified human breast milk is the best way to meet the nutritional needs of preterm infants. Human breast milk is fortified according to the estimated nutrient content of mature breast milk; however, because the content of breast milk is highly variable, the macronutrient support may be more or less than needed. The goal of this study was to analyze the macronutrient content of preterm human milk during the first 6 weeks of lactation. Methods The study included 32 mothers of preterm infants with a gestational age of ≤32 weeks. Breast milk was collected in 24-h cycles and analyzed daily using mid-infrared (MIR) spectroscopy. We measured protein, fat and lactose concentrations in the breast milk, and the energy content was calculated. Results The protein content was high during the first weeks of lactation, but decreased as lactation progressed. The fat, energy and lactose contents of the breast milk were low during the first 2 weeks of lactation, increased as lactation progressed and remained constant thereafter. In women with high body mass index (BMI), higher protein levels were found in transitional milk. In women who had high income level, higher fat and energy levels were found in transitional milk. Conclusion Our findings indicate that the macronutrient content of preterm breast milk changes throughout the course of lactation, with BMI and income level. Knowledge of the macronutrient composition of breast milk is necessary to ensure that preterm infants receive the appropriate types and quantities of nutrients to promote optimal growth, and to ensure that breast milk is fortified according to individual needs. Our findings may be useful for the provision of optimal nutritional support for preterm infants.

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Breast Milk Lipids and Fatty Acids in Regulating Neonatal Intestinal Development and Protecting against Intestinal Injury

Nutrients ◽

10.3390/nu12020534 ◽

2020 ◽

Vol 12 (2) ◽

pp. 534 ◽

Cited By ~ 4

Author(s):

David Ramiro-Cortijo ◽

Pratibha Singh ◽

Yan Liu ◽

Esli Medina-Morales ◽

William Yakah ◽

...

Keyword(s):

Fatty Acids ◽

Breast Milk ◽

Human Milk ◽

Preterm Infants ◽

Gastrointestinal Disease ◽

Essential Fatty Acids ◽

Intestinal Injury ◽

Human Breast Milk ◽

Intestinal Development ◽

Human Breast

Human breast milk is the optimal source of nutrition for infant growth and development. Breast milk fats and their downstream derivatives of fatty acids and fatty acid-derived terminal mediators not only provide an energy source but also are important regulators of development, immune function, and metabolism. The composition of the lipids and fatty acids determines the nutritional and physicochemical properties of human milk fat. Essential fatty acids, including long-chain polyunsaturated fatty acids (LCPUFAs) and specialized pro-resolving mediators, are critical for growth, organogenesis, and regulation of inflammation. Combined data including in vitro, in vivo, and human cohort studies support the beneficial effects of human breast milk in intestinal development and in reducing the risk of intestinal injury. Human milk has been shown to reduce the occurrence of necrotizing enterocolitis (NEC), a common gastrointestinal disease in preterm infants. Preterm infants fed human breast milk are less likely to develop NEC compared to preterm infants receiving infant formula. Intestinal development and its physiological functions are highly adaptive to changes in nutritional status influencing the susceptibility towards intestinal injury in response to pathological challenges. In this review, we focus on lipids and fatty acids present in breast milk and their impact on neonatal gut development and the risk of disease.

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Bioactive Factors in Human Breast Milk Attenuate Intestinal Inflammation during Early Life

Nutrients ◽

10.3390/nu12020581 ◽

2020 ◽

Vol 12 (2) ◽

pp. 581 ◽

Cited By ~ 4

Author(s):

Julie D. Thai ◽

Katherine E. Gregory

Keyword(s):

Breast Milk ◽

Preterm Infants ◽

Early Life ◽

Protective Factor ◽

Intestinal Inflammation ◽

Critical Role ◽

High Morbidity ◽

Human Breast Milk ◽

Bioactive Components ◽

Human Breast

Human breast milk is well known as the ideal source of nutrition during early life, ensuring optimal growth during infancy and early childhood. Breast milk is also the source of many unique and dynamic bioactive components that play a key role in the development of the immune system. These bioactive components include essential microbes, human milk oligosaccharides (HMOs), immunoglobulins, lactoferrin and dietary polyunsaturated fatty acids. These factors all interact with intestinal commensal bacteria and/or immune cells, playing a critical role in establishment of the intestinal microbiome and ultimately influencing intestinal inflammation and gut health during early life. Exposure to breast milk has been associated with a decreased incidence and severity of necrotizing enterocolitis (NEC), a devastating disease characterized by overwhelming intestinal inflammation and high morbidity among preterm infants. For this reason, breast milk is considered a protective factor against NEC and aberrant intestinal inflammation common in preterm infants. In this review, we will describe the key microbial, immunological, and metabolic components of breast milk that have been shown to play a role in the mechanisms of intestinal inflammation and/or NEC prevention.

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Nutrient-enriched formula milk versus human breast milk for preterm infants following hospital discharge

Cochrane Database of Systematic Reviews ◽

10.1002/14651858.cd004862.pub2 ◽

2007 ◽

Cited By ~ 2

Author(s):

Ginny Henderson ◽

Tom Fahey ◽

William McGuire

Keyword(s):

Breast Milk ◽

Hospital Discharge ◽

Preterm Infants ◽

Human Breast Milk ◽

Human Breast ◽

Formula Milk

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