Early probiotic intervention reduces overall mortality in premature infants: Study

The study published in Nutrients​ evaluated whether probiotics administered at clinician discretion benefit preterm infants and assessed if the timing of probiotic initiation affects their efficacy.

Probiotic supplementation for preterm babies has been a contentious issue due to a variety of factors related to the unique health risks of premature infants, inconsistent research findings, regulatory concerns, and the complexity of neonatal care.

Preterm infants and probiotics ​

Preterm birth, defined as a gestational age of less than 37 weeks, ranks among the leading causes of death in children under the age of five.

It is also associated with various complications​, such as respiratory distress syndrome (RDS), intraventricular hemorrhage (IVH), bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), retinopathy of prematurity (ROP) and periventricular leukomalacia (PVL).

Studies​ using next-generation sequencing have linked preterm birth-related morbidities, especially NEC and sepsis, to the gut microbiota. Dysbiosis, characterized by a lack of beneficial bacteria and an overgrowth of pathogens, plays a central role in both conditions, as microbial imbalance combined with the immature immune system and gut barrier can lead to excessive inflammation, tissue damage and bacterial translocation.

Preterm infants are particularly susceptible to microbial imbalances due to premature birth, prolonged antibiotic use, mechanical ventilation and environmental factors.

Early microbiome assessments in preterm infants reveal colonization by pathogenic and hospital-associated bacteria, such as Staphylococci​, Enterococcus spp​. and Klebsiella spp​.

In contrast, full-term infants primarily have microbiomes of vaginal, maternal fecal, or skin origin, dominated by Lactobacilli spp​. and Bifidobacterium spp​. To counter these imbalances, neonatal care has long used probiotic supplementation to prevent conditions like NEC and sepsis.

Study details ​

The study involved 330 extremely low birth weight (ELBW) infants. Of these, 206 consumed probiotics (60 early and 146 late) and 124 did not.

Findings indicated that probiotic supplementation, especially combinations of Lactobacillus​ and Bifidobacterium​, significantly reduced overall mortality and mortality related to NEC or LOS.

Early intervention with probiotics lowered overall mortality, NEC/LOS-related mortality, and unrelated mortality, while late probiotic adminsitration reduced overall and NEC/LOS-related mortality. Early probiotic use also accelerated the achievement of full enteral feeding.

The researchers concluded that probiotics lower mortality and improve feeding tolerance in preterm infants, highlighting the need for guidelines on their use.

"We found that even in the absence of guidelines and with decisions to administer probiotics primarily at the discretion of clinicians, probiotics continue to provide benefits to preterm infants," they wrote.

They did however note that they did not obtain data on the intestinal microbiome, which limited understanding of how it interacts with probiotics, and recommend that future studies on gut microbiota in preterm infants thoroughly investigate the effects of probiotics, particularly their relationships with acute health problems and long-term outcome.

In addition, the study called for clearer guidelines, noting: "It is imperative for our neonatologists to establish standardized guidelines to optimize probiotic effectiveness and enhance outcomes for preterm infants."

Strain specific research needed​

Experts at the recent International Scientific Association for Probiotics and Prebiotics (ISAPP) meeting discussed the relative risks of giving probiotics to preterm infants​ and emphasized the need for more research.

Consultant neonatal pediatrician Janet Berrington explained that while some studies show probiotics reduce NEC and related deaths, concerns about potential risks, such as sepsis, remain. Following an FDA warning​ in 2023, U.S. neonatal units reduced probiotic use, though UK units remained largely unaffected.

Berrington noted that factors like feeding practices and specific care units can impact probiotic effectiveness, suggesting more data is needed to optimize their use.

During a panel discussion, experts acknowledged the complexity of balancing the risks of NEC and probiotic-related sepsis and highlighted the need for personalized care based on individual health factors.

They also discussed the lack of consensus on probiotic strains and inconsistent NEC diagnoses, which complicates the determination of probiotic benefits. The panel recommended future research focus on comparing different probiotic products and dosages.

European guidelines, such as those from ESPGHAN, conditionally recommend specific probiotic strains, while the UK's National Health Service (NHS) advises using probiotics for preterm and at-risk infants but does not endorse any single product.

Source: Nutrients​ 2024, 16​(17), 2995
doi: 10.3390/nu16172995​
“Impact of Clinical Use of Probiotics on Preterm-Related Outcomes in Infants with Extremely Low Birth Weight.”
Authors: Wu, Wei-Hung et al.