evaluation of Total and Conjugate bilirubin levels before and
Indian Journal of Public Health Research & Development, April-June 2018, Vol.9, No. 2 171 oxidation-reduction reactions. The predominant bilirubin
isomer in humans is IX-alpha (Z,Z), which, because of its lipophilic nature, can cross phospholipid membranes. In fetal life, this characteristic permits passage of bilirubin through the placenta into the maternal organism for excretion. Postpartum, this same characteristic enables passage of bilirubin across the blood-brain barrier, which is why clinicians worry about jaundice in newborns.
Bilirubin is transported in serum bound to albumin.
When the bilirubin-albumin complex reaches the liver, bilirubin is transferred into the hepatocytes, where it is bound to ligandin. The next step, which occurs inside the hepatocyte, is binding of bilirubin to glucuronic acid (conjugation) through the enzyme uridine diphosphate glucuronyl transferase (UDPGT). Both ligandin and UDPGT have very low concentrations and activities in the fetus, but activity increases greatly after birth.
However, during the time required to increase these enzyme activities, bilirubin accumulates. An important factor in this process is increased bilirubin production through the breakdown of fetal erythrocytes. Once conjugated in the liver, bilirubin is excreted into the bile and transported through the gut with food and further broken down, contributing to the color of stool.
Deconjugation and reabsorption of bilirubin can occur in the bowel, a process known as enterohepatic circulation.
Increased enterohepatic circulation is believed to contribute to prolonged jaundice in some newborns and may be partially responsible for human milk-associated jaundice.
In the absence of conjugates, the total bilirubin concentration in plasma is the sum of bilirubin bound to albumin plus a minimal amount of free bilirubin.
Bilirubin is excreted more slowly in newborns than in adults. Although no clinical tests can measure bilirubin uptake and conjugation by the liver, an elevated hour-specific total bilirubin value when bilirubin production is normal or decreasing is a sign of impaired or abnormally delayed bilirubin excretion. The differential diagnosis in this older age group differs markedly from that in newborns and young infants. Jaundice may be the presenting feature of life-threatening conditions such as fulminant liver failure, a prompt and logical evaluation is necessary to identify the more serious disorders that require urgent management. Bilirubin is a product of heme metabolism. Heme is converted in the reticuloendothelial (RE) system to biliverdin and then to bilirubin by heme oxygenase and biliverdin reductase,
respectively.In most cases, the elevation of serum-conjugated bilirubin is a biochemical manifestation of cholestasis, which is the pathologic reduction in bile formation or flow. It is a common problem that can be the presenting sign for many disorders. The challenge for the physician is to identify patients who need additional evaluation. The differential diagnosis for jaundice is age-specific the study aim is to compare Total Serum bilirubin (TSB) and Conjugate Serum Bilirubin (CSB) readings before and after phototherapy.
MATeRIAl ANd MeThOd
This study was conducted 50 Neonates from dec 2013 to December 2016 at the Department of paediatrics Sri Lakshmi Naryana Institute of Medical Sciences, Pondicherry. The institutional ethical committee was obtained. Participants Term and preterm neonates who had a birth weight 2000 g who were cared for in the outpatient clinic or being admitted to the NICU after delivery and requiring phototherapy were eligible to participate in the study. Infants who had previous phototherapy or exchange transfusion were excluded.
Written informed consent was obtained from parents.
Neonates receiving in-hospital phototherapy underwent measurements alongside routine Total and Conjugate Bilirubin before and after treatment. Phototherapy The need for the baseline phototherapy threshold is set at 20 mg/dL. For corrected gestational age below 38 weeks, the threshold was calculated as gestational age in weeks minus 20 (mg/dL). The threshold was further reduced by 2 mg/dL for a positive antiglobulin test and for each day below age 3 days. All neonates received 1 or more complete cycles of intermittent phototherapy, consisting of 3 consecutive 4-hour treatment/4-hour pause periods, giving a total light exposure of 12 hours. The need for an additional cycle was based on serum bilirubin levels, by using the decision criteria described above. Assessed total and conjugate Bilirubin levels (T&CSB) before and after phototherapy, Time points for measurement were scheduled according to clinical appraisal. Comparison of bilirubin levels before phototherapy was based on the last simultaneous pair of TSB and TCB before treatment. Measures after cessation of light exposure were categorized in groups of 24, 48, 72 hrs and 8th day before and after phototherapy.
Statistical Analysis: Only cases with information on date of birth, start and duration of phototherapy, and
172 Indian Journal of Public Health Research & Development, April-June 2018, Vol.9, No. 2 both TSB and TCB measurement before phototherapy
were included in this analysis.
Statistical analysis was done by Anova method using Microsoft
Excel and SPSS for windows version 11.5 (SPSS, Inc., Chicago). A p value P<0.005 considered as significant.
ReSulTS
Table.1: Total bilirubin and conjugate bilirubin levels and after phototherapy (Mean ± SD)
hours/days Total Bilirubin (mg/dl) Conjugate Bilirubin(mg/dl)
P value before
Phototherapy After
Phototherapy before
Phototherapy After Phototherapy
24 Hrs 15.6 ± 2.4 15.0 ± 2.2 10.3 ± 1.7 9.3 ±1.6 <0.001
72 Hrs 16.2 ± 2.3 12.3 ± 1.9 9.2 ± 1.5 0.8 ± 0.1 <0.001
8th Day 2.1 ± 0.3 --- 0.4 ± 0.08 --- <0.001
dISCuSSION
Clinical recognition and assessment of jaundice can be difficult. This is particularly, so in babies with darker skin tones. Once jaundice is recognised, there is uncertainty about when to treat, and there is widespread variation in the use of phototherapy and exchange transfusion. There is a need for more uniform, evidence-based practice and for consensus-evidence-based practice where such evidence is lacking. This guideline provides guidance regarding the recognition, assessment and treatment of neonatal jaundice. The advice is based on evidence where this is available and on consensus-based practice where it is not. In our study we found in neonates of 24hrs increased levels of total Bilirubin levels (15.6±2.4) and after 72 hrs highly increased levels (16.2±2.3). After photo therapy the total Bilirubin levels were decreased levels (15.0±2.2) after 24 hrs and we found after 72 hrs (12.3±1.9) (P<0.001) and conjugated Bilirubin levels were increased (10.3±1.7) in first 24 hrs highly increased (9.2±1.5) conjugate Bilirubin levels upto 72 hrs. After phototherapy conjugate Bilirubin levels were found to decreased (9.3±1.6) for 24 hrs and (0.8±0.1) (p<0.001) for 72 hrs. Both the parameters again assessed on 8th day after completion of final phototherapy, total bilirubin levels were decreased(2.1±0.3) and conjugate bilirubin levels were decreased(0.4±0.08) (p<0.001) levels were found in our study after 7th day total conjugated bilirubin levels were came down to normal after phototherapy. There are no good data to guide the clinician in dealing with the occasional infant who has a significant elevation of direct-reacting or conjugated bilirubin. Kernicterus has been described in term infants with TSB levels >20mg dl/1 (314 mmol l/1) but in whom,because of significant elevations in direct
bilirubin levels, the indirect bilirubin levels were well below 20 mg/dl6-7. There is some evidence that elevated direct bilirubin levels can decrease the infant’s albumin-binding capacity8 and it has been suggested, but not confirmed, that infants with the bronze baby syndrome might be at an increased risk of developing bilirubin encephalopathy8-9. As a general rule, when considering the use of phototherapy or exchange transfusion, the direct-reacting (or conjugated) bilirubin level should not be subtracted from the total. Infants with conjugated bilirubin levels >50% of the TSB require individual expert evaluation.
Hemolytic disease Infants with hemolytic disease are generally considered to be at a greater risk for the development of bilirubin encephalopathy than are nonhemolyzing infants with similar bilirubin levels10. Thus, exchange transfusion is recommended at lower levels for infants who have hemolytic disease. The use of intravenous gamma-globulin has been shown, in several randomized controlled trials, to reduce the need for exchange transfusions in both Rh and ABO hemolytic disease.
Phototherapy in most infant’s p35 weeks of gestation is generally used in a prophylactic mode the goal being to prevent further elevation of the TSB. The most effective irradiance is delivered by a light source (such as special blue fluorescent lamps or LED systems) that will deliver irradiance predominately in the 430 to 490 nm band11-12. Detailed information on phototherapy use can be found in a recent technical report12. If, in spite of phototherapy, the TSB continues to rise, either the irradiance can be increased by bringing the phototherapy lamp closer to the baby (except when halogen or tungsten lights are used) or
Indian Journal of Public Health Research & Development, April-June 2018, Vol.9, No. 2 173 by increasing the body surface area of the infant exposed
to phototherapy (by placing a light source beneath the infant and reflecting material around the incubator or radiant warmer bed). Because there is significant variation in the irradiance measurements provided by commercial radiometers12-13, it is difficult to recommend a specific irradiance level. Nevertheless, when possible, clinicians should use the radiometer recommended by the manufacturer of the phototherapy system and provide sufficient irradiance to prevent an increase in the TSB14-16. Jaundice attributable to physiological immaturity of neonates to handle increased bilirubin production is termed as ‘physiological jaundice’. Visible jaundice usually appears between 24 to 72 hours of age.
Biochemically TSB level usually rises in term infants to a peak level of 12 to 15 mg/dL by 3 days of age and then falls. In preterm infants, the peak level occurs on the 3 to 7 days of age and TSB can rise over 15 mg/dL17. Babies with serum bilirubin ≥20 mg/dl and those who require exchange transfusion should kept under follow-up in the high- risk clinic for neuro-developmental outcome.
CONCluSION
Infants having T and CSB levels were decreased in phototherapy. Photo therapy is highly effective and It acts by converting insoluble bilirubin (unconjugated) into soluble isomers that can be excreted in urine and feces. The adequacy of breastfeeding should be assessed by history, observation of breastfeeding session, and degree of weight loss. We recommend at lower bilirubin levels found after phototherapy, although our thresholds are similar to the other studies recommendations. A large sample size is required for further studies.
Conflict of Interest: Nil
Source of Funding: Diagnostic kits are provided by institution as on complimentary basis for research.
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