The physiological and biological significances of human atrial natriuretic peptide in neonates

The purpose of our study was to analyze the physiological and biological significances of the high human atrial natriuretic peptide (hANP) levels during early post-natal period. The absolute values or changes of plasma hANP concentrations did not correlate with the absolute values or changes of body weight, blood pressure, urinary sodium/creatinine and urinary aldosterone/creatinine ratios. Gel permeation chromatography of samples from two neonates revealed the presence of two molecular forms of hANP, alpha and beta, both in the plasma and urine. In the plasma, the beta-hANP was predominant on the 3rd day of life and the alpha-hANP on the 6th day of life. The change from one form to another was independent of the absolute value of hANP. We obtained no evidence suggestive of a physiological role of the high plasma hANP concentration during the early post-natal period. However, because of biological differences between these two fractions, their distribution must be taken into account when attempting to interpret the high hANP values observed in neonates.     

Concentrations of human atrial natriuretic peptide in the cord blood and the plasma of the newborn

Concentrations of human atrial natriuretic peptide (hANP) in the cord blood and the plasma were measured in 25 newborns. The level of hANP in 0 to 1 post-natal days (212.8 +/- 118.1 pg/ml; mean +/- SD) was significantly higher than that in cord blood (69.7 +/- 53.2 pg/ml) (p less than 0.005). There were no significant differences in the levels of hANP at the ages of 0 to 1, 4 and 6 post-natal days. The level of hANP did not show any significant correlation with urinary excretion of Na, urinary Na/Cr or Na/K ratios. Further evaluations should be made in order to clarify the role of hANP during the early post-natal period.     

Concentrations of Human Atrial Natriuretic Peptide in the Cord Blood and the Plasma of the Newborn

ABSTRACT. Concentrations of human atrial natriuretic peptide (hANP) in the cord blood and the plasma were measured in 25 newborns. The level of hANP in 0 to 1 post-natal days (212.8±118.1 pg/ml; mean±SD) was significantly higher than that in cord blood (69.7±53.2 pg/ml) ( p < 0.005). There were no significant differences in the levels of hANP at the ages of 0 to 1, 4 and 6 post-natal days. The level of hANP did not show any significant correlation with urinary excretion of Na, urinary Na/Cr or Na/K ratios. Further evaluations should be made in order to clarify the role of hANP during the early post-natal period.     

Urinary β2 microglobulin in the newborn

ABSTRACT. Twelve full-term, healthy newborn infants had daily urinary β2 microglobulin, albumin and creatinine levels measured during the first five days of life.
A marked elevation in urinary β2 microglobulin was demonstrated. There was a marked variation from day to day with a range of 20–11,000μg/l. The relatively steady creatinine and albumin excretion levels suggest there is a true increased excretion of β2 microglobulin in the neonatal period with a tendency for the excretion rate to rise during the first five days of life.     

Developmental pattern of urinary bile acid profile in preterm infants

Background:  Bile acid metabolism in preterm infants is yet to be fully characterized. We compared the developmental pattern of urinary bile acid profiles in ten infants born at gestational ages from 25 to 33 weeks with previous data from full-term infants from birth to about 7 months of age.
Methods:  Gas chromatography–mass spectrometry was performed on serial samples.
Results:  Total urinary bile acid concentrations gradually increased until 1 to 2 months of age. After this peak of excretion (30 to 60 µmol/mmol creatinine), total urinary bile acid concentrations gradually decreased to less than 20 µmol/mmol creatinine. The percentage of usual bile acids (mainly cholic acid) relative to total urinary total bile acids gradually deceased from approximately 30% at birth to less than 15% at 7 months of age. On the other hand, 1β-hydroxylated bile acids (mainly 1β,3α,7α,12α-tetrahydroxy-5β-cholan-24-oic acid) relative to total urinary bile acids were increased gradually from 60% at birth to reach 70% to 80% at 1 month of age. The percentage of 1β-hydroxylated bile acids relative to total urinary bile acids then remained stable at a high percentage (70% to 90%) until the age of 7 months.
Conclusion:  Physiological cholestasis in preterm infants persists longer than in full-term infants. Moreover, as large amounts of cholic and 1β,3α,7α,12α-tetrahydroxy-5β-cholan-24-oic acids were detected in urine from preterm infants during this study, the 25-hydroxylation pathway may be particularly important for bile acid synthesis in early preterm infants.     

尿S100B蛋白和乳酸/肌酐在新生儿缺氧缺血性脑病早期诊断中的应用价值

目的探讨尿S100B蛋白、尿乳酸／肌酐比值对新生儿缺氧缺血性脑病（HIE）早期诊断的应用价值。方法检测58例足月HIE患儿在生后第1天、第2天、第3天,尿S100B蛋白、尿乳酸／肌酐比值水平．并在生后7天内进行HIE临床分度,以同期25例足月正常新生儿对照组。结果HIE组出生后3天内尿S100B蛋白含量和出生后1天内尿乳酸／肌酐比值明显高于对照组（P〈0．001）;3天内尿S100B蛋白和1天内尿乳酸／肌酐比值之间及与HIE的临床分度呈正相关（P〈0．001）;当尿S100B蛋白水平在0．47μg／L,尿乳酸／肌酐比值在0．55时,单独检测第3天尿S100B蛋白敏感度、特异度分别为90．4％、91．9％;尿乳酸／肌酐比值预测HIE的敏感度和特异度以出生后第1天最高,分别为91．5％和90．3％;如检测第3天尿S100B蛋白的同时监测生后1天内尿乳酸／肌酐比值可显著提高HIE诊断的准确性,联合应用两项指标进行检测,诊断的敏感度和特异度分别为98.8％、97．4％,较两种方法单独应用敏感度和特异度均提高。结论对窒息患儿以临床表现为基础,同时监测出生后3天内尿S100B蛋白和尿乳酸／肌酐比值,对提高HIE的早期诊断和临床分度具有一定的应用价值。     

Spot urine samples for evaluating solute excretion in the first week of life

AIM: To evaluate whether the urinary creatinine concentration is a reliable reference value to standardise urinary solute excretion in a spot urine sample during the first week of life. METHODS: Spontaneously voided urine specimens were obtained in 48 healthy, full term neonates, aged 1 to 6 days (median 2.4) and in 168 healthy older children with a median age of 1.5 years (range 1 month to 3 years). In 62% of the children two urine samples were available with an interval of 2 to 4 (neonates) and 7 days (older children). RESULTS: In neonates both the urinary creatinine concentration and the urinary creatinine:osmolality ratios were significantly higher than in the older children, and were spread over a wider range. During the first postnatal week of life the mean urinary creatinine and urinary creatinine: osmolality ratio values in the first urine samples were also significantly higher than in the second samples. In children aged between 1 month and 3 years of age, these data were remarkably stable without any significant changes between repeat urine samples. CONCLUSIONS: The urinary creatinine concentration during the first days of life is high and variable, even when corrected for urinary osmolality. This is the opposite of what is found in older children and adults. Urinary creatinine and the urinary creatinine:osmolality ratio, therefore, cannot be used to standardise the urinary excretion of solutes in the first week of life.     

LOW MOLECULAR WEIGHT ORGANIC ACIDS IN THE URINE OF THE NEWBORN

Abstract The urinary excretion of seven selected low molecular weight organic acids in normal neonates was measured by gas chromatography. First and third to fourth day of life excretion of the following compounds was significantly unchanged: 3-OH-butyric acid (<13 μmol/mmol creatinine), succinic acid (approx. 43 μmol/mmol creatinine), adipic acid (approx. 12 μmol/mmol creatinine), 2-OH-glutaric acid (approx. 23 μmol/mmol creatinine), 3-OH-3-Me-glutaric acid (approx. 25 μmol/mmol creatinine) and citric acid (approx. 115 μmol/mmol creatinine). The excretion of 4-OH-phenyl-acetic acid increased during the first four days of life (from <8 μmol/mmol creatinine to approx. 20 μmol/mmol creatinine). It is postulated that urinary organic acid excretion in the neonate, which is clearly different from the adult urinary pattern, is a reflection of the specific neonatal metabolic situation, including a high fatty acid utilisation and a low protein catabolism.     

Are serum and urine neutrophil gelatinase‐associated lipocalin predictive of renal graft function in short term?

Rahimzadeh N, Otukesh H, Hoseini R, Sorkhi H, Otukesh M, Hoseini S, Torkzaban M. Are serum and urine NGAL predictive of renal graft function in short term? Abstract: NGAL is a member of the lipocalin protein family that has diverse function but similar structure. The functions of NGAL are not clear, but it appears to be expressed in stress conditions and in tissues undergoing involution. Varied studies have shown increased levels of plasma or urinary NGAL in diverse renal damages. The aim of this study was the serial measurement of serum and urinary NGAL within the first week after renal transplantation in children to predict immediate and short‐term graft function. A total of 27 patients were assessed. These patients were classified into those with rapid reduction in serum creatinine (more than 50% reduction in serum creatinine in the first day after transplantation) and patients with slow reduction in serum creatinine (<50% reduction in serum creatinine). We also assessed the absolute reduction in serum creatinine before and after transplantation. Serum and urinary NGAL on the first day post‐transplantation were higher in recipients with slow reduction in serum creatinine (urinary NGAL at the first day: 197 ± 153 [s.e.m.] vs. 22.54 ± 8.5 [s.e.m.], p = 0.04; serum NGAL at the first day: 199 vs. 69.8, p = 0.003). The cutoff point of serum NGAL at the first day after transplantation for prediction of slow creatinine reduction was 174 ng/mL with a sensitivity of 100% and specificity of 95.5%. However, we did not find association between the absolute reduction in serum creatinine before and after transplantation with the amount of serum and urinary NGAL post‐transplant. Additionally, we did not find any effect of high serum and urine NGAL concentration on the graft function at the first year post‐transplant. Although it is supposed that high serum and urine NGAL may predict ischemia of graft in early phases; however, it appears that this mild ischemic injury to graft without DGF or SGF cannot affect the graft function in short‐term period. Further studies are needed using larger transplant recipients in pediatric age group. It is also needed to determine the effects of mild ischemic injuries on the graft function in long‐term period in future studies.     

Inflammatory mediators in perinatal asphyxia and infection

Aim : To determine serum levels of interleukin-6 (IL-6), IL-1β, tumor necrosis factor-α (TNF-α), soluble intercellular adhesion molecule-1 (sICAM-1) and C-reactive protein (CRP) in asphyxiated neonates and compare these inflammatory factors with those found in neonates with perinatal infection. Methods : 88 neonates were studied, of whom 36 were asphyxiated, 18 were infected and the remaining 34 were controls. Peripheral blood samples were obtained on the 1st, 3rd and 5th postnatal days. Results : Cytokines IL-6 and IL-1β as well as sICAM-1 serum levels did not differ between asphyxiated and infected neonates; however, at most time periods, their values were significantly higher than controls. TNF-α was similar in the three groups of neonates. CRP serum values were significantly higher in the infected neonates than in the asphyxiated or control subjects. Among the 54 asphyxiated and infected neonates, 15 were considered as severe cases and 39 as mild. The severe cases, at most time periods, had significantly higher IL-6, IL-1β and sICAM-1 levels compared with the mild ones. Through receiver operating characteristic curves the cut-off points, sensitivities, and specificities for distinguishing neonates at risk or at high risk for brain damage were established.
Conclusion : Similar increases in serum levels of IL-6, IL-1β and sICAM-1 were found in perinatally asphyxiated and infected neonates. As these increases correlated with the severity of the perinatal insults, neonates at high risk for brain damage might be detected.     

Quantification of L-type fatty acid binding protein in the urine of preterm neonates

We measured urinary excretion of L-type fatty acid binding protein (L-FABP) in preterm neonates on days 1, 5-10, and 25-30 of life. Urinary L-FABP levels (expressed as the ratio to creatinine) in preterm neonates were considerably higher than those of healthy adults. They did not change significantly during the study period. Urinary L-FABP levels showed significant positive correlation with those of urinary N-acetyl-beta-D-glucosaminidase activity on day 1, and with those of 8-hydroxy-2'-deoxyguanosine on days 25-30. These results suggest that L-FABP is expressed in the neonatal kidney. Our results may also point to potential effects of proximal tubular damage and oxidative stress on urinary excretion of L-FABP.     

Urinary aquaporin-2 excretion in preterm and full-term neonates

The study was undertaken to define the role of aquaporin-2 (AQP2) in renal concentrating performance by measuring urinary AQP2 excretion and urine osmolality in healthy preterm and full-term neonates during early postnatal life. Random urine samples were obtained from 9 full-term newborn infants (mean birth weight 3,218 g, mean gestational age 39.2 weeks) at postnatal ages of 1, 3 and 5 days. Five premature infants with a mean birth weight of 1,570 g and mean gestational age of 30.6 weeks were studied at the end of the 1st week and then weekly up to the 6th week. Urine osmolality (Knauer osmometer), creatinine (modified Jaffé's method) and AQP2 concentrations (radioimmunoassay) were measured. In full-term neonates, urinary AQP2 excretion showed no consistent changes over the age period studied, while urine osmolality decreased significantly with advancing age. In premature infants, urinary AQP2 excretion remained practically unchanged during the first 4 weeks followed by an abrupt increase thereafter. Urine osmolality did not follow the developmental pattern of AQP2 excretion; its mean values varied only from 78 +/- 39 to 174 +/- 146 mosm/l during the experimental period. It is concluded that during the early postnatal period, urinary AQP2 excretion does not serve as a direct marker of the renal action of AVP and the renal capacity to concentrate urine.     

Calcium, sodium and potassium urinary excretion during the first five days of life in very preterm infants

BACKGROUND: Hypercalciuria has been associated with the risk of nephrocalcinosis and renal stones in both adults and children. Renal calcifications are frequently encountered in preterm infants because this particular population presents most of the risk factors of increased urinary calcium excretion. Urinary calcium excretion has been shown to correlate with sodium and potassium excretions in adult patients, but these correlations have not been demonstrated in the early neonatal period yet. OBJECTIVE: To define the relationship between calcium urinary excretion and sodium or potassium excretions in the first 5 days of life in preterm babies. METHODS: A prospective study was conducted in 16 preterm infants born before 32 weeks of gestation (body weight 1,373 +/- 310 g; gestational age 29.1 +/- 1.6 weeks). Fifteen consecutive 8-hour urine collections were performed for each infant from the 8th hour of life. A plasma sample was obtained at the end of each urine collection. Sodium, potassium, calcium and creatinine were measured in urine and blood samples as often as possible. RESULTS: (1) Urine sodium excretion was 6.56 +/- 4.35 mmol/kg per day. (2) Urinary calcium excretion was 5.9 +/- 5.4 mg/kg per day and the urinary calcium/creatinine ratio was 0.48 +/- 0.39 mg/mg. (3) Urinary calcium and sodium excretion were positively correlated (r = 0.65, p = 0.0001), while an inverse correlation was found between calcium and potassium excretion (r = 0.31, p = 0.004). CONCLUSION: The mean values of urinary calcium excretion and calcium/creatinine ratio observed in our population were higher than 4 mg/kg per day and 0.4 mg/mg, respectively, i.e. boundary values previously associated with an increased risk of nephrocalcinosis. We hypothesize that an increase in urinary sodium excretion in this population may facilitate calcium excretion.     

Urinary lithogenic and inhibitory factors in preterm neonates receiving either total parenteral nutrition or milk formula

The aim of this study was to evaluate prospectively the influence of nutrition on certain factors which may inhibit or promote nephrocalcinosis in two groups of preterm infants, receiving total parenteral nutrition (TPN) and special preterm milk formula respectively, but not furosemide. A total of 37 preterm infants, 15 on TPN and 22 fed a special preterm formula were studied at the end of the 1st, 2nd and 3rd weeks of life, at which time serum and 8 h urine specimens were collected. High ratios of urinary calcium to urinary creatinine (UCa/cr), urinary oxalate to urinary creatinine (Uox/cr) and urinary calcium to urinary citrate (UCa/cit) indicates an increased risk for nephrocalcinosis while high urinary citrate to urinary creatinine (Ucit/cr) ratio indicates protection. Uox/cr increased significantly (P<0.05) in those infants fed preterm formula, from the end of 2nd week of life and was two-fold higher than in the TPN group of preterm infants (P<0.01). Ucit/cr was higher throughout the study period in the formula fed than in the TPN preterm infants. UCa/cit was five-fold higher (P<0.01) in the TPN group, by the end of the 3rd week. Urinary calcium and magnesium was similar in both groups during the study period. Two of the infants studied (5.4%), one from each group, developed nephrocalcinosis.CONCLUSION: In preterm neonates on total parenteral nutrition, urinary oxalate -to-creatinine ratio (a potent lithogenic factor) was lower and urinary citrate -to-creatinine ratio (a lithoprotective factor) also lower than in formula fed neonates. The type of feeding (total parenteral nutrition or special preterm milk formula) seems to affect urinary oxalate and citrate but not calcium and magnesium in non-furosemide treated preterm infants during the first 3 weeks of life.     

Urinary excretion of epidermal growth factor and transforming growth factor-alpha in breast-fed and formula-fed infants

Urinary epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-α) concentrations were determined by radioimmunoassay in a longitudinal study analyzing 348 24-h urine specimens of 32 infants (16 breast-fed, 16 formula-fed) during the first 16 weeks of life. EGF excretion showed a statistically significant increase from 6.0 ±2.5 to 14.1±4.9 μg/g creatinine (mean± 1 SD) during the investigation period. TGF-α levels were fairly constant throughout this period. Comparing breast-fed infants, with more than 100-fold higher ingestion of EGF and TGF-α, with formula-fed infants, no significant differences in urinary EGF and TGF-α excretion were observed. These results do not rule out a systemic effect of EGF and TGF-α after intestinal absorption in breast-fed infants. The results suggest, however, that urinary EGF and TGF-α originate mainly from sources other than intestinal absorption.     

Urinary Concentrations of Total Protein, β2-Microglobulin and Amino Acids in Healthy Newborn Infants

The urinary concentrations of total protein, low molecular weight proteins, amylase, and total amino acid were determined from 104 healthy newborn infants during the first 15 days of life. The urine samples were collected after spontaneous voiding every two hours. Neonatal proteinuria was found in 70 per cent of 2 day old infants. No infant older than 8 days showed proteinuria. The ratio of mean value of β2-microglobulin to creatinine was highest on the 5th day of life, followed by a rapid decrease after the 6th day. On the 15th day the β2-microglobulin concentration was still high. The mean ratios of total amino acid to creatinine and amylase to creatinine increased gradually during the first 9 days of life, and then decreased rapidly after the 10th day. The highest urinary concentration of other low molecular weight proteins was found between the 7th and 8th day. On the other hand, the lowest concentration of albumin was found between the 7th and 8th day. These findings suggest that the proximal tubular function is immature in the newborn period. (Acta Paediatr Jpn 23(3):326–332 1981)     

Plasma creatinine in the first month of life.

The creatinine-kinetics method of analysis was used to study the changes, during the first month of life, in plasma creatinine levels in 34 newborn infants receiving no treatment with drugs. Plasma creatinine values during the first 5 days of life ranged from 188 to 17 mumol/l. After day 5 plasma levels were fairly stable throughout the first month, with a mean value of 35 +/- 2 (range 12-62) mumol/l. Twenty-two infants receiving treatment with gentamicin-ampicillin-cloxacillin were also studied. Seven of them had raised plasma creatinine concentrations after day 5, well beyond the range of concentrations found for infants receiving no drugs. Plasma creatinine, measured by the kinetic method, appears to provide a useful index of renal function in the neonatal period.     

Profile of urinary bile acids in familial intrahepatic cholestasis with Coombs'negative haemolytic anaemia

We present two male siblings with intrahepatic cholestasis and prolonged indirect hyperbilirubinaemia. Their familial intrahepatic cholestasis syndrome was characterized by Coombs'negative haemolytic anaemia, without giant cell transformation of hepatocytes and high concentrations of serum γ-glutamyl transpeptidase and cholesterol. By gas chromatography-mass spectrometry, we detected large amounts of 1β-hydroxylated bile acids, especially lβ,3α,7α,12α-tetrahydroxy-5β-cholan-24-oic acid (25.5-67.9% of total urine bile acids) in the urine during phenobarbital therapy. However, the amount of urinary 1β-hydroxylated bile acids gradually decreased as the disease progressed. At the end-stage, we detected large amounts of 7α,12α-dihydroxy-3-oxochol-4-en-24-oic acid (19.6% of total urine bile acids). The ratio of 7α,12α-dihydroxy-3-oxochol-4-en-24-oic acid to cholic acid in the urine was 0.8. We conclude that in infants with end-stage liver failure, the microsomal hydroxylation of bile acids is impaired and the excretion of Δ⁴-3-oxo bile acids is increased. Familial intrahepatic cholestasis, Coombs'negative haemolytic anaemia, 1β-hydroxylated bile acids, unsaturated ketonic bile acids     

Plasma creatinine in the first month of life

The creatinine-kinetics method of analysis was used to study the changes, during the first month of life, in plasma creatinine levels in 34 newborn infants receiving no treatment with drugs. Plasma creatinine values during the first 5 days of life ranged from 188 to 17 mumol/l. After day 5 plasma levels were fairly stable throughout the first month, with a mean value of 35 +/- 2 (range 12-62) mumol/l. Twenty-two infants receiving treatment with gentamicin-ampicillin-cloxacillin were also studied. Seven of them had raised plasma creatinine concentrations after day 5, well beyond the range of concentrations found for infants receiving no drugs. Plasma creatinine, measured by the kinetic method, appears to provide a useful index of renal function in the neonatal period.     

Values for urinary β-microglobulin and N-acetyl-β-D-glucosaminidase in normal healthy infants

Abstract Background : Measuring urinary β₂ microglobin (B2M) and N -acetyl-β-D-glucosaminidase (NAG) excretion is widely used as a valuable clinical tool in assessing renal tubular lesions. However, few data are available on normal values for urinary excretion of B2M and NAG in infancy.
Methods : Urinary B2M and NAG were measured in healthy infants. The logarithmic values of urinary B2M, NAG. B2M/creatinine ratio and NAG/creatinine ratio were distributed almost normally and reference ranges were calculated from the logarithms of the observed values.
Results : The levels of urinary B2M and B2M/creatinine ratio were highest in the 1-month-old group, followed by a decrease during the first 3 months. Urinary B2M excretions in the 3-monfh-old group showed rather lower levels than those of the 12-month-old and 36-month-old groups. Although urinary NAG excretions were almost constant throughout all groups, urinary NAG/creatinine ratio decreased gradually until 3 years of age.
Conclusions : We suggest that these reference ranges are of importance in evaluating tubular damage due to a variety of renal diseases in infancy.