Utility of routine urine CMV PCR and total serum IgM testing of small for gestational age infants: a single center review.

BACKGROUND: Due to the extremely low incidence of TORCH (toxoplasmosis, rubella, CMV, herpes simplex virus) infections, diagnostic testing of all small for gestational age (SGA) infants aimed at TORCH etiologies may incur unnecessary tests and cost. OBJECTIVE: To determine the frequency of urine CMV PCR and total IgM testing among infants with birth weight <10% and the rate of test positivity. To evaluate the frequency of alternative etiologies of SGA in tested infants. METHODS: Retrospective chart review of SGA infants admitted to the neonatal intensive care unit (NICU) at NYU Langone Medical Center between 2007 and 2012. Subjects were classified as being SGA with or without intrauterine growth restriction (IUGR). The IUGR subjects were then further categorized as having either symmetric or asymmetric IUGR utilizing the Fenton growth chart at birth. Initial testing for TORCH infections, which included serum total IgM, CMV PCR and head ultrasound, were reviewed and analyzed. RESULTS: Three hundred and eighty-six (13%) infants from a total of 2953 NICU admissions had a birth weight ≤10th percentile. Of these, 44% were IUGR; 34% being symmetric IUGR and 10% asymmetric. A total of 32% of SGA infants had urine CMV PCR and total IgM tested with no positive results. As expected, significantly higher percentage of symmetric IUGR infants were tested compared to asymmetric IUGR and non-IUGR SGA infants, (64% vs. 47% vs. 19%) P≤0.01. However, 63% of infants with a known cause for IUGR had same testing done aimed at TORCH infections. We calculated additional charges of $64,065 that were incurred by such testing. CONCLUSIONS: The majority of infants in our study who received testing for urine CMV PCR and total IgM aimed at TORCH infections had one or more other known non-infectious etiologies for IUGR. Because the overall yield of such testing is extremely low, we suggest tests for possible TORCH infections may be limited to symmetric IUGR infants without other known etiologies. Improved guidelines testing for TORCH infections can result in reducing hospital charges and unnecessary studies.

Urinary ß2-microglobulin and bronchopulmonary dysplasia: Trends in preterm infants.

BACKGROUND: The developmental process of bronchopulmonary dysplasia (BPD) is not identical between very preterm infants born small for gestational age (SGA) and those born appropriate for gestational age (AGA). In this study, we compared the pattern of the inflammatory response in infants of each group, by measuring urinary ß2-microglobulin (Uß2M) as an alternative, concise, and less-invasive biomarker. METHODS: Uß2M and clinical details were examined at birth and at 4 weeks of age in 146 very preterm infants. RESULTS: Of the 57 infants diagnosed with BPD, 18 were SGA, and 39 were AGA. Uß2M at birth was significantly lower in SGA BPD infants than in AGA BPD infants, but it increased with time. The prevalence of chorioamnionitis (CAM) was significantly lower in SGA BPD infants than in AGA BPD infants, while that of pregnancy-induced hypertension was the opposite. CONCLUSIONS: Exposure to prenatal factors other than CAM may sensitize fetal lungs to become vulnerable to postnatal inflammation in very preterm SGA infants with BPD.

Gonadotropin levels in urine during early postnatal period in small for gestational age preterm male infants with fetal growth restriction.

OBJECTIVE: The objective of this study was to estimate gonadotropin concentrations in small for gestational age (SGA) male infants with the reactivation of the hypothalamic-pituitary-gonadal axis during the first few months of life that is important for genital development. STUDY DESIGN: We prospectively examined 15 SGA and 15 appropriate for gestational age (AGA) preterm male infants between 2013 and 2014 at Kyoto University Hospital. Gonadotropin concentrations (luteinizing hormone (LH) and follicle-stimulating hormone (FSH)) were measured in serial urine samples from the postnatal days 7 to 168 and compared between SGA and AGA infants using the Mann-Whitney test. RESULTS: A longitudinal analysis showed that SGA infants had higher LH and lower FSH concentrations (P=0.004 and P=0.006, respectively) than AGA infants. CONCLUSION: Male infants who are SGA at birth because of fetal growth restriction have gonadotropin secretion abnormalities in the first few months of life.

Urinary podocalyxin as a possible novel marker of intrauterine nephrogenesis and extrauterine podocyte injury.

BACKGROUND: The number of nephrons at birth is determined during fetal development and is modulated thereafter by postnatal podocyte injury. Hyperfiltration, caused by a reduced number of nephrons, is a risk factor for chronic kidney disease. It is therefore important to monitor the formation of nephrons. METHODS: Urine samples were collected from infants within 1-2 days of birth, with follow-up sampling for preterm infants at 37-39 weeks of corrected age. Urinary levels of podocalyxin (PCX), ß2-microglobulin (ß2MG), N-acetyl-ß-D-glucosaminidase (NAG), total protein (TP), microalbumin (mAlb) and creatinine were measured and the relationship between these markers evaluated. RESULTS: Seventy-nine neonates were enrolled in this study. Urinary levels of PCX at birth were higher than normal adult reference values, with levels increasing up to a gestational age of 36 weeks (p = 0.0242). At 37-39 weeks corrected age, urinary levels of PCX decreased to adult levels. The levels of PCX in the urine at birth were not correlated to urinary levels of ß2MG, NAG, TP and mAlb. CONCLUSIONS: An increased urinary level of PCX may be a marker of both active nephron formation and podocyte injury sustained at birth. As such, changes in urinary levels of PCX are likely to reflect adaptation of renal function to the extra-uterine environment.

The C in TORCH: a cost-effective alternative to screening small-for-gestational-age infants.

BACKGROUND: Infants born with birth weights under the 10th percentile for their gestational age are classified as small for gestational age (SGA). TORCH infections are reported to be associated with SGA infants. With the low incidence of infections, screening is likely to be expensive and of low utility. OBJECTIVE: The objective of this study was to determine the utility and cost-effectiveness of screening SGA infants with TORCH serology titers, urine cytomegalovirus (CMV) cultures and cranial ultrasounds. METHODS: A retrospective review was conducted on all infants admitted to the neonatal intensive care unit (NICU) at Los Angeles County and University of Southern California (LAC+USC) Medical Center from January 2003 to December 2011 with a diagnosis of SGA or intrauterine growth restriction. Birth characteristics such as birth weight, length, head circumference and gestational age were recorded. TORCH titer results, urine CMV results and cranial ultrasound findings were collected. RESULTS: Between 2003 and 2011, 232 SGA infants were admitted to the NICU at LAC+USC Medical Center. Of these, 117 infants (50%) had TORCH titer testing performed; there was only 1 positive CMV IgM and 1 positive HSV IgM result. Repeat urine CMV testing was performed on 109 infants (47%), with a total of 296 urine CMV samples collected from these infants; 6 infants had positive results, of whom 3 had repeat positive urine CMV samples. Overall, 149 of the infants had a cranial ultrasound done, none of which were positive for calcifications. CONCLUSIONS: TORCH titer testing, urine CMV screening and cranial ultrasound screening are of low yield in screening clinically asymptomatic SGA infants for TORCH infections. Given the low number of positive results, a cost-effective alternative of selective TORCH testing may be limited to infants with additional clinical findings. This study serves as a reminder to periodically examine testing practices and patient population to maximize cost-effectiveness.

Is routine TORCH screening and urine CMV culture warranted in small for gestational age neonates?

BACKGROUND: congenital infections are associated with a wide variety of clinical symptoms, including small for gestational age (SGA). AIMS: to determine the co-occurrence of SGA and congenital TORCH infections, as diagnosed by TORCH serologic tests and/or cytomegalovirus (CMV) urine culture. STUDY DESIGN: we performed a retrospective study of all neonates admitted to our neonatal intensive care unit from January 2004 to February 2010 in whom SGA was diagnosed and TORCH serologic tests and/or CMV urine cultures were performed. RESULTS: TORCH serologic tests (in neonatal or maternal serum) and/or a CMV urine culture were performed in 112 neonates with SGA. None of the neonates tested positive for Toxoplasma gondii, Rubella, and Herpes simplex virus. Positive CMV urine culture was detected in 2% (2/112) of neonates, but their CMV IgM titers were negative. CONCLUSIONS: the co-occurrence of TORCH congenital infection in infants with SGA is rare. Routine TORCH screening in neonates with isolated SGA does not seem warranted and should be limited to CMV urine cultures.

Biomarkers of oxidative stress and antioxidant status in children born small for gestational age: evidence of lipid peroxidation.

Children born small for gestational age are known to be at increased risk for adult diseases such as hypertension, diabetes, and coronary heart disease. Oxidative stress is a common feature of these pathogenic conditions and can be the key link between size at birth and increased morbidity later in life. The purpose of this study was to analyze the parameters of lipoperoxidation and changes in antioxidant defense system as well as assess their relationship to birth weight. Concentrations of thiobarbituric-acid-reactive-substances and F2-isoprostanes, total antioxidant status, and the activity of both superoxide dismutase and glutathione peroxidase were measured in 65 children (33 boys, 32 girls; ages 8-13 y). Thiobarbituric-acid-reactive-substances and F2-isoprostane levels were significantly elevated in children born small for gestational age. Nevertheless, superoxide dismutase activity was significantly elevated in these children and the levels of both glutathione peroxidase activity and total antioxidant status were unchanged. Moreover, we found that systolic blood pressure was positively associated with thiobarbituric-acid-reactive-substances levels in race- and gender-adjusted models but not in a multivariable regression model. In conclusion, the current study revealed that there is evidence of oxidative stress in children born small for gestational age as supported by increased lipid peroxidation.

Increased catecholamines and heart rate in children with low birth weight: perinatal contributions to sympathoadrenal overactivity.

BACKGROUND: Low birth weight is associated with cardiovascular disease. The underlying mechanisms are unknown. We hypothesized that perinatal stress alters autonomic regulation of the cardiovascular system. In this study, catecholamines, heart rate (HR) and blood pressure (BP) were measured in healthy children with low birth weight. METHODS: This clinical study included 105 children (mean age 9.6 years) in three groups; born at term with normal birth weight (controls, n=37), born at term but small for gestational age (SGA, n=29) and born preterm (Preterm, n=39). Dopamine, adrenaline and noradrenaline were determined in urine. HR and BP were measured at rest, during an orthostatic test and after a mathematical mental stress test. RESULTS: Children in the Preterm and SGA groups excreted higher levels of catecholamines when compared with controls. HR (mean [SD] values) were higher at rest and after mental stress in Preterm (at rest 76 [9] and after mental stress 82 [12] min(-1)) and in SGA (79 [8] and 82 [10]) when compared with controls (70 [9] and 75 [9]). HR correlated with urinary catecholamines (r=0.24-0.27, P<0.05). Blood pressures measured at rest, during orthostatic testing and after mental stress did not differ between the groups. CONCLUSIONS: Preterm birth and fetal growth restriction are associated with increased sympathoadrenal activity in childhood, as indicated by stress-induced increases in HR and urinary catecholamines. These findings suggest that the cardiovascular control is differently programmed in these children with possibly higher risk of developing hypertension in adulthood.

The role of serum and urinary urea in the evaluation of enteral protein intake in adequate and small-for-gestational-age very low birth weight infants

INTRODUÇÃO E OBJETIVOS: Os recém-nascidos de muito baixo-peso (RNMBP) têm necessidades nutricionais especiais. Existe uma tendência atual de se individualizar a oferta protéica para essas crianças. O objetivo do trabalho é determinar a utilidade da uréia sérica e urinária como indicadores da oferta protéica em RNMBP adequados (AIG) e pequenos para a idade gestacional (PIG). TIPO DE ESTUDO E LOCAL: Estudo prospectivo realizado no Berçário Anexo à Maternidade Instituto da Criança "Prof. Pedro de Alcântara" do Hospital das Clínicas, Departamento de Pediatria da Faculdade de Medicina, Universidade de São Paulo, Brasil. MÉTODOS: Setenta e dois RNMBP (oferta protéica média = 3,7 g/kg/dia) foram incluídos, em um estudo de coorte prospectivo, em dois grupos: AIG (n = 34) e PIG (n = 38). Amostras de sangue, coletas de urina de seis horas (Ur6h) e em amostras isoladas (AIUr) foram obtidas para determinação de uréia e creatinina após a 3ª semana de vida e duas semanas após. Análise estatística: teste t de Student, correlação de Pearson e regressão linear (p < 0,05). RESULTADOS: Não houve diferença entre os grupos quanto aos níveis de uréia sérica, uréia Ur6h e uréia AIUr, bem como entre as duas avaliações dentro de cada grupo. A uréia sérica correlacionou-se à uréia Ur6h nos RNAIG e nos PIG, bem como à uréia AIUr nos RNPIG. A uréia Ur6h correlacionou-se à uréia AIUr nos RNAIG e nos RNPIG. Não houve correlação entre a oferta protéica e a uréia sérica ou urinária. CONCLUSÕES: A uréia sérica e a urinária não refletiram a oferta protéica quando foram utilizadas ofertas médias de 3,7 g/kg/dia. Uréia AIUr pode ser tão confiável quanto uréia da urina coletada por períodos mais longos.

The role of serum and urinary urea in the evaluation of enteral protein intake in adequate and small-for-gestational-age very low birth weight infants.

CONTEXT AND OBJECTIVE: Very low birth weight (VLBW) infants have special nutritional needs. There is a current tendency to individualize their protein needs. The objective of this study was to determine the suitability of serum and urinary urea as indicators for protein intake in adequate-for-gestational-age (AGA) and small-for-gestational-age (SGA) VLBW infants. DESIGN AND SETTING: Prospective study in the nursery attached to the Maternity Ward of the "Prof. Pedro de Alcântara" Children's Institute, Hospital das Clínicas, Department of Pediatrics, Faculdade de Medicina da Universidade de São Paulo, Brazil. METHODS: Seventy-two VLBW infants (mean protein intake = 3.7 mg/kg/day) were enrolled in a prospective cohort study in two groups: AGA (n = 34) and SGA (n = 38). Blood samples, six-hour urine (6hUr) collections and urine sample tests (STUr) were obtained for urea and creatinine assays at three and five weeks of life. STATISTICAL ANALYSIS: Student's t test, Pearson correlation and linear regression (p < 0.05). RESULTS: There were no differences between groups for serum urea, 6hUr and STUr, or between two assessments within each group. Serum urea correlated with 6hUr in both AGA and SGA, and to STUr in SGA; 6hUr correlated with STUr in both AGA and SGA. There was no correlation between protein intake and serum or urine urea. CONCLUSIONS: Serum and urinary urea did not reflect protein intake when mean intakes of 3.7 g/kg/day were used. Sample tests of urinary urea can be as reliable as urea from urine collected over longer periods.

Urinary excretion of calcium and phosphate in preterm infants.

The aims of this study were to determine reference ranges for the urinary calcium (UCa/Cr) and phosphate (UPO(4)/Cr) creatinine ratios and to study factors influencing these ratios in a representative population of preterm infants managed according to current nutritional guidelines. Spot urine samples were obtained from 186 preterm infants (gestation 24-34 weeks) for measurement of UCa/Cr and UPO(4)/Cr ratios as part of a routine metabolic bone screening program, once every 2-4 weeks from the 3rd to the 18th week of life. Data were also collected on gender, appropriate or small for gestational age (SGA), nutrition [total parenteral nutrition (TPN), preterm or term formula, and breast milk], plasma Ca, P0(4), urea, and electrolytes and on the use of drugs (frusemide, dexamethasone, and theophylline). Data from infants treated with any of these three drugs were analyzed separately and not included in establishing the reference ranges for UCa/Cr and UPO(4)/Cr. The mean gestational age of the study population was 28 weeks (range 24-34 weeks). The 95th percentile for UCa/Cr at 3 weeks of age was 3.8 mmol/mmol and decreased significantly with increasing postnatal age (P<0.001). The 95th per-centile for UPO(4)/Cr was 26.69 mmol/mmol at 3 weeks of age, but this did not change significantly with increasing postnatal age (P=0.296). On univariate analysis there was no significant association of UCa/Cr and UPO(4)/Cr with gender and type of enteral nutrition. The UCa/Cr was lower in infants who were SGA (P=0.013) and with low plasma Ca (P=0.008). Infants on TPN had significantly higher UCa/Cr (P =0.019) and lower UPO(4)/Cr ratios(P<0.001). Multivariate analysis confirmed the decrease in UCa/Cr ratio with increasing postnatal age, but the SGA effect was eliminated. The use of furosemide(P<0.001) and theophylline (P=0.003) was associated with a significant increase in the UCa/Cr ratio. The use of dexamethasone was also associated with an increase in UCa/Cr ratio, but this did not achieve statistical significance (P=0.339). The use of furosemide, theophylline,and dexamethasone had no effect on UPO(4)/Cr. We report a reference range for UCa/Cr and UPO(4)/Cr ratios and factors influencing these ratios in a representative population of preterm infants between 24 and 34 weeks gestation, managed according to current nutritional guide-lines.

Correlation between urinary epidermal growth factor excretion and serum thyroid hormone in premature and term neonates.

Eighty neonates, including 14 full-term, 31 premature, 27 twin or triplet, 6 small-for-gestational-age, and 2 infants with hyperthyroidism, were evaluated. The urinary epidermal growth factor/creatinine ratio (EGF/Cr) on the 1st postnatal day was not statistically different among full-term, premature, multiple-pregnancy, and small-for-gestational-age infants (F = 1.06, p = 0.6). There was no difference in urinary EGF/Cr between the 1st postnatal day and the 7th day (p = 0.4 by paired t test). The urinary EGF/Cr was not correlated with the serum thyroid-stimulating hormone level (r = -0.162, n = 60, p = 0.21), but showed a positive correlation with serum total T3 (r = 0.526, n = 60, p < 0.001) and with serum total T4 (r = 0.460, n = 60, p < 0.001). The correlation between urinary EGF/Cr and serum free T4 was even much better (r = 0.727, n = 25, p < 0.001). These results implicate that thyroid hormone may play a role in regulating urinary EGF excretion.

Hepatic biotransformation capacity in low-birth-weight infants as measured with the [15N]methacetin urine test: influences of gestational age, postnatal age, and intrauterine growth retardation.

The influences of the gestational age (range: 28-36 weeks) and the postnatal age (range: 6-100 days) on the biotransformation capacity of the liver were studied in 51 preterm appropriate-for-gestational-age infants and in 20 preterm small-for-gestational-age infants using the [15N]methacetin urine test. Methacetin is a test drug assessing a two-step pathway of biotransformation including monooxygenation and conjugation. After oral administration of 3 mg [15N]methacetin/kg body-weight, the cumulative 15N excretion in urine during the consecutive 9 h was measured and used as a marker of microsomal biotransformation capacity. In preterm appropriate-for-gestational-age infants, the biotransformation capacity increases with gestational age as well as with postnatal age, but the strongest correlation could be found between cumulative [15N] excretion and postmenstrual age. Intrauterine growth retardation results in lower biotransformation capacity (26.3 +/- 11.3 vs. 36.1 +/- 9.6% [15N] excretion, expressed as percentage of intake) and disturbed postnatal development of this hepatic function. The data indicate that normal intrauterine development is a prerequisite for normal postnatal development of the biotransformation capacity, which might have consequences for the metabolism and efficacy of certain drugs in small-for-gestational-age infants.

Postnatal development of urea- and ammonia-excretion in urine of very-low-birth-weight infants small for gestational age.

In 12 very-low-birth-weight (VLBW) infants with intrauterine growth retardation and in 14 VLBW-infants appropriate for gestational age (AGA) fed a human milk (HM) formula (HM enriched with 6 g freeze dried HM per 100 ml) the renal excretion of urea and ammonia was studied on the 10th, 21st and 42nd days of life. The lowest excretion of urea was found in both groups on the 10th day of life. Up to the 42nd day of life the excretion raised significantly more in the AGA- than in the small for gestational age (SGA)-infants. In contrast to the urea excretion the excretion of ammonia was highest on the 10th day of life in both groups, but the excretion was significantly higher in the SGA-infants if compared to the AGA-infants. In the AGA-infants excretion of ammonia decreased with postnatal age whereas in the SGA-infants the high excretion remained up to the 42nd day of life. The data suggest that in VLBW-infants the urea synthesizing capacity is decreased and develops within the first weeks of postnatal life. The postnatal development is delayed in SGA-infants when compared to AGA-infants. The differences are more pronounced with increasing degree of intrauterine growth retardation.

The effect of polycythemia and hypoxia on urinary N-acetyl-beta-D-glucosaminidase activity in newborns.

Urinary N-acetyl-beta-D-glucosaminidase activity was assayed in fullterm and preterm polycythemic neonates, in preterm infants with hypoxia, and in healthy newborns. There were no significant differences between fullterm and preterm babies or between appropriate for gestational age and small for gestational age neonates in the normal group. N-acetyl-beta-D-glucosaminidase excretion on the first day of life was significantly raised in polycythemic newborns (P less than 0.01). Fourteen days after partial plasma exchange the enzyme activity returned to normal. N-acetyl-beta-D-glucosaminidase activities in preterm babies with respiratory distress syndrome were significantly (P less than 0.01) raised on the 1st, 2nd, 4th days and fell sharply to the 14th day. N-acetyl-beta-D-glucosaminidase isoenzyme studies revealed that urine samples taken from preterm babies with respiratory distress syndrome in the first week after birth contained increased amounts of intermediate and B isoenzyme forms while there was a concomitant reduction in the amount of the A form present.

Comparison of urinary growth hormone and IGF-I excretion in small- and appropriate-for-gestational-age infants and healthy children.

The output of urinary growth hormone (GH) and IGF-I were quantitated by RIA in 12-h urine collections obtained from infants who were preterm, small for gestational age (PT-SGA, n = 13); preterm, appropriate for gestational age (PT-AGA, n = 27); full term, small for gestational age (FT-SGA, n = 13); and full term, appropriate for gestational age (FT-AGA, n = 29); and from normal children (n = 33). The amounts of GH and IGF-I (mean +/- SEM) excreted by the PT-SGA and FT-SGA infants were not significantly lower than those excreted by the PT-AGA and FT-AGA groups, respectively [GH (micrograms/kg): PT-SGA 13.7 +/- 3.1 versus PT-AGA 14.0 +/- 2.2, FT-SGA 7.8 +/- 2.4 versus FT-AGA 6.6 +/- 1.8; IGF-I (nmol/kg): PT-SGA 0.52 +/- 0.09 versus PT-AGA 0.53 +/- 0.04, FT-SGA 0.31 +/- 0.05 versus FT-AGA 0.35 +/- 0.04]. All infant groups exhibited significantly greater outputs of urinary GH and IGF-I compared with the children (p less than 0.01). The plasma concentrations of GH in all infant groups were high, whereas the plasma IGF-I levels were low. Microalbumin and beta-2 microglobulin excretion did not correlate with urinary GH and IGF-I output. Despite the higher microalbumin output in FT babies, urinary GH and IGF-I excretion was lower in these groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Cocaine and pregnancy: clinical and toxicological implications for the neonate.

Recent studies show that the rate of cocaine use by pregnant women in the United States is much higher than realized hitherto, and an increasing number of infants are being born to cocaine-using mothers. In an ongoing research project to study the effects of cocaine on pregnancy outcome, we studied 70 infants born to cocaine-using women. These infants were matched to a drug-free comparison group selected from the population of the same hospital: children of pregnant women of a similar racial and socioeconomic distribution, but with no history or evidence of licit or illicit drug use during pregnancy. Cocaine-exposed infants had lower birth weight, shorter gestation, and a smaller head circumference than control infants. Cocaine-exposed infants also had neurobehavioral abnormalities at initial evaluation and a higher rate of perinatal complications. Toxicological evaluation of urines of neonates born to cocaine-using women showed that benzoylecgonine, a primary metabolite of cocaine, persisted in the urines for as long as 120 h after delivery. We discuss the role of the immature fetal and neonatal system in the clinical and toxicological outcome of the infant, and emphasize that further long-term studies of this will be needed.

Increased neonatal urinary ammonia: a marker for in utero caloric deprivation?

The decline in the urinary urea to ammonia ratio represents a simple measure of nutritional status in the adult. We examined the relationship of this ratio to nutrient-related fetal growth retardation. Levels of ammonia and urea nitrogen were measured in the first voided urine and cord blood from 15 term infants exhibiting a wide range of growth. Analysis by multiple regression with neonatal ponderal index as the primary dependent variable revealed a significant correlation between lowered ponderal index and decreased urinary urea and ammonia. The correlation was primarily a function of increasing ammonia levels, with no relationship between fetal leanness and urinary urea. Comparable cord artery and vein ammonia suggest that placental ammoniagenesis was not a major determinant of observed elevations in urinary ammonia. Confirmation of the striking correlation between increased urinary ammonia and lowered neonatal ponderal index may afford a simple test for the identification of nutrient-related growth retardation.

Heterogeneity of pepsinogens in the urine of children.

The existence of a significant linear relationship between the concentration of chlorides and the activity of pepsinogen (PG) in the urine was ascertained in the case of full-term infants 3 days to 6 weeks of age. At the age of 4-6 weeks, a significant relationship was found between the urinary pepsinogen activity and the urinary creatinine concentration, and between the urinary pepsinogen activity in the urine and the urine osmolality. Immediately after birth, the Pg7 fraction of PG II in the urine was found in all cases and, at the age of 4-6 weeks, in 11% of cases. In regard to the time factor, the conspicuous drop in the occurrence of the Pg7 fraction corresponds to the new qualitative relationship between the pepsinogen activity in the urine and the creatinine concentration in the urine and between the former and the urine osmolality. In premature infants, the Pg7 fraction disappears more slowly. The spectrum of pepsinogens in the urine was examined in children suffering from various diseases. In a girl with lymphoma, we found the Pg7 fraction, but this finding was temporary only.