167 - Non-linear Relationship Between Hematocrit and Gut Dysbiosis in Preterm Infants

Publication Number: 2161.167

Thao Ho, University of South Florida, Tampa, FL, United States; Melissa Olsen, University of South Florida, Tampa, FL, United States; Laura Szalacha, USF Health Morsani College of Medicine, Tampa, FL, United States; Ryan Pace, University of South Florida, Tampa, FL, United States

Background: Even though transfusion practice at lower thresholds of anemia did not yield higher rates of adverse outcomes in clinical trials, transfusion-related gut injuries have been observed in preterm infants. Anemia itself has been linked to systemic and local intestinal inflammation, gut injury, and dysbiosis in preterm infants. However, the hematocrit (Hct) level at which these effects emerge is not well established.

Objective: To identify the Hct threshold associated with worsening gut dysbiosis and to characterize the temporal relationship between dysbiosis and anemia severity in preterm infants

Design/Methods: This nested cohort study included 109 preterm infants born < 1500 g from a larger cohort of 400 infants, with a 4:1 case-to-control ratio. Cases and controls were matched by birth gestational age (+/- 1 wk) and postnatal age at stool collection. A total of 485 serial weekly stool samples collected from enrollment to discharge underwent 16S rRNA gene sequencing for microbiome analysis. Hematocrit values corresponding to each stool sample collection date were recorded. A composite dysbiosis index (CDI) was calculated by the log-transformed relative abundances of Klebsiella, Enterococcus, Escherichia, Staphylococcus, and Clostridium. Both CDI and Hct were standardized to z-scores, and postnatal age was represented in 10-day increments. Multilevel mixed-effects models tested the longitudinal association between CDI and Hct, adjusting for birth gestational age, antibiotic exposure, and transfusion history.

Results: The mean birth gestational age was 27.8 +/- 2.6 weeks, and the mean birth weight was 1064 +/- 374 grams. Stool samples were collected between 3 and 109 days after birth. On average, infants received 1.7 +/- 2.7 blood transfusions and were exposed to 1.8  2.0 antibiotic courses. CDI and Hct changed in tandem during the first 60 days of life but diverged thereafter (Figure 1). A mixed-effects model including linear, quadratic, and cubic Hct terms (Hct, Hct2, and Hct3) and adjusted for postnatal age revealed a significant non-linear relationship (p < 0.05). CDI increased when Hct = 20 -26%, plateaued at Hct = 26 - 27%, and decreased thereafter (Figure 2).

Conclusion(s): Gut dysbiosis in preterm infant exhibits a non-linear relationship with Hct, with the greatest dysbiotic burden observed at Hct 26 - 27%. Chronic anemia occurring after 2 months of age were associated with increasing dysbiosis. Integrating microbiome and metabolomic biomarkers can strengthen the predictive models and guide individualized anemia management strategies.

Figure 1: Hematocrit and Gut Dysbiosis Overtime
Temporal changes in composite dysbiosis index (CDI) and Hct over postnatal age in 10-day increments. The arrow indicates postnatal age at which the associated changes diverged.

Figure 2: Non-linear Relationship Between Gut Dysbiosis and Hct.
The predicted CDI z-scores, from a mixed-effects model including Hct, Hct2, Hct3, and postnatal age, increased from severely anemic to moderately anemic (Hct = 20 - 26%), plateaued at Hct = 26 - 27%, then declined with higher Hct (p < 0.05).