625 - Exposure to multi-strain probiotics affects neurodevelopment and growth in premature infants

Publication Number: 1602.625

Timothy Boly, University of Iowa, Iowa City, IA, United States; Kathryn Ritter, Medical College of Wisconsin, Sussex, WI, United States; Amy A. Hobson, University of Iowa Stead Family Children's Hospital, Iowa City, IA, United States; John M. Dagle, University of Iowa Stead Family Children's Hospital, Iowa City, IA, United States; Jennifer Bermick, University of Iowa Stead Family Children's Hospital, Iowa City, IA, United States

Background: Probiotics are microorganisms that maintain a homeostatic environment within the digestive tract. Increased proportions of probiotic organisms within the intestinal microbiome have been associated with improvement in morbidity and mortality in premature infants. In 2023, the FDA banned probiotics in the NICU due to concerns of sepsis due to translocation of a probiotic strains in this patient population.

Objective: To evaluate the effect of probiotics supplementation on growth and developmental outcomes in premature infants. A secondary outcome was to assess safety of probiotic use in this patient population.

Design/Methods: A retrospective cohort study performed for infants born at less than 33 weeks' gestation who received a multi-strain probiotics product at the University of Iowa HealthCare NICU for a 6-year period compared to infants of the same gestational age in the 6 years prior to probiotics initiation. Demographic data, common neonatal morbidities, mortality, indices of growth and results of neurodevelopmental testing by the Bayley Scales of Infant and Toddler Development at 2 years of age were collected by review of the electronic medical record.

Results: The probiotics cohort consisted of 1666 infants with 1070 infants included in the control group. Significantly increased motor development scores were found in the probiotics group (Fig 1). Significantly increased cognitive and motor scores were seen in the most premature infants who received probiotics when controlled for severe IVH. When controlled for confounding variables (IVH, SIP, NEC, culture-positive sepsis and congenital anomalies), the significant increase in motor scores was again seen. Probiotics exposure was associated with significantly improved weight Z-score at time of discharge and significantly improved weight gain (g/days of admission, Fig 2). When stratified by gestational age, infants born at 27-34 weeks' with probiotics exposure had significantly higher weight gain. When stratified by birth weight cohorts, ELBW and VLBW populations had the most benefit from probiotics in admission weight gain. No sepsis events related to probiotics were identified.

Conclusion(s): Probiotic supplementation is associated with improved motor outcomes at 2 years of age, with further benefit seen in periviable infants born at 22-26 weeks'. Probiotics use was associated with improved weight gain and weight Z-score at discharge. Without any episodes of culture-positive sepsis from a sterile source, probiotics can be considered a safe intervention to use in this population.

Table 1
Demographics data of included infants in the control and probiotics group. Data is presented as mean +/- standard deviation or n (%). IVH: intraventricular hemorrhage; PVL: periventricular leukomalacia; NEC: necrotizing enterocolitis; SIP: spontaneous intestinal perforation

Figure 1
(A) Subcomponent scores by chronologic and adjusted ages when stratified exposure group (No Probiotics vs Probiotics). Shaded area demonstrates distribution of mean score±1SD. (B) Subcomponent scores by chronologic and adjusted ages when stratified by gestational age (22-26 weeks' vs 27-32 weeks') and probiotic exposure. Shaded area demonstrates distribution of mean score±1SD. (C) Subcomponent scores by chronologic and adjusted ages stratified by GA when severe IVH (grades III and IV) removed. (D) Subcomponent scores by chronologic and adjusted ages when possible confounders (severe IVH, culture-positive sepsis, SIP, NEC, and congenital anomalies) removed.

Figure 2
(A) Discharge weight, length, and fronto-occipital circumference (FOC) Z-score by exposure group. (B) Admission weight gain in grams/day by exposure group. (C) Admission weight gain in grams/day by exposure group and gestational age category. (D) Admission weight gain in grams/day by exposure group and birth weight category.