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Published on: November 15, 2019
Intestinal Barrier Maturation in Very Low Birthweight Infants: Relationship to Feeding and Antibiotic Exposure
Bushra Saleem1, Adora C Okogbule-Wonodi1, Alessio Fasano2
1Department of Pediatrics, University of Maryland School of Medicine, Baltimore, MD.
Insights
Feeding and antibiotic exposure impact intestinal barrier maturation in preterm infants. Breast milk promotes faster maturation, while prolonged antibiotic use may delay it.
Area of Science:
- Neonatal Physiology
- Gastrointestinal Health
- Infant Nutrition
Background:
- Intestinal barrier function is crucial for preterm infant health.
- Maturation of the intestinal barrier is influenced by various postnatal factors.
- Understanding these factors is key to improving outcomes for premature infants.
Purpose of the Study:
- To investigate the effects of feeding and antibiotic exposure on intestinal barrier maturation in preterm infants.
- To assess changes in intestinal permeability (IP) biomarkers over the first two weeks of life.
- To correlate feeding practices and antibiotic use with IP patterns.
Main Methods:
- Prospective study measuring IP biomarkers (lactulose/rhamnose, zonulin, alpha-1-anti-trypsin) in infants <33 weeks gestational age.
- Serial urine and serum samples collected on days 1, 8, and 15.
- High-performance liquid chromatography, Western blot, and ELISA used for biomarker analysis.
Main Results:
- Intestinal permeability (IP) decreased over two weeks but remained higher in infants born at ≤28 weeks gestation.
- Exclusive breast milk feeding was associated with more rapid intestinal barrier maturation.
- Trends suggested prolonged antibiotic exposure and delayed feeding initiation were linked to abnormal IP patterns.
Conclusions:
- Intestinal barrier maturation in preterm infants is dependent on gestational age and postnatal age.
- Breast milk feeding has a positive maturational effect on the intestinal barrier.
- Antibiotic exposures may influence intestinal barrier development in preterm infants.
Objective:
To test the hypothesis that feeding and antibiotic exposures affect intestinal barrier maturation in preterm infants, we serially measured intestinal permeability (IP) biomarkers in infants <33 weeks gestation (gestational age [GA]) during the first 2 weeks of life.
Study Design:
Eligible infants <33 weeks GA were enrolled within 4 days of birth in a prospective study of IP biomarkers (NCT01756040). Study participants received the nonmetabolized sugars lactulose/rhamnose enterally on study days 1, 8, and 15 and lactulose/rhamnose were measured in urine by high-performance liquid chromatography. Serum zonulin and fecal alpha-1-anti-trypsin, 2 other IP markers, were measured by semiquantitative Western blot and ELISA, respectively.
Results:
In a cohort of 43 subjects, the lactulose/rhamnose ratio was increased on day 1 and decreased over 2 weeks, but remained higher in infants born at ≤28 weeks of gestation compared with IP in infants born at >28 weeks of gestation. Exclusive breastmilk feeding was associated with more rapid maturation in intestinal barrier function. A cluster analysis of 35 subjects who had urine samples from all time points revealed 3 IP patterns (cluster 1, normal maturation: n = 20 [57%]); cluster 2, decreased IP during the first week and subsequent substantial increase: n = 5 [14%]); and cluster 3, delayed maturation: n = 10 [29%]). There were trends toward more prolonged antibiotic exposure (P = .092) and delayed initiation of feeding ≥4 days (P = .064) in infants with abnormal IP patterns.
Conclusions:
Intestinal barrier maturation in preterm infants is GA and postnatal age dependent, and is influenced by feeding with a maturational effect of breastmilk feeding and possibly by antibiotic exposures.
Trial Registration:
ClinicalTrials.gov: NCT01756040.
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