Effect of increased enteral protein intake on plasma and urinary urea concentrations in preterm infants born at < 32 weeks gestation and < 1500 g birth weight enrolled in a randomized controlled trial - a secondary analysis.

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.

Acute kidney injury in premature newborns-definition, etiology, and outcome.

BACKGROUND: Neonatal acute kidney injury (AKI) is common and is associated with poor outcomes. New criteria for the diagnosis of AKI were introduced based on the increase in serum creatinine (SCr) levels and/or reduction of urine output (UOP). Yet, there is no generally accepted opinion so far, which criteria (whether SCr, UOP, or their combination) are the most appropriate to diagnose neonatal AKI. METHODS: The retrospective study included 195 prematurely born neonates who fulfilled all inclusion criteria (with at least two SCr measurements). In all the neonates included in the study, AKI was diagnosed using three different definitions: (1) SCr criteria (an increase in SCr values of ≥0.3 mg/dl), (2) UOP criteria (UOP < 1.5 ml/kg/h), and (3) SCr + UOP criteria. RESULTS: Out of all of the patients the study included, 85 (44%) were diagnosed with AKI. The neonates who had AKI had a significantly lower gestational age, birth weight, and Apgar score, longer duration of mechanical ventilation, and a higher mortality rate. SCr + UOP criteria showed higher sensitivity for prediction of death compared to SCr or UOP alone (p = 0.0008, 95% CI 0.040-0.154, and p = 0.0038, 95% CI 0.024-0.125, respectively). If only SCr or only UOP criterion are used, they fail to identify AKI in 61 and 67%, respectively. AKI was an independent risk factor for death (OR 7.4875; CI 3.1887-17.5816). CONCLUSIONS: Similar to other studies, our data showed that neonates with AKI have worse outcome. Neonatal AKI defined based on SCr + UOP criteria is a better predictor of death than neonatal AKI defined based only on the SCr or UOP criteria. Also, by using SCr + UOP criteria for diagnosing neonatal AKI, more patients with AKI are recruited than when only one of those criteria is used.

Increased urinary neutrophil gelatinase-associated lipocalin in very-low-birth-weight infants with oliguria and normal serum creatinine.

BACKGROUND: In infants, oliguria is defined as a urine output of <1.5 mL/kg/h. The aim of our study was to assess the impact of oliguria on urinary neutrophil gelatinase-associated lipocalin (NGAL) and serum cystatin C (CysC) levels in very-low-birth-weight infants (VLBWIs) with a normal serum creatinine (Cr) level. METHODS: Fifty-seven VLBWIs were enrolled in the study. Urinary NGAL, serum CysC and Cr levels and urinary NGAL/Cr ratios were measured. Infants with Apgar scores of >5 at 5 min and/or a serum Cr level of >1.5 mg/dL or those treated for patent ductus arteriosus were excluded. In case of antibiotic treatment, blood and urine samples were collected at ≥48 h after discontinuation of antibiotic treatment. RESULTS: There was a significant difference in gestational age between infants with oliguric episodes during hospitalization and those without, but not in birth weight, perinatal or postnatal factors. Gestational age was negatively correlated with urinary NGAL and serum CysC levels and urinary NGAL/Cr ratio (p < 0.05), whereas postnatal age was negatively correlated with serum Cr level and urinary NGAL/Cr ratio (p < 0.05). Of the 117 urine and blood samples collected, 25 (21.4%) were obtained from neonates with oliguric episodes. After adjusting for gestational age and postnatal age, comparison of samples collected in infants with and without oliguric episodes revealed significant differences in the mean level of urinary NGAL and in the urinary NGAL/Cr ratio, but not in mean serum CysC or serum Cr levels. The urinary NGAL level [area under the curve (AUC) 0.886, 95% confidence interval (CI) 0.814-0.937] and urinary NGAL/Cr ratio (AUC 0.853, 95% CI 0.775-0.911) showed significantly greater discrimination for oliguria than serum CysC (AUC 0.610, 95% CI: 0.515-0.699) or serum Cr (AUC 0.747, 95%CI 0.659-0.823) levels. CONCLUSIONS: Urinary NGAL level and urinary NGAL/Cr ratio were more sensitive markers for the presence of oliguria in VLBWIs with normal serum Cr levels than serum CysC level.

Trace elements, oxidative status and antioxidant capacity as biomarkers in very low birth weight infants.

Reference data on trace elements, oxidative status and antioxidants in very low birth weight infants (VLBW) are limited and need to be updated for use in clinical settings. Serum and urine of 30 VLBW infants (mean weight, 1167g) at mean age of 23.8 (t0) and 37.8 (t1) days were analyzed. Cadmium (Cd), copper (Cu), iron (Fe), mercury (Hg), manganese (Mn), selenium (Se) and zinc (Zn), nitrate/nitrite (NOx), catalase (CAT), CuZnFeMn-superoxide dismutases (CuZnFeMn-SODs), total antioxidant capacity (SAC: sum of thiols, proteins, bilirubin, uric acid, ß-beta-carotene, ascorbic acid, vitamin E) and total oxidative status (SOS: sum of lipo- and hydroperoxides) were determined. A higher urinary excretion of Cu and Zn was observed at t0 than at t1; while an increase in urine Cd was found at t1 respect to t0. A deficiency in serum levels of Cu and Zn was also found. A lower CAT activity, a higher total oxidants level (SOS) and a reduction of total antioxidant barriers (SAC) were observed in some infants. No Fe and Mn deficiency or Hg overload was found; also CuZnFeMn-SODs and NOx levels did not change. The findings showed that losses of trace elements and incomplete mineral body stores were more pronounced in the earlier life stage (at 23.8th day) than later on; moreover, antioxidant defenses were poor and lipo- and hydroperoxides were higher still at 5 weeks of infants' life.

Effect of vitamin A supplementation on the urinary retinol excretion in very low birth weight infants.

UNLABELLED: Despite high-dose vitamin A supplementation of very low birth weight infants (VLBW, <1500 g), their vitamin A status does not improve substantially. Unknown is the impact of urinary retinol excretion on the serum retinol concentration in these infants. Therefore, the effect of high-dose vitamin A supplementation on the urinary vitamin A excretion in VLBW infants was investigated. Sixty-three VLBW infants were treated with vitamin A (5000 IU intramuscular, 3 times/week for 4 weeks); 38 untreated infants were classified as control group. On days 3 and 28 of life, retinol, retinol-binding protein 4 (RBP4), glomerular filtration rate, proteinuria, and Tamm-Horsfall protein were quantified in urine. On day 3 of life, substantial retinol and RBP4 losses were found in both groups, which significantly decreased until day 28. Notwithstanding, the retinol excretion was higher (P < 0.01) under vitamin A supplementation as compared to infants of the control group. On day 28 of life, the urinary retinol concentrations were predictive for serum retinol concentrations in the vitamin A treated (P < 0.01), but not in the control group (P = 0.570). CONCLUSION: High urinary retinol excretion may limit the vitamin A supplementation efficacy in VLBW infants. Advanced age and thus postnatal kidney maturation seems to be an important contributor in the prevention of urinary retinol losses.

Impact of gestational age, sex, and postnatal age on urine biomarkers in premature neonates.

BACKGROUND: Urine proteins may help in understanding physiology and diagnosing disease in premature infants. Determining how urine proteins vary by degree of prematurity, sex, and postnatal day is warranted. METHODS: We performed a prospective cohort study to assess the independent correlation of 14 urine biomarkers (measured on postnatal days 1-4) with gestational age (GA), sex, and postnatal age in 81 premature infants (mean, 1017 g) without acute kidney injury using a random-effects mixed model. RESULTS: Neutrophil gelatinase-associated lipocalin (NGAL) and vascular endothelial growth factor (VEGF) showed significant associations for sex, GA, and postnatal age. Cystatin C, osteopontin (OPN), and trefoil factor 3 (TFF3) were associated with postnatal age and GA, but not sex. Epithelial growth factor (EGF) and uromodulin were associated with GA only. Clusterin was associated with postnatal age and sex. Albumin was associated with sex only. Beta-2-microglbulin (B2M), osteoactivin, kidney injury molecule -1 (KIM-1), and alpha glutathione S-transferase (αGST) were associated with postnatal age only. CONCLUSIONS: Postnatal age affects B2M, cystatin C, NGAL, OPN, clusterin, Kim-1, osteoactivin, TFF3, VEGF, αGST. GA affects cystatin C, EGF, NGAL, OPN, UMOD, TFF3, and VEGF. Sex affects albumin, NGAL, and clusterin. Interpretation of urine biomarkers will need to account for these associations.

Increased urinary angiotensinogen is an effective marker of chronic renal impairment in very low birth weight children.

BACKGROUND: Recent advancements in perinatal and neonatal care have increased the survival of preterm infants with lower birth weight and very low birth weight (VLBW; < 1,500 g) infants. Such infants are exposed to a higher risk of renal insufficiency in later life due to congenitally fewer nephrons; however, urinalysis in order to detect renal insufficiency in those infants at school age has not yet been established. The aim of the study was to assess chronic renal impairment in VLBW infants during their childhood after discharge from the neonatal intensive care unit (NICU) until adolescence using urinary angiotensinogen (uAGT). METHODS: We compared serum levels of angiotensinogen (sAGT), creatinine, ß2-microglobulin (sß2MG) and cystatin C (sCysC), and urinary levels of uAGT, creatinine (uCre),ß2-microglobulin (uß2MG) and albumin between two infant groups-the VLBW group (50 children who were admitted to our NICU as infants), and a control group of 25 children who were born as full-term infants with birth weight ≥2,500 g. The median age of the VLBW group and control group infants was 60 months (range 7-135) and 57 months (range 5-144), respectively, at the time of evaluation. RESULTS: In the VLBW group, sCysC levels were high (p < 0.05) and estimated glomerular filtration rate (eGFR) was low (p < 0.05). There were no significant differences in the ratios of uß2MG to creatinine and urinary albumin to creatinine between the two groups. Although there were no differences in concentration of sAGT between the two groups (p = 0.062), the ratio of uAGT to creatinine was significantly higher in the VLBW group (p < 0.01). The examination of 19 VLBW infants (19/50) with eGFR ≤90 ml/min/1.73 m(2) showed a positive correlation between uAGT/creatinine and urinary albumin/creatinine (r = 0.531, p < 0.05). Furthermore, the analysis of correlation between the ratio of uAGT to creatinine and eGFR showed a reverse correlation in 19 VLBW infants (19/50) with eGFR ≤90 ml/min/1.73 m(2), 18 of whom had stage II chronic kidney disease and one who had stage III disease (r = -0.512, p ≤ 0.05). CONCLUSIONS: uAGT is an effective marker for predicting the progression of chronic renal impairment in preterm VLBW infants after their growth. uAGT measurement is easier to conduct, less invasive and more sensitive than conventional uß2MG or urinary albumin measurement.

Fat emulsion given to very low-birthweight infants increases urinary L-FABP.

BACKGROUND: In premature infants, many factors influence the function of renal tubules, such as asphyxia, respiratory disorders, use of high-concentration oxygen, hypotension, and drug treatment. When tubular ischemia and oxidative stress develop due to renal microcirculatory pathology, urinary L-type fatty acid-binding protein (L-FABP) level increases. METHODS: Urinary L-FABP level was measured over time in very low-birthweight infants (VLBWI), and the effect of fat emulsion on L-FABP level was investigated. Thirty-one VLBWI were divided into two groups with regard to treatment with fat emulsion: the lipid group (n = 20) and the control group (n = 11). Urinary L-FABP was measured before (0-3 days of age), during (7-14 days of age), and after fat emulsion treatment (21-28 days of age) in the two groups. RESULTS: Median urinary L-FABP level before treatment was 459 ng/mgCr (range, 22.7-5100 ng/mgCr; mean, 1067 ± 1570 ng/mgCr) and 797 ng/mgCr (range, 69-3900 ng/mgCr; mean, 1066 ± 1188 ng/mgCr) in the lipid and control groups, respectively, showing no significant difference. Median urinary L-FABP level was 624 ng/mgCr (range, 50-2050 ng/mgCr; mean ± SD, 799 ± 655 ng/mgCr) and 273 ng/mgCr (range, 31-987 ng/mgCr; mean ± SD, 359 ± 323 ng/mgCr) at 7-14 days of age, respectively, showing that the level was significantly higher in the lipid group. At 21-28 days of age, the median level was 462 ng/mgCr (range, 49-1867 ng/mgCr; mean ± SD, 557 ± 534 ng/mgCr) and 130 ng/mgCr (range, 20-993 ng/mgCr; mean ± SD, 290 ± 329 ng/mgCr), respectively, showing that L-FABP level tended to be higher in the lipid group. CONCLUSIONS: Fat emulsion treatment induced a significant increase in urinary L-FABP level, suggesting that fat emulsion affected the proximal tubule in VLBWI.

Oxidative stress early in infancy and neurodevelopmental outcome in very low-birthweight infants.

BACKGROUND: Reactive oxygen species may be involved in serious diseases in premature infants. The objective of this study was to assess the relationship between neurodevelopmental outcome and oxidative stress marker level in the urine of very low-birthweight (VLBW) infants. METHODS: Spot urine samples were collected from 35 VLBW infants. Urinary excretion of 8-hydroxy-2″-deoxyguanosine (8-OHdG), a marker of oxidative DNA damage, and 8-iso-prostaglandin F2α (8-isoPGF), a marker of lipid peroxidation, was measured at 1, 2, 4, and 6 weeks of age. Neurodevelopmental outcome at 18 months' corrected age was assessed using the Bayley Scales of Infant Development (BSID)-II. RESULTS: Significant correlations were found between urinary 8-OHdG at 2 and 4 weeks and the Mental Development Index of the BSID-II. No significant correlation was found between urinary 8-isoPGF and indices of the BSID-II. CONCLUSIONS: In VLBW infants, urinary 8-OHdG level correlated with mental development rather than psychomotor development at 18 months' corrected age; urinary 8-OHdG might be a predictive marker of neurodevelopmental outcome in VLBW infants.

Reference values of parathyroid hormone in very low birth weight infants.

PURPOSE: The primary goal was to estimate reference values of parathyroid hormone (PTH) in very low birth weight infants without severe neonatal morbidity. A secondary objective was to assess the relationship between PTH serum levels and selected laboratory markers of bone metabolism. METHODS: Ninety two infants with birth weight less than 1500 g met the inclusion criteria of the study. Serum levels of PTH, 25-hydroxyvitamin-D [25(OH)D], C3-epi-25(OH)D, total calcium, phosphorus, and alkaline phosphatase, and urinary levels of calcium, phosphorus, and creatinine were examined on day 14 and subsequently every 2 weeks until discharge. RESULTS: Of the total 167 serum samples examined for PTH levels in infants without 25(OH)D deficiency the estimated range was 0.9-11.9 pmol/l (8.5-112.3 pg/mL). During the first month, no statistically significant correlation was observed between PTH level and that of 25(OH)D, C3-epimers of 25(OH)D, S-Ca, S-P, or ALP, nor with urinary excretion of calcium and phosphorus. From the second month of life, there was a moderately significant correlation between PTH and 25(OH)D (Rho = -0.40, P =< .001), between PTH and calcium/creatinine ratio (Rho = -0.56, P = < .001), and between PTH and phosphorus/creatinine ratio (Rho = 0.51, P = < .001). CONCLUSIONS: The physiological range for PTH levels for preterm neonates without 25(OH)D deficiency was estimated as 0.9-11.9 pmol/l (8.5-112.3 pg/mL). It seems that elevation of serum PTH above this range can be considered as hyperparathyroidism in very low birth weight infants.

Urinary neutrophil gelatinase-associated lipocalin in septic preterm babies: a preliminary study.

OBJECTIVE: This study was conducted to evaluate the predictive value of urinary neutrophil gelatinase-associated lipocalin (uNGAL) for acute kidney injury (AKI) among septic preterm infants. METHODS: Twenty-six very low-birth-weight (VLBW) babies were separated into three groups: group I, healthy preterms; group II, preterms with sepsis but without AKI; group III, preterms with sepsis and AKI. Demographic, clinical, and laboratory data of the babies were recorded. uNGAL and creatinine values were obtained on days 1, 3, and 7 of life. RESULTS: uNGAL levels differed statistically among three groups for all 3 days. Levels in group I (days 1, 3, and 7) were significant lower than levels in both groups II and III [median (interquartile range): 4.5 (10.8) µ/L, 8.7 (18.5) µ/L, and 4.3 (1.1) µ/L, respectively]. In group III, uNGAL levels on days 1 and 3 were significantly higher than levels in group II (p = 0.001, 0.016, respectively). CONCLUSION: First-day uNGAL levels were higher in VLBW preterm infants who later developed sepsis; whether the baby had AKI or not; but uNGAL levels were higher in septic babies with AKI compared with the infants without AKI. uNGAL is a promising early biomarker of AKI in VLBW infants with sepsis.

Baseline values of candidate urine acute kidney injury biomarkers vary by gestational age in premature infants.

Acute kidney injury (AKI) is common in premature infants and is associated with poor outcomes. Novel biomarkers can detect AKI promptly. Because premature infants are born with underdeveloped kidneys, baseline biomarker values may differ. We describe baseline values of urinary neutrophil gelatinase-associated lipocalin (NGAL), IL-18, kidney injury molecule-1 (KIM-1), osteopontin (OPN), beta-2 microglobulin (B2mG), and Cystatin-C (Cys-C). Next, we test the hypothesis that these biomarkers are inversely related to GA. Candidate markers were compared according to GA categories in 123 infants. Mixed linear regression models were performed to determine the independent association between demographics/interventions and baseline biomarker values. We found that urine NGAL, KIM-1, Cys-C, and B2mG decreased with increasing GA. With correction for urine creatinine (cr), these markers and OPN/cr decreased with increasing GA. IL-18 (with or without correction for urine creatinine) did not differ across GA categories. Controlling for other potential clinical and demographic confounders with regression analysis shows that NGAL/cr, OPN/cr, and B2mG/cr are independently associated with GA. We conclude that urine values of candidate AKI biomarkers are higher in the most premature infants. These findings should be considered when designing and analyzing biomarker studies in newborn with AKI.

Urinary neutrophil gelatinase-associated lipocalin at birth predicts early renal function in very low birth weight infants.

Preterm infants are exposed to conditions that can impair renal function. We evaluated the ability of serum and urinary neutrophil gelatinase-associated lipocalin (sNGAL and uNGAL) to predict renal function in the first weeks of life. From September 2008 to July 2009, infants weighing ≤1500 g at birth with no major congenital anomalies or sepsis were eligible. We measured sNGAL and uNGAL levels at birth. To evaluate renal function, we determined changes in serum creatinine (sCreat) and estimated GFR (eGFR) from birth to d 21. Forty neonates (mean GA, 27 ± 2 wk) completed the study. Renal function improved in 32 of 40 (80%) infants (normal renal function, NRF group) (sCreat, from 0.97 ± 0.2 to 0.53 ± 0.13 mg/dL; eGFR, from 15.3 ± 4.1 to 28.6 ± 7.9 mL/min), whereas renal function worsened in 8 of 40 (20%) infants (impaired renal function, IRF group) (sCreat, from 0.71 ± 0.27 to 0.98 ± 0.43 mg/dL; eGFR from 23 ± 14.7 to 16.4 ± 9.1 mL/min). The uNGAL/urinary creatinine (uCreat) ratio at birth was higher in the IRF group (31.05 ng/mg) than the NRF group (6.0 ng/mg), and uNGAL was significantly higher in IRF group, detecting IRF with a cutoff of 100 ng/mL. uNGAL levels at birth may have a predictive role in very LBW (VLBW) infants.

Urinary neutrophil gelatinase-associated lipocalin is a promising biomarker for late onset culture-positive sepsis in very low birth weight infants.

Need for the early identification of sepsis in very low birth weight (VLBW) infants has led to the search for reliable biomarkers. This study aims to determine whether urinary neutrophil gelatinase-associated lipocalin (uNGAL) rises in culture-positive sepsis and, if so, is elevated at the time sepsis is suspected. This is a prospective study of 91 VLBW infants whose urine was collected daily for uNGAL analysis. In 65 episodes of suspected sepsis, four groups were identified: a) culture-positive sepsis; b) single culture positive for Staphylococcus epidermidis; c) and d) negative culture with antibiotic treatment for >or=7 d and <7 d, respectively. Daily means of uNGAL of each group were estimated for comparison. Mean uNGAL in group A (179 ng/mL) was significantly elevated on the day blood culture was drawn (day 0) compared with the mean of healthy VLBW infants (6.5 ng/mL), and to the means in groups B, C, and D (p<0.05). In group A, mean uNGAL was significantly elevated on day 0 and daily for 5 days when compared with that of the day before culture (p<0.05 to <0.005). uNGAL shows promise as an early marker for culture-positive sepsis in VLBW infants.

The clinical utility of urinary neutrophil gelatinase-associated lipocalin in the neonatal ICU.

PURPOSE OF REVIEW: Urinary neutrophil gelatinase-associated lipocalin (uNGAL) has been identified as an early marker of acute kidney injury (AKI) in pediatric and adult populations. The aim of this review is to provide the most recent and relevant knowledge about the use of uNGAL as an early marker of renal failure and, possibly, of other morbid conditions in full-term and very low birth weight infants. RECENT FINDINGS: A recently provided reference range for uNGAL in very low birth weight infants shows that normative values for this population are similar to those of older children and adults. Increased production of uNGAL is associated with AKI in young children undergoing cardiac bypass. uNGAL is acutely produced in critically ill newborns with or without AKI. SUMMARY: Further studies to confirm uNGAL's potential to predict AKI in cardiac and noncardiac populations of newborns are required prior to utilizing this promising biomarker in clinical practice. The finding of markedly elevated uNGAL levels in critically ill newborns with normal renal function strongly suggests that uNGAL may have a role in the detection of nonrenal morbid conditions such as sepsis.

Lower urinary α-Klotho is associated with lower angiotensin-(1-7) and higher blood pressure in young adults born preterm with very low birthweight.

Early-life factors including preterm birth and VLBW increase the risk of hypertension, but the mechanisms remain poorly understood. Reductions in the anti-aging protein α-klotho are associated with hypertension, possibly due to angiotensin (Ang) II activation, but the mechanisms are incompletely understood and clinical evidence is lacking. The association of α-klotho with the alternative Ang-(1-7) pathway, which counteracts Ang II to lower BP, is undescribed. We hypothesized that lower urinary α-klotho is associated with higher BP and lower urinary Ang-(1-7) in preterm-born VLBW young adults. In a cross-sectional analysis of data from a prospective cohort of 141 preterm-born VLBW young adults, we assessed the associations among urinary α-klotho/creatinine, Ang II/creatinine, Ang-(1-7)/creatinine, Ang II/Ang-(1-7), and BP using generalized linear models adjusted for age and hypertensive pregnancy and conducted a sensitivity analysis in 32 term-born young adults. Among those born preterm, lower α-klotho/creatinine was associated with higher systolic BP (adjusted ß (aß): -2.58 mm Hg, 95% CI -4.99 to -0.17), lower Ang-(1-7)/creatinine (ln aß: 0.1, 0.04-0.16), and higher Ang II/Ang-(1-7) (ln aß: -0.14, -0.21 to -0.07). In term-born participants, α-klotho/creatinine was inversely associated with Ang II/creatinine (ln aß: -0.15, -0.27 to -0.03) and Ang II/Ang-(1-7) (ln aß: -0.15, -0.27 to -0.03). In preterm-born young adults with VLBW, lower urinary α-klotho/creatinine was associated with higher SBP, lower urinary Ang-(1-7)/creatinine, and higher urinary Ang II/Ang-(1-7). Reduced renal α-klotho expression could lead to renal Ang-(1-7) suppression as a novel mechanism for the development of hypertension among individuals born preterm with VLBW.

Urinary NT-proBNP as a potential noninvasive biomarker for screening of pulmonary hypertension in preterm infants: a pilot study.

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.

Reference values of urinary neutrophil gelatinase-associated lipocalin in very low birth weight infants.

In very low birth weight (VLBW) infants, acute renal impairment (ARI) is common, but there is no consensus about criteria for its diagnosis. Neutrophil gelatinase-associated lipocalin (NGAL) is an early and sensitive indicator of renal impairment in experimental animals, children, and adults. Urinary NGAL (UNGAL) is detectable in VLBW infants; however, there is no reference range in this population. The objective of this study is to define the reference range for UNGAL in VLBW infants with no risk factors for acute renal impairment. UNGAL concentration was determined in urine samples collected from day of life (DOL) 4 through DOL 30 in 50 newborns with uncomplicated clinical courses, selected from a total of 145 prospectively enrolled appropriate for gestational age inborn VLBW premature infants. The birth weight and gestational age ranges were 790-1490 g and 26-33 wk, respectively. The median, 95th and 99th percentiles, and range of pooled UNGAL values were 5 ng/mL, 50 ng/mL, 120 ng/mL, and 2-150 ng/mL, respectively. Greater variability and higher quantile levels of UNGAL were observed in females versus males. In conclusion, a reference range for UNGAL in VLBW infants, similar to that in children and adults, has been established.

A comparative study of sanitary napkins and absorbent nappy pads for urine output measurement in neonates.

AIM: To compare sanitary napkins and absorbent nappy pads (ANP) for urine output (UO) measurement. METHODS: Phase 1: Freshly passed neonatal urine (5, 10 and 15 mL) was poured onto preweighed sanitary napkins or ANP, which were juxtaposed to the genital area of manikins placed in incubators/warmers and weighed at (1/2), 1, 2, 4, 5 and 6 hr. Outcome was percentage weight change from baseline. Phase 2: Five very low birth weight boys in incubators had UO measurement by test tubes. A sanitary napkin or ANP was co-applied with the test tube for 4 h each. Urine collected in the test tube was measured and poured on the device, which was reapplied. Weight and wetness were checked. RESULTS: Phase 1: Mean urine loss was 8.35, 13.8, 20.1, 25.2, 33.1, 38.7 and 42.6% at (1/2), 1, 2, 3, 4, 5 and 6 h, respectively (repeated measures ANOVA [RM-ANOVA], p < 0.001). Loss was higher with ANP than sanitary napkins (32.1% vs. 13.4%, two-way RM-ANOVA, p = 0.001). There was less loss in incubators versus radiant warmers at 6 h (p = 0.09). Phase 2: There was 12.1 and 26% deficit with sanitary napkin and ANP, respectively. Wetness was felt in one and four cases, respectively. CONCLUSION: Urinary losses are less from sanitary napkins than ANPs.

Reference range of urinary neutrophil gelatinase-associated lipocalin in very low-birth-weight infants: preliminary data.

We sought to determine the reference range for urinary neutrophil gelatinase-associated lipocalin (UNGAL) in very low-birth-weight (VLBW) infants with uncomplicated clinical courses. Samples of urine from 53 VLBW infants between 3 and 28 days of life were prospectively collected weekly for measurement of UNGAL. A subset of 22 infants with uncomplicated medical courses without risk factors for renal impairment was selected for study. Mean +/- standard deviation and range for birth weight and gestational age of study infants were 1156 +/- 191, 790 to 1440 g and 29 +/- 2, 27 to 33 weeks, respectively. The 95th and 99th percentiles for UNGAL concentration from this group of infants were 25 ng/mL and 75 ng/mL, respectively. Bootstrapped mean 95th and 99th percentile values and their standard errors and 95 percent confidence intervals in ng/mL were 33.1 +/- 13.0 (7.7, 58.6) and 67.5 +/- 15.1 (37.9, 97.1), respectively. These values fall within the adult reference range. UNGAL values were stable across the ranges of gestational and postnatal age of the study infants. A preliminary reference range for UNGAL in VLBW infants has been established. Further investigation with more frequent urine collections in a larger population of VLBW infants that includes those with birth weights < 750 g and gestational ages < 27 weeks is necessary to confirm this reference range.