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ISSN: Print -2349-0977, Online - 2349-4387

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Year : 2017  |  Volume : 4  |  Issue : 3  |  Page : 139-143

Comparative Study on Prediction and Course of Significant Hyperbilirubinemia in Term and Late Preterm Babies

1 Department of Paediatrics, GSVM Medical College, Kanpur, Uttar Pradesh, India
2 Department of Obstetrics, GSVM Medical College, Kanpur, Uttar Pradesh, India

Date of Web Publication30-Jan-2018

Correspondence Address:
Arpita Gupta
Department of Paediatrics, VM Medical College & Safdarjung Hospital, New Delhi
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/astrocyte.astrocyte_80_17

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Objectives: To study the course and prediction of significant hyperbilirubinemia in healthy late preterm and term newborns. Material and Methods: study comprises of 150 neonates: 92 term newborns and 58 late preterm neonates, each with birth weight >2000g, without Rh or ABO incompatibility or G6PD deficiency. A thorough clinical examination with biochemical measurement of serum bilirubin was done in both groups serially at 6th hour of birth, 2nd day of life, 3rd day, 4th day and on 7th day respectively and the pattern of rise of serum bilirubin and development of significant hyperbilirubinemia were compared in both groups. Results: Out of total 150 neonates, significant hyperbilirubinemia requiring phototherapy or exchange transfusion was noted in 28 patients (18.6%); 12 were term (13%) and 16 were late preterm babies (27.5%) i.e. late preterm babies were 2 times more likely to develop significant hyperbilirubinemia. Conclusion: Since late preterm babies are more vulnerable than their term counterparts, to the complications associated in early life especially hyperbilirubinemia, special attention is required in treating these babies.

Keywords: Term, late preterm, serum bilirubin, significant hyperbilirubinemia

How to cite this article:
Gupta A, Tripathi V N, Singh RD, Pandey K. Comparative Study on Prediction and Course of Significant Hyperbilirubinemia in Term and Late Preterm Babies. Astrocyte 2017;4:139-43

How to cite this URL:
Gupta A, Tripathi V N, Singh RD, Pandey K. Comparative Study on Prediction and Course of Significant Hyperbilirubinemia in Term and Late Preterm Babies. Astrocyte [serial online] 2017 [cited 2020 Jun 6];4:139-43. Available from: http://www.astrocyte.in/text.asp?2017/4/3/139/224200

  Introduction Top

Neonatal jaundice presents with a wide spectrum of severity ranging from clinically undetectable bilirubin levels to very high level that puts the newborn at risk of associated complications. Immature newborn brain is susceptible to toxicity from unconjugated bilirubin, resulting in kernicterus or bilirubin brain damage. Studies indicate that there is no specific bilirubin level that is definitely safe or toxic for all newborns.[1],[2],[3],[4]

Jaundice is an important problem in the first week of life and a cause of concern for the physician and a source of anxiety for the parents. It becomes apparent in the newborn when the serum bilirubin level is greater than 7 mg/dl. Jaundice can be either physiological or pathological depending upon the time of appearance and its serum levels. Physiological jaundice is characterized by appearance between 24 and 72 hours of life, maximum rise between 4 and 5 days in term and 7 days in preterm with values not exceeding 15 mg/dl and resolution between 7 and 10 days of life (maximum by 14 days).[1],[2],[5],[6],[7]

Pathological jaundice is characterized by appearance before 24 hours of age or persistence after 14 days, rise in serum bilirubin by more than 5 mg/dl/day, direct bilirubin level more than 2 mg/dl, or more than 20% of the total bilirubin level, associated with clay-colored stools or dark urine staining the clothes. Intervention is generally required in the form of phototherapy or exchange blood transfusion. This classification of neonatal jaundice helps to appropriately identify the newborns at risk of developing long-term complications of hyperbilirubinemia and dreaded complication i.e., kernicterus; therefore, requiring early institution of therapy. Approximately 60–70% of neonates develop jaundice in the first week of life due to various factors such as increased bilirubin load on the hepatic cell, defective uptake from plasma into liver cell, defective conjugation, decreased excretion, and increased enterohepatic circulation, but only 20–30% require intervention.[2],[5],[8],[9] There are certain risk factors in the neonatal period which may lead to pathological jaundice, and identification of which may be of some help in triaging the newborns. These factors include blood group incompatibility (Rh or ABO), hemolytic disease (e.g., G6PD deficiency), very preterm newborns (gestational age <32 weeks), cephalhematoma or significant bruising, previous siblings with neonatal jaundice requiring intervention, neonatal sepsis, babies receiving parenteral nutrition or intravenous fluids, and very low birth weight.[2],[8]

The study prospectively evaluates the demographic and laboratory characteristics of significant hyperbilirubinemia and pattern of serum bilirubin levels of near-term newborns by comparing them with those of term newborns longitudinally in the first 7 days of life.

  Materials and Methods Top

This prospective study was conducted in the neonatal intensive care unit of the department of pediatrics in collaboration with the postnatal wards of UISE Maternity Hospital, GSVM Medical College and LLR and Associated Hospitals, Kanpur. A total of 150 neonates meeting the inclusion criteria were part of the study cohort. The cases were selected from the newborns of all booked mothers admitted to the postnatal wards of UISE Maternity Hospital, who were of 34–42 completed weeks of gestation determined on the basis of the first day of the last menstrual period and New Ballard Scoring.[3] Parent of each newborn was duly counselled and informed about the nature of the study. History was obtained from the mother regarding any illness during pregnancy, mode of delivery, risk factors for sepsis, previous child with neonatal jaundice, and feeding of the baby along with thorough physical examination followed by biochemical investigation done for each baby. Study cohort was divided into term (37–42 weeks) and late preterm or late preterm (34–36). Newborns of 34–42 weeks of gestation, i.e., term and late preterm or late preterm newborns and birth weight >2000 g were included.[4],[7] However, newborns with gestational age <34 weeks and >42 weeks, babies small for their gestational age and large for their gestational age, birth weight <2000 g, newborns with any congenital malformation, babies requiring resuscitation at birth with APGAR score of <6 at 5 min, multiple gestations, clinical or culture proven sepsis, newborns with blood group A or B and born to mothers with blood group O (ABO incompatibility) or rhesus factor positive neonates born to rhesus factor negative mothers (Rh incompatibility), newborns with glucose-6 phosphate deficiency, and newborns with inability to initiate or maintain oral feeds within 3 h of birth were excluded.[1]

A thorough clinical examination of every newborn was done in daylight and gestational age by New Ballard Scoring System, birth weight within 24 h of birth, vitals, icterus by Kramer's clinical criteria, pallor, cyanosis, edema, skin, and its appendages were noted.[3],[5],[10],[11],[12] Systemic examination was done with per abdomen examination to rule out hepatosplenomegaly.

Biochemical investigations such as mother and baby's blood group and baby's G6PD levels were done on all the babies. On the basis of above two investigations inclusion of baby was decided in the study therefore it was being done in all healthy newborns with a gestational age of 34–42 weeks and birth weight >2000 g. Serial serum bilirubin levels were sent for all enrolled neonates at 6th hour of birth, 2nd day of life, 3rd day, 4th day, and on 7th day, i.e., total of five samples were sent over a week.[1],[3]

Effect of each study group was compared to each other. Serial serum bilirubin levels were determined from capillary blood using Jendrassic and Groff method for 7 days. The infants who developed significant hyperbilirubinemia were further divided according to the need and type of intervention required. The intervention required, i.e., phototherapy and exchange transfusion, were decided according to the graphs. The development of complications of hyperbilirubinemia were examined and compared between the two study groups.[2],[8]

Statistical evaluation

Correlation of the findings obtained by serial measurement of serum bilirubin levels in term and late preterm newborns along with demographic characteristics and associations, e.g., breastfeeding was done. Statistical data were analyzed with descriptive analysis and independent-sample t- test and chi-square tests. Demographic and laboratory characteristics of the near-term or late-preterm and term groups and of the newborns with and without significant hyperbilirubinemia were compared with the independent sample t-test and chi- square tests. Statistical analysis was done using SPSS software.

  Results Top

Demographic profile

Gestational age distribution: All the babies included in the study were newborns observed from the first day of life and followed up till 7 days. Out of the total 150 newborns, 92 were term newborns and 58 were late-preterm newborns (38.6%).

Birth weight distribution: The weight of the study cohort was in the range of 2000 g to 3400 g [Table 1]. Maximum number of babies was in the birth weight group of 2500 g to 3000 g (59.3%). The minimum weight was 2000 g and the maximum weight was 3450 g. The mean birth weight of all newborns was 2600 g.
Table 1: Birth weight distribution

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Out of the total term neonates, maximum were in the weight range of 2500–3000 g (78.2%), whereas late-preterm neonates were mainly in the weight range of 2000–2500 g (70.6%). The average birth weight of term babies was 2800 g and that of late-term babies was 2325 g.

Characteristics of neonatal hyperbilirubinemia

Development of jaundice was noted almost in all newborns during the first week of life but significant hyperbilirubinemia requiring phototherapy or double column exchange blood transfusion was noted in 18.6% of the babies [Figure 1].
Figure 1: Distribution of neonatal hyperbilirubinemia.

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Gestational age distribution of significant hyperbilirubinemia: Out of the total 28 patients with significant hyperbilirubinemia, 12 were term (13%) and 16 were late-preterm babies (27.5%). Late-preterm babies were at two times greater risk than term babies for developing significant hyperbilirubinemia [Table 2].
Table 2: Gestational distribution and incidence of significant hyperbilirubinemia

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Sex distribution: Out of the total with significant hyperbilirubinemia, 60.7% were males whereas 39.2% were females. The male-to-female ratio in term babies with significant hyperbilirubinemia was 1:1 and in late preterm 2.2:1 [Figure 2].
Figure 2: Gender distribution of significant hyperbilirubinemia.

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Birth weight distribution: Approximately 53.5% of infants who developed significant hyperbilirubinemia were low birth weight (2000–2500 g). Thirteen infants (46.4%) with significant hyperbilirubinemia weighed between 2500 and 3000 g. None of the babies weighing >3000 g developed significant hyperbilirubinemia [Figure 3].
Figure 3: Birth weight distribution of significant hyperbilirubinemia.

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Type of feeding: Out of the total 28 babies with significant hyperbilirubinemia, 20 were exclusively breastfed (71.4%), top feeds were given in 3 infants, and 5 were given mixed feeding [Table 3].
Table 3: Distribution of significant hyperbilirubinemia according to the type of feeds

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Biochemical characteristics

The hematocrit levels in both the groups were measured and compared [Table 4].
Table 4: Mean hematocrit level

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The serum bilirubin levels of two groups were measured on 6th hour, 2nd, 3rd,, and 7th day [Table 5]; [Figure 4].
Table 5: Mean standard deviation of daily serum bilirubin levels and number of newborns with and without significant hyperbilirubinemia in term and late preterm babies

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Figure 4: Line diagram representing the pattern of serial bilirubin level in term and late-preterm babies.

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Out of the total 28 neonates who developed significant hyperbilirubinemia, only 1 required exchange transfusion, rest (96.4%) were treated with phototherapy. None of the babies developed complications.

  Discussion Top

This prospective study attempted to evaluate the prediction and course of significant hyperbilirubinemia in healthy-term and late-preterm neonates and correlate these findings with the difference among the two groups and the need for any intervention. Of the 150 newborns included in this study, 92 (61.4%) were term babies and 58 (38.6%) were late-preterm babies. The incidence of significant hyperbilirubinemia in the two study groups was 13.04% in term babies and 27.5% in late-preterm babies, which was statistically significant (P-value < 0.005). This study found that late-preterm infants were 2.1 times higher risk of developing significant jaundice than their term counterparts. The above finding was in concordance with a study conducted in 2004 in which the risk of developing significant hyperbilirubinemia was observed to be 2.4 times more in the late-preterm group. In another study, infants born at 37 or less weeks of gestation were found to be more likely (four times) to develop a serum bilirubin level of ≥13 mg/dL than those born at 40 weeks of gestation.

The male-to-female ratio in study population was 1.1:1, and in term and late-preterm groups the ratio was 1.1:1 and 1:1, respectively. No significant gender skew was found in the total study population. However, there was a significant difference in male-to-female distribution in late preterm babies that developed significant hyperbilirubinemia, 11 (68.75%) babies in this group were males whereas only 5 (31.25%) were females. However, no difference was found in term babies where the distribution was equal. This is probably an observation and does not have any clinical relevance as none of the previous studies showed such a gender difference in the development of significant hyperbilirubinemia.

In the present study, birth weight of the babies ranged from 2000 g to 3500 g, the minimum being 2000 g and maximum 3450 g; mean birth weight was 2600 g. There was a significant disparity between the birth weight of term and late-preterm babies; approximately 41 (70.6%) of late-preterm newborns weighed between 2000 g and 2500 g whereas only 5 (5.4%) term babies fell in this group. Also, majority of newborns who developed significant hyperbilirubinemia fell in this range. Fifteen (32.6%) babies in the birth weight range of 2000–2500 g developed significant hyperbilirubinemia, whereas only 14.6% babies with birth weight in the range of 2500–3000 g developed significant hyperbilirubinemia, which was statistically significant observation (P-value <0.01). The finding is in concordance with the fact that late preterm infants are more vulnerable to low birth weight as they are not fully developed compared to their term counterparts, and majority of infants who developed significant hyperbilirubinemia were late preterm newborns which correlate well with the above finding. A study by Maisels described low birth weight as one of the risk factors in the development of significant hyperbilirubinemia in neonates.[13],[14],[15],[16]

In accordance with the current recommendation, all mothers were encouraged to give breast feed to their children up to 6 months of age starting immediately after birth. In our study also, majority of newborns were exclusively breastfed (46.6%). Formula milk was given in 48 (32%) infants and mixed feeding was practiced in a total of 21.3% babies. When the feeding pattern of babies with significant hyperbilirubinemia was assessed, an important finding was observed, 20 (71.4%) of the 28 infants were exclusively breast fed, in 17.8% mixed feeds were given, and only 10.7% were top fed. The difference was significant with a P-value of <0.005.

The hematocrit values were compared between both the groups and no significant difference was observed (P-value > 0.01); no difference was found in the hematocrit value of babies who developed significant hyperbilirubinemia in comparison with those who did not.

The increase in bilirubin level was compared in both the groups longitudinally over a week. It was seen that in almost all babies there was an increase in serum bilirubin levels over the first week of life, but only some babies developed significant hyperbilirubinemia requiring phototherapy or exchange transfusion. The difference among the two groups, i.e., term and late preterm was studied and plotted on a graph. It was observed that there was an initial rise in serum bilirubin levels with a plateau on 4th day and significant fall on 7th day of life in term neonates, whereas in late-preterm group, serum bilirubin showed a gradual rise in the first week and total fall at 7th day was negligible compared to the term group. Moreover, the serum bilirubin levels in late-preterm group were significantly higher than their term counterparts on any postnatal day. This difference was clinically significant (P-value < 0.001) and in concordance with the previous study by Sarici et al.[17],[18] Because other risk factors for development of neonatal jaundice (e.g., sepsis, G-6PD deficiency, ABO and Rh incompatibility, and any malformation) were already taken care of, this difference in serum bilirubin levels between the two groups was entirely attributed to the difference in gestational age and birth weight. Furthermore, considering the gestational age-dependent physiologic deficiency of uridine-diphosphate-glucuronyl transferase enzyme (which at 30 and 40 weeks' gestations has only 0.1% and 1% of the activity found in adults, respectively, not reaching adult values until 8–15 weeks of postnatal age), this difference can be explained.

It was seen that most newborns who developed significant hyperbilirubinemia required phototherapy (96.1%) whereas one baby had to undergo exchange transfusion. This baby belonged to the late-preterm group with a gestational age of 35 weeks. The difference was insignificant (P-value > 0.01), but the fact that serum bilirubin levels reaching such high levels where it required exchange transfusion in an otherwise healthy late-preterm baby should not be overlooked.

  Conclusion Top

In the present study, it was found that the risk of development of significant hyperbilirubinemia in late-preterm newborns is 2.1 times higher than their term counterparts. So much so, that one baby required double volume exchange blood transfusion. It was also noticed that the pattern of rise of serum bilirubin level in term and late-preterm newborns also differs significantly. While in term babies there is an initial rise of serum bilirubin level reaching a plateau with subsequent fall at the end of first week, late-preterm group followed a different pattern, showing an initial rise and a later peak at the end of first week of life when a fall in serum bilirubin level is expected.

Likewise, this study shows a positive correlation of breastfeeding with development of significant hyperbilirubinemia. Although it is an important finding and cannot be neglected, the fact that mother's milk is superior and essential for baby's development is strongly supported. Taking this in consideration, exclusive breastfeeding is advised for every baby till 6 months of age.

We, therefore, conclude that late-preterm newborns are more vulnerable to the complications associated in early life and should not be treated as their term counterparts, especially in the approach to management of hyperbilirubinemia.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Alpay F1, Sarici SU, Tosuncuk HD, Serdar MA, Inanç N, Gökçay E. 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. 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. 2
Ballard JL, Khoury JC, Wediq K, Wang L, Eilers-Walsman BL, Lipp R. New Ballard score expanded to include extremely premature infants. J Pediatr. 1991;119:417-23.  Back to cited text no. 3
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. 4
Carbonell X, Botet F, Figueras J, Riu-Godó A. Prediction of hyperbilirubinaemia in the healthy term newborn. Acta Paediatr 2001;90:166-70.  Back to cited text no. 5
Coughtrie MW, Burchell B, Leakey JE, Hume R. The inadequacy of perinatal glucuronidation: Immunoblot analysis of the developmental expression of individual UDP- glucuronosyltransferase isoenzymes in rat and human liver microsomes. Mol Pharmacol 1988;34:729-35  Back to cited text no. 6
Ebbesen F, Andersson C, Verder H, Grytter C, Pedersen-Bjergaard L, Petersen JR, et al. Extreme hyperbilirubinaemia in term and near-term infants in Denmark. Acta Paediatr 2005;94:59-64.  Back to cited text no. 7
Ip S, Chung M, Kulig J, O'Brien R, Sege R, Glicken S, et al. An evidence-based review of important issues concerning neonatal hyperbilirubinemia. Pediatrics 2004;114:e130-e153.  Back to cited text no. 8
Kawade N, Ohishi S. The prenatal and postnatal development of UDP glucuronyl transferase activity towards bilirubin and the effect of premature birth on this activity in the human liver. Biochem J 1981;196:257-60.  Back to cited text no. 9
Kelly JM. General care. In: Avery GB, Fletcher MA, MacDonald MG, editors. Neonatology. Pathophysiology and Management of the Newborn. Philadelphia, PA: Lippincott Williams & Wilkins; 1999. pp 333-43.  Back to cited text no. 10
Keren R, Tremont K, Luan X, Cnaan A. Visual assessment of jaundice in term and late preterm infants. Arch Dis Child Fetal Neonatal Ed 2009;94:F317-22.  Back to cited text no. 11
Lloyd I. Kramer cephalocaudal progression of neonatal jaundice. J Dis Child 1969;118:454-8.  Back to cited text no. 12
Maisels MJ, Baltz RD, Bhutani VK, Newman TB, Rosenfeld W, Stevenson DK, et al. Neonatal jaundice and kernicterus. Pediatrics 2001;108:763-5.  Back to cited text no. 13
Maisels MJ, Baltz RD, Bhutani V, Newman TB, Palmer H, Rosenfeld W, et al. Management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics 2004;114:297-316.  Back to cited text no. 14
Maisels MJ, Gifford K, Antle CE, Leib GR. Jaundice in the healthy newborn infant: A new approach to an old problem. Pediatrics 1988;81:505-11.  Back to cited text no. 15
Maisels MJ, Newman TB. Kernicterus in otherwise healthy, breast-fed term newborns. Pediatrics 1995;96:730-3.  Back to cited text no. 16
Sarici SU, Serdar MA, Korkmaz A, Erdem G, Oran O, Tekinalp G, et al. Incidence, Course, and Prediction of Hyperbilirubinemia in Near-Term and Term Newborns. Pediatrics 2004;113;775-80.  Back to cited text no. 17
Sarici SU, Yurdakok M, Serdar MA, Oran O, Erdem G, Tekinalp G, et al. An early (sixth-hour) serum bilirubin measurement is useful in predicting the development of significant hyperbilirubinemia and severe ABO hemolytic disease in a selective high-risk population of newborns with ABO incompatibility. Pediatrics 2002;109:e53.  Back to cited text no. 18


  [Figure 1], [Figure 2], [Figure 3], [Figure 4]

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]


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