|Year : 2017 | Volume
| Issue : 1 | Page : 1-5
Hyperbilirubinemia management in neonates <2000 g screened for glucose-6-phosphate dehydrogenase deficiency in a tertiary neonatal unit
Maad Bakr Saleem1, Muhammad Jawad Hashim2, Nusrat Khan1, Mohammad Yousef Khassawneh3
1 Department of Pediatric, Tawam Hospital, Abu Dhabi, United Arab Emirates
2 Department of Family Medicine, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates
3 Department of Pediatric, Tawam Hospital, Abu Dhabi, United Arab Emirates; Department of Pediatric, Jordan University of Science and Technology, Irbid, Jordan
|Date of Web Publication||8-Feb-2017|
Dr. Maad Bakr Saleem
Tawam Hospital, PO Box 15258, Al Ain, Abu Dhabi
United Arab Emirates
Source of Support: None, Conflict of Interest: None
Background: Prematurity and glucose-6-phosphate dehydrogenase (G6PD) deficiency are considered important risk factors in neonatal hyperbilirubinemia. G6PD screening is performed by many neonatal units to identify this risk factor. Few studies evaluated the role of this screening on the management of hyperbilirubinemia in preterm infants during their neonatal hospitalization. This study aims to evaluate effects of G6PD screening on treatment of hyperbilirubinemia in infants <2000 g admitted to Neonatal Intensive Care Unit. Methods: All neonates <2000 g who were admitted to neonatal unit for 3 years (2013–2015) were retrospectively included in the study. Data related to risk factors and management of hyperbilirubinemia were collected and analyzed on these infants. A number of phototherapy units used for treatment, duration phototherapy, and level of bilirubin were compared between G6PD deficient and nondeficient infants and presented. Results: Included in this retrospective study were 621 infants. About half on included infants were < 1500 g. Gestational age groups as follow: ≤28 weeks, 23.3%; 29–32 weeks, 37.5%; 33–36 weeks, 33.6%; and ≥37 weeks, 5.6%. Prevalence of G6PD deficiency was 10.3%. The highest recorded serum bilirubin was significantly higher in G6PD deficient group compared with nondeficient one (161.6 μmol/l ± 57.5 vs. 145.4 μmol/l ± 46.4, P = 0.01). G6PD deficient infants were treated with more phototherapy than nondeficient group (85.9% vs. 64.5%, P < 0.001). G6PD deficient low birth weight neonates were more likely to receive intensive phototherapy. None of the G6PD deficient patients was treated with exchange transfusion. Conclusion: Prevalence of G6PD deficiency among low birth weight infant in the United Arab Emirates is similar to data reported in full-term infants. Screening for G6PD in preterm infant is associated with more treatment using phototherapy and may contribute in preventing severe hyperbilirubinemia.
Keywords: Glucose-6-phosphate dehydrogenase, low birth weight infant, neonatal hyperbilirubinemia, phototherapy
|How to cite this article:|
Saleem MB, Hashim MJ, Khan N, Khassawneh MY. Hyperbilirubinemia management in neonates <2000 g screened for glucose-6-phosphate dehydrogenase deficiency in a tertiary neonatal unit. J Clin Neonatol 2017;6:1-5
|How to cite this URL:|
Saleem MB, Hashim MJ, Khan N, Khassawneh MY. Hyperbilirubinemia management in neonates <2000 g screened for glucose-6-phosphate dehydrogenase deficiency in a tertiary neonatal unit. J Clin Neonatol [serial online] 2017 [cited 2020 Mar 30];6:1-5. Available from: http://www.jcnonweb.com/text.asp?2017/6/1/1/199753
| Introduction|| |
Neonatal jaundice is a common disorder in both term and preterm infants. The American Academy of Pediatrics guideline for the management of neonatal jaundice uses risk zones that depend mainly on gestational age at birth and presence of risk factors such as glucose-6-phosphate dehydrogenase (G6PD) deficiency. G6PD deficiency is a global health problem with varying prevalence. In the United Arab Emirates, the prevalence of G6PD deficiency among newborn infants was reported to be 9.1%. Routine G6PD screening performed for all infants admitted to Neonatal Intensive Care Unit (NICU) is practiced by many neonatal units. The clinical implication of this screening on this population is not clear. This approach may allow early detection and prevention of severe hyperbilirubinemia and subsequently may decrease the risk of bilirubin-induced neurological disease. Few studies have evaluated association between hyperbilirubinemia and G6PD deficiency in preterm infants. Some reports found an association with more significant hyperbilirubinemia., Few studies reported massive hemolysis with severe neonatal jaundice in G6PD deficient newborns., A recent review article by Kaplan et at. has also pointed out that, coexistence of G6PD deficiency and prematurity may cause sudden and severe hyperbilirubinemia. Other studies reported no contribution of G6PD deficiency on the development of neonatal jaundice in preterm infants. We could not identify any studies that describe the pattern of hyperbilirubinemia among G6PD screened preterm infant and how this will be reflected on management and outcome of their neonatal jaundice.
Our study aims to evaluate the effects of G6PD screening on defining infants with G6PD deficient and how this will affect the management of hyperbilirubinemia among infants <2000 g who are admitted to NICU for any reason. This study will evaluate the relationship between G6PD deficiency and need for, intensity, and duration of phototherapy compared to G6PD normal infants in that cohort.
| Methods|| |
This study is a retrospective study on all low birth weight neonates weighing <2000 g admitted to tertiary NICU at a hospital in the United Arab Emirates who were screened for G6PD activity. The study included data for 3-year period from January 2013 to December 2015. Birth weight of <2000 g is one of the main criteria for admission to the neonatal unit, and this study focuses on neonatal hyperbilirubinemia among G6PD screened infants. All newborns admitted to neonatal unit with a birth weight <2000 g were identified from electronic medical record systems for the study period. Data were extracted from the electronic medical records for each patient. Data collection included both demographic data and clinical laboratory data. Demographic data include admission and discharge date, gender, birth weight, and gestational age in weeks.
As part of screening regardless of serum bilirubin or the need for phototherapy, G6PD quantitative assay was done with first blood collection after admission to neonatal unit for all infants regardless of their condition. First, bilirubin was collected routinely at 12 h of age, thereafter done every 24 h until deemed low according to the guideline and follow-up are unnecessary. For each patient, all serum bilirubin results (in µmol/l) measured during the first 10 days of age were obtained. Patient's age at the time of doing each bilirubin level was recorded in hours. In our neonatal unit, the decision to use phototherapy was based on treatment guideline for infants <2500 g used by Emory University [Appendix 1] and [Appendix 2]. Based on birth weight, age in hours, and G6PD status, bilirubin levels were plotted on these risk zones, and the need for phototherapy was determined according to this guideline. According to G6PD quantitative assay results, cases were classified as either deficient or nondeficient according to our laboratory normal cutoff values. Mothers of G6PD deficient infants were informed and counseled immediately (documented in infant charts) about current and future G6PD-related precautions. The normal range between 4.5 and 19.5 units/g Hb (Pointe Scientific Inc., 5449 Research Drive, Canton, MI 48188 USA). It is important to mention that using chemical testing for screening for G6PD will only accurately assess prevalence in males, whereas females prevalence of G6PD may seem lower because genetic testing is needed to identify cases without abnormality in chemical testing. Data collected included time of start of phototherapy, total number of days of phototherapy, number of phototherapy unit used, use of 360° intensive phototherapy machine, need to perform exchange transfusion, blood groups incompatibility, and direct agglutination test results. The research was approved by Al Ain Medical District Human Research Ethics Committee.
Descriptive statistics including bivariate analyses using Chi-square, unpaired t-test, and correlation coefficients were obtained using IBM SPSS (version 23, IBM Inc., Chicago, IL, USA, 2016). P< 0.05 was used to assess for statistical significance while using two-tailed testing.
| Results|| |
Data were analyzed for 621 neonates; males constituted 52.2% of the study group. The mean gestational age was 31.1 ± 3.5 weeks and mean birth weight of 1435 ± 406 g. The weight groups as follow: ≥1500 g - 51.4% (n = 319), 1000–1499 g - 29.1% (n = 181), and <1000 g - 19.3% (n = 120). ABO incompatibility exists in 88 infants (14.2%). Positive direct agglutination test was seen only in six infants (1.0%).
There were 119 infants weighing <1000 g, of them 98 infants needed phototherapy in the first 2 days of life. In 55.1% (n = 54), serum bilirubin at onset of phototherapy was <85 µmol/l (5 mg/dl), and in the remaining (44.9%, n = 44), bilirubin was equal or more than 85 µmol/l (5 mg/dl).
The prevalence of G6PD deficiency was 10.3% (64 out of 621 neonates), with a higher proportion among males (16.5% compared to females 4.6%, P < 0.001).
There was no statistically significant difference between the G6PD normal and G6PD deficient groups in terms of gestational age or birth weight. The highest recorded bilirubin was significantly higher in G6PD deficient group compared to G6PD nondeficient infants (161.6 µmol/l ± 57.5 vs. 145.4 µmol/l ± 46.4, respectively, P = 0.01).
Overall, G6PD deficient infants were treated with more phototherapy than nondeficient group (85.9% compared to 64.5%, respectively). Double phototherapy or more were more frequently used in G6PD deficient infants (25%) versus 7.4% in G6PD nondeficient group (P < 0.001) [Table 1].
|Table 1: Hyperbilirubinemia and its management in glucose-6-phosphate dehydrogenase deficient and glucose-6-phosphate dehydrogenase nondeficient low birth weight neonates|
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G6PD deficiency proportions were similar in newborns with or without ABO incompatibility (n = 88 infants, P = 0.267). In this group, those with G6PD deficiency received more days of phototherapy (mean 2.3 days, standard deviation [SD] 1.61) compared to those without the deficiency (1.4 days, SD 1.39; P = 0.032, t-test).
[Figure 1] shows the trend of bilirubin in G6PD normal and G6PD deficient infant in first 10 days of life. G6PD deficient preterm infant has their mean serum bilirubin continued to rise till 10 days of age, but this was not statistically significant difference from nondeficient group (P = 0.671 and 0.179, respectively, unpaired t-tests). This difference was more obvious after the 6th day of life.
|Figure 1: Mean serum bilirubin levels by glucose-6-phosphate dehydrogenase status. Error bars indicate 1 standard deviation (only one-sided error bars shown for clarity)|
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| Discussion|| |
G6PD screening in infants <2000 g admitted to neonatal unit allowed identification of G6PD deficient neonates from their 1st day of life. In our study, G6PD deficient low birth weight infants have significantly higher recorded bilirubin than G6PD nondeficient infants. These G6PD deficient infants also received phototherapy earlier and with a higher number of phototherapy units used than G6PD normal infants. Among infants with ABO incompatibility setup, G6PD deficiency was also associated with more phototherapy use. The latter findings are in contrary with Kaplan et al. who found that ABO-incompatible G6PD deficient neonates, compared with those with either condition alone, are not at increased risk for hemolysis or hyperbilirubinemia. However, our patients are low birth infants, and this may explain high incidence of hyperbilirubinemia among them. As it was explained by Kaplan et al., smaller preterm infants may be at an advantage in that they remain hospitalized and under observation for the immediate postnatal period. Late preterm infants are often discharged earlier along with their term counterparts and may develop hyperbilirubinemia of sudden and acute onset while at home. This may explain that no infant in our study reached bilirubin level to require exchange transfusion.
The prevalence of G6PD deficiency in our study (10.3%) was nearly similar to previously reported prevalence in term infants (9.1%) and in preschool children in the United Arab Emirates., Although G6PD deficiency is seen more in males, prevalence in female infants <2000 g was still relatively high (4.6%). It is obvious that males are affected more than females as G6PD is an X-linked recessive disease and missing gene on X chromosome mean no G6PD activity. However, it is also known that preterm female infants who are heterozygous may have severe hemolysis even with normal chemical testing for G6PD assay were sufficient., The World Health Organization recommends G6PD screening where 3% to 5% of males are affected. In addition to its value in care of neonates, G6PD screening could prevent future possible complications such as food- or drug-induced hemolysis. G6PD screening has helped in identification and management of low birth weight neonates who are at risk of hyperbilirubinemia. This could had prevented more severe hyperbilirubinemia as none of the infants in the study needed exchange transfusion, and only two infants were treated with phototherapy using a machine that provides 360° phototherapy light. This increased risk of jaundice is explained by imbalance between increased bilirubin load in these conditions and the immature excretory mechanisms in preterm infants., It is important to mention here that routine measurement of intensity of phototherapy is not available data for our study, and so the reporting use of more phototherapy is used to reflect a higher level of phototherapy.
Treatment of hyperbilirubinemia in infants <35 weeks of gestation varies from one institution to others. This is generally not evidence-based practice as a randomized clinical trial in this disorder is not feasible. Recently, Maisels et al. published guidelines for the treatment of jaundice in this population. This guideline relay on corrected gestational age and weight for phototherapy usage. Compared to Maisels et al.'s guidelines, a lower bilirubin level was used to initiate treatment in our study. Their minimum starting bilirubin threshold for infants <35 weeks was 5 mg/dl (85 µmol/l), whereas in our study, more than half of infants weighing <1000 g received phototherapy with bilirubin levels <85 µmol/l. Recent reports suggest increased mortality among infants <700 g who used phototherapy.
This study has some limitations. It is a retrospective study. The treatment threshold used to decide need for treatment was based on nonevidence-based guidelines. The guidelines used are plotted on graphs rather than absolute numbers at corresponding age in hours. This could results in interpreter bias, particularly when age calculated in hours. In this study, the decision to treat with phototherapy also may have been biased by the physician's knowledge of G6PD deficiency and so more than a real need for treatment.
| Conclusion|| |
Prevalence of G6PD deficiency among low birth weight infant in the United Arab Emirates is similar to data reported in full-term infants. Screening for G6PD in preterm infant is associated with more treatment using phototherapy and may contribute in preventing severe hyperbilirubinemia. Future prospective study will be needed to do further evaluation of such important risk factor in this population.
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Conflicts of interest
There are no conflicts of interest.
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