Cholestasis refers to impaired bile flow from the liver to the intestine. In neonates, cholestasis causes poor growth and may progress to liver failure and death. Normal bile flow requires an intact ...liver-gut-microbiome axis, whereby liver-derived primary bile acids are transformed into secondary bile acids. Microbial bile salt hydrolase (BSH) enzymes are responsible for the first step, deconjugating glycine- and taurine-conjugated primary bile acids. Cholestatic neonates often are treated with the potent choleretic bile acid ursodeoxycholic acid (UDCA), although interactions between UDCA, gut microbes, and other bile acids are poorly understood. To gain insight into how the liver-gut-microbiome axis develops in extreme prematurity and how cholestasis alters this maturation, we conducted a nested case-control study collecting 124 stool samples longitudinally from 24 preterm infants born at mean 27.2 ± 1.8 weeks gestation and 946 ± 249.6 g, half of whom developed physiologic cholestasis. Samples were analyzed by whole metagenomic sequencing, in vitro BSH enzyme activity assays optimized for low biomass fecal samples, and quantitative mass spectrometry to measure the bile acid metabolome. In extremely preterm neonates, acquisition of the secondary bile acid biosynthesis pathway and BSH genes carried by Clostridium perfringens are the most prominent features of early microbiome development. Cholestasis interrupts this developmental pattern. BSH gene abundance and enzyme activity are profoundly reduced in cholestatic neonates, resulting in decreased quantities of unconjugated bile acids. UDCA restores total fecal bile acid levels in cholestatic neonates, but this is due to a 522-fold increase in fecal UDCA. A majority of bile acids in early development are atypical positional and stereo-isomers of bile acids. We report novel associations linking isomeric bile acids and BSH activity to neonatal growth trajectories. These data highlight deconjugation of bile acids as a key microbial function that is acquired in early neonatal development and impaired by cholestasis.
Quantify blood fatty acids and growth outcomes in preterm infants fed the exclusive human milk diet.
A prospective cohort study of 30 infants 24-34 weeks gestation and ≤1250 g fed the exclusive human ...milk diet. Blood fatty acids were quantified at two time points. Comparisons were made using two-sample t-tests and Wilcoxon rank sum.
Donor human milk-fed (n = 12) compared to mother's own milk-fed infants (n = 18) from birth to after 28 days of life, had an increased interval change of linoleic to docosahexaenoic acid ratio (5.5 vs. -1.1 mole percent ratio, p = 0.034). Docosahexaenoic and eicosapentaenoic acid interval changes were similar between groups. The arachidonic acid change was similar between groups (-2.3 vs. -0.9 mole percent, p = 0.37), however, both experienced a negative change across time. At 36 weeks postmenstrual age, growth velocities were similar for groups.
An exclusive human milk diet maintains birth docosahexaenoic and eicosapentaenoic acid concentrations. However, the postnatal deficit in arachidonic acid was not prevented.
Background
An exclusive human milk–based diet has been shown to decrease necrotizing enterocolitis and improve outcomes for infants ≤1250 g birth weight. Studies have shown that infants who received ...an exclusive human milk diet with a donor‐human milk–derived cream supplement (cream) had improved weight and length velocity when the cream was added to mother's own milk or donor‐human milk when energy was <20 kcal/oz using a human milk analyzer. Our objective was to compare growth and cost outcomes of infants ≤1250 g birth weight fed with an exclusive human milk diet, with and without human milk cream, without the use of a human milk analyzer.
Methods
Two cohorts of human milk–fed premature infants were compared from birth to 34 weeks postmenstrual age. Group 1 (2010–2011) received a donor‐human milk fortifier, whereas Group 2 (2015–2016) received donor‐human milk fortifier plus the commercial cream supplement, if weight gain was <15 g/kg/d.
Results
There was no difference in growth between the 2 groups for weight (P = 0.32) or head circumference (P = 0.90). Length velocity was greater for Group 1 (P = 0.03). The mean dose of donor‐human milk fortifier was lower in Group 2 (P < 0.001). Group 2 saved an average of $2318 per patient on the cost of human milk products (P < 0.01).
Conclusions
Infants receiving a human milk diet with cream supplementation for growth faltering achieve appropriate growth in a cost‐effective feeding strategy.
Spontaneous intestinal perforation (SIP) and necrotizing enterocolitis (NEC) are complications of extremely low birth weight (ELBW, ≤1000 g) infants. ELBW infants at Texas Children's Hospital receive ...an exclusive human milk-based diet, which has been associated with a reduction of NEC.
1) Assess incidence of SIP and NEC (Stage II or greater) in ELBW infants receiving 100% human milk-based diet, 2) Describe mortality rates of ELBW infants with SIP and NEC.
Prospective single-center observational cohort study of ELBW infants born between 2010 and 2014 with SIP or NEC (exclusion: congenital anomalies and death within 48 h).
Of 379 ELBW infants, 345 were eligible. Of these, 28 (8.1%) had SIP and 8 (2.3%) had NEC (medical n = 1, surgical n = 7). SIP infant mortality was 32% (n = 9) compared to 63% (n = 5) for NEC patients. Of SIP infants with PD (n = 25), 52% required subsequent exploratory laparotomy (LAP). Of NEC infants with peritoneal drainage (PD) (n = 2), both required subsequent LAP.
Using an exclusive human milk-based diet, the incidence of SIP exceeds NEC in ELBW infants at our institution. This shows a changing trend in the incidence of these two diagnoses in the era of human milk, as NEC had previously been more prevalent in ELBW infants. More than half of infants who initially received PD later required LAP. There were no differences in survival outcomes in both SIP and NEC groups based on surgical management.
Perioperative malnutrition in infants with congenital heart disease can lead to significant postnatal growth failure and poor short- and long-term outcomes. A standardized approach to nutrition is ...needed for the neonatal congenital heart disease population, taking into consideration the type of cardiac lesion, the preoperative and postoperative period, and prematurity. Early enteral feeding is beneficial and should be paired with parenteral nutrition to meet the fluid and nutrient needs of the infant.
Background
In an era of improved management and treatment options, this study aims to describe the long‐term outcomes and factors predictive of outcomes of neonatal‐onset intestinal failure (IF) due ...to surgical short bowel syndrome (SBS).
Methods
Retrospective, single‐center cohort study of infants born between January 2011 and December 2018 with inclusion criteria: <44 weeks postmenstrual age at SBS diagnosis, <28 days on admission, parenteral nutrition dependence >60 days, and documented intestinal resection. Primary outcomes included survival and achievement of enteral autonomy (EA). Data analysis utilized Fisher.s exact test, Kruskal‐Wallis test, survival analysis methods, Cox proportional hazards regression, linear regression and logistic regression.
Results
Ninety‐five patients (males 56%) were studied with median follow‐up of 38 months (IQR 19, 59). Survival at last follow‐up was 96%, and EA was achieved in 85%. Forty‐eight patients had documented residual bowel length (RBL) with median length of 49 cm (IQR 36, 80). Survival in patients with RBL of <30cm (n = 8), 30‐59cm (n = 19), and >60cm (n = 21) was 100%, 95%, and 95% respectively. Shorter RBL was associated with longer time to achieve EA (p = 0.007), but not with survival (p = 0.81). Delay in achieving EA was associated with absence of ileocecal valve (p = 0.002) and bloodstream infections (p < 0.001). Peak conjugated bilirubin correlated with increased mortality (p = 0.002).
Conclusion
Overall high rate of survival and achievement of EA was found in neonatal onset IF due to SBS. EA but not survival was correlated with RBL. Ileocecal valve, bloodstream infections, and conjugated bilirubin levels were the other predictive factors of outcomes.
