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. infantisprophylactically 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