Infections and necrotizing enterocolitis, major causes of mortality and morbidity in preterm infants, are reduced in infants fed their own mother's milk when compared with formula. When own mother's milk is not available, human donor milk is considered a good alternative, albeit an expensive one. However, most infants at modern neonatal intensive care units are predominantly fed with own mother's milk. The benefits of add-on donor milk over formula are not clear. OBJECTIVE To determine whether providing donor milk instead of formula as supplemental feeding whenever own mother's milk is insufficiently available during the first 10 days of life reduces the incidence of serious infection, necrotizing enterocolitis, and mortality. DESIGN, SETTINGS, AND PARTICIPANTS The Early Nutrition Study was a multicenter, double-blind randomized clinical trial in very low-birth-weight infants (birth weight <1500 g) admitted to 1 of 6 neonatal intensive care units in the Netherlands from March 30, 2012, through August 17, 2014. Intent-to-treat analysis was performed. INTERVENTIONS Infants received pasteurized donor milk or preterm formula during the first 10 days of life if own mother's milk was not (sufficiently) available. MAIN OUTCOMES AND MEASURES The primary end point was cumulative occurrence of serious infection (sepsis or meningitis), necrotizing enterocolitis, or mortality during the first 60 days of life. RESULTS A total of 930 infants were screened for inclusion; 557 were excluded, resulting in 373 infants (183 receiving donor milk and 190 receiving formula) who were evaluated by intent-to-treat analysis (median birth weight, 1066 g; mean gestational age, 28.4 weeks). Own mother's milk comprised 89.1% and 84.5% of total mean intake during the intervention period for the donor milk and formula groups, respectively. The incidence of the combined outcome was not different (85 [44.7%] [formula] vs 77 [42.1%] [donor milk]; mean difference, 2.6%; 95% CI, −12.7% to 7.4%). The adjusted hazard ratio was 0.87 (95% CI, 0.63-1.19; P = .37). CONCLUSIONS AND RELEVANCE In the current study, pasteurized donor milk and preterm formula as supplemental feeding during the first 10 days of life yielded similar short-term outcomes in very low-birth-weight infants regarding safety and efficacy when own mother's milk availability was insufficient. Future studies investigating longer duration of use of human donor milk on short-term and long-term outcomes are necessary. TRIAL REGISTRATION trialregister.nl Identifier: NTR3225

We speculate that gestational age and its associated intensity of care ( antibiotics and respiratory support) affects intestinal microbiota composition and activity in preterm infants. As the gut microbiota plays a major role in development of the neonate, gestational age and its associated factors could set the stage for early and later life health complications via interference with microbiota development.

Antibiotic treatment is common practice in the neonatal ward for the prevention and treatment of sepsis, which is one of the leading causes of mortality and morbidity in preterm infants. Although the effect of antibiotic treatment on microbiota development is well recognised, little attention has been paid to treatment duration. We studied the effect of short and long intravenous antibiotic administration on intestinal microbiota development in preterm infants. Faecal samples from 15 preterm infants (35 ± 1 weeks gestation and 2871 ± 260 g birth weight) exposed to no, short (≤ 3 days) or long (≥ 5 days) treatment with amoxicillin/ceftazidime were collected during the first six postnatal weeks. Microbiota composition was determined through 16S rRNA gene sequencing and by quantitative polymerase chain reaction (qPCR). Short and long antibiotic treat ment significantly lowered the abundance of Bifidobacterium right after treatment (p = 0.027) till postnatal week three (p = 0.028). Long treatment caused Bifidobacterium abundance to remain decreased till postnatal week six (p = 0.009). Antibiotic treatment was effective against members of the Enterobacteriaceae family, but allowed Enterococcus to thrive and remain dominant for up to two weeks after antibiotic treatment discontinuation. Community richness and diversity were not affected by antibiotic treatment, but were positively associated with postnatal age (p < 0.023) and with abundance of Bifidobacterium (p = 0.003). Intravenous antibiotic administration during the first postnatal week greatly affects the infant’s gastrointestinal microbiota. However, quick antibiotic treatment cessation allows for its recovery. Disturbances in microbiota development caused by short and, more extensively, by long antibiotic treatment could affect healthy development of the infant via interference with maturation of the immune system and gastrointestinal tract.Electronic supplementary materialThe online version of this article (10.1007/s10096-018-3193-y) contains supplementary material, which is available to authorized users.

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