Translate this page into:
Cord blood bilirubin as a predictor for neonatal hyperbilirubinemia in term and late preterm neonates
*Corresponding author: Prakruthi V. Gopal, Department of Pediatrics, A J Institute of Medical Sciences, Mangaluru, Karnataka, India. pakuvgp4@gmail.com
-
Received: ,
Accepted: ,
How to cite this article: Jakati AA, Gopal PV, Chandrashekhar. Cord blood bilirubin as a predictor for neonatal hyperbilirubinemia in term and late preterm neonates. Karnataka Paediatr J. 2025;40:214-8. doi: 10.25259/KPJ_41_2025
Abstract
Objectives:
The most frequent reason for readmission in the early neonatal period is hyperbilirubinemia. For economic reasons, the early discharge of healthy term newborns after delivery has been a frequent practice. The objective was to assess the accuracy of cord blood bilirubin in predicting hyperbilirubinemia in newborns ≥35 weeks at 48–72 h of life and to compare the transcutaneous bilirubin levels’ accuracy with total serum bilirubin levels in late preterm and term neonates between 48 and 72 h of life.
Material and Methods:
A prospective observational study was carried out on 60 neonates, ≥35 weeks, delivered in the A J Institute of Medical Sciences and Hospital during the period from February 2021 to August 2022. Cord blood bilirubin levels are checked at birth and serum bilirubin levels and transcutaneous bilirubin levels are checked in babies who develop clinical icterus at 48–72 h of life.
Results:
Among 60 neonates included in the study, 40 (66.7%) were male and 20 (33.3%) were female. Among them, 51 (85%) were term and 9 (15%) were late preterm neonates. We performed a receiver operator characteristic curve analysis to find a cutoff point level of cord blood bilirubin for the development of significant hyperbilirubinemia. Cord bilirubin levels cutoff was 2.25 ± 0.476 mg/dL, with a sensitivity of 60%, specificity of 67%, positive predictive value of 89.1% and negative predictive value of 27.15%, with an area under the curve of 0.61; hence, we can use cord blood bilirubin as a good predictor for neonatal hyperbilirubinemia. Transcutaneous bilirubin meter (BiliCare) showed positive correlation with serum bilirubin levels at 48–72 h (r = +0.963, P < 0.001 in term and r= + 0.872, P < 0.01 in late preterm).
Conclusion:
In the present study, a cutoff value of ≥2.25 mg/dL for cord blood bilirubin had a sensitivity of 60%, a specificity of 67% and an area under the curve of 0.61 to predict hyperbilirubinemia at 48–72 h of life. As a result, it can be utilised as a reliable predictor for neonatal hyperbilirubinemia and to make plans for early discharge. Transcutaneous bilirubin meter (BiliCare) showed positive correlation with serum bilirubin levels in term and late preterm; hence, we can use this instrument to check hyperbilirubinemia at 48–72 h of life so that pricking for blood sampling can be avoided.
Keywords
Bilirubin
Cord blood
Hyperbilirubinemia
Neonates
INTRODUCTION
Neonatal hyperbilirubinemia remains one of the most common causes of hospital readmission in the early neonatal period. It affects approximately half of all term newborns and up to 80% of preterm infants, typically manifesting between the 2nd and 4th day of life and resolving within one to 2 weeks without intervention.[1,2] However, with the increasing trend toward early postnatal discharge, the risk of missing severe cases has grown, as highlighted by reports of kernicterus even in otherwise healthy term neonates.
In India, it is not uncommon for neonates to be discharged within the first 24 h of life, often without adequate evaluation for jaundice or any structured post-discharge guidance. Even those discharged beyond 48 h frequently do not undergo bilirubin assessment.[3,4] Early prediction strategies for hyperbilirubinemia are, therefore, essential in both clinical and community settings. Prior studies have evaluated the utility of cord blood bilirubin (CBB) as an early marker, along with non-invasive tools like transcutaneous bilirubinometry. The present study aims to assess the predictive accuracy of CBB and evaluate the performance of the BiliCare™ transcutaneous bilirubin metre in comparison to standard total serum bilirubin (TSB) levels measured at 48–72 h of life.
Objectives of the study
Primary objective: - To evaluate the predictive value of CBB in identifying newborns or ≥35 weeks for subsequent hyperbilirubinemia.
Secondary objective: - Compare the transcutaneous bilirubin levels accuracy with the TSB levels in late-preterm and term neonates between 48 and 72 h of life.
MATERIAL AND METHODS
Source of data
All term and late preterm neonates (≥35 weeks) delivered in the AJ Institute of Medical Science Hospital, Mangalore, from February 2021 to August 2022? Newborns born at ≥35 weeks of gestation were included in this study. Those newborns with significant illness (sepsis, respiratory distress syndrome, hypoxia and infant of a diabetic mother) that could aggravate hyperbilirubinemia and newborns with major congenital anomalies, ABO and Rh blood type incompatibility and glucose-6-phosphate dehydrogenase deficiency were excluded from the study.
The Institutional Ethical Committee approval was obtained before conducting the study. Detailed history and clinical examination were done, risk factors for hyperbilirubinemia, for example ABO or Rh incompatibility, maternal drug intake and presence of cephalhematoma. Cord blood samples (6 mL) will be collected from all newborns who comply with the protocol inclusion criteria. The samples will be sent for the assaying of total, unconjugated, conjugated bilirubin and albumin levels and the baby’s blood group.
Methods
The umbilical cord was doubly clamped and cut within 10 s of the baby being delivered. Cord blood was obtained as soon as the newborn was taken out of the operating room. Six mL of blood were taken from the umbilical vein, and 3 mL were placed in a plain tube. The serum was then tested for albumin and bilirubin, and three 3 mL were placed in an ethylenediaminetetraacetic Acid (EDTA) tube to test for haemoglobin, packed cell volume (PCV) and blood group. After 48 h, newborns were monitored for transcutaneous bilirubin levels using a transcutaneous bilirubin meter and for total and direct serum bilirubin using a peripheral venous sample.[5] The semi-automated colorimetric diazo technique and the diazotised sulphanilic acid reaction with the Diamond reagent were used to analyse bilirubin. Using Diamond reagent and a semi-automated bromocresol green dye-binding procedure, albumin was examined. Infants were placed supine while transcutaneous bilirubin levels were assessed, and breastfeeding was discontinued for a brief period of time. A novel transcutaneous bilirubin metre called the BiliCare uses an ear clip on the upper pinna to assess TcB. The light source is a green and blue light-emitting diode, which has a longer lifespan and requires less calibration maintenance. Bilirubin levels are estimated using the property of light absorption.[6] If necessary, the serum bilirubin levels were checked more frequently. The blood sample that is taken needs to be kept out of the light. According to Norwegian recommendations, the cutoff for TSB at 48 h for hyperbilirubinemia is >15.88 mg/dL.[7] Moreover, the Transcutaneous Bilirubin Nomogram states that the threshold for hyperbilirubinemia is >11 mg/dL.[6] The sample is kept chilled until the serum bilirubin measurement is completed, between 2 and 8°C. Within 12 h of sample collection, the serum bilirubin level was estimated using the diazotised sulfanilic test. Statistical analysis was done.
The data obtained were coded and entered into a Microsoft Excel spreadsheet. Categorical data was expressed as rate, ratio and percentage. Continuous data will be expressed as mean ± standard deviation. The comparison of the categorical data was done by the Chi-square test and the comparison of the continuous data (mean value) was done by the independent sample t-test.
The prediction of neonatal hyperbilirubinemia by CBB was done by area under the curve (AUC) using the receiver operator characteristic curve (ROC Curve). If the AUC is ≥0.9, it was considered an excellent prediction, if AUC 0.8–0.89 will be considered as good and 0.6–0.79 as fair. The accuracy of CBB in predicting neonatal hyperbilirubinemia was expressed in terms of sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) at different cutoff values. At a 95% confidence interval (CI) P < 0.05 was considered as statistically significant. To determine the correlation between the serum bilirubin levels and transcutaneous bilirubin levels, Karl Pearson co-efficient was used in this study.
Based on the study conducted by El Mashad et al. With p=81.8% with 95% CI and 10% allowable error , the sample size estimated for this study is 59.[8] Further assuming non response rate, final sample size to be considered 60. A convenience sampling technique was adopted to select study subjects.
RESULTS
Baseline demographic and clinical characteristics
Out of 60 neonates, 51 (85%) were term, and 9 (15%) were late preterm. Among them, 40 (66.7%) were male and 20 (33.3%) were female. The mean gestational age was 38.5 ± 1.2 weeks for term neonates and 36.2 ± 0.6 weeks for late preterms. Antenatal comorbidities were present in 18.3% of mothers, with anemia (13.3%) and hypothyroidism (5.0%) being the most common [Table 1].
| Parameter | Term neonates (n=51 [%]) | Late preterm (n=9 [%]) | Total (n=60 [%]) |
|---|---|---|---|
| Sex | |||
| Male | 36 (70.6) | 4 (44.4) | 40 (66.7) |
| Female | 15 (29.4) | 5 (55.6) | 20 (33.3) |
| Mode of delivery | |||
| NVD | 30 (58.8) | 6 (66.7) | 36 (60) |
| LSCS | 21 (41.2) | 3 (33.3) | 24 (40) |
| Mean birth weight (kg) ± (SD) | 3.03±0.33 | 2.89±0.48 | 2.96±0.46 |
| Mean gestational age (weeks) ± (SD) | 38.5±1.2 | 36.2±0.6 | 38.1±1.5 |
| Antenatal comorbidities | |||
| None | 41 (80.4) | 8 (88.9) | 49 (81.7) |
| Anemia | 7 (13.7) | 1 (11.1) | 8 (13.3) |
| Hypothyroidism | 3 (5.9) | 0 | 3 (5.0) |
LSCS: Lower segment cesarean section, NVD: Normal vaginal delivery, SD: Standard deviation
CBB and hyperbilirubinemia risk
CBB was collected at birth from all neonates. ROC curve analysis was performed to assess the CBB for predicting hyperbilirubinemia at 48–72 h.
Mean CBB (term neonates): 2.32 ± 0.476 mg/dL
Mean CBB (late preterm neonates): 2.27 ± 0.480 mg/dL
Difference: Not statistically significant (P = 0.777).
A cutoff value of ≥2.25 mg/dL for CBB was identified as the optimal threshold for predicting hyperbilirubinemia [Table 2].
| CBB level (mg/dL) | Number of neonates | Developed hyperbilirubinemia | Percentage |
|---|---|---|---|
| <2.25 | 22 | 5 | 22.7 |
| ≥2.25 | 38 | 34 | 89.5 |
CBB: Cord blood bilirubin
Comparison of cord bilirubin with period of gestation
While there was no significant difference in mean CBB between term and late preterm neonates, the majority of neonates who developed hyperbilirubinemia had CBB ≥2.25 mg/dL.
Transcutaneous versus TSB correlation
All neonates were assessed for jaundice using both TSB and TcB at 48–72 h post-birth.
-
Term neonates:
Mean TSB: 13.04 ± 2.40 mg/dL [Figure 1]
TcB showed strong correlation with TSB (r = 0.963, P < 0.001)
-
Late preterm neonates [Figure 2]:
Mean TSB: 11.89 ± 2.24 mg/dL
TcB also correlated well with TSB (r = 0.872, P = 0.002)
- Scatter plot: Transcutaneous bilirubin versus total serum bilirubin in term neonates. Linear regression analysis showing strong correlation.
- Scatter plot: Transcutaneous bilirubin versus total serum bilirubin in late preterm neonates. Moderate to strong positive correlation observed.
DISCUSSION
Neonatal hyperbilirubinemia is one of the most frequently encountered conditions in the neonatal period. While most cases are benign and physiological, unmonitored hyperbilirubinemia may progress to serious complications such as acute bilirubin encephalopathy or kernicterus, especially in preterm or late preterm neonates. This necessitates the early identification of neonates at risk, particularly in settings where early postnatal discharge is common.
In our study, the mean CBB was 2.25 ± 0.476 mg/dL. Receiver operating characteristic analysis revealed that a CBB cutoff of ≥2.25 mg/dL yielded a sensitivity of 60%, specificity of 67% and a PPV of 89.1%. The area under the ROC curve (AUC) was 0.61 [Figure 3]. Although these values indicate only moderate predictive ability overall, the high PPV implies that neonates with a CBB above this threshold are significantly more likely to develop hyperbilirubinemia and require intervention.
- Receiver operator characteristic curve for cord blood bilirubin in predicting hyperbilirubinemia. Area under curve = 0.61; sensitivity = 60%; specificity = 67%; positive predictive value = 89.1% and negative predictive value = 27.15.
Previous studies have also demonstrated the value of CBB in predicting subsequent jaundice. El Mashad et al. found that a CBB level of 1.88 mg/dL had a sensitivity of 83.3% and a specificity of 66% for predicting significant hyperbilirubinemia in neonates ≥35 weeks of gestation.[8] Anand et al. reported that a threshold of 2.1 mg/dL predicted the need for phototherapy with 88% sensitivity and a PPV of 77.49%.[9] These findings are consistent with our results and support the use of cord bilirubin as a simple, early and noninvasive screening tool to stratify risk and determine follow-up needs.
However, one limitation in relying solely on CBB is its relatively low negative predictive value NPV, observed as 27.15% in our study. This suggests that while high values are predictive, low values cannot definitively rule out future hyperbilirubinemia. This aligns with other studies, which note that factors such as late feeding initiation, breastfeeding challenges, and genetic predispositions (e.g. Gilbert’s syndrome and Glucose-6-phosphate Dehydrogenase [G6PD] deficiency) may contribute to delayed onset jaundice despite initially normal cord bilirubin levels.[2,10]
The second major objective of our study was to assess the utility of transcutaneous bilirubin (TcB) measurement using the BiliCare device. In term neonates, TcB levels showed an excellent positive correlation with TSB levels (r = 0.963, P < 0.001), and in late preterm neonates, the correlation remained strong (r = 0.872, P < 0.01). This confirms that TcB is a reliable, non-invasive alternative to serum bilirubin testing.
Multiple previous studies have validated this finding. Bhutani et al. demonstrated strong correlation coefficients between TcB and TSB in healthy neonates (r = 0.91).[11] Janjindamai et al. found a correlation of r = 0.95,[12] while Rubaltelli et al. reported r = 0.89.[13] Our findings add further weight to the growing consensus that TcB devices, especially those with fibre-optic technology and consistent calibration like BiliCare, are suitable for use in both term and late preterm neonates.
The main advantage of TcB is its ability to provide real-time, non-invasive and painless bilirubin estimation, reducing the need for repeated blood sampling. This is particularly important in the context of minimising interventions in healthy newborns and improving parental satisfaction during early discharge programs. However, clinicians must be aware of TcB limitations in situations such as dark skin pigmentation, oedema or after phototherapy exposure, where readings may vary.[14,15]
This study’s strengths include its prospective design, inclusion of both term and late preterm neonates and simultaneous evaluation of both predictive (CBB) and diagnostic (TcB) strategies. However, certain limitations exist: the small sample size (n = 60), exclusion of high-risk neonates (e.g., with Rh incompatibility or sepsis) and the single-centre setting may limit generalizability. Moreover, maternal variables such as blood group incompatibility and feeding status were not explored in detail, which may have affected outcomes.
CONCLUSION
CBB at birth offers moderate sensitivity but excellent predictive value for neonatal hyperbilirubinemia and may aid early risk stratification. Meanwhile, TcB levels show strong correlation with TSB and can be reliably used for follow-up monitoring at 48–72 h of life. Together, these tools can reduce the burden of late detection, unnecessary hospital stays and invasive testing in neonatal care.
Ethical approval:
The research/study approved by the Institutional Review Board at A J Institute of Medical Sciences and Research Centre, number AJEC/REV/94/2021, dated 17th February 2021.
Declaration of patient consent:
The authors certify that they have obtained all appropriate patient consent.
Conflicts of interest:
There are no conflicts of interest.
Use of artificial intelligence (AI)-assisted technology for manuscript preparation:
The authors confirm that there was no use of artificial intelligence (AI)-assisted technology for assisting in the writing or editing of the manuscript and no images were manipulated using AI.
Financial support and sponsorship: Nil.
References
- Early recognition of neonatal hyperbilirubinemia and its emergent management. Semin Fetal Neonatal Med. 2006;11:214-24.
- [CrossRef] [PubMed] [Google Scholar]
- 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.
- [CrossRef] [PubMed] [Google Scholar]
- Loss of concern about jaundice and the reemergence of kernicterus in full-term infants in the era of managed care In: Fanaroff AA, Klaus MH, eds. The year book of neonatal and perinatal medicine. Philadelphia: Mosby Yearbook; 1996. p. :17-28.
- [Google Scholar]
- Neonatal jaundice: Continuing concern and need for research. Pediatr Res. 2001;50:674-5.
- [CrossRef] [PubMed] [Google Scholar]
- Diagnosis and management of hyperbilirubinemia in the term neonate: For a safer first week. Pediatr Clin North Am. 2004;51:843-61. 7
- [CrossRef] [PubMed] [Google Scholar]
- Reproducibility of BiliCareTM transcutaneus bilirrubin meter in Mexican newborns. Int J Pediatr. 2019;2019:3812152.
- [CrossRef] [PubMed] [Google Scholar]
- Guidelines for management of the jaundiced term and near-term infant. Clin Perinatol. 1998;25:555-74.
- [CrossRef] [PubMed] [Google Scholar]
- Cord blood albumin-bilirubin as a predictor for neonatal hyperbilirubinemia. Menoufia Med J. 2019;32:1071-7.
- [CrossRef] [Google Scholar]
- Cord bilirubin as a predictor for development of hyperbilirubinemia in term neonates. Int J Pediatr Res. 2016;3:308-12.
- [CrossRef] [Google Scholar]
- Hyperbilirubinemia and bilirubin toxicity in the late preterm infant. Clin Perinatol. 2006;33:839-52.
- [CrossRef] [PubMed] [Google Scholar]
- Noninvasive measurement of total serum bilirubin in a multi-racial pre-discharge newborn population to assess the risk of severe hyperbilirubinemia. Pediatrics. 2000;106:E17.
- [CrossRef] [PubMed] [Google Scholar]
- Transcutaneous bilirubin measurement: A comparison of two devices and validation against laboratory-based total serum bilirubin. J Med Assoc Thai. 2012;95:1255-60.
- [Google Scholar]
- Transcutaneous bilirubin measurement: A multicenter evaluation of a new device. Pediatrics. 2001;107:1264-71.
- [CrossRef] [PubMed] [Google Scholar]
- Transcutaneous bilirubinometry. Semin Perinatol. 2014;38:438-51.
- [CrossRef] [PubMed] [Google Scholar]
- Non-invasive assessment of neonatal jaundice using BiliCheck™ transcutaneous bilirubin meter. Clin Pediatr (Phila). 2001;40:513-20.
- [Google Scholar]