|Year : 2020 | Volume
| Issue : 2 | Page : 112-117
Evaluation of cord blood alkaline phosphatase levels as an indicator of neonatal jaundice
Doha Mohammed El-Amin1, Yasser Abd El-Rheman Ahmed2, ALaa Mohammed Hashim3, Ahmed Hagag Asmail4
1 Resident of Pediatric and Neonatology at Minia General Hospital, El-Minia, Egypt
2 Professor of Pediatric and Neontology, Faculty of Medicine, Al-Azhar University, Assiut, Egypt
3 Assistant Professor of Clinical Pathology, Faculty of Medicine, Al-Azhar University, Assiut, Egypt
4 Lecturer of Pediatric and Neonatology, Faculty of Medicine, Al-Azhar University, Assiut, Egypt
|Date of Submission||01-Jul-2019|
|Date of Decision||03-Sep-2019|
|Date of Acceptance||01-Oct-2019|
|Date of Web Publication||24-Jul-2020|
Doha Mohammed El-Amin
Ahmed Ali, BSc, 2012 – Minia University, Resident of Pediatric and Neonatology at Minia General Hospital El-Minia
Source of Support: None, Conflict of Interest: None
Introduction Neonatal jaundice remains an important neonatal issue, and the condition is mostly benign. Jaundice is a complex disease of high bilirubin levels in the body and yellowing of the skin and mucous membranes. Hyperbilirubinemia is associated with encephalopathy and kernicterus, resulting in permanent disability. Because babies are discharged early, detection and diagnosis of hyperbilirubinemia are delayed in some cases. Therefore, early diagnosis of jaundice and timely actions are necessary. Several methods have been used to determine the risk of neonatal hyperbilirubinemia. Alkaline phosphatase (ALP) is an intracellular enzyme found abundantly in red blood cells. It is a hydrolase enzyme and responsible for removing phosphate from many types of molecules. Our aim in this study was to investigate whether cord blood ALP level during the first 6 h of live of newborn could be used for the early diagnosis and prediction of hyperbilirubinemia in newborns.
Patients and methods This was a prospective study carried out during the period from June 2018 to December 2018 at El-Mania General Hospital. This study included a total of 60 neonates: 30 full-term infants and 30 preterm infants. A total of 60 babies were evaluated, starting from the sixth hour after birth, and cord blood ALP levels were analyzed. We performed an assessment of the complete medical history (maternal history and neonatal history). Third day of live measured transcutaneous bilirubin of neonate, and seventh day we measured serum bilirubin (total and direct).
Results The present study showed that infants with high cord blood ALP levels are at risk of developing significant indirect neonatal hyperbilirubinemia that requires interventions with an accuracy of 82.2%, a sensitivity of 72%, a specificity of 85.71%, a positive predictive value of 83.43%, and a negative predictive value of 75.37%.
Conclusion The cord blood ALP level can be used as a predictor of severe neonatal jaundice.
Keywords: alkaline phosphatase, cord blood, hyperbilirubinemia, jaundice, newborn
|How to cite this article:|
El-Amin DM, Ahmed YE, Hashim AM, Asmail AH. Evaluation of cord blood alkaline phosphatase levels as an indicator of neonatal jaundice. Al-Azhar Assiut Med J 2020;18:112-7
|How to cite this URL:|
El-Amin DM, Ahmed YE, Hashim AM, Asmail AH. Evaluation of cord blood alkaline phosphatase levels as an indicator of neonatal jaundice. Al-Azhar Assiut Med J [serial online] 2020 [cited 2020 Aug 11];18:112-7. Available from: http://www.azmj.eg.net/text.asp?2020/18/2/112/290611
| Introduction|| |
Hyperbilirubinemia is a common and, in most cases, benign problem in neonates. Jaundice is observed during the 1st week of life in ∼60% of term infants and 80% of preterm infants . It refers to the yellowish coloration of the skin and sclera caused by the accumulation of bilirubin in the skin and mucous membranes . It is very common because almost every newborn develops an unconjugated serum bilirubin level of more than 30 mmol/l (1.8 mg/dl) during the first week of life . Acute bilirubin encephalopathy is a potentially devastating condition that can lead to death or life-long neurodevelopment handicaps . In rare instances, the total serum bilirubin reaches levels that can cause kernicterus, a condition characterized by bilirubin staining of neurons and neuronal necrosis involving primarily the basal ganglia of the brain and manifested in athetoid cerebral palsy, hearing loss, dental dysplasia, and paralysis of upward gaze . Cord blood sample predicts hyperbilirubinemia earlier than the serum sample taken after birth. In addition, the neonate may not be lost to follow-up because of early discharge, and also cord blood alkaline phosphatase (ALP) may be a predicting marker for neonatal jaundice that can exceed 10 mg/dl. There was a significant difference in the levels of cord blood ALP between the nonjaundiced and clinically jaundiced newborns, and it was significantly higher in patients with hyperbilirubinemia requiring treatment .
| Aim|| |
The aim of this work is to examine the validity of cord blood ALP levels for predicting neonatal hyperbilirubinemia.
| Patients and methods|| |
This is a prospective study carried out during the period from June 2018 to December 2018 at El-Mania General Hospital. This study included a total of 60 neonates: 30 full-term infants and 30 preterm infants with gestational age between 33 and 42 weeks, weighing more than 2500 g born to healthy mothers. Five milliliter of cord blood was taken after birth and sent for determination of ALP levels. Serum ALP was measured using an auto analyzer by MAXCOM MC-6100 (SPINREACT, S.A./S.A.U Ctra, Santa Coloma, 7 E-17176 SANT ESTEVE DE BAS (GI) SPAIN) . We measured transcutaneous bilirubin on the third day of life by Draeger JM103 (Draeger Singapore Pte. Ltd., 61 Science Park Road The Galen #04-01, Singapore) ; we follow up neonates measured serum bilirubin in seventh day . These were included in the treatment group and neonates without clinical jaundice were included in the nonjaundiced group. Data were collected, revised, verified, coded, and then entered PC for statistical analysis carried out using IBM SPSS statistical package, version 20.
- Healthy neonate (full term and preterm).
- APGAR score of over 7 at the first minute and 10 at the fifth minute of life.
- Absence of significant illness or of major congenital.
- Healthy mother.
- Age: first 6 h from birth.
- Infants who were born to mothers with diseases such as eclampsia, diabetes, bone, kidney, and liver diseases.
- APGAR score below 7 at the first minute and 10 at the fifth minute of life.
- Infant who were born to a mother blood with group (o) and RH −ve.
- Neonates with hemolytic anemia either isoimmune as Rh and Abo incompatibility or nonimmune as spherocytosis and G6PD.
- Neonates with sepsis and extensive bruises.
- Neonate with low birth weight.
All the included neonates were subjected to the following:
- Assessment of complete medical history
- Maternal history including
- Mother’s age.
- Complications during any previous pregnancy.
- Mode of delivery (normal vaginal delivery or cesarean section).
- Substance abuse.
- Neonatal history including
- Gestational age.
- Apgar score at 1 and 5 min.
- Resuscitation steps in the delivery room.
- Thorough clinical examination (neonatal examination):
- General examination:
- Vital signs.
- Measurements (weight, length, head circumference, and abdominal circumference).
- Suckling reflex.
- Moro reflex.
- Head and neck.
- Back and genitalia.
- Systemic examination:
- Respiratory examination.
- Cardiovascular examination.
- Abdominal examination.
- Neurological examination.
- Laboratory investigations:
- Routine investigations:
- Complete blood count including hemoglobin, total leukocytic count, platelet count, differential count, and retics count for hemolytic anemia.
- Blood group and Rh of mother and neonate.
- Special investigations:
- Cord blood ALP (first 6 h of life).
- Transcutaneous bilirubin (third day of life).
- Total serum bilirubin and direct serum bilirubin.
Ethical consideration and consent
This study was approved by the Medical Committee of El-Mania General Hospital, and written and verbal consent was obtained from each parent’s case before enrollment in the study.
Data management and analysis
Data were collected, revised, verified, coded, and then entered into a PC for statistical analysis, which was carried out using IBM SPSS statistical package, version 20.
The following were carried out.
- For qualitative data: number and percentage.
- For quantitative data: mean and SD.
- Independent quantitative data using an independent-sample t test.
- Comparison of categorical data by the χ2 test.
- Bivariate Pearson correlation analysis for association analysis.
- Linear regression plots of transcutaneous versus serum estimates were performed.
- Specificity, sensitivity, positive predictive value, and negative predictive value of the ALP were calculated including receiver operating characteristic (ROC) curves to assess the accuracy.
For all tests P was considered:
- Nonsignificant if more than or equal to 0.05.
- Significant if less than 0.05.
- Highly significant if less than 0.01.
- Very highly significant if less than 0.001.
Grade of correlation or association:
- 0.24: weak or no association.
- 0.25–0.49: fair association.
- 0.50–0.74: moderate association.
- 0.75+: strong association.
| Result|| |
A total of 60 cases were followed up. This study was carried out on 60 neonates, 21 males and 39 females, 30 infants were born by cesarean section and 30 by vaginal delivery; 30 case full-term infant and 30 preterm infant. Apgar scores were normal (8–10) at birth in all cases. The mean gestational age was 37.38 weeks and the mean birth weight was 3272.5 g ([Table 1]).
Our study was carried on 60 neonates; 25 cases were clinically jaundiced whereas 35 cases were nonjaundiced. On comparing delivery mode, oxytocin use, APGAR score (1 and 5 min) gestational age, birth weight, sex, previous sibling with jaundice, and feeding patterns in both groups, we found no statistically significant difference (P>0.05).
On analysis of laboratory results in both groups, there was a statistically significant difference between both groups in consanguinity (P<0.029) and antenatal care (P<0.016) ([Table 2]).
|Table 2 Comparison between the nonjaundiced and jaundiced neonates in the demographic data|
Click here to view
[Table 3] shows a comparison of cord blood ALP (collected from neonates during the first 6 h of life) in clinically jaundiced (25) cases and nonjaundiced (35) cases by analysis of laboratory results in both groups; there was a statistically significant difference between both groups P value less than 0.001 very highly significant. ALP clinically jaundice (25) case with range 325 (138–525) mean±SD 159.5±31.9.
|Table 3 Comparison of alkaline phosphatase in nonjaundiced and jaundiced neonates|
Click here to view
ALP nonjaundice (35) case with range 142 (138–332) mean±SD 59.8±10.1 ([Table 3]). The analysis of ROC curves of the ALP levels showed that a cord blood ALP level more than 145 IU/l was the most suitable cut-off value for predicting jaundice. This cut-off value was associated with an accuracy of 82.2%, a sensitivity of 72%, a specificity of 85.71%, a positive predictive value of 83.43%), and a negative predictive value of 75.37% ([Table 4], [Figure 1]).
|Figure 1 Receiver Operating Characteristic (ROC) Curve of Cord Blood Alkaline Phosphatase.|
Click here to view
| Discussion|| |
In this prospective observational study, there were 60 neonates, 21 males and 39 females, 30 case full-term infants and 30 preterm infants, 30 normal vaginal delivery, 30 cesarean section. The current study showed that there was no difference between both groups in sex (P>0.05) and this is in agreement with several studies carried out by Rostami et al. , Taks et al. , and Sahu et al.  that concluded no significant relation between sex and significant neonatal hyperbilirubinemia. In contrast to this, a study carried out by El-Gendy et al.  showed that male sex was considered a significant dependent factor of neonatal hyperbilirubinemia. A study carried out by Satrya et al.  also found a significant difference in sexes between newborns who did and did not develop significant hyperbilirubinemia. The difference in these results may be because of the difference in the sample size or ethnicity of the groups studied.
In terms of the mode of delivery, this study showed no difference between the two groups (P>0.05). This is in agreement with studies carried out by Rostami et al. , Taks et al. , and Satrya et al. . Also Chary et al.  found similar results but previously. A study carried out by Awasthi and Rehman  had reported that peak serum bilirubin was significantly higher in neonates delivered vaginally. There was no difference between the two groups in the present study in the gestational age and this is in contrast to the study carried out by Watchko  that found that neonatal hyperbilirubinemia occurs less commonly with increasing gestational age.
In the present study, there was no significant difference between the groups of neonates who developed significant hyperbilirubinemia and those who did not regarding previous sibling affection. This is consistent with the AAP Subcommittee on Hyperbilirubinemia guidelines in 2004 that considered a previous sibling with jaundice to be a minor risk factor for the development of severe hyperbilirubinemia.
In terms of the feeding patterns, we observed that there was no difference between the two groups. In agreement with our study. the study carried out by Mutlu et al.  found a nonsignificant difference in the mode of feeding. Our study was not in agreement with Gartner , who stated that late-onset, prolonged neonatal jaundice was more frequent in breast-fed infants than in artificially fed infants, and the association of breast-feeding with prolonged and exaggerated physiological jaundice of the newborn has been considered a regular and frequently occurring phenomenon, with an incidence more than two-thirds of all breast-fed infants. In the present study, there was a highly significant difference between the two groups in the cord ALP level (P<0.001). This is consistent with Ahmadpour-Kacho et al.  and also Al Assal et al.  was in agreement with our study. ROC curve analysis shows that cord ALP cut-off value more than 145 IU/l has a good predictive value for newborns who developed significant neonatal hyperbilirubinemia with a sensitivity of 72% and a specificity of 85.71%. This is similar to Ahmadpour-Kacho et al. , who reported a cord blood ALP level of more than 314 μ/l to have a sensitivity of 80% and a specificity of 63% in predicting the risk of neonatal hyperbilirubinemia requiring treatment . It is also similar to Al Assal et al. , who reported a cord blood ALP level of more than 314 μ/l to have a sensitivity of 84.21% and a specificity of 84.48% in predicting the risk of neonatal hyperbilirubinemia requiring treatment. They concluded that cord blood ALP level can be used as an early predictor of neonatal jaundice. Accordingly, the present study showed that infants with cord blood ALP more than or equal to 145 IU/l are at risk of developing significant indirect neonatal hyperbilirubinemia needing interventions. This can be considered an early predictor for neonatal hyperbilirubinemia. By correlation of cord blood AP in each baby to perinatal data, no statistically significant correlation was recorded in mode of delivery, oxytocin use, sex, and feeding pattern, previous sibling with jaundice, and Apgar score after 1 min and Apgar score after 5 min (P>0.05). However, we found a statistically significantly positive correlation between level of cord blood AP in each baby with consanguinity and antenatal care (P<0.05).
From the results of our study, we can recommend the following:
- Cord blood ALP could be used as an indicator of risk of hyperbilirubinemia in newborns.
- The use of the cut-off cord blood ALP of more than 145 IU/l in all healthy preterm and full-term newborns, respectively, could be a useful predictor of significant hyperbilirubinemia that will need phototherapy and avoid the risk of severe hyperbilirubinemia that may need exchange transfusion.
- Close follow-up of newborns whose cord blood ALP level is more than or equal to 314.5 μ/l.
- Transcutaneous bilirubinometry on the third day of life could be used as a screening test to all the same time with screening for hypothyroidism for early detection of severe hyperbilirubinemia.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Ambalavanan N, Carlo WA. Jaundice and hyperbilirubinemia in the Newborn. In Kliegman RM, Behrman RE, Stanton BF, Schor NF, St Geme III JW eds. Nelson text book of Peadiatrics. 20th ed. Philadellphia: New Delhi Elseviers 2015; 102:871–872.
Rennie J, Burman-Roy S, Murphy MS. Neonatal jaundice: summary of NICE guidance. BMJ 2010; 340:2409.
American Academy of Pediatrics Subcommittee on Hyperbilirubinemia. Management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics 2004; 114:297.
Bahr T, Christensen R, Agarwal A, George T, Bhutani V. The Neonatal Acute Bilirubin Encephalopathy Registry (NABER): background, aims, and protocol. Karger J 2019; 115:242–246.
Zabeen B, Nahar J, Nabi N, Baki A, Tayyeb S, Azad K et al.
Risk factors and outcome of neonatal jaundice in a tertiary hospital. Ibrahim Med Coll J 2010; 4:70–73.
Ahmadpour-Kacho M, Pasha YZ, Haghshenas M, Rad ZA, Firouzjahi A, Bijani A et al.
Cord blood alkaline phosphatase as an indicator of neonatal jaundice. Iran J Pediatr 2015; 25:718.
Wenger C, Kaplan A, Rubaltelli FF, Hammerman C. Alkaline phosphatase. In Kaplan A, editor. Clinical chemistry. St Louis: Mosby; 1984. 1094–1098.
Chimhini GL, Chimhuya S, Chikwasha V. Evaluation of transcutaneous bilirubinometer (DRAEGER JM 103) use in Zimbabwean newborn babies. Matern Health NeonatolPerinatol 2018; 4:1.
Balistreri WF. Liver function. Fundamentals Clin Chem 1987;729–761.
Rostami N, Mehrabi YE, Asadzadeh F. Identifying the newborns at risk for developing significant hyperbilirubinemia by measuring cord bilirubin levels. Sci Inform Datebase 2005; 9:365.
Taks A, Vilhekar K, Jain M, Zade P, Atkari S, Verkey S. Prediction of the development of neonatal hyperbilirubinemia by increased umbilical cord blood bilirubin. Curr Pediatr Res 2005; 9:5–9.
Rostami Taks Sahu S, Abraham R, John J, Mathew MA, Res M. Cord blood albumin as a predictor of neonatal jaundice. Int J Biol Med Res 2011; 2:436–438.
El-Gendy FM, Hassane FM, Khattab AA, El-Lahony DM, Ashour NM. Predictive ability of first-day serum bilirubin and haptoglobin for subsequent significant hyperbilirubinemia in healthy-term and near-term newborn. Menouf Med J 2013; 26:127.
Satrya R, Effendi SH, Gumida DA. Correlation between cord blood bilirubin level and incidence of hyperbilirubinemia in term newborns. Paediatr Indonesiana 2009; 49:349–354.
Chary E, Bharadwaj N, Kumar P, Vivekand N, Sailaja V, Harika B. Umbilical cord blood bilirubin level measurement in predicting the development of significant hyperbilirubinemia. Indian J Mednodent All Sci 2014; 2:144.
Awasthi S, Rehman H. Early prediction of neonatal hyperbilirubinemia. Indian J Pediatr 1998; 65:131–139.
Watchko JF. Hyperbilirubinemia and bilirubin toxicity in the late preterm infant. Clin Perinatol 2006; 33:839–852.
Mutlu M, Çayır Y, Aslan Y. Urinary tract infections in neonates with jaundice in their first two weeks of life. World J Pediatr 2014; 10:164–167.
Gartner LM. Breastfeeding and jaundice. J Perinatol 2001; 21:25.
Al Assal H, Hablas H, Afia A, Khedr M, Al kzaz H. NewYork Sci J 2017; 10.
[Table 1], [Table 2], [Table 3], [Table 4]