Lyophilized (freeze-dried) human milk for preterm infants: a scoping review.

Freeze-drying (FD), or lyophilization, is commonly used to preserve foods. FD offers potential to create a human milk-derived human milk fortifier, and an alternative to freeze-storing human milk. However, processing human milk is known to affect its components. This scoping review explores the effect of FD on the; macronutrient, micronutrient, vitamin, bioactive components, microbes and anti-microbial factors in human milk, and studies where lyophilized human milk has been given to newborn infants. 48 articles were identified after full text review. FD human milk reduces the fat globule size and as well as the quantity of enzymes, vitamin C and immunoglobulin. Common serum electrolyte disturbances have been reported when preterm infants' are fed FD human milk however it appears a promising method to avoid exposure of preterm infants' to cows' milk. Due to limited data, further studies exploring the safety and efficacy of FD human milk in preterm infants are needed.

A Quality Improvement Initiative to Reduce Necrotizing Enterocolitis in Very Preterm Infants.

OBJECTIVE: To reduce the incidence of necrotizing enterocolitis (NEC) among very preterm infants in the Calgary Health Region to ≤2% within 2 years. METHODS: A multidisciplinary team developed key drivers for NEC. Targeted interventions included strategies to increase mothers' own milk (MOM), improve compliance with feeding regimens, standardize management of feeding intolerance, prevent intestinal microbial aberrations, and feed conservatively during blood transfusion and the treatment of patent ductus arteriosus. The outcome measure was NEC (≥ stage 2). Changes in NEC rates were examined among racial and ethnic groups. Process measures included MOM feeding at discharge, the difference between actual and expected time to reach full feeds, lowest hemoglobin, and the duration of empirical antibiotics. Growth, the rate of blood transfusion, and the duration of parenteral nutrition were balancing measures. The preintervention, intervention, and sustainment periods were January 2013 to June 2016, July 2016 to December 2018, and December 2018 to December 2021, respectively. RESULTS: We included 2787 infants born at ≤326/7 weeks' gestation (1105 preintervention, 763 during intervention, and 919 in sustainment). NEC decreased from 5.6% to 1.9%. Process measures indicated increased MOM feeding at discharge, improved compliance with feeding regimens, increased lowest hemoglobin levels, and shorter durations of empirical antibiotics. Balancing measures revealed improved weight Z-scores, shorter durations on parenteral nutrition, and increased rates of blood transfusion. CONCLUSIONS: Quality improvement initiatives to increase MOM, improve compliance with feeding regimens, feed conservatively during blood transfusion and treatment of patent ductus arteriosus, and prevent intestinal microbial aberrations were associated with reduced NEC.

Effect of an Exclusive Human Milk Diet on the Gut Microbiome in Preterm Infants: A Randomized Clinical Trial.

Importance: The effect of using an exclusive human milk diet compared with one that uses bovine products in preterm infants is uncertain, but some studies demonstrate lower rates of key neonatal morbidities. A potential mediating pathway is the gut microbiome. Objective: To determine the effect of an exclusive human milk diet on gut bacterial richness, diversity, and proportions of specific taxa in preterm infants from enrollment to 34 weeks' postmenstrual age. Design, Setting, and Participants: In this randomized clinical trial conducted at 4 neonatal intensive care units in the United Kingdom from 2017 to 2020, microbiome analyses were blind to group. Infants less than 30 weeks' gestation who had only received own mother's milk were recruited before 72 hours of age. Statistical analysis was performed from July 2019 to September 2021. Interventions: Exclusive human milk diet using pasteurized human milk for any shortfall in mother's own milk supply and human milk-derived fortifiers (intervention) compared with bovine formula and bovine-derived fortifier (control) until 34 weeks' postmenstrual age. Fortifier commenced less than 48 hours of tolerating 150 mL/kg per day. Main Outcomes and Measures: Gut microbiome profile including alpha and beta diversity, and presence of specific bacterial taxa. Results: Of 126 preterm infants enrolled in the study, 63 were randomized to control (median [IQR] gestation: 27.0 weeks [26.0-28.1 weeks]; median [IQR] birthweight: 910 g [704-1054 g]; 32 [51%] male) and 63 were randomized to intervention (median [IQR] gestation: 27.1 weeks [25.7-28.1 weeks]; median [IQR] birthweight: 930 g [733-1095 g]; 38 [60%] male); 472 stool samples from 116 infants were analyzed. There were no differences in bacterial richness or Shannon diversity over time, or at 34 weeks between trial groups. The exclusive human milk diet group had reduced relative abundance of Lactobacillus after adjustment for confounders (coefficient estimate, 0.056; P = .03), but not after false discovery rate adjustment. There were no differences in time to full feeds, necrotizing enterocolitis, or other key neonatal morbidities. Conclusions and Relevance: In this randomized clinical trial in preterm infants using human milk-derived formula and/or fortifier to enable an exclusive human milk diet, there were no effects on overall measures of gut bacterial diversity but there were effects on specific bacterial taxa previously associated with human milk receipt. These findings suggest that the clinical impact of human milk-derived products is not modulated via microbiomic mechanisms. Trial Registration: ISRCTN trial registry identifier: ISRCTN16799022.

Gestational Development of the Human Immune System.

Building an immune system is a monumental task critical to the survival of the fetus and newborn. A functional fetal immune system must complement the maternal immune system in handling in utero infection; abstain from damaging non-self-reactions that would compromise the materno-fetal interface; mobilize in response to infection and equip mucosal tissues for pathogen exposure at birth. There is growing appreciation that immune cells also have noncanonical roles in development and specifically may contribute to tissue morphogenesis. In this review we detail how hematopoietic and lymphoid organs jointly establish cellular constituents of the immune system; how these constituents are organized in 2 mucosal sites-gut and lung-where early life immune function has long-term consequences for health; and how exemplar diseases of prematurity and inborn errors of immunity reveal dominant pathways in prenatal immunity.

T Cells in Preterm Infants and the Influence of Milk Diet.

Preterm infants born before 32 weeks gestational age (GA) have high rates of late onset sepsis (LOS) and necrotizing enterocolitis (NEC) despite recent improvements in infection control and nutrition. Breast milk has a clear protective effect against both these outcomes likely due to multiple mechanisms which are not fully understood but may involve effects on both the infant's immune system and the developing gut microbiota. Congregating at the interface between the mucosal barrier and the microbiota, innate and adaptive T lymphocytes (T cells) participate in this interaction but few studies have explored their development after preterm delivery. We conducted a literature review of T cell development that focuses on fetal development, postnatal maturation and the influence of milk diet. The majority of circulating T cells in the preterm infant display a naïve phenotype but are still able to initiate functional responses similar to those seen in term infants. T cells from preterm infants display a skew toward a T-helper 2(Th2) phenotype and have an increased population of regulatory cells (Tregs). There are significant gaps in knowledge in this area, particularly in regards to innate-like T cells, but work is emerging: transcriptomics and mass cytometry are currently being used to map out T cell development, whilst microbiomic approaches may help improve understanding of events at mucosal surfaces. A rapid rise in organoid models will allow robust exploration of host-microbe interactions and may support the development of interventions that modulate T-cell responses for improved infant health.

Outcome of babies with no detectable heart rate before 10†minutes of age, and the effect of gestation.

OBJECTIVE: Current resuscitation guidelines suggest that it is reasonable to consider stopping resuscitation where no heart rate (cardiac activity) has been detected for 10 min in a newborn baby from birth. We aimed to determine the mortality rate and 2-year neurodevelopmental outcome of all babies born with no heart rate before 10 min of age where resuscitation was attempted in a tertiary referral centre over a 5-year period. DESIGN: To identify all babies with no heart rate before age 10 min we examined two groups:▸ All babies classified as live born who received cardiac massage at birth between January 2009 and December 2013.▸ All babies classified as stillborn between January 2009 and December 2013 where attempts were made at resuscitation beyond 10 min. RESULTS: 87 babies received cardiac massage. 81 babies were live born and 6 were classified as stillborn. Twenty-two babies had no heart rate before 10 min of age. Eight babies survived to 2-year follow-up. 6/11 term babies survived, 2/4 babies born between 32 weeks and 37 weeks survived, and no infants born less than 32 weeks survived (n=7). Of the survivors, 5/8 had a normal neurodevelopmental outcome at 2 years' age. One patient was lost to follow-up, while the other two patients had hemiplegia. CONCLUSIONS: Our results add to the body of evidence suggesting that having no heart rate before 10 min of age, in term babies, may not be an appropriate prompt to discontinue resuscitation.