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 wks gestation (GA) during the first two weeks of life. Study design Eligible infants <33 wks GA were enrolled within 4 days of birth in a prospective study of IP biomarkers (NCT01756040). Study participants received the non-metabolized sugars lactulose/rhamnose (La/Rh) enterally on study days 1, 8 and 15 and La/Rh were measured in urine by HPLC. Serum zonulin and fecal alpha-1 antitrypsin, two other IP markers, were measured by semi-quantitative western blot and ELISA, respectively. Results In a cohort of 43 subjects, the La/Rh ratio was elevated on day 1 and decreased over 2 weeks, but remained higher in infants ≤28 wk GA compared with IP in infants >28 wk GA. 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 three 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 towards more prolonged antibiotic exposure (p=0.092) and delayed initiation of feeding ≥4 days (p=0. 0.064) 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 may be by antibiotic exposures.

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Preterm neonates in the isolette are at risk of inadvertent exposure to ethanol. The expected blood alcohol level from this exposure is small and below 1 mg/dL level recommended by European Medicines Agency to limit the ethanol exposure in children. The unintended ethanol exposure can be avoided by rubbing hands for at least 20 s after applying EBHS.

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