Clinical Outcomes of Single vs. Two-Strain Probiotic Prophylaxis for Prevention of Necrotizing Enterocolitis in Preterm Infants.

Background: The administration of live microbiota (probiotic) via enteral route to preterm infants facilitates intestinal colonization with beneficial bacteria, resulting in competitive inhibition of the growth of pathogenic bacteria preventing gut microbiome dysbiosis. This dysbiosis is linked to the pathogenesis of necrotizing enterocolitis (NEC), an acquired multi-factorial intestinal disease characterized by microbial invasion of the gut mucosa, particularly affecting preterm infants. Probiotic prophylaxis reduces NEC; however, variations in strain-specific probiotic effects, differences in administration protocols, and synergistic interactions with the use of combination strains have all led to challenges in selecting the optimal probiotic for clinical use. Aim: To compare any differences in NEC rates, feeding outcomes, co-morbidities in preterm infants receiving single or two-strain probiotics over a 4-year period. The two-strain probiotic prophylaxis was sequentially switched over after 2 years to the single strain probiotic within this 4-year study period, in similar cohort of preterm infants. Methods: During two consecutive equal 2-year epochs, preterm infants (<32 weeks and or with birth weight <1,500 g) receiving two-strain (Lactobacillus acidophilus and Bifidobacterium bifidum) and single strain (Bifidobacterium breve M-16 V,) probiotic prophylaxis for prevention of NEC were included in this retrospective, observational study. The primary outcome included rates of NEC; secondary outcomes included prematurity related co-morbidities and feeding outcomes. Time to reach full enteral feeds was identified as the first day of introducing milk feeds at 150 ml/kg/day. Results: There were 180 preterm infants in the two-strain, 196 in the single strain group from the two equal consecutive 2-year epochs. There were no differences in the NEC rates, feeding outcomes, all-cause morbidities except for differences in rates of retinopathy of prematurity. Conclusion: In our intensive-care setting, clinical outcomes of single vs. two-strain probiotic prophylaxis for prevention of NEC were similar. Although our study demonstrates single strain probiotic may be equally effective than two-strain in the prevention of NEC, small sample size and low baseline incidence of NEC in our unit were not sufficiently powered to compare single vs. two-strain probiotic prophylaxis in preventing NEC. Further clustered randomized controlled trials are required to study the effects of single vs. multi-strain probiotic products for NEC prevention in preterm infants.

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

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.

Breastfeeding for 3 Months or Longer but Not Probiotics Is Associated with Reduced Risk for Inattention/Hyperactivity and Conduct Problems in Very-Low-Birth-Weight Children at Early Primary School Age.

(1) Background: We aimed to evaluate the effect of proposed "microbiome-stabilising interventions", i.e., breastfeeding for ≥3 months and prophylactic use of Lactobacillus acidophilus/ Bifidobacterium infantis probiotics on neurocognitive and behavioral outcomes of very-low-birthweight (VLBW) children aged 5-6 years. (2) Methods: We performed a 5-year-follow-up assessment including a strength and difficulties questionnaire (SDQ) and an intelligence quotient (IQ) assessment using the Wechsler Preschool and Primary Scale of Intelligence (WPPSI)-III test in preterm children previously enrolled in the German Neonatal Network (GNN). The analysis was restricted to children exposed to antenatal corticosteroids and postnatal antibiotics. (3) Results: 2467 primary school-aged children fulfilled the inclusion criteria. In multivariable linear regression models breastfeeding ≥3 months was associated with lower conduct disorders (B (95% confidence intervals (CI)): -0.25 (-0.47 to -0.03)) and inattention/hyperactivity (-0.46 (-0.81 to -0.10)) as measured by SDQ. Probiotic treatment during the neonatal period had no effect on SDQ scores or intelligence. (4) Conclusions: Prolonged breastfeeding of highly vulnerable infants may promote their mental health later in childhood, particularly by reducing risk for inattention/hyperactivity and conduct disorders. Future studies need to disentangle the underlying mechanisms during a critical time frame of development.

Probiotics prophylaxis in pyelonephritis infants with normal urinary tracts.

BACKGROUND: Pyelonephritis in infants is considered as a major factor for the formation of renal scar. To prevent recurrent pyelonephritis and renal damage, prophylaxis is extremely important. The aim of this study was to compare the effectiveness of probiotic and antibiotic prophylaxis or no-prophylaxis in infants with pyelonephritis and normal urinary tract. METHODS: Altogether 191 infants, who were diagnosed with acute pyelonephritis, proven to have normal urinary tracts and followed up for 6 months on prophylaxis, were retrospectively evaluated. According to the types of prophylaxis, the infants were divided into three groups [probiotics (Lactobacillus species), antibiotics (trimethoprim/sulfamethoxazole, TMP/SMX), and noprophylaxis]. The incidence of recurrent urinary tract infection (UTI) during 6 months after the development of pyelonephritis, main causative uropathogens, and its antimicrobial sensitivities were compared. RESULTS: The incidence of recurrent UTI in the probiotic group was 8.2%, which was significantly lower than 20.6% in the no-prophylaxis group (P=0.035) and was not significantly different from 10.0% of the antibiotic group (P=0.532). The significant difference between the probiotic and no-prophylaxis groups was seen only in male infants (P=0.032). The main causative organism of recurrent UTI was Escherichia coli (E.coli), which was not different among the three groups (P=0.305). The resistance rate of E. coli to TMP/SMX was 100% in the antibiotic group, which was significantly higher than 25.0% in the probiotic group and 41.7% in the no-prophylaxis group (P=0.008). CONCLUSION: Probiotic prophylaxis was more effective in infants with pyelonephritis and normal urinary tract than in those with no-prophylaxis. It could be used as a natural alternative to antibiotic prophylaxis.