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Year : 2020  |  Volume : 33  |  Issue : 1  |  Page : 167-172

Study of some factors associated with prolonged neonatal jaundice

1 Department of Pediatrics, Faculty of Medicine, Menoufia University, Menoufia, Egypt
2 Department of Pediatrics at Ministry of Health, Benha, Qaliobia, Egypt

Date of Submission10-Sep-2018
Date of Decision13-Oct-2018
Date of Acceptance22-Oct-2018
Date of Web Publication25-Mar-2020

Correspondence Address:
Ismail A.A. Abdulhadi
Sidi-Mosy Mosque, Sobk El Dahhak, Bagor, Menoufia 32831
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/mmj.mmj_279_18

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The aim was to study some factors associated with prolonged neonatal jaundice and to find out the important investigations that should be performed to such cases.
Prolonged neonatal jaundice represents a dilemma for many doctors. Many factors are responsible for its occurrence.
Patients and methods
This is a cross-sectional study on 55 cases of prolonged neonatal jaundice, conducted from Menoufia and Benha university hospitals from November 2017 to July 2018. All cases were subjected to history taking, clinical assessment, and investigations including complete blood count, c-reactive protein, total and direct serum bilirubin, blood group and RH factor for the cases and their mothers and urine analysis. We investigated cases with prolonged direct hyperbilirubinemia for alanine aminotransferase, aspartate aminotransferase and abdominal ultrasonography.
Cases aged ranged from 14 to 49 days of life, with mean age '19.3 ± 5.3' that included nine preterm and 46 full term. Prolonged indirect neonatal hyperbilirubinemia was found in 85% of cases, while 15% had direct hyperbilirubinemia. All cases showed normal complete blood count. C-reactive protein is negative in all cases. Breast-milk jaundice was found in 32.7%, ABO incompatibility in 22%, while RH incompatibility in only 3.6% of cases. Pyuria greater than or equal to 6 pus cells/ High power field (HPF) was found in 20% of cases and they had higher serum bilirubin than the other cases without pyuria.
The most common associated factor was breast-milk jaundice, then ABO incompatibility and then pyuria. Blood group identification to the mother and their neonates and urine analysis have a great diagnostic value in these cases. Larger studies are needed to confirm these findings.

Keywords: breast-milk jaundice, neonatal urinary tract infection, prolonged jaundice

How to cite this article:
Tawfeek MA, Ellahony DM, Abdulhadi IA. Study of some factors associated with prolonged neonatal jaundice. Menoufia Med J 2020;33:167-72

How to cite this URL:
Tawfeek MA, Ellahony DM, Abdulhadi IA. Study of some factors associated with prolonged neonatal jaundice. Menoufia Med J [serial online] 2020 [cited 2020 Aug 15];33:167-72. Available from: http://www.mmj.eg.net/text.asp?2020/33/1/167/281293

  Introduction Top

Prolonged jaundice can be defined as yellowish discoloration of skin and mucous membranes after 14 days in term neonates, and 21 days in preterm neonates. Distinguishing between conjugated and unconjugated hyperbilirubinemia is important to establish diagnosis. Unconjugated hyperbilirubinemia is defined as a conjugated bilirubin level less than 20% of total bilirubin. The most common cause of which is breast-milk jaundice, with a reported incidence of 36% in the third week of life[1]. Newborns with breast-milk jaundice are clinically well and there is no any reported case of kernicterus from breast-milk jaundice[2]. If breastfeeding is stopped, the bilirubin level will fall rapidly in 48 h and if nursing is then resumed, the bilirubin may rise for 2–4 mg/dl but usually will not reach the previous high level[3]. Some pathological conditions can also cause prolonged unconjugated hyperbilirubinemia as haemolytic diseases (due to Rh or AB0 incompatibility, or G6PD deficiency), urinary tract infection (UTI), Crigler-Najjar or Gilbert syndromes[4],[5]. UTI is attributed a very important reason for prolonged jaundice, and it is well known that UTI can occur without apparent signs, and jaundice is an important and sometimes the presenting feature of UTI[6] and it occurs in 3–21% of term neonates with unexplained indirect hyperbilirubinemia during the first 2 weeks of life[7]. Nickavar et al.[8] and Hannam et al.[9]studies recommended performing urine analysis to cases of prolonged neonatal jaundice to exclude associated UTI; theydepended on urine bag in collecting samples from males and females. Three studies have proved that the presence of pyuria is a promising factor for diagnosis of UTI. Chaudhari et al.[10] study recommended that pyuria thresholds of three white blood cells (WBC)/HPF in dilute urine and six WBC/HPF in concentrated urine are recommended for the presumptive diagnosis of UTI. Whiting et al.[11] studyfound that the pyuria threshold used for the presumptive diagnosis of UTI ranged from greater than or equal to 5 to 10 WBC/HPF by manual microscopy, while Shah et al.[12] study, using an automated system recommended the dependence on only greater than or equal to 2 pus cells/HPF in the presumptive diagnosis of UTI. Indirect hyperbilirubinemia associated with UTI is considered to be due to haemolysis caused by Escherichia coli and other Gram (–) microorganisms. Even slight haemolysis may increase the levels of serum bilirubin due to immature conjugation mechanisms in infants. So, bilirubin levels may rise as an alerting sign even in clinically less severe UTIs[13]. Omar et al.[6] study found that the duration of phototherapy is shorter and exchange transfusion requirements were less likely in jaundiced neonates with UTIs. These data suggested that neonatal hyperbilirubinemia associated with UTI leads to fewer complications. Prolonged conjugated hyperbilirubinemia is defined as a conjugated bilirubin level greater than 20% of the total bilirubin, it is only related to the neonatal causes of cholestatic liver disease such as biliary atresia, hepatitis and metabolic disorders[14]. The National Institute for Health and Care Excellence (NICE) recommended screening infants presenting with prolonged jaundice with complete blood count, total and direct serum bilirubin, Coombs test, urine culture and metabolic screening[15]. The aim of our study was to study some factors associated with prolonged neonatal jaundice and to find out the important investigations that should be performed to such cases.

  Patients and Methods Top

The study protocol was approved by the ethical committee of Faculty of Medicine, Menoufia University. The study was a cross-sectional study, conducted on 55 neonates with prolonged neonatal jaundice from November 2017 to July 2018 in the neonatal intensive care unit (NICU) and outpatient clinic of Menoufia University Hospital and Benha Children Hospital.

We have excluded from our study the cases of neonatal septicaemia or meningitis or encephalitis. Also, we excluded babies with chromosomal disease or congenital anomalies. All cases were subjected to full detailed history taking, meticulous clinical examination was done to all cases, including general and local examinations. General examination includes anthropometric measures which involve weight, length and head circumference. We did not forget to record vital signs for all cases including temperature, respiratory rate pulse and blood pressure measurement or any abnormal skin and mucous membrane colours like pallor, jaundice or cyanosis. Local examination was done to all cases by full systematic review but special emphasis on head examination to exclude the presence of cephalohematoma, chest examination including symmetry, breath sounds and signs of respiratory distress, heart examination including heart rate and presence of audible murmurs abdominal examination to exclude any abdominal mass or hepatosplenomegaly, genitalia to exclude erythema, structural abnormalities, phimosis, periurethral or tenderness in the external urethra or presence of congenital anomalies like hypospadias in male causing UTI, neurological examination including muscle tone (hypotonia or hypertonia) and reflexes (Moro and grasp reflexes) to assess neurological status of the baby. Investigations were done to all cases, including laboratory investigations as complete blood count using electronic counter system kx-21N USA, c-reactive protein using latex serology test[16], total and direct serum bilirubin and alanine aminotransferase, aspartate aminotransferase using automated (Cobas C 111, Basel) (Roche, Switzerland), blood group and RH for babies and their mothers by slide test on EDTA blood sample use ABO antisera[17] and urine analysis using urine bag and under complete aseptic technique for microscopic examination[18]. Radiology was done only to cases with direct hyperbilirubinemia in the form of abdominal ultrasonography using ultra sonogram 'GE Healthcare LOGIQ 180' (Chicago, Illinois, United States).

The cases were divided into two groups: group A and group B according to their gestational age. Group A contains term babies more than or equal to 37 weeks including 46 neonates. Group B contains preterm babies less than 37 weeks including nine neonates.

After that, and according to the presence of pyuria (≥6 pus cells/HPF), all cases were divided into two groups: group 1 and group 2 in concentrated urine by manual microscopy to demonstrate the effect of the presence of pyuria on having prolonged jaundice. Group 1 includes cases whose urine analysis contains pus cells greater than or equal to six pus cells per high-power field, while group 2 includes cases whose urine analysis is free from pus cells.

Statistical analysis

Continuous variables with normal distribution were expressed as the mean ± SD, while quantitative variables with non-normal distribution were presented as range. The statistics was done using IBM SPSS Statistics for Windows, version 20 (IBM Corp., Armonk, N.Y., USA) Also, we used Microsoft Office Excel 2007 (Microsoft Way, Redmond, Washington, U.S.A) to make charts of results.

  Results Top

A total of 55 well infants aged 14–49 days were referred for the study. As shown in [Table 1] which demonstrates the demographic data of cases, all cases present greater than or equal to 14th day of life with predominance (78%) from 14th to 21st day. There was obvious male predominance and feeding methods were vastly different: 18 babies were exclusively breast fed, nine were formula fed and the remaining cases were mixed feeding. [Table 2] shows the clinical data and vital signs of studied cases and fortunately, most findings were normal. As shown in [Table 3], the complete blood count of all studied cases showed normal findings, but c-reactive protein was negative in all cases. Prolonged indirect hyperbilirubinemia was found in 49 (85%) of cases, while eight (15%) cases had prolonged direct hyperbilirubinemia. Many risk factors were found among cases as shown in [Table 4]. Breastfeeding had the upper hand among all risk factors. Eighteen cases had breast-feeding jaundice (32.7%) of cases. ABO incompatibility was found in 12 (22%) cases of cases. Pyuria greater than or equal to six pus cells per high-power field was found in 11 (20%) of cases. RH incompatibility was found only in two (3.6%) of cases. Abdominal ultrasonography, done to cases of direct hyperbilirubinemia, showed an almost muddy gall bladder for follow-up except one case where there was a dilated common bile duct for hepatobiliary scintigraphy.
Table 1: Demographic data of studied cases

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Table 2: Clinical data of studied cases

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Table 3: Laboratory investigations of studied cases

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Table 4: The various risk factors that all cases were subjected

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On dividing the cases into two groups, group A 'term babies' and group B 'preterm babies, group A includes cases whose gestational age is greater than or equal to 37 weeks, there were 46 (83.6%) of all cases (23 males and 23 females) and their age ranged from 14 to 35 days with mean age of 18 ± 4. Group B includes cases less than 37 weeks, there were nine (16.4%) cases of all cases (six males and three females), and their age ranged from 21 to 49 days with mean age of 24 ± 8.2 days. Both the groups A and B did not show any difference regarding the exposure to ABO incompatibity '22% in both groups', breast feeding was exclusive to term group A '40% in group A 0% in group B', while pyuria and Rh incompatibity were higher in preterm group B '33%, 11%' than group A '17%, 2%', respectively.

By dividing the cases into two groups 1 and 2; group 1 contains 11 cases (nine males and two females), and their age ranged from 15 to 42 with mean age of '18 ± 3.6' days and mean weight of '3150 ± 348 g', while group 2 contains 44 cases (21 males and 23 females), and their age ranged from 14 to 49 with mean age of '19.5 ± 5.6' days and mean weight of '3305 ± 482 g'.

As shown in [Figure 1], the male predominance of group 1 was obvious (81%), while there was no difference in gender in group 2. According to gestational age, the majority of the cases in both the groups was full term but the prematurity was larger in group 1 '18%' in contrast to group 2 '9%'. Caesarian section delivery had a big chance in both groups 1 and 2: 81%, 91%, respectively, but normal vaginal delivery was 18% in group 1 and 9% in group 2. [Table 5] shows the different laboratory findings in group 1 and 2; the total leucocytic count mean is slightly elevated in group 1 compared to group 2. Also, serum bilirubin mean was higher in group 1 than in group 2. The two groups were widely different in exposure to risk factors. As shown in [Figure 1], group 1 had higher association to the prematurity, vaginal delivery, RH incompatibility, and maternal UTI than group 2.
Table 5: The comparison between group 1 and group 2 in different laboratory findings

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Figure 1: The comparison between group 1 and group 2 according to exposure to risk factors.

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  Discussion Top

This study was performed to identify the common risk factors associated with prolonged neonatal hyperbilirubinemia. In accordance with the 'NICE[15]' guidelines, we have found that all term babies presented with prolonged jaundice after the 14th day with mean age of 18, while all preterm babies presented after 21 days with mean age of 24. There is no relationship between the gender and the prolongation of neonatal jaundice except if the baby had UTI. In our study, the most common risk factor was breastfeeding '32.7%', then ABO incompatibility '22%' and then pyuria '20%'. Parvathamma et al.[1] study found that breast-feeding jaundice was also the most common associated risk factor 82% among studied cases, and UTI in only 2% of cases. In contrast to Omar et al.[6] study, they found that UTI was 21% in infants younger than four weeks. Tola et al.[19] study found that 11% of 1750 Iranian neonates with prolonged jaundice had UTI, and all of them recommended screening of UTI in asymptomatic prolonged jaundiced infants. After dividing the All cases into two groups according to the presence or absence of pyuria, we have found that the mean weight of group 1 is less than the mean of group 2, the prematurity is higher in group 1 than group 2 and this means that UTI is more common in lower-birth-weight infants and preterm babies. Bilgen et al.[20] study and Omar et al.[6] study found the same results. However, birth weight and gestational age had no significant correlation to UTI in Nickavar et al.[8] study. Male predominance was found in 82% of patients less than 8 weeks due to increased incidence of structural abnormalities, phimosis, periurethral colonization, and increased sensitivity to bacterial infections [8,21–23] and this is the same result we have found. In our study, the vaginal delivery percentage was more in group 1 and this means that UTI is more associated with babies delivered vaginally and Chen et al.[24] and Omar et al.[6] studies found the same results. A lot of risk factors have been associated with babies of group 1 such as breastfeeding which was more than those in group 2 and this is in agreement with Omar et al.[6] study; also, the presence of maternal UTI during pregnancy was present only in group 1 and this is with the fact that maternal urinary tract infection is as a risk factor for neonatal urinary tract infection which is recommended by both Tola et al.[19] and Emamgorashi et al.[25] studies. In group 1, the mean of the total leucocytic count is slightly higher than group 2, meaning that UTI is associated with elevated leucocytic count, this is with Nickavar et al.[8] study. Also, the mean of prolonged total serum bilirubin was larger in group 1 than in group 2 and this is in agreement with all studies that found that prolonged neonatal hyperbilirubinemia is associated with UTI[6],[7],[13],[19],[24],[26],[27],[28]. Also, indirect hyperbilirubinemia was higher in group 1 than group 2 and this is in agreement with Omar et al.[6] study.

  Conclusion Top

The study showed that the most common associated factor of prolonged neonatal jaundice was breast-milk jaundice, then ABO incompatibility and then pyuria. Blood group identification to the mother and infant and urine analysis have a great diagnostic value in these cases. Pyuria greater than or equal to 6 pus cells/HPF is found in 20% of cases, also these cases had higher mean serum bilirubin 'total, direct and indirect' than the cases with free urine analysis, so UTI must be excluded in cases with prolonged neonatal hyperbilirubinemia. Larger studies are needed to confirm these findings.

Our recommendations are to increase the medical awareness about the prolonged neonatal hyperbilirubinemia; to take the history of feeding as the breast-feeding jaundice is the main associated risk factor, to do blood grouping of mother and infant to exclude the haemolysis due to ABO incompatibility and finally, to do routine urine analysis in these infants to exclude the presence of pyuria.

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Conflicts of interest

There are no conflicts of interest.

  References Top

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  [Figure 1]

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


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