Serum bilirubin neonatal

In adults, yellowing of the skin or jaundice usually occur when serum bilirubin is higher than 50 pmol/L. In neonates, a bilirubin level in... 

Jaundice indicates that the total serum bilirubin is raised above 50 pmol/L in adults or 80 pmolfL in neonates. 

Graziani, L.J., Mitchell, D.G., Komhauser, M., Pidcock, F.S., Merton, D.A., Stanley, C., McKee, L. (1992). Neurodevelopment of preterm infants neonatal neurosonographic and serum bilirubin studies. Pediatrics 89 229-34. 

Special illuminating conditions need to be considered during the blue-lamp phototherapy for neonatal jaundice (hyperbilirubinemia). In practice, the neonate is placed under a blue fluorescent lamp having a at about 450 nm, at an irradiance level between 4 and 6 pW/cm. This procedure is very effective in decreasing serum bilirubin concentrations. The high irradiance levels used in phototherapy may also enhance the degradation of drugs in concurrent use. 

Bilirubin - an apolar, water-insoluble lipophile substance - is potentially toxic. It is bound to serum albumin and transported to the sinusoidal membrane of the liver cell as a bilirubin-albumin complex, (s. fig. 3.1) The binding capacity of albumin is exceeded only at a serum bilirubin concentration of >4—5 mg/dl. In the case of decreased albumin binding (e. g. in acidosis) or oversaturated binding capacity, there is a danger of toxic cell damage due to the diffusion of unbound bilirubin into the cells (in some cases accompanied by kernicterus). Neonates and premature babies are at particular risk because of their immature blood-cerebrospinal fluid barrier. Albumin-bound bilirubin can function as an antioxidant to intercept free radicals and/or O2 radicals. (93) (s. tab. 3.25)... 

In about 90% of all neonates, jaundice occurs after the first 2-5 days of life and rarely exceeds 6 mg/dl serum bilirubin. In premature infants, bilirubin levels can rise to 10-12 mg/dl. The cause is related to a number of factors .) reinforced degradation of haemoglobin as a result of the short erythrocyte survival span of 70-90 days (120 days in adults), (2.) reduction in cellular transport proteins, above all ligandin, (i.) deficiency of uri-dyltransferase and glucuronosyltransferase, and (4.) increasing intestinal absorption of meconium bilirubin. 

A critical review of the available data on the risk of hexachlorophene bathing or other kinds of hexachlorophene use in neonatal skin care has suggested that there is ample evidence of the toxic potential of this disinfectant. It is absolutely contraindicated in infants with a low birth weight (under 2000 g), excoriated areas of the skin, and raised serum bilirubin. The use of a dusting powder with a maximal concentration of 0.3-0.5% seems to be connected with a lower risk of toxicity, but there was marked absorption of hexachlorophene after the application of 0.33% hexachlorophene dusting powder (20) and further information is needed about the pharmacokinetics of hexachlorophene in neonates. 

Brett, E.M., Boeckx, R.L. and Hicks, J.M. (1981). The problem of bilirubin interference in the analyses of serum from neonates. Clin. Chem. 27, 1607, Abstr. 214. 

Kodak Ektachem clinical chemistry slides for the analysis of neonatal serum bilirubin. Clin. Chem. 28, 1552, Abstr. 16. 

E367 Mullon, C.J.-P. and Langer, R. (1987). Determination of conjugated and total bilirubin in serum of neonates, with use of bilirubin oxidase. Clin. Chem. 33, 1822-1825. 

The physiological jaundice of the newborn rarely produces serum bilirubin values greater than 5mg/dL (85 Xmol/L). Distinguishing this naturally occurring phenomenon from other conditions that produce neonatal hyperbilirubinemia may be difficult, and the chronological course of the hyperbilirubinemia is important. 

Normal neonates are frequently hyperbilirubinemic (Table 29-2). Birth interrupts normal placental elimination of pigment, and the immature liver of the neonate must take over. Normally serum bilirubin levels rise on the first day of life, reaching a maximum (rarely greater than 10 mg/dL) by the third or fourth day. This type is mostly unconjugated. If the placenta is functioning normally, jaundice will not be present at birth. If jaundice is present at birth, a cause other than hepatic immaturity must be sought. 

In a second example, a small blood filter containing immobilized bilirubin oxidase to reduce serum bilirubin concentrations was developed for potential application in the treatment of neonatal jaundice. 

Barbiturates such as phenobarbital, amobarbital, and butabarbital induce glucuronyl transferase, an enzyme obligatory in bilirubin metabolism. Thus, they may be used in patients with chronic cholestasis. Phenobarbital is also used for lowering serum bilirubin in the neonate. 

Fractionation of serum bilirubin conjugates in the exploration of the pathogenesis of significant neonatal bilirubinemia associated with glucose-6-phosphate dehydrogenase deficiency. 

An infant with glucose-6-phosphate dehydrogenase (G6PD) deficiency developed severe hyperbilirubinemia and transient bilirubin encephalopathy that the reporting authors indicated as being likely related to consumption of Chinese herbs, including coptis. The peak serum bilirubin was 562 pmol/1 (Yeo and Tan 1996). A review of G6PD deficiency indicated that this condition is a potential source of severe neonatal hyperbilirubinemia and kernicterus (Kaplan and Hammerman 2002). 

Ethanol has been used recently in obstetrics and in neonatal pediatrics for three principal therapeutic reasons prevention of premature labor, reduction of anticipated neonatal hyperbilirubinemia, and parenteral nutrition. The use of ethanol in the prevention of premature labor is based on its inhibitory effect on uterine activity in early labor it presumably acts by inhibiting the release of oxytocin from the neurohypophysis (Fuchs l., 1967). Ethanol when administered to near-term or term pregnant patients has been shown to reduce hyperbilirubinemia in the neonates (Waltman t l., 1969). Its use has been suggested, therefore, to reduce anticipated hyperbilirubinemia in those neonates in which high serum bilirubin may be expected, such as premature infants. The reduction of bilirubin after ethanol administration is probably due to increased glucuronidation of bilirubin since ethanol has been demonstrated to stimulate a variety of microsomal enzymes in both animals and man (Rubin t l., 1968). 

Liver Ibuprofen has been hnked with hyperbilirubinemia in preterm neonates. In a retrospective comparison of 418 preterm infants receiving ibuprofen prophylaxis of patent ductus arteriosus and 288 infants who were not treated with ibuprofen those who received ibuprofen had a higher peak serum bilirubin concentration, needed more phototherapy, and had a longer duration of phototherapy [43. ... 

There is considerable variation in the protein binding among the cephalosporins. Drugs like ceftriaxone that have extensive protein binding (85-95%) may displace bilirubin from serum albumin. Consequently, ceftriaxone may increase the risk of kemicterus in jaundiced neonates. 

Glucuronidation of many substrates is low or undetectable in fetal mammalian tissues but increases with age. The rate of development is dependent upon the species, tissue, and substrate. The inability of newborns of most mammals, except the rat, to form glucuronides is associated with deficiencies in glucuronosyl transferase activity and the cofactor, UDPGA. The blood serum of newborn babies may contain pregnandiol, which is an inhibitor of glucuronide formation. Suppressed glucuroniation of bilirubin in newborns can result in neonatal jaundice. 

Kernicterus (that may result from hyperbihrubinaemia) manifests as various neurological deficits, seizures, abnormal reflexes and eye movements. The blood-brain barrier of the neonate is not fully developed and unconjugated bilirubin can freely pass into the brain interstitium. Some medications, such as the antibiotic co-trimoxazole (a combination of trimethoprim and sulphamethoxazole) may induce this disorder in the infant, either when taken by the mother or if given directly to the infant, due to a displacement of bilirubin from binding sites on serum albumin, thus allowing unconjugated bihrubin to pass across the blood-brain barrier. 

A serum total bilirubin level in excess of 50 pmol/L can produce clinical jaundice in adults. In neonates a level of 80 pmol/L or above... 

E569 Sonntag, O. and Biittner, J. (1989). Determination of bilirubin in neonatal serum using the Ektachem 700. J. Clin. Chem. Clin. Biochem. 27, 763-764, Abstr. VI 72. 

Karmen, A., Lent, R. and Chang, E.S. (1982). Measurement of bilirubin in neonatal serum with the Ames Seralyzer. Clin. Chem. 28, 1552-1553, Abstr. 19. Knopp, P.R. (1982). Erfahrungen mit der Trockenchemie im Praxislabor. No-tabene Medici 8,633-634. 

The complex formation of bilirubin with human serum albumin was investigated by Sinclair et al. 72) using 347 nm ruby laser flash photolysis technique. A high bilirubin level is found in new bom babies who suffer from jaundice (neonatal hyperbilirubinemia)73). Phototherapy has been found to be suitable for lowering the bilirubin level. In order to understand the mechanism of the phototherapy, investigation into the photophysics of bilirubin is essential. It is strongly bound to human serum albumin, lipids and cell membranes. 

In Crigler-Najjar syndrome type /activity of hepatic bilirubin UDP-glucuronyltransferase is undetectable and bilirubin conjugates are absent from the serum, bile, and urine, but biliary secretion of sulfobromophthalein and indocyanine green is normal. The disease is apparent shortly after birth, kemicterus develops, and death commonly occurs during the neonatal period. The effectiveness of phototherapy is often transient. The enzyme is not inducible by phenobarbital. This autosomal recessive defect occurs in all races. The Gunn strain of Wister rats has a similar genetic defect and has been used to study the syndrome. 

The neonate is at risk for kemicterus if the serum unconjugated bilirubin level is higher than 17 mg/dL. Kemicterus is characterized by yellow staining of clusters of neuronal cell bodies in the basal ganglia, cerebellum, and brain stem, leading to motor and cognitive deficits or death. Immaturity and f)erhaps hypoxia make the blood-brain barrier permeable to bilirubin and contribute to the likelihood of kemictems. The biochemical basis of bilirubin encephalopathy is due to many causes inhibition of RNA and protein synthesis, carbohydrate metabolism (both cAMP-mediated and Ca " -activated), phospholipid-dependent protein kinases, enzymes involved in the electron transport system, and impaired nerve conduction. 

---