Objective To evaluate intestinal barrier function in neonates undergoing cardiac surgery using lactulose/mannitol (L/M) ratio measurements also to determine correlations with early breast milk feeding. urine L/M ratios at pre-op post-op time 7 and post-op time 14 had been 0.06 0.12 and 0.17 respectively. In the trophic breasts dairy feeds group (n=14) the mean urine Cucurbitacin I L/M ratios at pre-op post-op time 7 and post-op time 14 were 0.09 0.19 and 0.15 respectively. Both groups had significantly higher L/M ratios at post-op day 7 and 14 compared with pre-op (p<0.05). Conclusions Neonates have increased intestinal permeability after cardiac surgery extending to at least post-op day 14. This pilot study was not powered to detect differences in benefit or adverse events comparing NPO with breast milk feeds. Further studies to identify mechanisms of intestinal injury and therapeutic interventions are warranted. Trial registration Registered with ClinicalTrials.gov: NCT01475357. Keywords: Nutrition growth failure congenital heart disease Gastrointestinal morbidity and growth failure continue to be widespread health problems amongst infants with congenital heart disease specifically those who require heart medical procedures as a neonate.(1-5) Most infants who require cardiac surgery in the neonatal period are appropriate weight-for-gestational-age at birth; yet they struggle with gastrointestinal morbidities and growth failure during the post-operative period and through the first 4-8 weeks after birth.(6 7 Gastrointestinal morbidities and growth failure PLAT Cucurbitacin I are increasingly important modifiable factors given their negative impacts on outcomes such as poor wound healing infections prolonged hospitalizations and longterm neurodevelopmental disability with worse school performance.(8 9 The etiologies of gastrointestinal morbidity and growth failure are likely multifactorial and include the increased metabolic stress of cardiac surgery inadequate caloric delivery mechanical feeding difficulties altered splanchnic perfusion and gastrointestinal complications e.g. malabsorption and severe reflux.(3 5 10 Despite the high incidence of gastrointestinal morbidity and growth failure in the cardiac infant population there is a paucity Cucurbitacin I of knowledge regarding the specific intestinal mucosal and barrier insults incurred during neonatal cardiac surgery. Urine lactulose/mannitol (L/M) ratios have been safely used as a marker of small intestinal maturation in premature infants and healthy term infants.(13 14 Following the ingestion of lactulose and mannitol there is systemic absorption of the markers as measured by increased serum and urine concentrations. The markers pass across the gut wall via different routes: lactulose by a paracellular pathway between the tight junctions of gut epithelial cells and mannitol via a transcellular pathway.(15) With advancing postnatal age intestinal permeability should decrease as evidenced by closer tight junctions less lactulose absorption lower concentration in urine and smaller urinary L/M ratios. In healthy control subjects the L/M ratio is typically low (<0.09) because permeability to the larger molecule lactulose is much lower than permeability to the smaller molecule mannitol.(14 16 We sought to determine perioperative intestinal barrier permeability using L/M ratio measurements and identify correlations with early breast milk feeding in neonates requiring cardiac surgery. We hypothesized that infants who received trophic breast milk feeding during the pre-operative period would have decreased intestinal permeability post-operatively. Methods The Institutional Review Board of the Medical University of South Carolina (MUSC) approved this study. This was a single-center prospective randomized pilot study of term neonates with structural heart disease requiring cardiac surgery. Written informed consent was obtained from the parents or legal guardians of the children who served as subjects of the investigation. All study subjects were consented and enrolled by the principal investigator (S.C.Z.). Inclusion criteria included: (1) term neonates ≥ 37 weeks gestation; (2) admission to the MUSC pediatric cardiac intensive care unit (PCICU) or neonatal intensive care unit (NICU); Cucurbitacin I (3) a diagnosis of structural heart disease; and (4) required cardiac surgery with cardiopulmonary bypass prior to hospital discharge. Exclusion criteria included: (1) infants who.