SAN DIEGO – Gestational age and postnatal age dependent intestinal barrier maturation in preterm infants may be altered by feeding and antibiotic exposures, a study conducted at two centers showed.
Mature, healthy intestinal mucosa is lined by a monolayer of epithelial cells that forms tight junctions and acts as a selective barrier to bacteria and harmful toxins, Dr. Rose M. Viscardi said at the annual meeting of the Pediatric Academic Societies. Intestinal permeability (IP) defines the leakiness of the mucosal barrier, and previous studies suggest that preterm infants have increased IP at birth that matures over time.
Dr. Rose M. Viscardi
According to Dr. Viscardi, professor of pediatrics at the University of Maryland, Baltimore, increased IP is a risk factor for necrotizing enterocolitis (NEC). IP is disturbed in the newborn, particularly in preterm infants, “because they’re exposed to antibiotics and often delivered by cesarean section,” she said. “This may alter the IP such that there is the potential for bacteria crossing through that paracellular pathway, leading to enhanced neutrophil recruitment and intense inflammatory response both locally in the intestines as well as systematically, leading to the development of NEC.”
Current methods of determining intestinal barrier function include measurements of lactulose (La) and rhamnose (Rh) in urine and plasma, as well as stool alpha 1 antitrypsin (A1AT), a 52-KD glycoprotein produced by the liver, intestinal macrophages, and mucous membrane cells. Dr. Viscardi and her associates set out to determine changes in IP measures by urinary La/Rh and stool A1AT in the first 2 weeks of life in neonates at 24-32 weeks gestational age. The secondary objective was to determine the effect of feeding practices and antibiotic exposure on the IP maturation process in the first 2 weeks of life in those same infants.
At two sites, the researchers enrolled 43 infants at 24-32 weeks gestational age who received 1 mL/kg La/Rh solution (8.6 g La plus 140 mg Rh/100 mL sterile water) administered enterally on study days 1, 8, and 15, with urine collected after 4 hours. The researchers collected .5 mL blood by heel stick 90-120 minutes post La/Rh for serum La/Rh, and stool within 8 hours of La/Rh dose for fecal A1AT and later microbiome analysis.
Of the 43 subjects, 23 (53%) were male, 23 (53%) were African American, their mean gestational age was 30 weeks, and their mean birth weight was 1,336 g. A total of 38 subjects completed measurements at baseline, on day 8, and on day 15. Dr. Viscardi and her associates found that the La/Rh ratio decreased between day 1 and day 8 in 97% of subjects, but increased greater than .048 between day 8 and day 15 in 21% of subjects.
In addition, exclusively breast milk–fed infants were less likely than were formula-fed (with or without breast milk) infants to experience an increase in IP between day 8 and day 15 (11% vs. 50%, respectively; P =. 019). They also observed a trend toward the use of ceftriaxone and increased IP between day 8 and day 15 (50% vs. 16%; P = .094). No subject developed NEC of stage 2 or higher.
“The data demonstrate that the preterm intestine is ‘leaky’ at birth and barrier function improves over time in a gestational and postnatal age-dependent manner,” Dr. Viscardi concluded. “Exclusive breast milk feeding may prevent increases in IP related to the introduction of oral feeding.”
The National Center for Complementary and Alternative Medicine and the Gerber Foundation funded the study. Dr. Viscardi reported having no relevant financial conflicts.
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