Lactobacillus Acidophilus/Bifidobacterium Infantis Probiotics Are Beneficial to Extremely Low Gestational Age Infants Fed Human Milk.

Ingmar Fortmann,Jan Rupp,Bastian Siller,Wolfgang Göpel,Anja Stein,Juliane Spiegler,Michael Zemlin,Dimitra Stavropoulou,Christian Wieg,Dorothee Viemann,Julia Pagel,Leila Eyvazzadeh,Egbert Herting,Alexander Humberg,Kirstin Faust,Sabine Pirr,Kathrin Hanke,Kim Brenner,Thorsten Körner,Philipp Henneke,Claudia Roll,Janina Marißen,Christoph Derouet,Birte Tröger,Christoph Härtel

doi:10.3390/nu12030850

Abstract

Objective: To evaluate the nutrition-related effects of prophylactic Lactobacillus acidophilus/Bifidobacterium infantis probiotics on the outcomes of preterm infants <29 weeks of gestation that receive human milk and/or formula nutrition. We hypothesize that human-milk-fed infants benefit from probiotics in terms of sepsis prevention and growth. Methods: We performed an observational study of the German Neonatal Network (GNN) over a period of six years, between 1 January, 2013 and 31 December, 2018. Prophylactic probiotic use of L. acidophilus/B. infantis was evaluated in preterm infants <29 weeks of gestation (n = 7516) in subgroups stratified to feeding type: (I) Exclusively human milk (HM) of own mother and/or donors (HM group, n = 1568), (II) HM of own mother and/or donor and formula (Mix group, n = 5221), and (III) exclusive exposure to formula (F group, n = 727). The effect of probiotics on general outcomes and growth was tested in univariate models and adjusted in linear/logistic regression models. Results: 5954 (76.5%) infants received L. acidophilus/B. infantis prophylactically for the prevention of necrotizing enterocolitis (NEC). Probiotic use was associated with improved growth measures in the HM group (e.g., weight gain velocity in g/day: effect size B = 0.224; 95% CI: 2.82–4.35; p < 0.001) but not in the F group (effect size B = −0.06; 95% CI: −3.05–0.28; p = 0.103). The HM group had the lowest incidence of clinical sepsis (34.0%) as compared to the Mix group (35.5%) and the F group (40.0%). Only in the Mix group, probiotic supplementation proved to be protective against clinical sepsis (OR 0.69; 95% CI: 0.59–0.79; p < 0.001). Conclusion: Our observational data indicate that the exposure to L. acidophilus/B. infantis probiotics may promote growth in exclusively HM-fed infants as compared to formula-fed infants. To exert a sepsis-preventive effect, probiotics seem to require human milk.

Highlights

Probiotics that act as gut colonizers of human-milk-fed infants [1] have a high potential to foster the early microbiome development [2]
ToTo account forfor time trends in in enteral feeding practices and current developments in in human milk account time trends enteral feeding practices and current developments human milk banks, we evaluated the proportion of infants receiving human milk, mix, banks, we evaluated the proportion of infants receiving human milk, mix, or or exclusively formula according to to thethe year of of thethe infant’s discharge
Our large-scale population-based data support the hypothesis that the source of enteral feeding has an impact on the effects of L. acidophilus/B. infantis probiotics in highly vulnerable preterm infants

Summary

Introduction

Probiotics that act as gut colonizers of human-milk-fed infants [1] have a high potential to foster the early microbiome development [2]. They might prevent dysbiosis-associated complications such as necrotizing enterocolitis (NEC) and sepsis [3,4]. Numerous studies on the therapeutic effects of probiotics in preterm infants have been performed [4]. Despite the use of probiotics in >80% of extremely low-birth-weight infants (ELBWI), NEC and sepsis still remain significant causes of morbidity and mortality in this vulnerable population [9]. Human milk contains numerous immune-related compounds such as leukocytes, lysozymes, nucleotides, and cytokines [11], whereas

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Conclusion