Hyperbilirubinemia with urinary tract infection in infants younger than eight weeks old.

BACKGROUND: Hyperbilirubinemia is one of the most common causes for hospital admission in neonatal infants. Previous studies have found that jaundice may be one of the initial symptoms related to urinary tract infection (UTI) in infants. This study is to evaluate the incidence and related factors of neonatal infants with the initial presentation of hyperbilirubinemia and final diagnosis of UTI in a tertiary teaching hospital. METHODS: We retrospectively investigated the medical records of admitted infants younger than 8 weeks old with hyperbilirubinemia between January and December 2008. The jaundiced infants having tests of urinalysis were enrolled into our study and grouped into UTI or no UTI group according to the findings of urinary culture. RESULTS: A total of 217 neonatal jaundiced infants were enrolled. Among them, 12 cases (5.5%) were grouped into the UTI group, and the most common cultured bacterium from their urine was Escherichia coli. There was no significant difference in the babies' birth weight, maternal conditions, or total bilirubin levels between the two groups. There was also no significant difference between the two groups in their admission age (9.7 ± 13.5 days vs. 6.1 ± 6.7 days in UTI and no UTI groups, respectively) or the ratio of outpatients (50% vs. 25% in UTI and no UTI groups, respectively) (p > 0.05). The cases of UTI group had significantly lower hemoglobin (15.2 ± 2.7 g/dL vs. 17.2 ± 2.3 g/dL, respectively) and higher formula feeding rate (8.3% vs. 2.9%, respectively) than the no UTI group (p < 0.05). CONCLUSION: The incidence of UTI in the admitted infants with hyperbilirubinemia was as high as approximately 5.5%. The most common cultured bacterium in urine was E coli. Therefore, performing urinary tests to exclude the possibility of coincidental UTI may be necessary for admitted jaundiced infants younger than 8 weeks old.

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 micromol/mmol creatinine), total urinary bile acid concentrations gradually decreased to less than 20 micromol/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, 1beta-hydroxylated bile acids (mainly 1beta,3alpha,7alpha,12alpha-tetrahydroxy-5beta-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 1beta-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 1beta,3alpha,7alpha,12alpha-tetrahydroxy-5beta-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.

Neonatal hyperbilirubinemia and its association with thyroid hormone levels and urinary iodine excretion.

OBJECTIVE: To investigate, if, urinary iodine contents as a marker of iodine deficiency and hypothyroidism are associated with the incidence of neonatal hyperbilirubinemia. METHODS: One hundred neonates with total serum bilirubin > or = 15 mg/dl and with no known cause of jaundice were included in the study as a jaundice group. An equal number (n = 100) of non-jaundiced neonates (bilirubin < or = 14.9 mg/dl) with matching for age, gestation period and weight were enrolled in the study as a control group. RESULTS: Thirteen neonates (13%) in the study group had urinary iodine levels < 100 mg/dl as against only 2 (2%) in the control group (p < 0.05). Thirty-four (34/200-17%) neonates i.e. 17 each in the study and control groups had serum TSH > 5 mU/ml and hence an indirect indicator of iodine deficiency in the study population. The mean serum levels of total T3, T4 and TSH in the study neonates were 1.52 +/- 1.23 ng/ml, 15.8 +/- 12.0 micrograms/dl & 3.13 +/- 3.0 mU/ml respectively and did not differ significantly from the mean levels in the control group. Only one neonate in the study group had serum TSH > 20 mU/ml which was suggestive of hypothyroidism, but had normal T3 & T4. Seven neonates in the study group and 8 in the control group had low T4. There was no significant correlation between the maternal and neonatal urine iodine levels, thyroid functions and the bilirubin levels (p > 0.01). CONCLUSION: The jaundiced babies had lower urine oidine levels than the control population. Since, there was no significant difference in the levels of the thyroid hormones, no cause and effect relationship could be inferred between iodine deficiency and jaundice.

Investigation of prolonged neonatal jaundice.

UNLABELLED: Jaundice persisting beyond 14 d of age (prolonged jaundice) can be a sign of serious underlying liver disease. Protocols for investigating prolonged jaundice vary in complexity and the yield from screening has not been assessed. In order to address these issues, we carried out a prospective study of term infants referred to our neonatal unit with prolonged jaundice over an 18 mo period. Infants were examined by a paediatrician and had the following investigations: a total and conjugated serum bilirubin, liver function tests, full blood count, packed cell volume, group and Coombs' test, thyroid function tests, glucose-6-phosphate dehydrogenase levels and urine for culture. One-hundred-and-fifty-four infants were referred with prolonged jaundice out of 7,139 live births during the study period. Nine infants were referred to other paediatric specialties. One infant had a conjugated hyperbilirubinaemia, giving an incidence of conjugated hyperbilirubinaemia of 0.14 per 1,000 live births. Diagnoses included: giant cell hepatitis (n = 1), hepatoblastoma (n = 1), trisomy 9p (n = 1), urinary tract infections (n = 2), glucose-6-phosphate dehydrogenase deficiency (n = 3) and failure to regain birthweight (n = 1). CONCLUSIONS: In conclusion, a large number of infants referred to hospital for prolonged jaundice screening had detectable problems. The number of investigations may safely be reduced to: a total and conjugated bilirubin, packed cell volume, glucose-6-phosphate dehydrogenase level (where appropriate), a urine for culture and inspection of a recent stool sample for bile pigmentation. Clinical examination by a paediatrician has a vital role in the screening process.

Renal function in full-term neonates with hyperbilirubinemia.

The purpose of this study was to investigate the effect of unconjugated hyperbilirubinemia on endogenous creatinine clearance and urinary excretion of sodium, phosphorus, lysozyme, and amino acids in full-term infants. Thirty-seven healthy, breast-fed newborns who were not exposed to phototherapy were studied on their third to fifth day of life. Twenty had neonatal hyperbilirubinemia with a mean indirect bilirubin value of 16.4 mg/dl, whereas 17 who were used as controls had a mean indirect bilirubin value of 7.8 mg/dl. Urine was collected, and samples were taken for examination of creatinine, lysozyme, sodium, and phosphorus concentration. Urinary sediment, glucose, and amino acid levels were also measured. Serum total and direct bilirubin, creatinine, sodium, and phosphorus measurements were taken at the beginning of urine collection. Calculations were made for creatinine clearance, fractional excretion of sodium (FENa), and tubular reabsorption of renal phosphate per deciliter glomerular filtrate (TP/GFR). The means (+/-1 SD) of creatinine clearance, FENa, and TP/GFR were 27.0 +/- 14.2 ml/min/1.73 m2, 0.53% +/- 0.49%, and 5.72 +/- 1.16 mg/dl GF, respectively, in the hyperbilirubinemic group compared with 21.1 +/- 9.4 ml/min/1.73 m2, 0.4% +/- 0.47%, and 6.01 +/- 0.51 mg/dl GF, respectively, in the controls. No statistically significant differences were found between the groups for any of the examined parameters of either glomerular or tubular function. Neonatal hyperbilirubinemia < 20.8 mg/dl has no detrimental effect on renal function of healthy, breast-fed, full-term newborns, and no modification in the approach regarding renal function is necessary in these babies.

Urinary enzyme changes in newborns with unconjugated hyperbilirubinemia.

Various changes in renal function caused by unconjugated hyperbilirubinemia in newborns have been suggested in previous reports. Disclosing an injury in renal tubulus epithelium is feasible by measurement of urinary enzymes. Thus, renal function tests and urinary enzymes in 25 terms newborns with unconjugated hyperbilirubinemia were evaluated before and after phototherapy. Ten healthy term newborns without hyperbilirubinemia formed the control group. Mean values of the variables obtained before and after phototherapy in the study group and in the controls were, respectively: urine osmolality (osm/kg H2O): 0.147 +/- 0.009, 0.174 +/- 0.011, and 0.153 +/- 0.018; endogenous creatinine clearance (mL/min per 1.73 m2): 45.7 +/- 2.15, 46.0 +/- 1.6 and 46.7 +/- 3.9; fractional excretion of sodium (%): 1.27 +/- 0.30, 0.79 +/- 0.19 and 1.24 +/- 0.07; tubular phosphorus reabsorption (%): 85.8 +/- 3.3, 87.8 +/- 2.8 and 86.6 +/- 1.7; urinary N-acetyl-beta-D glucosaminidase/creatinine (IU/mg): 0.617 +/- 0.226, 0.574 +/- 0.214 and 0.619 +/- 0.210; fractional excretion of alkaline phosphatase (%): 0.422 +/- 0.103, 1.001 +/- 0.374 and 0.596 +/- 0.201; fractional excretion of lactic dehydrogenase (LDH; %): 0.102 +/- 0.019, 0.121 +/- 0.023 and 0.119 +/- 0.041; fractional excretion of AST (%): 0.433 +/- 0.127, 0.530 +/- 0.113 and 0.502 +/- 0.074; fractional excretion of alanine aminotransferase (ALT; %) 0.856 +/- 0.413, 1.619 +/- 1.076 and 1.066 +/- 0.366. No significant difference was found between these values before and after phototherapy in the study group, or between the values before phototherapy in hyperbilirubinemic neonates and in the control group. In conclusion, unconjugated hyperbilirubinemia up to a serum level of 18.4 mg/dL in term neonates does not seem to result in injury of normal tubulus epithelium as shown by urinary enzyme levels.

Urinary D-glucaric acid excretion in idiopathic neonatal jaundice.

OBJECTIVE: To determine the extent to which immaturity of hepatic microsomal enzyme activity might contribute to physiological jaundice. METHODS: Urinary excretion of D-glucaric acid, expressed in mumol glucaric acid/ mmol creatinine, was measured in 122 Chinese full-term healthy newborn babies during the first five days of life. Among the 122 babies, 22 were born by normal spontaneous delivery at the British Military Hospital and 100 were born by caesarean section at the Prince of Wales Hospital. RESULTS: In all babies the excretion of D-glucaric acid was highest on the first day of life and gradually decreased over the following 5 days. Five babies born by spontaneous delivery and six babies born by caesarean section developed jaundice during the study period. The excretion of D-glucaric acid in the jaundiced babies was significantly higher on the first two days than in the non-jaundiced babies. CONCLUSIONS: D-glucaric acid excretion was increased in jaundiced newborn babies in the first few days of life. This finding does not indicate less liver microsomal enzyme activity in the jaundiced babies compared to those non-jaundiced. On the contrary, it suggests that in idiopathic neonatal jaundice compensatory mechanism might operate from a very early stage to excrete a higher bilirubin load that might be present through haemolysis.

Quantitative analysis of 1-naphthol in urine of neonates exposed to mothballs: the value in infants with unexplained anaemia.

In Nigeria, severe NNJ is common in babies exposed to mothballs and other icterogenic agents. High-performance liquid chromatographic (HPLC) method was employed for quantitative analysis of 1 and 2-naphtol in the urine of 50 neonates aged one to 19 days. Five of the 25 babies who had a history of exposure to mothballs, and none of the babies without a history of exposure had 1-naphtol in their urine. The value of 1-naphtol ranged between 0.75 and 11.69 micrograms/ml with mean of 5 +/- 5 micrograms/ml. The overall correlation coefficient (r) between bilirubin values and 1-naphtol was 0.1 while it was 1 in the three G-6-PD deficient infants. The procedure will be very useful in the evaluation of infants with unexplained NNJ, anaemia, acute haemolytic jaundice and haemoglobinuria if naphthalene poisoning is suspected.

Renal function in neonatal hyperbilirubinemia.

A total of 75 jaundiced infants with gestational ages ranging from 37 to 42 weeks were studied during the first 10 days of age to evaluate renal function by measuring endogenous creatinine clearance (Ccr), fractional excretion of N-acetyl-beta-D-glucosaminidase (NAG) to creatinine, fractional excretion of sodium (FENa) and urine osmolality. All jaundiced infants were divided into two groups. Group 1 infants (n = 35) had total serum bilirubin levels ranging between 21 and 39.6 mg/dl (mean 27.2). Exchange transfusions were performed in all group 1 infants at the time of the initial study. Group 2 infants (n = 40), whose total serum bilirubin levels ranged between 12.3 and 20 mg/dl (mean 16.4), received phototherapy, except for 2. Conjugated bilirubin levels were less than 1.0 mg/dl in all these infants. Results were compared with 25 untreated control infants with corresponding gestational and postnatal ages. Follow-up studies were done in 27 of the 35 group 1 infants and in 32 of the 40 group 2 infants prior to hospital discharge, when total serum bilirubin levels had decreased to less than 10 mg/dl. Ccr, fractional excretion of NAG to creatinine, FENa and urine osmolality of group 1 infants were statistically significantly different when compared to those of group 2 and the control infants. The measured parameters in the post-treatment follow-up study of group 1 infants returned to near-normal levels when total serum bilirubin levels became normal. However, no significant differences were seen between group 2 and the control infants in any of the measured parameters.(ABSTRACT TRUNCATED AT 250 WORDS)

Late referral for biliary atresia--missed opportunities for effective surgery.

To assess whether clinicopathological features other than the age at operation influence prognosis after surgery for extrahepatic biliary atresia (EHBA) and to determine whether the age at referral has fallen since a previous survey, 50 consecutive cases with EHBA referred between February, 1985, and December, 1987, were reviewed. Liver or spleen size, liver function tests, or histological appearance of liver biopsy specimen before surgery were not predictive of outcome. The jaundice cleared up in 12 of 14 children operated on by age 8 weeks, but in only 13 of 36 operated on later. In 41 referral was delayed. All 25 children in whom surgery was successful are alive and well, while 13 of 25 with unsuccessful surgery have died, at a median age of 1 year. To improve the prognosis of infants with EHBA parents and health staff need a better awareness of the early clinical features of EHBA and of the necessity for prompt referral. Liver disease should be suspected in any infant jaundiced after 14 days of age.

[Disorders of acid-base equilibrium in neonatal physiologic jaundice]. / Anomalie dell'equilibrio acido-base nell'ittero fisiologico neonatale.

38 healthy term jaundiced infants were tested. On 3rd day of life we obtained a blood sample from a peripheric vein to determine red blood cells and reticulocytes count, serum albumin, total, conjugated and unconjugate bilirubin. On 3rd, 4th, 5th, 6th day of life 4 standard heparinized microtubes were filled after lancing the heel: 2 microtubes to estimate the mean value of total bilirubin, 2 for the mean value of pH. The urine pH was evaluated every morning. The results of total bilirubin (T.B.), pH, pCO2 and Base Deficit were analyzed using T-test. All tested infants were free-bilirubin jaundiced. Infants treated with phototherapy had a T.B. ranging from 15.2 mg/dl on 3rd day of life to 10.5 mg/dl on 6th, while in controlled infants T.B. never exceeded 10 mg/dl. In treated infants the pH was higher than in controlled ones: p was less than 0.001 on 4th day, less than 0.005 on 5th day and less than 0.001 on 6th day. In both groups the urine pH ranged from 5 to 6.5 every day. The marked increase in respiratory rate during phototherapy is a well known side effect. But a significant decrease in pCO2 was present before starting phototherapy. A mixed disturbance of acid-base balance could be suspected: an already existing mild metabolic acidosis in phototherapy group with respiratory alkalosis due to anion gap variety, with unknown determining causes. We relate the initial metabolic acidosis to the depressed oxidative phosphorylation (with lactic acidosis) in the neonatal liver.(ABSTRACT TRUNCATED AT 250 WORDS)

Kallikrein and kininase activities excretion in newborns affected by jaundice.

In a homogeneous group of 30 newborns, aging between 10 hours--10 days, and affected by jaundice, urinary kallikrein and kininase activities were determined. The variable considered were: sex, time of life, weight and gestational age. Urinary samples were taken at the beginning and at the end of phototherapy.

Urinary excretion of an isomer of bilirubin during phototherapy.

Lumirubin, a water-soluble photoproduct of bilirubin formed in vivo during phototherapy, is excreted in the urine. In premature infants with little or no bilirubin conjugating activity, lumirubin is the principal yellow pigment found in the urine during phototherapy. The clearance rate of lumirubin in nine premature infants varied from 0.05 to 0.65 ml/min and increased with postconceptional age in parallel with increased creatinine clearance rate. The amount of lumirubin excreted per 24 h was estimated to be from 0.2 to 9.4 mg with a mean of 3.2 mg. The urinary excretion of lumirubin is a significant pathway for pigment elimination during phototherapy.