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 Table of Contents  
ORIGINAL ARTICLE
Year : 2018  |  Volume : 6  |  Issue : 2  |  Page : 218-222

First day serum bilirubin level, as predictor of significant hyperbilirubinemia in neonates


Department of Paediatrics, Kurji Holy Family Hospital, Patna, Bihar, India

Date of Web Publication27-Dec-2018

Correspondence Address:
Dr. Jehangir Bhat Allam
Department of Paediatrics, Kurji Holy Family Hospital, Patna, Bihar
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/amhs.amhs_42_18

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  Abstract 


Background: Age-specific (24 ± 6 h) predictive value of total serum bilirubin (TSB) ≤6 mg/dl in developing significant hyperbilirubinemia in infants. Materials and Methods: A prospective observational study on 200 term neonates having birth weight ≥2500 g and gestational age ≥37 weeks. Blood was collected from the venous site. The blood sample of all infants was sent for grouping and TSB estimation. Babies were clinically examined every day for jaundice. Whenever jaundice was clinically noticed to be >10 mg/dl, bilirubin estimation was repeated immediately and then every day until 5 days of age, and the highest reading was recorded as the peak TSB. Results: Significant hyperbilirubinemia (>17 mg/dl) was present in 13% of cases. At 24 ± 6 h, TSB >6 mg/dl was present in 47 cases and 26 of these developed hyperbilirubinemia (≥17 mg/dl), and TSB ≤6 mg/dl was present in 153 cases and two of them developed significant hyperbilirubinemia. The incidence of hyperbilirubinemia in babies whose mothers received oxytocin and those whose mothers did not receive oxytocin was 19.6% and 8.2%, respectively. The difference was highly significant. The mean values of TSB at 24 ± 6 h in oxytocin used and oxytocin not used groups were 3.94 ± 2.15 mg/dl and 3.36 ± 1.91 mg/dl, respectively, the difference was statistically significant; however, the mean values of peak TSB in oxytocin used and not used groups were 12.78 ± 4.28 mg/dl and 12.03 ± 3.42 mg/dl, respectively, which were statistically not significant. Conclusion: The incidence of significant hyperbilirubinemia in healthy babies is 13%. The use of oxytocin increased its incidence. TSB at 24 ± 6 h ≤6 mg/dl has a high predictive value in identifying those infants who are unlikely to develop subsequent hyperbilirubinemia. This study, thus, will help to discharge healthy term infants with TSB on 2nd day ≤6 mg/dl.

Keywords: First-day serum bilirubin level, neonatal hyperbilirubinemia, oxytocin-induced hyperbilirubinemia, significant hyperbilirubinemia


How to cite this article:
Allam JB, Kumar S, Kurmi R, Ara R, Kumar AM. First day serum bilirubin level, as predictor of significant hyperbilirubinemia in neonates. Arch Med Health Sci 2018;6:218-22

How to cite this URL:
Allam JB, Kumar S, Kurmi R, Ara R, Kumar AM. First day serum bilirubin level, as predictor of significant hyperbilirubinemia in neonates. Arch Med Health Sci [serial online] 2018 [cited 2019 Jan 16];6:218-22. Available from: http://www.amhsjournal.org/text.asp?2018/6/2/218/248665




  Introduction Top


Hyperbilirubinemia is a common and benign problem in neonates, and it is the most common cause of readmission after hospital discharge. Almost all newborn infants have a serum or plasma total bilirubin (TB) level >1 mg/dL in contrast to normal adults in whom the normal TB level is <1 mg/Dl.

Approximately 85% of term neonates and most of the preterm neonates develop jaundice during the 1st week. A significant hyperbilirubinemia occurs in about 5%–10% of healthy term neonates.[1] Physiological jaundice usually appears on the 2nd–3rd day, peaking between the 5th and 7th days of life. Jaundice may appear at birth or may appear any time during neonatal period depending on the cause.[2] Since we know hyperbilirubinemia has a deleterious effect such as kernicterus, choreoathetoid cerebral palsy, hearing impairment, and cognitive impairment if not treated at the time. Hence, meticulous screening of newborn is required to detect hyperbilirubinemia. Since the peak bilirubin level typically occurs at 72–96 h, after healthy newborns are discharged from their birth hospital, the follow-up is essential. Infants discharged before 72 h should be seen within the next 2 days. Infants at lower gestational ages or who have other risk factors should be seen earlier.[2] This is practically impossible in underdeveloped and even in developing nations because of poverty, low education, and cultural practice. Here, comes the role of prediction of neonatal hyperbilirubinemia.

Why the need for prediction?

In spite of jaundice being such a common and usually benign problem of neonates, pediatricians always have concern about it because of two specific reasons.

First, the high level of unconjugated bilirubin is potentially neurotoxic and can lead to widespread brain damage, most severely to basal ganglia (kernicterus).

Second, conjugated bilirubin, though not neurotoxic, usually indicates some serious underlying pathology.

Hence, an ability to predict becomes very important and life-saving in the context of a developing country such as India and especially so in the state of Bihar, where costly investigations and regular follow-up are beyond the reach of the vast majority.

Hence, this study has been proposed to help the doctors in the peripheral centers so that they can able to make a decision regarding the discharge of otherwise healthy neonates from their center.


  Materials and Methods Top


This prospective hospital-based study was conducted in the Department of Pediatrics and Neonatology, Kurji Holy Family Hospital (KHFH), Patna, Bihar, from January 17, 2014 to November 30, 2015. A total of 200 newborns, fulfilling the predefined inclusion criteria, delivered in our hospital were studied. Proper ethical and scientific clearance was taken from the concerned hospital department. Proper consent was taken from parents of babies after explaining the risks and benefits of neonatal jaundice, phototherapy, and blood sampling.

Inclusion criteria

  1. Gestational age ≥37 weeks (based on the last menstrual period)
  2. The absence of major congenital malformations
  3. Residing at Patna or nearby whose parents agree to come for follow-up
  4. Infants of Rh-negative mother would be included only if they are also Rh-negative.


Exclusion criteria

  1. Preterm (≤37 weeks) and postterm (≥42 weeks) neonates
  2. Presence of significant illness, (i.e., sepsis and hypothyroidism)
  3. Rh incompatibility
  4. ABO incompatibility
  5. Newborns with obvious life-threatening congenital malformation (trachea-esophageal fistula and anorectal malformation)
  6. Babies with conjugated hyperbilirubinemia.


All babies delivered in KHFH were examined, and a detailed antenatal and postnatal history was taken. Cases were selected if they fulfilled all the criteria set out above. The informed consent was taken from the parents, and blood was collected from the venous site. The blood sample of the mother was simultaneously collected and sent for blood grouping if it was not known from before. The blood sample of the infant was sent for grouping and total serum bilirubin (TSB) estimation.

All babies were breastfeed as soon as possible after birth. As per discharge policy, KHFH healthy vaginally delivering mothers were discharged the next day. Hence, parents were instructed to bring their neonates for clinical follow-up every day and to report as soon possible if they noticed yellowness of skin. However, in the case of mothers delivering by cesarean section, the neonates could be followed up clinically on a daily basis since patients were discharged only after 7 days. At 5 days of age, another venous sample was collected for TSB estimation.

Whenever jaundice was clinically noticed to be >10 mg/dl, bilirubin estimation was repeated immediately and then every day until 5 days of age, and the highest reading was recorded as peak TSB. Serum bilirubin >17 mg/dl was considered significant hyperbilirubinemia. Babies having significant hyperbilirubinemia were admitted to neonatal intensive care unit for treatment (phototherapy). Clinical assessment of jaundice was done according to Kramer's Rule which states: If on clinical examination we found jaundice in the Face and neck only – TSB >5 mg/dl, Jaundice on chest (upto umbilicus and back – TSB between 5 and 10 mg/dl, Jaundice from umbilicus to knees-10-15, and jaundice in palms and soles – TSB >15 mg/dl).

Bilirubin estimation

The serum bilirubin was estimated by microbilirubin (Jendrassik and Grof method) for that venous blood is taken in four microcapillaries and centrifuged at the rate of 10000 rpm for 5 min. Bilirubin estimation is done spectrophotometrically using beam method (55 nm wavelength) (micro la-300, Merck, Netherland). Calibration of bilimeter is done daily using labetalol solution.

Statistical analysis

Data analysis was carried out using Microsoft Excel sheet. In case of quantitative data, mean, and standard deviation as well as range (minimum and maximum value) are computed. For qualitative data, independence of variable/attributes is tested with the help of Chi-square test. Sensitivity, specificity, positive and negative predictive value of different cut-points of 24 ± 6 h and serum bilirubin is obtained. For determining the statistical significance of each test, P < 0.05 was used.


  Results Top


The total number of cases studied was 200. Out of which, 181 cases were delivered by cesarean and 19 vaginally. One hundred and twenty-three (61.5%) were male, and 77 (38.5%) were female, oxytocin had been used in 102 (51%) cases.

The incidence of clinical jaundice was 56%. A significant hyperbilirubinemia (>17 mg/dl) was present in 13% of cases. At 24 ± 6 h, TSB >6 mg/dl was present in 47 cases and 26 of these developed hyperbilirubinemia (≥17 mg/dl) and TSB ≤6 mg/dl was present in 153 cases and 2 of them developed significant hyperbilirubinemia. The incidence of hyperbilirubinemia in babies whose mothers received oxytocin and those whose mothers did not receive oxytocin was 19.6% and 8.2%, respectively, and the difference was highly significant. The mean values of TSB at 24 ± 6 h in oxytocin used and oxytocin not used groups were 3.94 ± 2.15 mg/dl and 3.36 ± 1.91 mg/dl, respectively, the difference was statistically significant; however, the mean values of peak TSB in oxytocin used and not used groups were 12.78 ± 4.28 mg/dl and 12.03 ± 3.42 mg/dl, respectively, which were statistically not significant.


  Discussion Top


Neonatal jaundice is a very common occurrence and poses a therapeutic dilemma to the pediatrician. As such, it is highly desirable to have a parameter to predict which babies are subsequently going to develop a significant level of bilirubinemia. The present study was designed to investigate whether a TSB level ≤6 mg/dl at 24 ± 6 h can predict whether children will or will not develop significant hyperbilirubinemia (≥17 mg/dl) and hence can be safely discharged.

In this study, cesarean section was the prominent mode of delivery. Cesarean deliveries accounted for 90.5% of the study group, and vaginal deliveries accounted for 9.5%. Such a significantly high incidence of cesarean deliveries is because of the design of the study. The attrition rate (i.e., cases who were lost to follow-up and did not report on the 5th day) was quite high (= 20%). All of these cases, which were lost to follow-up, were accounted for by vaginal deliveries. This led to an increased percentage of cesarean deliveries in the final list.

Oxytocin was used in a significant proportion of the deliveries (= 51%). It was used in 47.5% of the cesarean deliveries and in 84.22% of vaginal deliveries. This was in accordance with the management policies of the labor room unit.

[Table 1] shows the percentage of cases who developed clinical jaundice and cases who developed significant hyperbilirubinemia (i.e., peak TSB ≥17 mg/dl).
Table 1: Incidence of clinical jaundice and significant hyperbilirubinemia

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Clinical jaundice was noticed in 56% of the cases. This is in accordance with the figure quoted by most authorities on the subject: Avery's textbook of neonatology.[3] In this study, a significant hyperbilirubinemia developed in 13% of the cases. Previous studies which showed similar results are: Guaran et al.[4] found in a retrospective study of 88000 liveborn infants in Australia incidence of significant hyperbilirubinemia (>12 mg/dl) as 12.4%. Awasthi and Rehman et al.[5] in a review of 274 neonates from North India had found the incidence of hyperbilirubinemia (>15 mg/dl) to be 12.3%. Shivani Ramdev et al.[6] reviewed 200 neonates from IGMC Department of Neonatology, Shimla, and found the incidence of hyperbilirubinemia ≥17 mg% beyond 77 h of life is 12%.

[Table 2] compares the incidence of hyperbilirubinemia in infants who had TSB ≤6 mg/dl at 24 h with those who had TSB >6 mg/dl at 24 h. A TSB of ≤6 mg/dl was present in 76.5% of the cases. Out of these, only 1.3% of infants developed hyperbilirubinemia. TSB >6 mg/dl at 24 h was present in 23.5% of cases and 55.32% of these subsequently developed hyperbilirubinemias. The sensitivity of TSB >6 mg/dl in detecting which infants will develop hyperbilirubinemia was found to be 92.86%; specificity of the test was 87.79%; the positive predictive value (PPV) of the test was 55.31%; and the negative predictive value (NPV) of the test was 98.69%. These statistical figures, therefore, show that if neonate has TSB ≤6 mg/dl at 24 h, there is a decreased risk of development of hyperbilirubinemia (≥17 mg/dl) subsequently. Thus, it will be justifiable for doctors attending the nursery to discharge such infants. These results were comparable with the study by Agarwal et al. 2002.[7] They had found the sensitivity of TSB >6 mg/dl at 24 h was 95%, specificity was 70.6%, PPV was 27.2%, and NPV was 99.3%. They followed the neonates clinically until discharge at 72 h and again at 5 days. Jaundice was assessed clinically by two DM fellows, and TSB estimation was done for only those infants in whom the assessment of jaundice was more than 10 mg/dl. This design carried the possibility of error inherent in clinical assessment, and there were chances of missing some cases. In the present study, this problem was bypassed by the universal screening of all enrolled infants for TSB at 5 days.
Table 2: Distribution of hyperbilirubinemia cases

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In the present study, the mean age at the discharge of babies, who were delivered vaginally, was 24.0 ± 1.2 h. Of the vaginally delivered babies, only 2% turned up for clinical follow-up regularly. There is, thus, a theoretical risk in the rest that there might have been the transient elevation of TSB above 17 mg/dl, which had come down by the 5th day and thus some cases might have been missed. This risk was also present in the study by Agarwal et al.,[7] however, the risk was higher in the present study because of the longer duration of intervals between the assessment. However, as Agarwal et al. comment “even if this did happen this should not be a cause for concern in real-life situations.”

Alpay et al.[8] found the sensitivity and specificity of 1st day TSB ≥6 mg/dl to be 100% each in predicting the development of significant hyperbilirubinemia. Awasthi et al.[5] showed that TSB level of 3.99 mg/dl at 18–24 h was able to predict subsequent hyperbilirubinemia (>15 mg/dl) with a sensitivity and specificity of 67% each. The differences from this study were probably due to the different design of the study. In their study, complete follow-up was present in infants who stayed in the hospital for some neonatal or maternal illness. Bhutani et al.[9] demonstrated in a large cohort that hour-specific nomograms could predict which infants are at high risk for subsequent hyperbilirubinemia. Predischarge 6.1% of the study population had bilirubin values in the high-risk zone (>95th percentile), and 61.8% of cases were in low-risk groups (<40th percentile). They showed that in this low-risk group there was no measurable risk of significant hyperbilirubinemia. When the results of the present study were plotted on the nomogram developed by them, 83% of the infants were classified in the low-risk zone. Two percent of the cases fell in the high-risk zone, and the rest 15% of cases fell in intermediate risk.

[Table 3] compares the mode of delivery with respect to the incidence of hyperbilirubinemia, mean TSB values at 24 h, and mean peak TSB values. A statistically significant difference was found in the values between cesarean and vaginal deliveries, with vaginal deliveries having higher incidence.
Table 3: Compare the total serum bilirubin at 24±6 h and peak total serum bilirubin levels and the incidence of hyperbilirubinemia among cesarean and vaginal deliveries

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[Table 4] compares the incidence of hyperbilirubinemia based on whether the mother received or did not receive oxytocin, the mean TSB at 24 h, and peak TSB between these groups. In oxytocin used and oxytocin not received groups, the mean TSB at 24 ± 6 h was 3.44 ± 2.15 and 3.36 ± 1.91, and the mean Peak TSB level was 12.78 ± 4.28 and 12.03 ± 3.42, respectively. In oxytocin and not oxytocin received groups, the difference was found to be significant.
Table 4: Compare the total serum bilirubin at 24±6 h and peak total serum bilirubin levels and the incidence of hyperbilirubinemia oxytocin used and not used groups

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The comparison showed the significant difference between the two groups in the mean TSB at 24 ± 6 h; however, no significant difference in the mean peak TSB levels. These findings are in accordance with those of Ghosh and Hudson.[10] In their study of 197 babies, 94 deliveries took place without oxytocin being given. Of these only, 6% developed hyperbilirubinemia (>12 mg/dl). Of the 103 deliveries, in which, oxytocin was given, 17.4% of babies developed hyperbilirubinemia. Davies et al.[11] had also found the significant difference between the two groups with respect to TSB levels at the 2nd day as well as 5th day. However, in the present study, the difference was significant only with respect to the mean TSB levels at 24 ± 6 h. This variation may be related to the dose and duration of oxytocin drip.


  Conclusion Top


Our study showed the incidence of significant hyperbilirubinemia in healthy babies is 13%. The incidence is increased by the use of oxytocin.

TSB at 24 ± 6 h ≤6 mg/dl has a high predictive value in identifying those infants who are unlikely to develop subsequent hyperbilirubinemia subsequently. The importance of this study is that it will help pediatricians and doctors posted in the nursery in planning an early discharge of healthy term newborns. Thus, they will be justified in discharging healthy term infants with TSB on 2nd day ≤6 mg/dl early.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
American Academy of Pediatrics Subcommittee on hyperbilirubinemia. Management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics 2004;114:297-316.  Back to cited text no. 1
    
2.
Cloherty JP, Eichenwald EC, Hansen AR, Martin CR, Stark AR (eds). Cloherty and Stark's Manual of newborn care: Neonatal Hyperbilirubinemia. 7th ed. Wolter Kluwer: Philadelphia; 2008. p. 336-7.  Back to cited text no. 2
    
3.
William Taeush H, Ballard RA. Avery's Disease of Newborn. 8th ed. Elsevier: Philadelphia; 2004. p. 1242.  Back to cited text no. 3
    
4.
Guaran RL, Drew JH, Watkins AM. Jaundice: Clinical practice in 88,000 liveborn infants. Aust N Z J Obstet Gynaecol 1992;32:186-92.  Back to cited text no. 4
    
5.
Awasthi S, Rehman H. Early prediction of neonatal hyperbilirubinemia. Indian J Pediatr 1998;65:131-9.  Back to cited text no. 5
    
6.
Randev S, Grover N. Predicting neonatal hyperbilirubinemia using first day serum bilirubin levels. Indian J Pediatr 2010;77:147-50.  Back to cited text no. 6
    
7.
Agarwal R, Kaushal M, Aggarwal R, Paul VK, Deorari AK. Early neonatal hyperbilirubinemia using first day serum bilirubin level. Indian Pediatr 2002;39:724-30.  Back to cited text no. 7
    
8.
Alpay F, Sarici SU, Tosuncuk HD, Serdar MA, Inanç N, Gökçay E, et al. The value of first-day bilirubin measurement in predicting the development of significant hyperbilirubinemia in healthy term newborns. Pediatrics 2000;106:E16.  Back to cited text no. 8
    
9.
Bhutani VK, Johnson L, Sivieri EM. Predictive ability of a predischarge hour-specific serum bilirubin for subsequent significant hyperbilirubinemia in healthy term and near-term newborns. Pediatrics 1999;103:6-14.  Back to cited text no. 9
    
10.
Ghosh A, Hudson FP. Oxytocic agents and neonatal hyperbilirubinaemia. Lancet 1972;2:823.  Back to cited text no. 10
    
11.
Davies DP, Gomersall R, Robertson R, Gray OP, Turnbull AC. Neonatal jaundice and maternal oxytocin infusion. Br Med J 1973;3:476-7.  Back to cited text no. 11
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

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