Fatty acid concentrations in preterm infants fed the exclusive human milk diet: a prospective cohort study.

OBJECTIVE: Quantify blood fatty acids and growth outcomes in preterm infants fed the exclusive human milk diet. METHODS: 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. RESULTS: 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. CONCLUSION: An exclusive human milk diet maintains birth docosahexaenoic and eicosapentaenoic acid concentrations. However, the postnatal deficit in arachidonic acid was not prevented.

Cholestasis impairs gut microbiota development and bile salt hydrolase activity in preterm neonates.

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.

Human Milk Fortification: A Practical Analysis of Current Evidence.

Human milk (HM) with appropriate fortification is the recommended nutrition for very low birth weight (VLBW) infants. Fortification provides additional nutrients, vitamins, and minerals to support the growing preterm infant during critical periods of development. This article discusses the variability of HM including differences between maternal and pasteurized donor human milk (DHM), fortification of HM through the use of single- and multi-nutrient fortifiers, and clinical controversies including the timing of fortification, volume of feedings, and future innovations in HM fortification.

Optimizing the Use of Human Milk Cream Supplement in Very Preterm Infants: Growth and Cost Outcomes.

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.

Very preterm infants who receive transitional formulas as a complement to human milk can achieve catch-up growth.

OBJECTIVE: To evaluate the growth of premature infants fed a postdischarge diet of human milk (HM) complemented with transitional formula (TF) as compared with those fed TF only. STUDY DESIGN: In this prospective cohort study, 51 infants' diets and anthropometrics were collected at discharge and at 12-15 months corrected gestational age. RESULTS: Post discharge, infants in both groups exhibited similar growth velocities and changes in z-scores. The duration of infants' HM consumption was not correlated with weight gain (r = -0.25, p = 0.26). The duration of complementary TF feeds also did not correlate with increased growth (r = -0.11, p = 0.44). Both groups achieved catch-up growth and displayed growth velocities that significantly exceeded the upper limit of the World Health Organization (WHO) weight growth standard (p < 0.001). CONCLUSIONS: Preterm infants receiving HM and complementary TF post discharge had growth velocities at or exceeding weight gain projected by the WHO growth standard for term infants.