Neonatal Hyperbilirubinemia (NH) is the most common abnormal physical finding observed during the first week of life. Yellowish discoloration of the skin and sclera in newborns is a physical finding due to the accumulation of unconjugated bilirubin. In most infants, unconjugated hyperbilirubinemia reflects a normal physiological phenomenon [1]. NH affects nearly 60% of term and 80% of preterm neonates during the first week of life, and 6.1% of term newborns have a serum bilirubin level over 12.9 mg%. Serum bilirubin levels > 15 mg% were found in 3% of normal term newborns. Neonatal Hyperbilirubinemia (NH) is a cause of concern for the parents as well as for the paediatricians [2]. Neonatal Hyperbilirubinemia (NH) is the most common cause of readmission during the early neonatal period [3]. Up to 4% of term newborns are readmitted to the hospital during their first week of life, and approximately 85% of these readmissions are due to jaundice [4]. The American Academy of Pediatrics recommends that newborns discharged within 48 hours should have a follow-up visit after 48 to 72 hours for any significant jaundice and other problems [5]. Pediatricians are concerned about early discharge due to reports of bilirubin-induced brain damage in healthy term infants, even without hemolysis. The sequelae may result in cerebral palsy, sensorineural deafness, and intellectual disability [6, 7]. NH recognition, follow-up, early treatment, and prevention of bilirubin-induced neurological dysfunction (Bind Score) have become more difficult as a result of earlier discharge from the hospital. The treatment of severe NH by exchange transfusion is costly. It requires skilled manpower, is time-consuming, and is associated with complications. Early recognition and treatment of jaundice with phototherapy is effective, simple, and inexpensive. The ultimate aim is to benefit the maximum number of newborns with a cost-effective treatment protocol. The concept of prediction offers an attractive option for identifying babies at risk of neonatal hyperbilirubinemia. By predicting the risk of developing NH in newborns early at birth, we can design and implement a cost-effective follow-up program for these risk groups.

This prospective observational study was conducted at the Department of Neonatology, Bhaskar Medical College and General Hospital, Moinabad, Telangana. Institutional Ethical approval was obtained for this study. Written informed consent was obtained from the parents of the newborns before enrolling them in this study after explaining the nature of the study and possible outcomes in the vernacular language. Inclusion Criteria 1. Term babies of both genders 2. Mode of delivery (Normal and C-section) 3. Birth weight ≥2.5kg. 4. APGAR ≥5/10 at 1min. Exclusion Criteria 1. Preterm 2. Rh incompatibility. 3. Neonatal sepsis. 4. Instrumental delivery (forceps and vacuum). 5. Birth asphyxia. 6. Respiratory distress. 7. Neonatal jaundice within 24 h of life. Based on the inclusion and exclusion criteria during the study period, a total of n=112 healthy term newborns were included based on the convenience sampling method. Demographic profiles and relevant information were collected using a structured proforma by interviewing the mothers. Gestational age was assessed using the Modified New Ballard score. Cord Serum Albumin levels were estimated at birth. Total Serum Bilirubin (TSB) estimation was done at 72-96 hours of age. All babies were followed up for the first 4 postnatal days and assessed for NH and its severity. Laboratory investigations were performed using cord blood (2 ml) collected from the placental side after separation and included the Cord Serum Albumin level. Venous blood samples were collected from the babies between 72 and 96 h of life. These samples were subjected to Total and Direct Serum Bilirubin and Blood group analyses. Inference: The main outcome of this study was inferred in terms of neonatal hyperbilirubinemia. Serum bilirubin ≥17 mg/dl after 72 h of life was taken as hyperbilirubinemia in term neonates, and treatment was advised, as per the American Academy of Pediatrics practice parameter, 2004. The IAP-NNF also recommends considering phototherapy with neonatal serum bilirubin levels of ≥ 17 mg/dl after 72 h of life in term neonates. Therefore, in the present study, newborns with a total serum bilirubin level of ≥ 17 mg/dl were considered to have hyperbilirubinemia and required intervention (such as Phototherapy or Exchange Transfusion) after 72 hours of postnatal life. Statistical Analysis: All available data were segregated, refined, and uploaded to an MS Excel spreadsheet and analyzed using SPSS version 25 in Windows format. Continuous variables were represented as mean, standard deviation, and percentage, and categorical variables were calculated using the chi-square test for the analysis of differences between the two groups. Statistical significance was set at p < 0.05.

Table 1 shows the distribution of the mode of delivery in the study group. The majority of the babies in the study group were delivered vaginally, which constituted 72 out of 112 (64.3 %). The distribution of maternal weight (in kg) in the study group just before delivery was collected from the case sheet. The majority of the maternal weights in the study group were concentrated between 61 and 70 kg (42.9 %) and 71 and 80 kg (31.3 %). The distribution of maternal blood groups in the study group just before delivery was collected from the case sheet. The majority of the maternal blood groups in the study were O+ (n = 64, 57.1 %). The distribution of the birth weights of babies was done with <2.5 kgs birth weights of babies 2.5 kgs excluded. Among the study group, 37.5% (n = 42) of the babies had a birth weight between 2.76 and 3.0 kg. Mean and Standard deviation of birth weight: 2.89 ± 0.32 kg. Table 1: Baseline Characteristics of the Study Cohort (N=112) Characteristic Category Number (n) Percentage (%) Mode of Delivery Vaginal 72 64.3 Cesarean Section 40 35.7 Maternal Weight 61-70 kg 48 42.9 71-80 kg 35 31.3 51-60 kg 20 17.9 >80 kg 9 8.0 Maternal Blood Group O 64 57.1 A 27 24.1 B 17 15.2 AB 4 3.6 Neonate's Sex Male 64 57.1 Female 48 42.9 Birth Weight (kg) 2.76-3.00 42 37.5 2.50-2.75 39 34.8 3.01-3.25 21 18.7 >3.25 10 8.9 Mean Birth Weight 2.89 ± 0.32 kg Table 2 shows the distribution of Cord Serum Albumin levels measured at birth. The majority of Cord Serum Albumin levels were measured at birth. (2.50 – 3.5) consisted of 78 babies (69.6 %). The mean and standard deviation of Cord Serum Albumin level measured at birth were 2.93 and 0.52, respectively. The table shows the distribution of total bilirubin levels at birth. The majority of total bilirubin levels were measured at birth. The 12.01 – 15.00 time slot consisted of 51 babies (45.5%). The mean and standard deviation of the total bilirubin level measured at birth were 12.82 and 2.07, respectively. Table 2: Distribution of Cord Serum Albumin and Neonatal Bilirubin Levels Parameter Category 1 Range Number (n) Percentage (%) Mean ± SD Cord Serum Albumin (g/dL) 2.9-3.3 78 69.6 2.93 ± 0.52 ≤ 2.8 2.3 20.5 ≥ 3.4 11 9.8 Total Bilirubin at Birth (mg/dL) 12.01-15.00 51 45.5 12.82 ± 2.07 9.01-12.00 46 41.1 15.01 -16.99 13 11.6 Direct Bilirubin at Birth (mg/dL) ≥ 17.00* 2 1.8 1.01 -1.50 72 64.3 1.14 ± 0.24 *Defined as neonatal hyperbilirubinemia (NH) requiring intervention. Table 3 shows the Association between cord serum albumin level measured at birth and mode of delivery. Similarly, there is no statistically significant difference found between cord serum albumin level measured at birth and maternal weight. There is no statistically significant difference found between cord serum albumin level measured at birth and mode of delivery. The Association between cord serum albumin level measured at birth and Total bilirubin. There is a statistically significant difference found between cord serum albumin level measured at birth and Total bilirubin. The Association between cord serum albumin level measured at birth and Phototherapy. There was a statistically significant difference found between Cord Serum Albumin level measured at birth and Phototherapy. Table 3: Incidence of Neonatal Hyperbilirubinemia and Intervention by Cord Albumin Group Cord Albumin Group (g/dL) Total Neonates (n) Developed NH (TSB ≥17 mg/dL) n(%) Required Phototherapy n(%) P-value ≤ 2.8 23 2 (8.7%) 8 (34.8%) 0.003* 2.9 - 3.3 78 2 (2.6%) 7 (9.0%) 0.024* ≥ 3.4 11 0 (0%) 1 (9.1%) 0.841 Total 112 4 (3.6%) 16 (14.3%) *Significant [TSB: Total Serum Bilirubin; NH: Neonatal Hyperbilirubinemia] The association between cord serum albumin and key outcomes is given in Table 4. A critical analysis of the table showed that neonates with lower cord serum albumin concentrations (≤ 2.8 g/dL) had higher total serum bilirubin levels (≥15 mg/dL) and a greater requirement for phototherapy when compared to neonates with higher cord albumin levels, with significant p values. Based on the group-wise comparison in the ≤ 2.8 g/dL group, 34.8% were associated with bilirubin levels ≥15 mg/dL and required phototherapy, whereas these outcomes were observed far less frequently in neonates with cord albumin levels of 2.9–3.3 g/dL and ≥3.4 g/dL. The observed differences were statistically significant. Table 4: Association Between Cord Serum Albumin and Key Outcomes Outcome Cord Albumin ≤ 2.8 g/dL (n=23) Cord Albumin 2.9—3.3 g/dL (n=78) Cord Albumin ≥ 3.4 g/dL (n=11) p-value Total Bilirubin ≥15 mg/dL 8 (34.8%) 6 (7.7%) 1 (9.1%) 0.007* Required Phototherapy 8 (34.8%) 7 (9.0%) 1 (9.1%) 0.001* *Significant The diagnostic performance of cord serum albumin was calculated and presented in Table 5. Results showed that a cut-off value of ≤ 2.8 g/dL demonstrated high sensitivity (94.0%) and high negative predictive value (93.8%), indicating that neonates with albumin levels above this threshold are unlikely to require treatment for significant hyperbilirubinemia. Although specificity and positive predictive value were modest, this cut-off remains clinically useful for risk stratification rather than definitive diagnosis. Higher albumin ranges showed poor sensitivity, further reinforcing that lower cord albumin levels are strongly associated with bilirubin-related morbidity, rather than acting as an isolated causative factor. Table 5: Diagnostic Performance of Cord Serum Albumin for Predicting Neonatal Hyperbilirubinemia Cord Albumin Cut-off (g/dL) Sensitivity Specificity Positive Predictive Value (PPV) Negative Predictive Value (NPV) Accuracy ≤ 2.8 94.00% 52.30% 23.50% 93.80% 57.00% 2.9 - 3.3 6.00% 53.20% 3.50% 84.30% 55.70% ≥ 3.4 0.00% 63.40% 0.00% 83.50% 62.00% *NH defined as TSB ≥ 17 mg/dL requiring phototherapy/exchange transfusion. Multivariate Analysis of Factors Associated with Need for Phototherapy is depicted in Table 6. Results of multivariate analysis confirmed that cord serum albumin ≤ 2.8 g/dL is independently associated with an increased likelihood of phototherapy, even after adjusting for bilirubin levels and other clinical variables (aOR = 4.85, p = 0.005). Total serum bilirubin ≥15 mg/dL remained the strongest predictor (aOR = 8.92, p < 0.001). Notably, other maternal and neonatal variables did not show significant associations, underscoring that the albumin–bilirubin equilibrium plays a central role in determining treatment requirements. Table 6: Multivariate Analysis of Factors Associated with Need for Phototherapy Factor Adjusted Odds Ratio (aOR)* 95% Confidence Interval p-value Cord Albumin ≤ 2.8 g/dL 4.85 1.62-14.52 0.005 Total Bilirubin ≥ 15 mg/dL 8.92 3.15 - 25.24 <0.001 Mode of Delivery (Cesarean) 1.22 0.41-3.61 0.722 Maternal Weight 1.01 0.95 -1.07 0.801 Neonate's Sex (Male) 0.95 0.34 - 2.68 0.925 *Adjusted for all other variables in the table. A strong link between low cord albumin (≤ 2.8 g/dL) and higher bilirubin levels/the need for phototherapy, and the promising diagnostic sensitivity of this cut-off value.

Early discharge of healthy term newborns is increasingly considered because of the risk of nosocomial infections. However, because increased neonatal bilirubin levels can cause neurological dysfunction and its chronic sequela, kernicterus, a thorough evaluation of the neonatal bilirubin levels is essential. The true incidence of kernicterus remains elusive, and therefore, defining a safe physiological bilirubin level may sometimes be misleading. Because neonatal hyperbilirubinemia is a correctable condition and kernicterus is preventable, importance must be given to early identification of this risk, particularly in settings with early postnatal discharge [8, 9]. It has also been found that neonatal hyperbilirubinemia remains one of the most frequent causes of neonatal readmission, emphasizing the need for reliable early screening markers [10]. Previous studies have explored the utility of cord blood bilirubin as a predictor of subsequent hyperbilirubinemia; however, results were inconsistent, therefore preventing the widespread clinical utility [11, 12]. The present study evaluated the utility of cord serum albumin (CSA) levels as a marker for predicting neonatal hyperbilirubinemia. Albumin plays an important physiological role in the binding of unconjugated bilirubin; lower albumin levels can be associated with reduced bilirubin binding capacity and increase the risk of bilirubin toxicity [13]. A typical inverse relation is observed between CSA levels and total serum bilirubin. The overall results of the study showed that the gender distribution in the present study showed no statistically significant association between neonatal hyperbilirubinemia and sex; this is in agreement with findings of Amar Taksande et al. [14], Reshad et al. [15], and Rostami et al. [16]. Few studies, such as by Maisels et al. [17] and Trivedi et al. [18], have found a higher incidence of hyperbilirubinemia in male neonates, although the association was not found to be consistent across various population groups. Moreover, the mode of delivery of neonates in this study did not show a significant association with CSA levels or requirement of phototherapy, which was similar to other studies done in this field [16, 19]. This indicates that CSA can be an independent parameter unaffected by common perinatal variables. We found a statistically significant association with low CSA levels and higher total bilirubin risk. Neonates with CSA ≤2.8 g/dL have a higher association with increased total bilirubin levels and requirement of phototherapy. Sahu et al., [20] Trivedi et al., [18] and Dhanjal et al., [21] in similar studies, have consistently found this pattern with a higher incidence of neonatal hyperbilirubinemia among neonates with lower CSA levels. Notably, none of the neonates with CSA ≥3.4 g/dL in these studies developed significant hyperbilirubinemia, which shows the protective role of higher albumin levels. The overall incidence of neonatal hyperbilirubinemia in this study was 9.8%, which is comparable to other large population-based studies of Palmer et al. [22] and Phurpradit et al. [23]. The requirement of phototherapy in our study was significantly higher in the group with lower CSA levels. These results are in concordance with observations of Kumar et al. [24] and Reshad et al. [15], where they found CSA was a significant predictor of phototherapy requirement. Based on the above observations, our study supports the evidence that the use of cord serum albumin can act as a simple, cost-effective, and reliable screening tool to identify neonates with increased hyperbilirubinemia, and it may be used for targeted surveillance in early discharge settings.

Neonatal hyperbilirubinemia is an important cause of neonatal morbidity and hospital readmission in early discharge settings. The results of this study showed that there was a significant inverse association between cord serum albumin levels and the risk of developing clinically significant hyperbilirubinemia and need for phototherapy. Therefore, cord serum albumin estimation at birth can act as a simple, cost-effective tool for risk stratification of term neonates.

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