Probiotics Show Promise for Reducing Late-onset Sepsis in Preterm Infants

By: Valerie Lauer
Monday, August 1, 2016

Using a combination of probiotics, researchers in Slovenia were able to significantly reduce the incidence of late-onset sepsis in a group of preterm infants born with very low birth weights.

The study, part of a growing body of research seeking to better understand and standardize the role probiotics can play in the well-being of pediatric patients, appeared in the December 2015 issue of The Central European Journal of Medicine’s publication Wiener klinische Wochenschrift.

The study followed the progress of 80 infants who were born preterm with birth weights of less than 3 pounds, 4 ounces.

“The main problems with these patients after birth are lung immaturity and immune deficiency,” says the lead author of the study, Zlatka Kanic, MD, PhD, pediatrician, neonatologist and intensivist in a multidisciplinary ICU at University Medical Centre, Maribor. “Despite better knowledge and technical improvement, nosocomial infections and sepsis are still significant problems in very low birth weight infants. We wanted to find out whether oral supplementation with probiotics lowers the incidence of late-onset infections.”

Focusing In

In the study, 40 preterm infants with very low birth weights had their diets supplemented twice a day with a probiotic cocktail of Lactobacillus acidophylus, Enterococcus faecium and Bifidobacterium infantum, at a ratio of 1.5-to-1-to-1.5. Dr. Kanic and his colleagues used a reduced dosage for their study — 107 colony-forming units (CFUs) compared with the standard 109 CFU to 1011 CFU usually used in children and adults. Supplementation continued from their first feedings until the patients were discharged. A control group of 40 preterm infants with similar birth weights were fed as usual without any probiotics.

By the end of the study, 29 infants in the control group had developed late-onset sepsis, compared with 16 such cases in the experimental group. Though the sample size is small, the statistical difference is significant.

“Unfortunately, there are no international guidelines about the usage of probiotics in premature [infants],” Dr. Kanic says. “In our research, we established a lower number of late-onset sepsis and late-onset infections in very low birth weight infants by using a low dose of probiotics. Since this research, the probiotic combination and dosage is used regularly in these infants at our ICU.”

Understanding the Mechanism

At the University of Nebraska Medical Center, Ann Anderson Berry, MD, PhD, Associate Professor of the Division of Newborn Medicine, helped develop a standardized protocol for using probiotics in preterm infants cared for in the center’s newborn ICU. There, preterm infants receive probiotic combination therapy until the corrected gestational age of 34 weeks.

“The working theory is that the gut, the skin, everything is colonized by some [sort of bacteria] shortly after birth,” Dr. Anderson Berry says. “Children in a normal nursery are colonized by bacteria from the mother, father and visitors. If a baby is born prematurely, he or she is immediately transitioned into the NICU environment and surrounded by medical staff and medical equipment. The types of bacteria those children are colonized with can be different.”

That environment well describes the experience of preterm infants with very low birth weights. Mortality rates are higher in this population, and the infants’ ability to fight infection is compromised.

Introducing bacteria that is closer to what would be found in the microbiome of healthy, full-term children is thought to encourage better immune system development as well as reduce the incidence of conditions such as late-onset sepsis in this population. The findings of Dr. Kanic and his associates’ research lend credence to this theory.

Looking Ahead

Though Dr. Kanic’s research is an important step forward in the field of probiotic use in preterm infants, there is much yet to learn. He plans to research the long-term effects of probiotics on very low birth weight infants, as well as on infants in the extremely low birth weight category.

Further study could yield broader applications, says Sonia Michail, MD, FAAP, CPE, AGAF, attending physician, Professor of Clinical Pediatrics with Children’s Hospital Los Angeles and the Keck School of Medicine of the University of Southern California, who has researched probiotics and the microbiome for 20 years.

“Before widespread applicability of the use of probiotics is formalized as a standard practice, the appropriate studies should be conducted for specific probiotic products at specific doses for specific conditions,” Dr. Michail says. “We hope to see more research addressing delivery of therapies and potentially vaccines through probiotic organisms.”