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.

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(T h 2) phenotype and have an increased population of regulatory cells (T reg s). 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.

ImportanceThe 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.ObjectiveTo 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 ParticipantsIn 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.InterventionsExclusive 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 MeasuresGut microbiome profile including alpha and beta diversity, and presence of specific bacterial taxa.ResultsOf 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 RelevanceIn 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 RegistrationISRCTN trial registry identifier: ISRCTN16799022