ABSTRACT
INTRODUCTION: Hyaluronan (HA) is a major component of the extracellular matrix. Increased pulmonary HA concentrations are associated with several respiratory disorders and is a pathophysiological feature of lung disease. We investigated whether elevated urine HA is a biomarker of an unfavorable 40-week respiratory outcome in preterm infants. METHODS: Infants comprised a cohort of preterm neonates <31 weeks gestational age (GA) from the Prematurity-Related Ventilatory Control (Pre-Vent) multicenter study. HA was quantified in urine obtained at 1 week and 1 month of age. Respiratory status at 40 weeks post-menstrual age (PMA) was classified as unfavorable [either (1) deceased at or before 40 weeks PMA, (2) an inpatient on respiratory medication, O2 or other respiratory support at 40 weeks, or (3) discharged prior to 40 weeks on medications/O2/other respiratory support], or favorable (alive and previously discharged, or inpatient and off respiratory medications, off O2, and off other respiratory support at 40 weeks PMA). The association between urine HA and the unfavorable 40 week PMA outcome was examined using a multivariate logistic generalized estimation equation model. RESULTS: Infants with higher HA at 1 week (but not 1 month) showed increased odds of unfavorable respiratory outcome at 40 weeks PMA (OR [95% CI] = 1.87 per 0.01 mg [1.27, 2.73]). DISCUSSION AND CONCLUSION: Neonatal urine screening for HA could identify infants at risk for death or need for respiratory support at term-corrected age (40 weeks PMA). The relationship between elevated HA at 1 week and an unfavorable 40 week outcome was stronger in infants with lower GA.
Subject(s)
Biomarkers , Gestational Age , Hyaluronic Acid , Infant, Premature , Humans , Hyaluronic Acid/urine , Infant, Newborn , Male , Female , Infant, Premature/urine , Biomarkers/urine , Logistic Models , Multivariate Analysis , Prospective StudiesABSTRACT
INTRODUCTION: Preterm infants are at risk for a variety of somatic and neurological disorders. In recent years, biofluid proteomics has emerged as a potential diagnostic tool for biomarker analysis. The aim of this study was to determine gestational age (GA)-related patterns of the urinary peptidome in preterm infants for researching potential novel prognostic biomarkers. METHODS: We performed urinary peptidomics in longitudinal samples of 24 preterm (mean GA weeks 28 + 1 [24+1-31 + 6]) and 27 term born controls (mean GA weeks 39 + 2 [37+0-41 + 1]) using capillary electrophoresis combined with mass spectrometry (CE-MS). Peptides were sequenced using CE-MS/MS or LC-MS/MS analysis and were deposited, matched, and annotated in a Microsoft SQL database for statistical analysis. We compared their abundance in urine of preterm and term born infants and performed a validation analysis as well as correlations to GA and clinical risk scores. RESULTS: Our results confirmed significant differences in the abundance of peptides and the hypothesis of age-dependent urinary peptidome changes in preterm and term infants. In preterm infants, SLC38A10 (solute carrier family 38 member 10) is one of the most abundant peptides. Combined urinary peptides correlated with clinical risk scores (p < 0.05). CONCLUSION: This is the first study reporting GA-related urinary peptidome changes of preterm infants detected by CE-MS and a modulation of the peptidome with GA. Further research is required to locate peptidome clusters correlated with specific clinical complications and long-term outcome. This may identify preterm infants at higher risk for adverse outcome who would benefit from early intervention.
Subject(s)
Biomarkers , Gestational Age , Infant, Premature , Peptides , Proteomics , Tandem Mass Spectrometry , Humans , Infant, Newborn , Infant, Premature/urine , Female , Male , Biomarkers/urine , Proteomics/methods , Peptides/urine , Term Birth/urine , Electrophoresis, Capillary , Case-Control Studies , Chromatography, Liquid , Longitudinal StudiesABSTRACT
Acute kidney injury (AKI) is a susceptible factor for chronic kidney disease (CKD). There is still a lack of effective prevention methods in clinical practice. This study investigated the protective effect of the urinary exosomes from premature infants on cisplatin-induced acute kidney injury. Here we isolated exosomes from the fresh urine of premature infants. A C57BL/6 mice model of cisplatin-induced acute kidney injury was given 100 ug urinary exosomes 24 hours after model establishment. The kidneys were collected for pathological examination and the evaluation of renal tubular damage and apoptosis. In the in vitro experiment, human renal cortex/proximal tubular cells (HK-2) were induced by cisplatin to assess the effect of the urine exosomes from premature infants. Exosome microRNA (miRNA) sequencing technology was applied to investigate the miRNAs enriched in exosomes and the dual-luciferase gene reporter system to examine the targeting relationship of the miRNA with target genes. The results indicated that the urinary exosomes could decrease the serum creatinine level and the apoptosis of renal tubular cells, and reduce mice mortality. In addition, miR-30a-5p was the most abundant miRNA in the exosomes. It protected HK-2 cells from cisplatin-induced apoptosis by targeting and down-regulating the mitogen-activated protein kinase 8 (MAPK8). Together, our findings identified that the urinary exosomes derived from premature infants alleviated cisplatin-induced acute kidney injury and inhibited the apoptosis of HK-2 via miR-30a-5p, which could target MAPK8. These findings implied that urinary exosomes from premature infants riched in miR-30a-5p might become a potential treatment for AKI.
Subject(s)
Chemical and Drug Induced Liver Injury/therapy , Cisplatin/adverse effects , Exosomes/transplantation , Infant, Premature/urine , Mitogen-Activated Protein Kinase 8/genetics , Animals , Cell Line , Chemical and Drug Induced Liver Injury/blood , Chemical and Drug Induced Liver Injury/genetics , Chemical and Drug Induced Liver Injury/metabolism , Creatinine/blood , Disease Models, Animal , Down-Regulation , Exosomes/genetics , Female , HEK293 Cells , Humans , Infant, Newborn , Mice , Mice, Inbred C57BL , MicroRNAs/geneticsABSTRACT
BACKGROUND: Following preterm birth, the immature kidney is exposed to several harmful conditions, with an increased risk of renal impairment. We aimed to assess urinary biomarkers of renal function in very preterm infants during early nephrotoxic treatments. METHODS: Infants ≤32 weeks' gestation and ≤1500 g were enrolled in this observational prospective study. Urine samples were collected on day 1(T1), 2-4(T2), 5-7(T3), 8-10(T4), 11-13(T5). The following urinary biomarkers were determined: osteopontin (uOPN), epidermal growth factor (uEGF), neutrophil gelatinase-associated lipocalin (uNGAL), cystatin C (uCysC). The infants were grouped according to their exposure to amikacin or ibuprofen during the study period and a between-group comparison of urinary biomarkers at each time point was performed. RESULTS: Thirty-six infants were included. Urinary CysC, uOPN, and uNGAL rose significantly during ibuprofen or amikacin treatment, while no difference was observed for uEGF. After adjustment for possible influencing factors, amikacin administration was associated with higher uCysC at T1 (p = 0.007) and T2 (p = 0.016), whereas ibuprofen increased uOPN (p = 0.001) and uNGAL concentration (p = 0.009) at T3. CONCLUSION: Nephrotoxic therapies induce molecule-specific change patterns of renal function biomarkers in treated preterm infants. Serial assessments of these biomarkers may aid to identify neonates at risk of renal impairment and to develop tailored therapeutic approaches. IMPACT: Despite the wide use of nephrotoxic therapies in neonatal settings, little is known on their effect on renal function biomarkers in preterm infants. This study describes molecule-specific change patterns of urinary biomarkers during ibuprofen and amikacin administration, suggesting underlying pathophysiological effects on renal function. Given their low analytical costs and non-invasive collection, the urinary biomarkers investigated in this study represent a promising strategy for serial monitoring of renal function in at-risk neonates and may aid the early detection of renal function impairment at different kidney levels during nephrotoxic treatments.
Subject(s)
Acute Kidney Injury , Infant, Premature, Diseases , Premature Birth , Acute Kidney Injury/chemically induced , Acute Kidney Injury/diagnosis , Acute Kidney Injury/urine , Amikacin/adverse effects , Biomarkers/urine , Female , Humans , Ibuprofen/adverse effects , Infant , Infant, Newborn , Infant, Premature/urine , Kidney/physiology , Lipocalin-2/urine , Pharmaceutical Preparations , Prospective StudiesABSTRACT
BACKGROUND: Our understanding of the normative concentrations of urine biomarkers in premature neonates is limited. METHODS: We evaluated urine from 750 extremely low gestational age (GA) neonates without severe acute kidney injury (AKI) to determine how GA affects ten different urine biomarkers at birth and over the first 30 postnatal days. Then, we investigated if the urine biomarkers changed over time at 27, 30, and 34 weeks postmenstrual age (PMA). Next, we evaluated the impact of sex on urine biomarker concentrations at birth and over time. Finally, we evaluated if urine biomarkers were impacted by treatment with erythropoietin (Epo). RESULTS: We found that all ten biomarker concentrations differ at birth by GA and that some urine biomarker concentrations increase, while others decrease over time. At 27 weeks PMA, 7/10 urine biomarkers differed by GA. By 30 weeks PMA, 5/10 differed, and by 34 weeks PMA, only osteopontin differed by GA. About half of the biomarker concentrations differed by sex, and 4/10 showed different rates of change over time between males vs. females. We found no differences in urine biomarkers by treatment group. CONCLUSIONS: The temporal patterns, GA, and sex differences need to be considered in urine AKI biomarker analyses. IMPACT: Urine biomarker concentrations differ by GA at birth. Some urine biomarkers increase, while others decrease, over the first 30 postnatal days. Most urine biomarkers differ by GA at 27 weeks PMA, but are similar by 34 weeks PMA. Some urine biomarkers vary by sex in premature neonates. Urine biomarkers did not differ between neonates randomized to placebo vs. Epo.
Subject(s)
Acute Kidney Injury , Infant, Premature , Acute Kidney Injury/urine , Biomarkers/urine , Female , Gestational Age , Humans , Infant, Newborn , Infant, Premature/urine , Male , UrinalysisABSTRACT
OBJECTIVE: The aim of this study was to determine the effects of a 2-day prenatal course of indomethacin on the premature kidney as reflected by serum creatinine and urinary biomarkers. STUDY DESIGN: Urine of infants ≤32 weeks was collected for the first 14 days and analyzed for cystatin C, neutrophil gelatinase-associated lipocalin, osteopontin, ß2 microglobulin, epidermal growth factor, uromodulin, and microalbumin. Bivariate analysis compared serum creatinine and biomarkers of exposed (INDO) and unexposed (CONT) subjects. RESULTS: Fifty-seven infants (35 CONT and 22 INDO) were studied. The cohorts were similar in gestational age, birthweight, race, gender, nephrotoxic medication exposure, and Apgar's scores. CONT had more dopamine exposure and included more pre-eclamptic mothers (p = 0.005). No difference in creatinine-based acute kidney injury or the log transformed mean, maximum, and minimum values of urinary biomarkers was detected. CONCLUSION: Our findings suggest that a short course of tocolytic indomethacin does not result in neonatal acute kidney injury. KEY POINTS: · A short prenatal course of indomethacin does not result in neonatal acute kidney injury (AKI).. · Urinary EGF might have a promising role as a more sensitive biomarker for early detection of AKI in premature infants..
Subject(s)
Acute Kidney Injury , Tocolytic Agents , Acute Kidney Injury/diagnosis , Biomarkers , Creatinine , Cystatin C/urine , Dopamine , Epidermal Growth Factor/urine , Female , Humans , Indomethacin/adverse effects , Infant , Infant, Newborn , Infant, Premature/urine , Lipocalin-2/urine , Osteopontin/urine , Pregnancy , Tocolytic Agents/adverse effects , Uromodulin/urineABSTRACT
CONTEXT: Fetal zone steroids (FZSs) are excreted in high concentrations in preterm infants. Experimental data suggest protective effects of FZSs in models of neonatal disease. OBJECTIVE: We aimed to characterize the postnatal FZS metabolome of well preterm and term infants. METHODS: Twenty-four-hour urinary FZS excretion rates were determined in early preterm (<30 weeks' gestation), preterm (30-36 weeks), and term (>37 weeks) infants. Pregnenolone and 17-OH-pregnenolone metabolites (nâ =â 5), and dehydroepiandrosterone sulfate and metabolites (nâ =â 12) were measured by gas chromatography mass spectrometry. Postnatal concentrations of FZSs were compared with already published prenatal concentrations in amniotic fluid. RESULTS: Excretion rates of total FZSs and most of the single metabolites were highest in early preterm infants. In this group, excretion rates approach those of term infants at term equivalent postmenstrual age. Preterm infants of 30-36 weeks had more than half lower median excretion rates of FZSs than early preterm infants at the same time of postmenstrual age. Postnatal concentrations of FZSs were partly more than 100-fold higher in all gestational age groups than prenatal concentrations in amniotic fluid at midgestation. CONCLUSION: The excretion rates of FZSs as a proxy of the involution of the fetal zone of the most immature preterm infants approached those of term infants at term equivalent. In contrast, the fetal zone in more mature preterm infants undergoes more rapid involution. These data in exclusively well neonates can serve as a basis to investigate the effects of illness on the FZS metabolome in future studies.
Subject(s)
Fetus/metabolism , Gestational Age , Infant, Premature/urine , Steroids/urine , 17-alpha-Hydroxypregnenolone/urine , Adult , Aging/metabolism , Amniotic Fluid/chemistry , Cohort Studies , Dehydroepiandrosterone Sulfate/urine , Female , Gas Chromatography-Mass Spectrometry , Humans , Infant, Extremely Premature/urine , Infant, Newborn , Male , Pregnancy , Pregnenolone/urine , Sex CharacteristicsABSTRACT
BACKGROUND & AIMS: Human milk is the gold standard for infant nutrition. Preterm infants whose mothers are unable to provide sufficient own mother's milk (OMM), receive pasteurized donor human milk (DHM). We studied metabolic signatures of OMM and DHM and their effect on the interplay of the developing microbiota and infant's metabolism. METHODS: Metabolic fingerprinting of OMM and DHM as well as infant's urine was performed using liquid chromatography-mass spectrometry and the infant's stool microbiota was analyzed by 16S rRNA sequencing. RESULTS: Significant differences in the galactose and starch and sucrose metabolism pathways when comparing OMM and DHM, and alterations of the steroid hormone synthesis and pyrimidine metabolism pathways in urine were observed depending on the type of feeding. Differences in the gut-microbiota composition were also identified. CONCLUSION: The composition of DHM differs from OMM and feeding of DHM has a significant impact on the metabolic phenotype and microbiota of preterm infants. Our data help to understand the origin of the observed changes generating new hypothesis: i) steroid hormones present in HM have a significant influence in the activity of the steroid hormone biosynthesis pathway in preterm infants; ii) the pyrimidine metabolism is modulated in preterm infants by the activity of gut-microbiota. Short- and long-term implications of the observed changes for preterm infants need to be assessed in further studies.
Subject(s)
Gastrointestinal Microbiome/physiology , Infant, Premature/metabolism , Milk, Human , Mothers , Tissue Donors , Bacteria/classification , Bacteria/metabolism , Cohort Studies , Female , Galactose/metabolism , Gonadal Steroid Hormones/biosynthesis , Humans , Infant Nutritional Physiological Phenomena , Infant, Newborn , Infant, Premature/urine , Male , Metabolomics , Milk Banks , Prospective Studies , Pyrimidines/metabolism , Starch/metabolism , Sucrose/metabolismABSTRACT
Fortification of human milk (HM) for preterm and very low-birth weight (VLBW) infants is a standard practice in most neonatal intensive care units. The optimal fortification strategy and the most suitable protein source for achieving better tolerance and growth rates for fortified infants are still being investigated. In a previous clinical trial, preterm and VLBW infants receiving supplementation of HM with experimental donkey milk-based fortifiers (D-HMF) showed decreased signs of feeding intolerance, including feeding interruptions, bilious gastric residuals and vomiting, with respect to infants receiving bovine milk-based fortifiers (B-HMF). In the present ancillary study, the urinary metabolome of infants fed B-HMF (n = 27) and D-HMF (n = 27) for 21 days was analyzed by 1H NMR spectroscopy at the beginning (T0) and at the end (T1) of the observation period. Results showed that most temporal changes in the metabolic responses were common in the two groups, providing indications of postnatal adaptation. The significantly higher excretion of galactose in D-HMF and of carnitine, choline, lysine and leucine in B-HMF at T1 were likely due to different formulations. In conclusion, isocaloric and isoproteic HM fortification may result in different metabolic patterns, as a consequence of the different quality of the nutrients provided by the fortifiers.
Subject(s)
Enteral Nutrition/methods , Food, Fortified , Infant, Premature/urine , Milk, Human/metabolism , Nutritional Status , Animals , Carnitine/urine , Cattle , Choline/urine , Equidae , Female , Galactose/urine , Humans , Infant, Newborn , Leucine/urine , Lysine/urine , Male , Metabolome , Milk, Human/chemistryABSTRACT
BACKGROUND: Infants in the neonatal intensive care unit may be exposed to ethanol via medications that contain ethanol as an excipient and through inhalation of ethanol vapor from hand sanitizers. We hypothesized that both pathways of exposure would result in elevated urinary biomarkers of ethanol. METHODS: Urine samples were collected from infants in incubators and in open cribs. Two ethanol metabolites, ethyl sulfate (EtS) and ethyl glucuronide (EtG), were quantified in infants' urine. RESULTS: A subset of infants both in incubators and open cribs had ethanol biomarkers greater than the cutoff concentration that identifies adult alcohol consumption. These concentrations were associated with the infant having received an ethanol-containing medication on the day of urine collection. When infants who received an ethanol-containing medication were excluded from analysis, there was no difference in ethanol biomarker concentrations between the incubator and crib groups. CONCLUSIONS: Some infants who received ethanol-containing medications had concentrations of ethanol biomarkers that are indicative of adult alcohol consumption, suggesting potential exposure via ethanol excipients. IMPACT: Infants and newborns in the neonatal intensive care unit are exposed to concerning amounts of ethanol. No one has shown exposure to ethanol in these infants before this study. The impact is that better understanding of the excipients in medications given to patients in the NICU is needed. When physicians order medications in the NICU, the amount of excipient needs to be indicated.
Subject(s)
Ethanol/urine , Intensive Care Units, Neonatal , Intensive Care, Neonatal/methods , Biomarkers , Chromatography, Liquid , Ethanol/adverse effects , Female , Glucuronates/urine , Hand Sanitizers/adverse effects , Humans , Incubators , Infant , Infant, Newborn , Infant, Premature/urine , Male , Mass Spectrometry , Sulfuric Acid Esters/urineABSTRACT
BACKGROUND: A major challenge from the moment a child is delivered is the adaptation to the extrauterine life, where rapid metabolic changes take place. The study of these changes during the first days of human life may assist in the understanding of the metabolic processes that occur at this critical period, which is likely to provide significant clinical insights. To date, metabolomics has become a powerful field, ideal for the monitoring of such dynamic variations, since it offers the possibility to identify alterations in metabolic profiles, even on daily basis. METHODS: The study included 253 healthy newborns (GA 35 to 40 weeks) from the region of Western Greece. Urine samples were collected immediately after birth and at the third day of life. NMR-based metabolomics was used to compare the metabolic urinary profiles of newborns from the first and third day of their life, assessing the impact of six perinatal factors; delivery mode, prematurity, maternal smoking, gender, nutrition and neonatal jaundice. RESULTS: Analysis of urine metabolic fingerprint from the first and third day of life, coupled with multivariate statistics, provides insights into the details of early life metabolic profile differentiation. Αt the third day of life metabolic adaptations are evident, as many differences were noted in urine of healthy neonates within the first 72 h postpartum. Trends in differentiation of metabolites levels between the two groups, late preterm and term newborns, have been also observed. CONCLUSIONS: Newborn's urine metabolic profiles confirmed the rapid changes in their metabolism after birth. Further, ongoing research will enable us to develop one reference model of urinary metabolomics in healthy newborns during the period of adaptation to the extra-uterine life.
Subject(s)
Adaptation, Biological , Infant, Premature/metabolism , Metabolomics , Female , Humans , Infant, Newborn , Infant, Premature/urine , Magnetic Resonance Spectroscopy , MaleABSTRACT
The immature preterm kidney is likely to be vulnerable to acute kidney injury (AKI). However, the biomarkers currently used for AKI are not sensitive or specific and are also inadequate for the timely detection of AKI in preterm infants. The objectives of this study were to identify novel urinary biomarkers of AKI using proteomic techniques, and to verify and validate that the candidates can serve as early predictive biomarkers for AKI. In total, 1,810 proteins were identified in the discovery phase. Among those proteins, 174 were selected as the 1st targeted proteins. A total of 168 proteins were quantified, and the levels of 6 were significantly increased in the AKI group in the verification phase. Using a clinical assay, the results were confirmed and validated using samples of the first urine after birth from the biorepository. Finally, enzyme-linked immunosorbent assays revealed that the levels of annexin A5, neutrophil gelatinase-associated lipocalin (NGAL), and protein S100-P were significantly higher in the samples of the first urine from patients with AKI than in those from patients without AKI. In conclusion, urinary annexin A5, NGAL and protein S100-P levels are promising biomarkers for early, accurate prediction of AKI in preterm infants.
Subject(s)
Acute Kidney Injury/urine , Annexin A5/urine , Infant, Newborn, Diseases/urine , Infant, Premature/urine , Lipocalin-2/urine , Proteomics , S100 Proteins/urine , Biomarkers/urine , Female , Humans , Infant , Infant, Newborn , MaleABSTRACT
OBJECTIVE: This pilot study aimed to determine the feasibility of urinary NT-proBNP (NT-proBNP) as a potential noninvasive screening marker for pulmonary hypertension (PH). STUDY DESIGN: A prospective cross-sectional study was conducted. Preterm infants (PI) (birthweight <1500 gm and <30 weeks gestational age (GA)) were enrolled. Serial urinary NT-proBNP measurements and echocardiograms (ECHO) were performed at 28, 32, and 36 weeks. RESULTS: Thirty-six patients were included in the final analysis (BPD-PH group = 6, BPD group = 20, control = 10). Urinary NT-proBNP levels were higher in the BPD-PH group compared with BPD and control groups at all study intervals. A urine NT-proBNP cutoff level of 2345 pg/ml at 28 weeks of GA had a sensitivity and specificity of 83.3% and 84.2%, respectively, for detection of BPD-PH (AUC 0.816, p = 0.022). CONCLUSION: Urinary NT-proBNP measurement is feasible in preterm infants and appears to be a good noninvasive screening tool for PH.
Subject(s)
Hypertension, Pulmonary/diagnosis , Infant, Premature, Diseases/diagnosis , Infant, Very Low Birth Weight/urine , Natriuretic Peptide, Brain/urine , Peptide Fragments/urine , Adult , Biomarkers/urine , Cross-Sectional Studies , Echocardiography , Female , Humans , Hypertension, Pulmonary/urine , Infant, Newborn , Infant, Premature/urine , Infant, Premature, Diseases/urine , Male , Maternal Age , Pilot Projects , Prospective Studies , ROC Curve , Sensitivity and SpecificityABSTRACT
BACKGROUND: Premature infants have a high concentration of conjugated bilirubin in their blood, although they have a poor glucuronide conjugation of bilirubin. This may be due to developmental changes in the function of adenosine triphosphate binding cassette subfamily C member 2, which is involved in the cellular export of conjugated bilirubin. In the present study, we examined the developmental changes in the urinary coproporphyrin I/(urinary coproporphyrin I+ urinary coproporphyrin III) ratio (UCP (I/ [I + III])), a known biomarker for adenosine triphosphate binding cassette subfamily C member 2 function, in premature infants. METHOD: Twenty-one premature infants born between 25 and 32 weeks of gestation were included in the study. Urine samples were collected within 24 h of birth, and at 1 week and 3-4 weeks after birth. The samples were analyzed by high-performance liquid chromatography to calculate UCP (I/ [I + III]) to examine its association with postnatal age and corrected gestational age. Subjects were excluded if they had liver dysfunction, cholestasis, urinary tract infection, or chromosomal abnormalities. RESULTS: The average UCP (I/ [I + III]) within 24 h of birth, at 1 week, and at 3-4 weeks after birth was 0.84, 0.61, and 0.65, respectively. The UCP (I/ [I + III]) within 24 h of birth was significantly higher than that measured at 1 week or 3-4 weeks after birth. There was no significant correlation between UCP (I/ [I + III]) and the corrected gestational age. CONCLUSION: The UCP (I/ [I + III]) was higher within 24 h of birth. It decreased 1 week after birth and remained low without any significant changes for up to 4 weeks after birth.
Subject(s)
Coproporphyrins/urine , Infant, Premature/urine , Bilirubin/blood , Biomarkers/urine , Chromatography, High Pressure Liquid , Female , Gestational Age , Humans , Infant, Newborn , MaleABSTRACT
BACKGROUND: Early administration of colostrum may provide preterm infants with immune components. Previous studies illustrating the effects of oral colostrum (OC) have been confounded by the coincidence of enteral feedings. OBJECTIVE: To quantify OC absorption, as measured by urinary sIgA and lactoferrin, in preterm infants prior to enteral feedings. MATERIALS AND METHODS: Colostrum was obtained from mothers delivering infants ≤32 weeks and ≤1500 g. sIgA and lactoferrin were measured in infant urine, and microflora in saliva and tracheal aspirates were characterized. RESULTS: Urinary sIgA and lactoferrin were significantly greater in infants receiving OC by syringe compared to swab (p < 0.002). Urinary sIgA correlated with the total number of doses in 72 h (R2 = 43%, p < 0.01). CONCLUSIONS: Administration of OC by syringe and higher cumulative dose are associated with increased absorption of sIgA and lactoferrin, and early dosing may contribute to a more diverse tracheal microbiome.
Subject(s)
Colostrum/immunology , Immunoglobulin A, Secretory/urine , Infant, Premature/immunology , Infant, Very Low Birth Weight/immunology , Lactoferrin/urine , Administration, Oral , Analysis of Variance , Humans , Infant, Newborn , Infant, Premature/urine , Microbiota , Mouth/microbiology , Mouth Mucosa , Pilot Projects , Trachea/microbiologyABSTRACT
Pasteurized donor human milk (DHM) is the preferred alternative for infant nutrition when own mother's milk (OMM) is unavailable. Whether DHM is an efficient means for protecting preterm infants from oxidative stress remains unknown. We quantified a panel of oxidative stress biomarkers in urine samples from preterm infants (≤32 weeks of gestation and a birth weight ≤1500 g) receiving ≥80% of feeding volume as either DHM or OMM. The noninvasive in vivo assessment of oxidative stress showed no statistically significant difference between both groups at the time when full enteral nutrition (150 mL/kg body weight) was achieved and until hospital discharge. In addition, the changes of urinary biomarker levels with time were assessed. This is the first longitudinal study on oxidative stress levels in preterm infants fed with DHM in comparison with OMM. There is no statistically significant difference in urinary oxidative stress levels of preterm infants from both groups indicating that despite the effects of pasteurization, DHM is a valid alternative when OMM is not available. Based on the results, we raise the hypothesis that pasteurized DHM protects preterm infants from oxidative stress as good as OMM, and consequently, its use could prevent oxidative stress-related diseases. Antioxid. Redox Signal. 31, 791-799.
Subject(s)
Biomarkers/urine , Infant, Low Birth Weight/urine , Infant, Premature/urine , Milk, Human , Enteral Nutrition , Female , Humans , Infant, Low Birth Weight/growth & development , Infant, Newborn , Infant, Premature/growth & development , Longitudinal Studies , Oxidative Stress , Pasteurization , Prospective StudiesABSTRACT
OBJECTIVE: Delivery room (DR) management may play an important role in the development and prevention of lung injury. Therefore, in a cohort of low birth weight infants (LBW), we investigated the effects of two different lung recruitment maneuvers, such as positive pressure ventilation (PPV) and sustained inflation (SI) on adrenomedullin (AM), a well-established lung-specific vasoactive agent. STUDY DESIGN: This is a prospective case-control randomized study in 44 LBW infants spontaneously breathing with respiratory failure at birth requiring respiratory support. LBW were randomized to receive PPV (n = 22) or SI (n = 22) support. AM was measured from blood in samples collected at birth from arterial artery (BLT0) and at 1-hour (BLT1) and at 24-hour (BLT2) from peripheral venous site. AM assessment in urine samples was performed at 1-hour (URT1) and at 24-hour (URT2). RESULTS: No significant differences in AM (p > 0.05) blood (T0-T2) and urine (T1, T2) levels were observed between groups. CONCLUSION: The present data, showing the absence of any differences in AM blood and urine levels, suggest that PPV and SI are both feasible and equally effective DR maneuvers. The findings open the way to further studies evaluating the effects of PPV and SI on short-/long-term respiratory outcome through biomarkers assessment.
Subject(s)
Adrenomedullin/blood , Adrenomedullin/urine , Continuous Positive Airway Pressure , Infant, Low Birth Weight/blood , Positive-Pressure Respiration , Respiratory Insufficiency/therapy , Biomarkers/blood , Biomarkers/urine , Case-Control Studies , Female , Humans , Infant, Low Birth Weight/urine , Infant, Newborn , Infant, Premature/blood , Infant, Premature/urine , Male , Prospective Studies , Respiratory Distress Syndrome, Newborn/prevention & control , Respiratory Insufficiency/blood , Respiratory Insufficiency/urineABSTRACT
BACKGROUND: Feeding breast milk is associated with reduced morbidity and mortality, as well as improved neurodevelopmental outcome but does not meet the high nutritional requirements of preterm infants. Both plasma and urinary urea concentrations represent amino acid oxidation and low concentrations may indicate insufficient protein supply. This study assesses the effect of different levels of enteral protein on plasma and urinary urea concentrations and determines if the urinary urea-creatinine ratio provides reliable information about the protein status of preterm infants. METHODS: Sixty preterm infants (birthweight < 1500 g; gestational age < 32 weeks) were enrolled in a randomized controlled trial and assigned to either a lower-protein group (median protein intake 3.7 g/kg/d) or a higher-protein group (median protein intake 4,3 g/kg/d). Half the patients in the higher-protein group received standardized supplementation with a supplement adding 1.8 g protein/100 ml milk, the other half received individual supplementation depending on the respective mother's milk macronutrient content. Plasma urea concentration was determined in two scheduled blood samples (BS1; BS2); urinary urea and creatinine concentrations in weekly spot urine samples. RESULTS: The higher-protein group showed higher plasma urea concentrations in both BS1 and BS2 and a higher urinary urea-creatinine-ratio in week 3 and 5-7 compared to the lower-protein group. In addition, a highly positive correlation between plasma urea concentrations and the urinary urea-creatinine-ratio (p < 0.0001) and between actual protein intake and plasma urea concentrations and the urinary urea-creatinine-ratio (both p < 0.0001) was shown. CONCLUSIONS: The urinary urea-creatinine-ratio, just like plasma urea concentrations, may help to estimate actual protein supply, absorption and oxidation in preterm infants and, additionally, can be determined non-invasively. Further investigations are needed to determine reliable cut-off values of urinary urea concentrations to ensure appropriate protein intake. TRIAL REGISTRATION: Clinicaltrials.gov; NCT01773902 registered 15 January 2013, retrospectively registered.
Subject(s)
Bottle Feeding/methods , Creatinine/urine , Dietary Proteins/administration & dosage , Food, Fortified , Infant, Premature/blood , Infant, Premature/urine , Infant, Very Low Birth Weight/blood , Infant, Very Low Birth Weight/urine , Female , Gestational Age , Humans , Infant, Newborn , Male , Milk, HumanABSTRACT
BACKGROUND: The postnatal gonadotrophin surge is sexually dimorphic: FSH levels predominate in girls and LH levels in boys. However, in preterm (PT) girls, both gonadotrophin levels are higher than in PT boys. OBJECTIVE: To evaluate how gonadal maturation contributes to the sex differences in FSH and LH. DESIGN: Monthly follow-up of 58 full-term (FT, 29 boys) and 67 PT (33 boys) infants from 1 week (D7) to 6 months of age (M1-M6). Analyses were also carried out according to postmenstrual (PM) age in PT infants. METHODS: Urinary LH, FSH, oestradiol (E2), testosterone (T) and serum inhibin B (InhB) levels. RESULTS: High gonadotrophin levels in PT girls abruptly decreased (P < .001) by M2, corresponding to a PM age of 38-42 weeks, and LH levels fell below the levels found in boys. This decrease was parallel to a steep increase in E2 levels (P < .001), and, from M4 to M6, LH and E2 correlated positively in PT girls (P < .01). T levels in PT boys increased earlier than E2 levels in PT girls. In addition, InhB levels were high in PT boys already at D7, in contrast to low InhB in PT girls. InhB and FSH correlated negatively in the whole group (P < .001). CONCLUSIONS: Ovarian hormone synthesis is immature and incapable of responding to gonadotrophin stimulus before 38-42 PM weeks in PT girls, which may explain their highly elevated FSH and LH levels. The higher InhB levels in boys compared to girls may explain sexual dimorphism in FSH levels.
Subject(s)
Gonadotropins/urine , Luteinizing Hormone/metabolism , Ovary/metabolism , Testicular Hormones/metabolism , Testis/metabolism , Estradiol/urine , Female , Follicle Stimulating Hormone/urine , Humans , Infant , Infant, Newborn , Infant, Premature/metabolism , Infant, Premature/urine , Inhibins/urine , Luteinizing Hormone/urine , Male , Ovary/pathology , Testicular Hormones/urine , Testis/pathologyABSTRACT
BACKGROUND: Nonspecific clinical signs and suboptimal diagnostic tests limit accurate identification of late onset sepsis (LOS) and necrotizing enterocolitis (NEC) in premature infants, resulting in significant morbidity and antibiotic overuse. An infant's systemic inflammatory response may be identified earlier than clinical suspicion through analysis of multiple vital signs by a computerized algorithm (RALIS). AIM: To evaluate the revised RALIS algorithm for detection of LOS and NEC in preterm infants. METHODS: In this nested case-control study, VS data (heart rate, respiratory rate, temperature, desaturations, bradycardias) were extracted from medical records of infants 23-32â¯weeks gestation. RALIS generated an output, with scoreâ¯≥â¯5 triggering an alert. Patient episodes were classified based on culture, radiograph, and antibiotic data into categories: LOS, expanded LOS, NEC, and controls. Paired t-tests, linear regression and cross-validation analyses were used to evaluate the relationship between RALIS alert and LOS/NEC. RESULTS: Among 155 infants with 161 episodes, there were 41 expanded LOS (+blood, CSF, urine, respiratory culture), 31 LOS (+blood, CSF, urine), 9 NEC, and 93 controls. RALIS alert was 43.1⯱â¯79â¯h before culture in LOS (pâ¯=â¯.012). There was a significant association between RALIS alert and LOS/NEC (ßâ¯=â¯0.72, pâ¯<â¯.0001). Sensitivity and specificity for LOS/NEC were 84% and 80%, (PPVâ¯=â¯63%; NPVâ¯=â¯93%). The regression model demonstrated an AUC of 89.9%. CONCLUSIONS: For infants ≤32â¯weeks, RALIS detects systemic inflammatory responses in LOS and NEC in the first month of life. The algorithm can identify infection earlier than clinical suspicion, even for NEC with negative cultures. RALIS has high NPV to rule-out LOS and NEC, and may, after prospective validation, aid in antibiotic treatment decisions.