Urinary Metabolomic Profile of Preterm Infants Receiving Human Milk with Either Bovine or Donkey Milk-Based Fortifiers

Giribaldi, Marzia; Peila, Chiara; Coscia, Alessandra; Cavallarin, Laura; Antoniazzi, Sara; Corbu, Sara; Maiocco, Giulia; Sottemano, Stefano; Cresi, Francesco; Moro, Guido; Bertino, Enrico; Fanos, Vassilios; Marincola, Flaminia Cesare

doi:10.3390/nu12082247

Cited by 8 publications

(9 citation statements)

References 45 publications

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“…In the present study, citric acid was found to share a common metabolic fate through time, as its levels increased with age in both groups (3rd month compared to the 3rd day), as supported by Figure 3 and Figure 4 . In accordance with our results, a previous clinical intervention with subjects receiving bovine or donkey breast milk indicated citric acid as a maturation biomarker for this group [ 52 , 58 ]. However, citric acid is also a key compound of the metabolic excretion profile during the first days (1st to 7th day) of life in BF infants [ 1 , 52 , 59 ].…”

Section: Discussionsupporting

confidence: 92%

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Urine Metabolomic Profile of Breast- versus Formula-Fed Neonates Using a Synbiotic-Enriched Formula

Falaina

Fotakis

Boutsikou

et al. 2022

IJMS

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The aim of this study was to compare the urine metabolic fingerprint of healthy neonates exclusively breastfed with that of neonates fed with a synbiotic-enriched formula (Rontamil® Complete 1) at four time points (the 3rd and 15th days of life and the 2nd and 3rd months). The determination of urine metabolic fingerprint was performed using NMR metabolomics. Multivariate data analyses were performed with SIMCA-P 15.0 software and R language. Non-distinct profiles for both groups (breastfeeding and synbiotic formula) for the two first time points (3rd and 15th days of life) were detected, whereas after the 2nd month of life, a discrimination trend was observed between the two groups, which was further confirmed at the 3rd month of life. A clear discrimination of the synbiotic formula samples was evident when comparing the metabolites taken in the first days of life (3rd day) with those taken in the 2nd and 3rd months of life. In both cases, OPLS-DA models explained more than 75% of the metabolic variance. Non-distinct metabolomic profiles were obtained between breastfed and synbiotic-formula-fed neonates up to the 15th day of life. Discrimination trends were observed only after the 2nd month of the study, which could be attributed to breastfeeding variations and the consequent dynamic profile of urine metabolites compared to the stable ingredients of the synbiotic formula.

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Section: Discussionsupporting

confidence: 92%

“…Variations in the levels of citric acid produced during the tricarboxylic acid (TCA) cycle are affected by factors related to gestational age, lactation, height, weight, growth rate and energy demands of the newborn [ 58 ].…”

Section: Discussionmentioning

confidence: 99%

Urine Metabolomic Profile of Breast- versus Formula-Fed Neonates Using a Synbiotic-Enriched Formula

Falaina

Fotakis

Boutsikou

et al. 2022

IJMS

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“…The use of DF also reduced the frequency of gastroesophageal reflux in infants showing clinical signs of gastroesophageal reflux and cardiorespiratory symptoms associated to feeding intolerance [ 37 ]. A recent urinary metabolomics investigation revealed that the different quality of the nutrients provided resulted in different urinary metabolic patterns [ 38 ]. Moreover, we also reported that DF- and BF-arms had similar short-term growth outcome as well as long-term auxological and neurodevelopmental outcomes.…”

Section: Discussionmentioning

confidence: 99%

The “Fortilat” Randomized Clinical Trial Follow-Up: Neurodevelopmental Outcome at 18 Months of Age

et al. 2020

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Adequate nutrition is fundamental to neonatal survival and short-term outcomes, but it also has long-term consequences on quality of life and neurologic development of preterm infants. Donkey milk has been suggested as a valid alternative for children allergic to cows’ milk proteins, due to its biochemical similarity to human milk; we, hence, hypothesized that donkey milk could be a suitable basis for developing an innovative human milk fortifier for feeding preterm infants. The aim of the current study was to extend the findings and to evaluate the neurodevelopmental outcomes at 18 months of corrected age of the infants enrolled in the clinical trial named “Fortilat”. Infants born ≤1500 g and <32 weeks of gestational age were randomized to receive either a combination of bovine milk-based multicomponent fortifier and protein supplement or a combination of a novel multicomponent fortifier and protein supplement derived from donkey milk. The followed fortification protocol was the same for the two groups and the two diets were designed to be isoproteic and isocaloric. All infants enrolled were included in a developmental assessment program. The neurodevelopmental assessment was performed at 18 ± 6 months of corrected age. Minor and major neurodevelopmental impairment and General Quotient (GQ) at the Griffiths-II Mental Development Scale were considered. The GQ was considered both in continuous and as two classes: lower than and higher than (or equal to) a defined cutoff (GQcl). The difference in GQ and GQcl between the two arms was estimated using Mann–Whitney–Wilcoxon test or Fischer exact test, respectively, on the assumption of casual loss at follow-up. A further analysis was performed using generalized linear models. There were 103 children (bovine milk-derived fortifier arm = 54, donkey milk-derived fortifier arm = 49) included for the neurodevelopmental follow-up. All observations were included in the interval of 18 ± 6 months of corrected age. No significant difference was observed between the two arms in the incidence of neurologic sequelae and the GQs were similar in the two arms. Our results demonstrated no difference for the donkey milk-derived fortifier compared to standard bovine-derived fortifier regarding long-term neurodevelopmental outcomes.

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“…In an ancillary study, the use of DF reduced also the gastroesophageal reflux frequency in infants showing infants with clinical signs of gastroesophageal reflux and cardiorespiratory symptoms associated with feeding intolerance [27]. A recent urinary metabolomics investigation revealed that the different quality of the nutrients provided by isocaloric and isoproteic fortification with either DF and BF resulted in different urinary metabolic patterns [28].…”

Section: Introductionmentioning

confidence: 99%

The “Fortilat” Randomized Clinical Trial Follow-Up: Auxological Outcome at 18 Months of Age

et al. 2020

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Human milk fortification is a routine clinical practice for feeding preterm infants. We hypothesized that donkey milk can be a suitable basis for developing an innovative human milk fortifier. Our randomized controlled single-blind clinical trial, named “Fortilat”, evaluated the feeding tolerance, growth and clinical short-term outcomes in a population of preterm infants fed with a novel multi-component fortifier and a protein concentrate derived from donkey milk. The aim of the current study is to extend the previous findings and to evaluate the auxological outcomes of the infants enrolled in the “Fortilat” trial at 18 months of age. In the previous trial “Fortilat”, the fortification protocol followed was the same for the two groups, and the two diets were designed to be isoproteic and isocaloric. All infants enrolled in the trial were included in a premature infant developmental evaluation program consisting of hospital visits at 40 ± 1 weeks of postmenstrual age, and at 6, 12 and 18 months of corrected age. Weight, head circumference and length were expressed in z-score using neonatal Intergrowth21st and INeS charts at birth, and WHO 0–5 years growth charts at 18 months. 122 children (Bovine-arm = 62, Donkey-arm = 60) were included in this study. All the observations were recorded in the interval of 18 ± 3 months of the correct age. The two groups did not differ for head circumference, length or weight at 18 months of age. Our data show that fortifiers derived from donkey milk had not different long term auxological outcomes of standard bovine-derived fortifier, but the new donkey milk fortifier was well tolerated in our population.

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Urinary Metabolomic Profile of Preterm Infants Receiving Human Milk with Either Bovine or Donkey Milk-Based Fortifiers

Cited by 8 publications

References 45 publications

Urine Metabolomic Profile of Breast- versus Formula-Fed Neonates Using a Synbiotic-Enriched Formula

Urine Metabolomic Profile of Breast- versus Formula-Fed Neonates Using a Synbiotic-Enriched Formula

The “Fortilat” Randomized Clinical Trial Follow-Up: Neurodevelopmental Outcome at 18 Months of Age

The “Fortilat” Randomized Clinical Trial Follow-Up: Auxological Outcome at 18 Months of Age

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