Correlation of cord blood bilirubin values with neonatal jaundice in healthy newborns: A prospective observational study

Jehangir Allam Bhat; Sajad Ahmad Sheikh; Roshan Ara

doi:10.4103/amhs.amhs_2_19

ORIGINAL ARTICLE

Year : 2019 | Volume : 7 | Issue : 1 | Page : 48-52

Correlation of cord blood bilirubin values with neonatal jaundice in healthy newborns: A prospective observational study

Jehangir Allam Bhat¹, Sajad Ahmad Sheikh², Roshan Ara¹
¹ Department of Pediatrics, World College of Medical Sciences, Jhajjar, Haryana, India
² Department of Gastroenterology, Vikas Hospital Pvt Ltd, New Delhi, India

Date of Web Publication

12-Jun-2019

Correspondence Address:
Dr. Jehangir Allam Bhat
World College of Medical Sciences, Jhajjar, Haryana
India

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/amhs.amhs_2_19

Abstract

Background and Objective: Hyperbilirubinemia is the most common clinical condition requiring evaluation and treatment in the newborn and a frequent reason for hospital readmission during the 1^st week of life. Although generally a benign, postnatal, transitional phenomenon, a few neonates develop marked potentially hazardous bilirubin levels that can pose a direct threat of serious brain injury. The present study was conducted to investigate the predictability of pathological jaundice on cord blood bilirubin (CBB) values. Materials and Methods: This was a prospective observational study conducted on 289 healthy newborns. Babies were divided into two groups: Group A who developed physiological jaundice and Group B who developed pathological jaundice. CBB was estimated in all newborns who were then followed up to the 5^th day of life. Babies who developed jaundice requiring treatment were admitted in neonatal intensive care unit for phototherapy. Other neonates were checked regularly up to the 5^th day of life and values were recorded on the 5^th day by estimation of serum bilirubin. Results: Incidence of pathological hyperbilirubinemia in our study was 11.2%. A statistically significant correlation between CBB and development of pathological jaundice was observed. Gender, age, mode of delivery, and birth weight has no correlation with cord bilirubin and the subsequent development of jaundice. CBB <2.5 mg/dl when compared with subsequent development of jaundice has high specificity (83.92%) and negative predictive value (87.35%). Cord blood value of >3.5 mg/dl has high sensitivity (97.06%), specificity (99.22%), positive predictive value (94.29%), and negative predictive value (99.61%) in predicting future development of future pathological jaundice. Conclusion: The present study suggests that in healthy term babies (CBB ≤2.5 mg/dl), cord serum bilirubin can help to identify those newborns who are unlikely to require further evaluation and intervention. These newborns can be discharged with assurance to parents. Babies with CBB level ≥3 mg/dl should be followed more frequently. Thus, this study concludes that cord blood total bilirubin levels reliably predict the occurrence of pathological hyperbilirubinemia.

Keywords: Cord blood serum bilirubin, pathological jaundice, phototherapy, physiological jaundice

How to cite this article:
Bhat JA, Sheikh SA, Ara R. Correlation of cord blood bilirubin values with neonatal jaundice in healthy newborns: A prospective observational study. Arch Med Health Sci 2019;7:48-52

How to cite this URL:
Bhat JA, Sheikh SA, Ara R. Correlation of cord blood bilirubin values with neonatal jaundice in healthy newborns: A prospective observational study. Arch Med Health Sci [serial online] 2019 [cited 2023 Mar 31];7:48-52. Available from: https://www.amhsjournal.org/text.asp?2019/7/1/48/260006

Introduction

Hyperbilirubinemia is the most common clinical condition requiring evaluation and treatment in the newborn and a frequent reason for hospital readmission during the 1^st week of life. Although generally a benign, postnatal, transitional phenomenon, a few neonates develop marked potentially hazardous bilirubin levels that can pose a direct threat of serious brain injury.^[1] Acute bilirubin encephalopathy may ensue and evolve into kernicterus (chronic bilirubin encephalopathy), a permanent disabling neurologic condition classically characterized by (1) the movement disorders of dystonia and/or choreoathetosis, (2) hearing loss caused by auditory neuropathy spectrum disorders, and (3) oculomotor pareses.^[1] The genesis of neonatal hyperbilirubinemia reflects the interplay of developmental red blood cell, hepatic, and gastrointestinal immaturities that result in an imbalance favoring bilirubin production over hepatic–enteric bilirubin clearance.

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. Physiological jaundice usually appears on the 2^nd–3^rd day, peaking between the 5^th and 7^th 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 deleterious effects on neonates such as kernicterus, Choreoathetoid type of cerebral palsy, hearing impairment, and cognitive impairment if not treated at the time. Hence, meticulous screening of newborns 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, 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. Early discharge of healthy term newborns after delivery has become a common practice because of medical and social reasons and economic constraints.^[3] Thus, the recognition, follow-up, and early treatment of jaundice have become more difficult as a result of early discharge from the hospital. Severe jaundice and even kernicterus can occur in some full-term healthy newborns discharged early with no apparent early findings of hemolysis.^[4]

Materials and Methods

This prospective hospital-based study was conducted in the Department of Paediatrics and Neonatology, World College of Medical Sciences (WCMS), Jhajjar, Haryana, from January 17, 2016, to December 30, 2018. A total of 289 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

The inclusion criteria of this study were as follows:

Gestational age 35 weeks and above (based on last menstrual period)
The absence of major congenital malformations
Residing at Jhajjar or nearby whose parents agree to come for follow-up
Exclusive breastfed babies.

Exclusion criteria

The exclusion criteria of this study were as follows:

Presence of significant illness (i.e., sepsis and hypothyroidism)
Rh incompatibility
ABO incompatibility
Newborns with obvious life-threatening congenital malformation (tracheoesophageal fistula and anorectal malformation)
Babies with conjugated hyperbilirubinemia.

All babies delivered in WCMS were examined, and a detailed antenatal and postnatal history was taken. Cases were selected if they fulfilled all the criteria set out above. Informed consent was taken from the parents, and blood was collected from cord blood at birth. Blood sample of the mother was simultaneously collected and sent for blood grouping if it was not known from before. The cord blood sample of the infant was sent for grouping and total serum bilirubin estimation, and then, all babies were examined by senior registrars and experts for clinical assessment of bilirubin as per Kramer's scale and by transcutaneous bilirubinometer for continuous 5 days. Babies were divided into two groups: Group A developing jaundice within physiological range and Group B developing jaundice which needs treatment (pathological jaundice). Babies suspected of having high bilirubin were cross-checked by serum bilirubin level and admitted for treatment if needed as per American academy of pediatrics (AAP) nomogram for hyperbilirubinemia management. Remaining babies were checked for serum bilirubin on the 5^th day of life.

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, The Netherlands).

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), is computed. Sensitivity, specificity, positive predictive value, and negative predictive value of different cut-points of cord blood serum bilirubin were derived. For determining the significance of each test, P < 0.05 was used.

Results

Out of 300 newborns enrolled, 11 could not be included in the study because of refusal of consent, drop in follow-up, Rh/ABO incompatibility, and admission in neonatal intensive care unit because of cause other than hyperbilirubinemia. A total of 289 newborns were followed up for the first 5 days of life with clinical assessment and laboratory investigations. Of the enrolled newborns, 169 (58.48%) were male and 120 (41.52%) were female with mean cord blood bilirubin (CBB) and serum bilirubin during evaluation up to 5 days of 2.6 ± 0.8 and 13.9 ± 2.4 and 2.5 ± 0.4 and 12.9 ± 1.8, respectively, with P = 0.89, thus no statistical significance [Table 1].

Table 1: Distribution of the enrolled newborns according to gender, gestational age, birth weight, and mode of delivery

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In our study, 208 (71.179%) babies were >37 weeks of age and 81 (28.03%) were 35–37 weeks' babies. In our study 34 babies developed pathological jaundice, nine babies fall in 35-37 weeks and 25 in >37 weeks age group. Gestational age has no impact when comparison of cord blood bilirubin and mean serum bilirubin of neonates up to 5th day was done (P value=0.95). Similarly, birth weight and mode of delivery comparison of CBB and serum bilirubin when estimated up to the 5^th day has no statistical significance with P = 0.78 and 0.999, respectively, as depicted in [Table 1].

A total of 255 newborns (84.5%) (Group A) developed jaundice which was in physiological range so went home without any treatment. The mean (±standard deviation [SD]) serum TB in cord blood and on day 5 of the babies in this group was 1.6 (±0.4) mg/dl and 11.9(±2.4) mg/dl, respectively [Table 2]. Statistical correlation revealed no significance with P = 0.087.

Table 2: Mean±standard deviation at bilirubin levels in cord blood and 5^th-day blood of neonates and their association

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Total 34 (11.76%) (Group B) infants developed hyperbilirubinemia up to the 5^th day with mean CBB of 2.6 mg/dl with standard deviation of 0.8 mg/dl and mean serum bilirubin (when estimated up to the 5^th day of life) of 16.7 mg/dl with standard deviation of 1.8 and P = 0.0001 [Table 2].

[Table 3] illustrates statistical prediction of various cut off values of cord blood bilirubin in development of subsequent pathological jaundice. Cut off value of <2.5mg/dl has sensitivity of 8.82% (confidence interval [CI]: 1.86%–23.68%) and specificity of 83.92% (CI: 78.83%–88.21%) with positive predictive value and negative predictive value of 6.82% (2.34%–18.26%) and 87.35% (85.99%–88.59%) respectively.

Table 3: Statistics of cord blood bilirubin levels in predicting the development of significant hyperbilirubinemia

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Neonates having CBB level in the range of 2.5–3 when compared with their serum bilirubin recorded up to the 5^th day of life had sensitivity, specificity positive predictive value, and negative predictive value of 66.67% (49.03%–81.44%), 92.94% (89.07%–95.76%), 57.14% (44.67%–68.77%), and 95.18% (92.55%–96.91%), respectively. Similarly, CBB of > 3 mg/dl has sensitivity, specificity, positive predictive value, and negative predictive value of 97.06% (84.67%–99.93%), 99.22% (97.21%–99.91%), 94.29% (80.56%–98.50%), and 99.61% (97.36% to 99.94), respectively [Table 3].

Discussion

Jaundice is a common entity which needs attention up to some days of birth. Most of the jaundice which develops in healthy newborns is in physiological range except some 8%–10% healthy newborns who develop jaundice which is out of physiological range and needs interventions such as phototherapy, exchange transfusion, or new modalities of treatment. Thus, timely diagnosis and immediate treatment is essential because it could have a devastating effect on their future life because of kernicterus, which leads to mental retardation, choreoathetoid type of cerebral palsy, or hearing defect. Because of increased medical facility and public awareness about side effects of pathological neonatal hyperbilirubinemia, above mentioned sideeffects are less common nowadays. However, still, there is small fraction of newborns who fall prey to the devastating side effects of neonatal hyperbilirubinemia, especially in a developing country, because of poor follow-up, limited resources, and most important parental emotional attachment, who did not want their child to get hurt even from a single needle prick. Keeping in view all these factors, the objective of this research was framed. Our study presumption was that a high serum bilirubin level at birth would also predict a high peak later in life.

Incidence of pathological hyperbilirubinemia in our study was 11.2%, which is in accordance to studies conducted by other authors such as 12.80% in a study by Awasthi and Rehman,^[5] 12.00% as per a study by Randev and Grover,^[6] and 11.4% in a study by Dhanwadkar et al.^[7]

In our study, there was no relation between CBB and bilirubin monitored up to the 5^th day of life when gender, gestational age, birth weight, and mode of delivery were compared. Similar findings were noted by Awasthi and Rehman,^[5] 1998, and Alpay et al.,^[8] 2000.

In our study, mean CBB of those babies who developed pathological jaundice was 2.6 ± 0.6 mg/dl (mean ± SD). This finding was in accordance with the research of Knüpfer et al.^[9] and Bernaldo and Segre^[10] who investigated the predictability of umbilical cord blood unconjugated bilirubin concentration on subsequent hyperbilirubinemia and need for therapy. Utilizing a cutoff point of unconjugated bilirubin of 2.0 mg/dl, they showed that 53% of babies needed phototherapy, and raising the cutoff value to 2.5 mg/dl, they predicted that 72% of babies need phototherapy. Nahar et al.,^[11] 2009, found CBB of 2.5 mg/dl ± 0.5 which can predict the occurrence of pathological jaundice in neonates.

The present study revealed at CBB level of <2.5 mg/dl, sensitivity of 8.82%, specificity of 83.92%, and positive predictive value and negative predictive value of 6.82% and 87.35%, respectively. Thus, at cord blood <2.5 mg/dl, chances of not developing hyperbilirubinemia are 83.92%. This finding was supported by Rosenfeld^[12] who found 4% incidence of neonatal hyperbilirubinemia at CBB level of <2 mg/dl with specificity of 98.23%. Knüpfer et al.^[9] derived the incidence of just 0.30% at serum bilirubin level of 1.17–1.75 mg/dl. Other findings which we extracted from our study were sensitivity, specificity, positive predictive value, and negative predictive value at cord blood serum bilirubin level of 2.5–3 mg/dl and >3 mg/dl, and other studies which support this are shown in [Table 4].

Table 4: Studies on the predictive ability of cord blood bilirubin level and the neonatal hyperbilirubinemia

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As illustrated in [Table 4], our study predicts with high probability at serum bilirubin level >3 mg/dl, and chances of developing pathological neonatal hyperbilirubinemia are very high. Thus, these newborns must be meticulously checked on follow-up. CBB level of 2.5–3.5 also showed good specificity, but due to decreased sensitivity, these newborns can be categorized into intermediate risk. Hence, our study can classify newborns into three risk categories as per cord blood serum bilirubin.

Conclusion

The study concludes with result that there is a significant correlation between cord blood serum bilirubin and development of neonatal jaundice. CBB can be used to categorize neonates into risk group. Neonates with serum bilirubin <2 mg/dl have low risk for neonatal hyperbilirubinemia and thus can be kept in low priority as compared to neonates with cord blood serum bilirubin >3 mg/dl. Neonates with CBB level ≥3 mg/dl should be followed more frequently to reduce morbidity and mortality due to neonatal hyperbilirubinemia.^[16]

Acknowledgment

We are highly thankful to our pediatric department and its faculty who devoted their precious time to guide us while conducting this research. We are highly thankful to those little angels and their parents without them this research would not have been possible.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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