|Year : 2017 | Volume
| Issue : 4 | Page : 220-224
Significant hyperbilirubinemia in near-term and term newborns: A case–control Study
Nishanth Rajan, Peter Prasanth Kumar Kommu, Lalitha Krishnan, Manikandan Mani
Department of Pediatrics, Neonatal Unit, Pondicherry Institute of Medical Sciences, Puducherry, India
|Date of Web Publication||17-Oct-2017|
Department of Pediatrics, Neonatal Unit, Pondicherry Institute of Medical Sciences, Puducherry - 605 014
Source of Support: None, Conflict of Interest: None
Background: Hyperbilirubinemia is a common and in most cases, benign problem in neonates. Data in term and near-term infants with respect to the pattern of neonatal hyperbilirubinemia from South India are lacking, hence this study. Aim: The aim was to compare the incidence of significant hyperbilirubinemia between near terms and term neonates. Materials and Methods: A prospective case–control study done in a Tertiary Care Hospital, in South India over a period of 18 months (October 2012–April 2014) involving two hundred and sixty-four infants (cases 132 near-term babies, and 132 terms controls). Setting: Tertiary Care Hospital, in South India over a period of 18 months (October 2012–April 2014). Participants: Two hundred and sixty-four infants, cases 132 near-term babies, and 132 terms controls. Exclusion Criteria: Babies with hemolytic jaundice, polycythemia, hypothyroidism, culture-proven sepsis, major congenital anomalies. Cord and 24 h total serum bilirubin was done on cases and controls and all babies were followed up till 72 h or till discharge for significant hyperbilirubinemia. Results: Mean cord blood bilirubin values were significantly different between the near terms and terms 1.9 ± 1.41 and 1.46 ± 0.50 mg/dl (P = 0.0001). Mean 24 h serum bilirubin was higher in near terms, but the difference was not statistically significant (6.89 ± 0.41 and 6.83 ± 0.34, P = 0.764). Incidence of significant hyperbilirubinemia was statistically higher in the near terms as compared to terms (23/109 vs 7/125, P = 0.002). Conclusion: Although cord blood bilirubin was higher in near-term infants, the 24 h bilirubin did not show any significant difference between the two groups. Clinically, however, significant hyperbilirubinemia requiring phototherapy was significantly higher in near-term infants. There is clearly a requirement for at-risk assessment for severe hyperbilirubinemia before discharge and close follow-up thereafter for near-term infants.
Keywords: Near term, phototherapy, significant hyperbilirubinemia
|How to cite this article:|
Rajan N, Kumar Kommu PP, Krishnan L, Mani M. Significant hyperbilirubinemia in near-term and term newborns: A case–control Study. J Clin Neonatol 2017;6:220-4
|How to cite this URL:|
Rajan N, Kumar Kommu PP, Krishnan L, Mani M. Significant hyperbilirubinemia in near-term and term newborns: A case–control Study. J Clin Neonatol [serial online] 2017 [cited 2018 Nov 13];6:220-4. Available from: http://www.jcnonweb.com/text.asp?2017/6/4/220/216905
| Background|| |
Hyperbilirubinemia is a common and in most cases, benign problem in neonates. The production of bilirubin in neonates is two–three fold versus that of adults. Jaundice is observed during the 1st week of life in approximately 60% of term infants and 80% of preterm infants. As described by Stevenson et al., neonatal hyperbilirubinemia occurs when there is imbalance between bilirubin production and elimination. Although bilirubin may have a physiologic role as an antioxidant, elevations of unconjugated bilirubin are potentially neurotoxic. Near-term infants are functionally considered as full term in our common obstetric and pediatric practice. However, it may be inappropriate to continue practicing similarly. Near-term infants have increased the risk of complications such as neonatal hyperbilirubinemia, feeding problems, etc., when compared to term infants although the size and apparent functional maturity of both near-term and term infants are similar. Hence, there is a need for prolonged hospitalization due to the complications, which further increases the cost.,, Hence, these infants are representing an unrecognized at-risk neonatal population.,
Late preterm babies are at higher risk for severe hyperbilirubinemia than term infants since there is decrease in hepatic bilirubin conjugation capacity, and decrease in activity of the uridine diphosphate glucuronyltransferase (UDPGT) enzyme as the gestational age (GA) decreases.,, However, even in recent studies, regarding neonatal hyperbilirubinemia, near-term newborns are considered same as term babies though the strong negative correlation between GA and the risk for significant hyperbilirubinemia is well known.,,
The average length of hospital stay has dropped from 4 days in 1970s to 2 days presently. Rising bilirubin levels in neonates usually reach the maximum between 72 and 120 h of life, and there is an increased rate of readmission before 6 days of life for hyperbilirubinemia., Hospital readmission rates are also high in neonates discharged before 72 h of life.,,, In a study conducted in India, 8.3% of 831 early discharged infants needed readmission with the three most common conditions being jaundice, dehydration, or feeding problems., Consequently, reduced hospital stay potentially increases the risk of missing out significant hyperbilirubinemia since the discharge occurs when the serum bilirubin is still increasing. There is not enough conclusive evidence that infants discharged early have increased morbidity. One study has suggested that the addition of clinical risk factors, such as GA, can significantly increase the predictive accuracy of the predischarge bilirubin.
In a retrospective study of late preterm infants and term infants (n = 2,840), development of significant hyperbilirubinemia was almost three times more likely (odds ratio = 2.6, 95% confidence interval [0.5–4.5]) in infants born at <38 weeks gestation when compared with the reference group of infants born at 38 and 39 weeks gestation. Significant hyperbilirubinemia was defined as a postdischarge total serum bilirubin (TSB) >95th percentile on a TSB nomogram. One important limitation of this study is that GA was rounded to the nearest week.
There are no studies that compared term and near-term infants with respect to the pattern of neonatal hyperbilirubinemia in the first few days of life in South India, and hence, this study was planned with the aim of comparing the incidence of significant hyperbilirubinemia between near terms and term neonates.
| Procedure|| |
A prospective case–control study was done at a Tertiary Care Hospital, South India, over a period of 18 months (October 2012–April 2014). Two hundred and sixty-four inborn infants were included in the study (132 cases and 132 controls). Case: A near-term infant born between 35° and 37+6 weeks of gestation. Control: Next-term neonate born after 38 completed weeks of gestation, sex matched.
Sample size was calculated using the formula:
Where, P = (p1+ p2)/2, q = 1 − p, p1= number of babies with significant hyperbilirubinemia among the cases in an article referred, p2= number of babies with significant hyperbilirubinemia among the controls in an article referred, α – Level of significance (0.05) and β – Power of study (80%).
The primary outcome of the study was to compare the incidence of significant hyperbilirubinemia among the cases and controls. The secondary outcomes were to compare the mean serum bilirubin among cases and controls at birth (from cord) and at 24 h.
Babies with hemolytic jaundice, polycythemia requiring partial exchange, proven hypothyroidism, culture-proven sepsis and major congenital anomalies were excluded from the study. Parameters studied were cord blood and 24 h TSB, mother and baby's blood group, hemolytic work up when required (complete blood count, peripheral smear, reticulocyte count, direct Coomb's test, total and direct serum bilirubin)
The study protocol was approved by the Institutional Ethics Committee. Written informed consent was obtained for cord blood bilirubin. GA of the mother was determined by dating scan if available or according to the first day of the mother's last menstrual period or as decided by treating obstetrician. Blood group and type from cord blood and 24 h serum bilirubin are a routine service offered to all newborns in the department. Consent was also obtained from the mothers of cases and controls for using their baby's de-identified data for publication. If any baby had evidence of hemolysis (Rhesus hemolytic disease, a positive direct Coomb's test, reticulocytosis, or a peripheral smear compatible with hemolysis), they were excluded from the study. All babies received Vitamin K 1 mg intramuscularly immediately after birth. No prophylactic intervention for hyperbilirubinemia was employed. For all babies, who were enrolled in the study, serum bilirubin values were sent at 24 h of life. 1 ml of venous blood for serum bilirubin was collected under strict aseptic precautions after the mother was explained about the procedure. The samples were taken immediately to the biochemistry laboratory, and serum bilirubin measurements were done by colorimetric method in the INTEGRA 400 machine. The definition of significant hyperbilirubinemia for the newborns in the study was made on the basis of the American Academy of Pediatrics guidelines.
All newborns with significant hyperbilirubinemia were started on phototherapy and further management was done as per the attending physician. Environmental lighting was always constant throughout the study period.
Baby details such as birth weight, length, head circumference and chest circumference, the time of initiation of breastfeeding, number of times the baby was fed, number of urine, stools/day, and other clinical risk factors were documented.
The data were entered in Epi-info and analyzed in SPSS version 18 software.
Statistical analysis was performed using Student's t-test for continuous predictors (GA, maternal age, gender, anthropometry, no of breastfeeds/day, complications in the mother and mean serum bilirubin) and Chi-square test for categorical data (mode of delivery, gravida, and incidence of significant hyperbilirubinemia).
| Results|| |
This was a prospective case–control study done from October 2012 to April 2014 in a tertiary care hospital with level II neonatal intensive care. A total of 264 babies, 132 cases (near-term babies) and 132 controls (term babies) were recruited into the study after obtaining informed consent from the parents. Male and female ratio was the same in both groups since they were sex matched (males - 152 [57.5%] and females - 112 [42.5%]). The mean GA was 36.55 (0.75) weeks for the cases and that of controls was 39.25 weeks (0.84). Maternal and neonatal demographics did not show any statistically significant difference between the two groups [Table 1].
The mean cord blood bilirubin value for near term and term was 1.9 ± 1.41 and 1.46 ± 0.50 mg/dl, respectively. There was statistically significant difference between two groups in the mean cord blood bilirubin values (P = 0.0001). There was no statistically significant difference between the two groups in the mean serum bilirubin values at 24 h [Table 2].
However, 30 (11.3%) babies had significant hyperbilirubinemia of which 23/30 (76.6%) of them were near terms. There was statistically significant difference between two groups (P = 0.002) [Figure 1].
| Discussion|| |
Near-term infants are at a higher risk of mortality and morbidity than term infants as they are less physiologically and metabolically mature than term infants.
Jaundice in the newborn is a common cause for prolonged stay in hospital as well as hospital readmission during the first 2 weeks of life. Near terms are identified as one of the important risk factors for the development of significant hyperbilirubinemia thereby resulting in kernicterus.
Jaundice in near-term infants is more prevalent, pronounced, and protracted than term infants because of the delayed maturation and lower concentration of UDPGT and immature gastrointestinal function.
Early discharge is making the management of jaundice quite difficult since it is the one of the cause for hospital readmission.
Hence, in 2004, the American Academy of Pediatrics recommended all newborn infants be assessed before discharge for the risk of developing significant hyperbilirubinemia subsequently.
The aim of the study was to compare the incidence of significant hyperbilirubinemia in term and near-term infants.
Although the patients are from different socioeconomic status, most of the baseline characteristics are similar. There was no statistical significant difference between the two groups with respect to maternal age, antenatal complications, gravidae, and mode of delivery. GA and the anthropometry were statistically significant as expected.
The mean cord blood bilirubin for near terms (1.95 mg/dL) was higher as compared to terms (1.46 mg/dL) in our study. However, another study has shown the mean cord blood bilirubin levels to be more in term neonates and that they might develop significant hyperbilirubinemia later requiring phototherapy.
A prospective analytical study that studied the predictors of significant hyperbilirubinemia in late preterms concluded that bilirubin levels measured at 24 h better predicts the development of subsequent significant jaundice. This was not however seen in our study. Another study showed that predischarge screening for significant hyperbilirubinemia is a better predictor for subsequent phototherapy.
Many studies suggest that preterm/near-term babies are at higher risk for developing significant hyperbilirubinemia. In this study as in others, the incidence of significant hyperbilirubinemia was more in near-term infants when compared to term infants at 24 h.,,,,,,
Even though there was difference in the mean cord serum bilirubin, the rate of rise of bilirubin over 24 h showed no significant difference; significant hyperbilirubinemia was more prevalent in near-term infants. Another study showed that the rate of rise in bilirubin in their population was more rapid in the initial 24 h of life (0.22 mg/dL), comparing with 24–48 h and after 48 h. However, they failed to compare the near term/preterm and term group.
| Conclusion|| |
This study found cord blood bilirubin was higher in near-term infants, but the 24 h bilirubin did not show any significant difference between the two groups. Clinically, however, significant hyperbilirubinemia requiring phototherapy was significantly higher in near-term infants. There is clearly a requirement for at-risk assessment for severe hyperbilirubinemia before discharge and close follow-up thereafter for near-term infants.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Muslu N, Dogruer ZN, Eskandari G, Atici A, Kul S, Atik U, et al.
Are glutathione S-transferase gene polymorphisms linked to neonatal jaundice? Eur J Pediatr 2008;167:57-61.
Stevenson DK, Fanaroff AA, Maisels MJ, Young BW, Wong RJ, Vreman HJ, et al.
Prediction of hyperbilirubinemia in near-term and term infants. Pediatrics 2001;108:31-9.
Wang ML, Dorer DJ, Fleming MP, Catlin EA. Clinical outcomes of near-term infants. Pediatrics 2004;114:372-6.
Davidoff MJ, Dias T, Damus K, Russell R, Bettegowda VR, Dolan S, et al.
Changes in the gestational age distribution among U.S. Singleton births: Impact on rates of late preterm birth, 1992 to 2002. Semin Perinatol 2006;30:8-15.
Marrocchella S, Sestilli V, Indraccolo U, de Rosario F, Castellana L, Mastricci AL, et al.
Late preterm births: A retrospective analysis of the morbidity risk stratified for gestational age. Springerplus 2014;3:114.
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.
Lavanya KR, Jaiswal A, Reddy P, Murki S. Predictors of significant jaundice in late preterm infants. Indian Pediatr 2012;49:717-20.
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:e130-53.
Rather GN, Jan M, Rafiq W, Gattoo I, Hussain SQ, Latief M, et al.
Morbidity and mortality pattern in late preterm infants at a tertiary care hospital in jammu & kashmir, northern india. J Clin Diagn Res 2015;9:SC01-4.
Narang A, Gathwala G, Kumar P. Neonatal jaundice: An analysis of 551 cases. Indian Pediatr 1997;34:429-32.
Gourley GR. Breast-feeding, neonatal jaundice and kernicterus. Semin Neonatol 2002;7:135-41.
Schneider AP 2nd
. Breast milk jaundice in the newborn. A real entity. JAMA 1986;255:3270-4.
Newman TB, Easterling MJ, Goldman ES, Stevenson DK. Laboratory evaluation of jaundice in newborns. Frequency, cost, and yield. Am J Dis Child 1990;144:364-8.
Maisels MJ, Kring E. Transcutaneous bilirubin levels in the first 96 hours in a normal newborn population of and ≥35 weeks' gestation. Pediatrics 2006;117:1169-73.
Shapiro-Mendoza CK, Tomashek KM, Kotelchuck M, Barfield W, Nannini A, Weiss J, et al.
Effect of late-preterm birth and maternal medical conditions on newborn morbidity risk. Pediatrics 2008;121:e223-32.
Setia S, Villaveces A, Dhillon P, Mueller BA. Neonatal jaundice in Asian, white, and mixed-race infants. Arch Pediatr Adolesc Med 2002;156:276-9.
Tomashek KM, Shapiro-Mendoza CK, Weiss J, Kotelchuck M, Barfield W, Evans S, et al.
Early discharge among late preterm and term newborns and risk of neonatal morbidity. Semin Perinatol 2006;30:61-8.
Singhal PK, Singh M, Paul VK, Deorari AK, Ghorpade MG. Spectrum of neonatal hyperbilirubinemia: An analysis of 454 cases. Indian Pediatr 1992;29:319-25.
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.
Keren R, Bhutani VK, Luan X, Nihtianova S, Cnaan A, Schwartz JS, et al.
Identifying newborns at risk of significant hyperbilirubinaemia: A comparison of two recommended approaches. Arch Dis Child 2005;90:415-21.
Berk MA, Mimouni F, Miodovnik M, Hertzberg V, Valuck J. Macrosomia in infants of insulin-dependent diabetic mothers. Pediatrics 1989;83:1029-34.
Engle WA, Tomashek KM, Wallman C, Committee on Fetus and Newborn, American Academy of Pediatrics. “Late-preterm” infants: A population at risk. Pediatrics 2007;120:1390-401.
Huang HC, Yang HI, Chang YH, Chang RJ, Chen MH, Chen CY, et al.
Model to predict hyperbilirubinemia in healthy term and near-term newborns with exclusive breast feeding. Pediatr Neonatol 2012;53:354-8.
Ezhilvannan NR, Vani HN, Niranjan HS. Clinical profile and early hospital outcome of late preterms admitted in a tertiary care neonatal unit from South India. Int J Contemp Pediatr 2015;2:216-20.
Romagnoli C, Tiberi E, Barone G, Curtis MD, Regoli D, Paolillo P, et al.
Development and validation of serum bilirubin nomogram to predict the absence of risk for severe hyperbilirubinaemia before discharge: A prospective, multicenter study. Ital J Pediatr 2012;38:6.
Sun G, Wang YL, Liang JF, Du LZ. Predictive value of umbilical cord blood bilirubin level for subsequent neonatal jaundice. Zhonghua Er Ke Za Zhi 2007;45:848-52.
Yu Z, Han S, Wu J, Li M, Wang H, Wang J, et al.
Validation of transcutaneous bilirubin nomogram for identifying neonatal hyperbilirubinemia in healthy Chinese term and late-preterm infants: A multicenter study. J Pediatr (Rio J) 2014;90:273-8.
Bhutani VK, Stark AR, Lazzeroni LC, Poland R, Gourley GR, Kazmierczak S, et al.
Predischarge screening for severe neonatal hyperbilirubinemia identifies infants who need phototherapy. J Pediatr 2013;162:477-820.
[Table 1], [Table 2]