Glucose-6-Phosphate Dehydrogenase Deficiency and Neonatal Indirect Hyperbilirubinemia: A Retrospective Cohort Study Among 40 305 Consecutively Born Babies.

doi:10.21203/rs.3.rs-3614278/v1

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Glucose-6-Phosphate Dehydrogenase Deficiency and Neonatal Indirect Hyperbilirubinemia: A Retrospective Cohort Study Among 40 305 Consecutively Born Babies.

https://doi.org/10.21203/rs.3.rs-3614278/v1

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published 13 Mar, 2024

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Background and Objective: Glucose-6-phosphate dehydrogenase deficiency (G6PDD) being highly prevalent in the Middle East, the primary objective was to estimate the incidence of neonatal jaundice among G6PD-deficient neonates and to explore its association with various risk factors.

Methods: This retrospective cohort study includes 7 years data of neonates diagnosed with G6PDD between 1^st January 2015, and 30 September 2022, from Al Wakra Hospital, HMC Qatar.

Results: Among the 40,305 total births, 1013 had G6PDD with an incidence of 2.51%. Of all the G6PDD babies, 24.6% (249/1013) received phototherapy and three babies required exchange transfusion. Statistically significant associations were noted between the need for phototherapy and gestational age, gestational age groups, birth weight, and birth weight groups, but logistic regression analysis showed significant association for phototherapy only with the gestational age group.

Conclusion: Universal screening and proper follow-up is essential for G6PDD as it plays crucial role in neonatal jaundice.

Health sciences/Health care/Paediatrics

Health sciences/Health care/Diagnosis

G6PD deficiency

neonate

jaundice

G6PD deficiency is the most common enzymatic disorder described in humans, with a global distribution affecting more than 400 million people [1,2,3,4]. However, its prevalence is higher in tropical and subtropical zones of the Eastern Hemisphere, such as Africa, the Mediterranean, and Asian descent, where it may reach up to 25%. This prevalence parallels the incidence of malaria, as there is some evidence to suggest that G6PD deficiency offers protection against severe cases of malaria [5,6,7]. Approximately 10% of black males in the USA are estimated to be affected by G6PD deficiency, and 24% are reported to be carriers. G6PD enzyme activity is an essential component in protecting red blood cells against oxidative stress, and deficiency results in intravascular hemolysis and associated complications [8]. Over 200 G6PD variants have been described based on the genetic mutations associated with the X-linked recessive gene [6]. The World Health Organization has classified these variants according to the magnitude of the enzyme deficiency, with only class I, II, and III being of clinical significance due to the severity of hemolysis [9].

G6PD deficiency is known to be one of the risk factors for neonatal hyperbilirubinemia severe enough to cause kernicterus or jaundice-related morbidity [10,11]. However, in G6PD-deficient infants, these conditions are not well correlated with hemolysis, often because neonatal hyperbilirubinemia results from multiple endogenous factors in an infant's body that increase susceptibility to jaundice[12]. Neonatal red blood cells, which have a reduced lifespan and lower levels of enzymes like glutathione peroxidase and carbonic anhydrase, are more susceptible to oxidative damage in the presence of G6PD deficiency [13]. G6PD deficiency causing jaundice is perhaps attributed to the disruption of the oxidant-antioxidant balance and impaired recycling of peroxiredoxin 2, thus affecting bilirubin clearance [14]. It has also been reported that co-inheritance of a uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) gene variant is an additional risk factor for neonatal hyperbilirubinemia in G6PD-deficient male neonates [15].

In Qatar, screening for G6PD deficiency is routine, and it is performed on all neonates born in the country. In our hospital, we maintain a database of G6PD deficiency to provide family education and appropriate follow-up for G6PD-deficient babies. Most published studies on G6PD deficiency and neonatal jaundice have diagnosed neonatal jaundice first and then conducted G6PD deficiency testing as part of etiological evaluation, rather than as a universal test for all neonates [16]. In our study, all neonates underwent G6PD testing from cord blood, and they were followed prospectively in the jaundice clinic as part of routine well-baby follow-up. Therefore, we conducted a retrospective cohort study of all such G6PD-deficient neonates to estimate the prevalence of neonatal jaundice and its associations with various risk factors that increase the chance of neonatal jaundice."

This retrospective cohort study encompassed all newborn babies born with G6PD deficiency between January 1, 2015, and September 30, 2022, at Al Wakra Hospital, Hamad Medical Corporation, Qatar.

Maternal Data: For mothers, we collected data on gestational age at delivery, mode of delivery, year of delivery, nationality, and place of education regarding G6PD deficiency.

Neonatal Data: Collected neonatal data included sex, birth weight, the need for phototherapy due to jaundice, peak bilirubin levels, the day of peak bilirubin, and instances of rebound hyperbilirubinemia requiring phototherapy. Laboratory data collected encompassed G6PD levels, peak serum bilirubin levels, the lowest hemoglobin levels, and the highest reticulocyte cell count.

G6PD Testing:

Quantitative in vitro determination of Glucose-6- Phosphate Dehydrogenase in erythrocytes was done by using Randox G6PDH assay kit. The enzyme activity is determined by measurement of the rate of absorbance change at 340 nm due to the reduction of NADP+ by using spectrophotometer.

G6PD in RBC is released by lysing agent of reagent kit. G6PD of red cells catalyzes the glucose 6 phosphate with reduction of NADP to NADPH. The rate of reduction of NADP to NADPH is measured as increased absorbance at 340 nano meters which is proportional to the G6PD activity.

Phototherapy Criteria:

All neonates with G6PD deficiency identified through cord blood screening were observed in the postnatal ward for a minimum of 24 hours, during which their jaundice levels were monitored using a transcutaneous bilirubinometer. Any abnormal or borderline readings were confirmed by serum bilirubin tests. After discharge, they were routinely followed in a dedicated jaundice clinic, consistent with our hospital's protocol for high-risk neonates. Phototherapy was administered in accordance with the standard guidelines of the American Academy of Pediatrics Subcommittee on Hyperbilirubinemia from 2004 [17].

Data Collection and Confidentiality:

Data were extracted from our electronic documentation system, Cerner software, and collected in an Excel sheet. There was no direct interaction with human subjects, and the identity of the research subjects was not disclosed. Each patient was assigned a unique code, and all codes were securely stored in a computer system. The link between these codes and individual identifiers was deleted at the conclusion of the study, and the data will be kept in a secure locker for five years. Only the principal investigator will have access to this data, and subject identifiers will not be shared outside of the Hamad Medical Corporation.

This study adhered to the principles of the Declaration of Helsinki, Good Clinical Practice, and complied with the laws and regulations of the Ministry of Public Health (MOPH) in Qatar. It received approval from the institutional review board and ethical committee of the Medical Research Center, HMC, Qatar, with the protocol number MRC-01-23-039. Since this was a retrospective data collection study with no recruitment of subjects, informed consent was not required and was waived by the institutional review board and ethical committee. Reporting of this study followed the STROBE guidelines.

Statistical Considerations and Data Analysis:

Anonymous data were collected and entered into a standard electronic database designed for the study and its objectives. Descriptive statistics were used to summarize demographic, laboratory, clinical, and other characteristics of both the patients and their mothers. Mean and standard deviation or frequencies and percentages were used for reporting data and results. The primary outcome variable was neonatal jaundice among G6PD-deficient neonates. Associations between two or more qualitative variables were assessed using the chi-square (χ2) test or Fisher exact test. The mean of quantitative variables between two independent groups was analyzed using the unpaired t-test. The relationship between neonatal jaundice and various risk factors such as sex, G6PD level, gestational age, birth weight, etc., was estimated by deriving adjusted odds ratios (ORs) and confidence intervals from logistic regression models. All presented P values are two-tailed, and P values <0.05 were considered statistically significant. Statistical analyses were performed using the SPSS 27.0 software (SPSS Inc., Chicago, IL) and Epi-info software (Centers for Disease Control and Prevention, Atlanta, GA).”

A total of 40 305 babies were born during the study period from January 2015 to September 2022. Out of these, 1013 (2.51%) babies were G6PD deficient. Among males, the G6PD deficiency rate was 3.77% (776/20 580), and among females, it was 1.2% (237/19 725). The proportion of males among G6PD deficient babies was 76.6% (776/1013), while that of females was 23.4% (237/1013), resulting in a male-to-female ratio of 3.3:1. A total of 24.6% (249/1013) of G6PD deficient neonates received phototherapy. Other various parameters are presented in Table 1.

Table 1 here:

The G6PD deficiency rate varied across different populations: 3.8% (406/10 682) in the Middle East, 2.16% (335/16 229) in the Indian subcontinent, 1.72% (178/10 352) in African populations, and 3.46% (88/2 538) in Southeast Asian populations. In the rest of the countries, the rate was 1.19% (6/504)."

The mean G6PD levels were 51.2 mU/10^9RBC with a standard deviation of 55.56. G6PD levels in male and female babies were 34.4 ± 34.6 mU/10^9 RBC and 104.7 ± 73.3 mU/10^9 RBC, respectively, and this difference was statistically significant (P < 0.001). However, the need for phototherapy did not show statistical significance between the sexes; 25.7% (200/776) of male babies and 20.6% (49/237) of female babies received phototherapy (P-value 0.11). This data is summarized in Table 2.

Table 2 here:

Associations of various parameters with the need for phototherapy among G6PD deficient babies were calculated (Table 3). Statistically significant associations were found with gestational age, gestational age groups, birth weight, and birth weight groups, but no statistically significant association was observed with sex or G6PD level.

Table 3 here:

Adjusted odds for the need for phototherapy with various parameters were calculated using logistic regression analysis (Table 4). Only the gestational age group showed statistically significant odds; in the 'gestational age <35 weeks group,' the adjusted odds (confidence interval) were 4.03 (1.05 to 15.5), and in the 'gestational age 35 to 37+6 weeks group,' the adjusted odds (confidence interval) were 2.18 (1.19 to 3.99) compared to the 'gestational age 38 weeks or more group'.

Table 4 here:

Out of the 249 babies who received phototherapy, 200 (80.7%) were boys, and 49 (19.2%) were girls. The mean day of onset of jaundice that required phototherapy was 2.14 days (standard deviation 1.49). Among them, 13.7% of babies experienced rebound hyperbilirubinemia once, and 4% had it twice after receiving initial phototherapy. Additional parameters are presented in Table 5.

Table 5 here:

Sixteen babies had blood group incompatibility and a positive direct Coombs test. Among them, 11 babies had ABO incompatibility, 3 babies had both ABO and Rh incompatibility, one baby had Rh incompatibility alone, and one baby had minor blood group incompatibility.

Associations of sex with various parameters among babies who received phototherapy are detailed in Table 6.

Table 6 here:

Out of the 3 babies who required exchange transfusion, all were full-term male newborns. In 2015, one baby boy had a bilirubin level of 513 umol/L on the 4th day of life and required exchange transfusion. Another baby boy born in 2019 had a bilirubin level of 414 umol/L on the 2nd day of life and needed exchange transfusion. In 2021, another baby boy had a bilirubin level of 616 umol/L on the 4th day of life and required exchange transfusion.

Neonatal indirect hyperbilirubinemia (NIH) is a common problem among infants. It affects 60% of full-term and 80% of preterm newborns in the first three days of life [18]. NIH carries a substantial risk for harmful complications, including long-term neurologic impairments and death [15]. Although significant complications of NIH have become rare in recent years, even with effective therapeutic interventions such as phototherapy, bilirubin-induced neuronal damage is still a significant problem in resource-limited countries [15]. Severe NIH secondary to reduced Glucose 6-phosphate dehydrogenase (G6PD) activity is still complicated by kernicterus, which is a serious neurological disease [4,15,19].

The global prevalence of G6PD deficiency was estimated to be 4.9% [5]. There is a wide geographical distribution of G6PD deficiency, with the highest prevalence reported across sub-Saharan Africa [20]. In our study, the incidence of G6PD deficiency was 2.51 per 100 live births. Among them, males accounted for 76.6%, and females for 23.4%.

G6PD deficiency is an X-linked recessive disease. In our study, we detected a male-to-female ratio of 3.3 to 1. A similar ratio was reported by other studies [19,21], and interestingly, the rate of neonatal jaundice needing phototherapy was also not significantly lower in females than in males; 20.6% and 25.7% in females and males, respectively. The mean G6PD level was 51.2 mU/10^9 RBC with a standard deviation of 55.56. G6PD levels of male and female babies were 34.4 ± 34.6 mU/10^9 RBC and 104.7 ± 73.3 mU/10^9 RBC, respectively, and were statistically significant (P < 0.001). However, the need for phototherapy was not statistically significant between sex groups.

G6PD deficiency is a major risk factor for neonatal hyperbilirubinemia. Multiple reports have shown that G6PD-deficient infants are predisposed to neonatal jaundice [10,22]. In a study conducted on African American neonates, among G6PD-deficient neonates, the rate of phototherapy was 20.3% compared to control subjects at 5.7% (relative risk: 3.53; 95% confidence interval: 1.91-6.56) [23]. In our study, about 25% of G6PD-deficient neonates developed jaundice needing phototherapy.

We found that gestational age, gestational age groups, birth weight, and birth weight groups had a statistically significant association with the need for phototherapy among G6PD-deficient babies (Table 3). No statistically significant association with sex or G6PD level was observed. We calculated adjusted odds for the need for phototherapy with various parameters using logistic regression analysis and found that only the gestational age group had statistically significant odds. In the 'gestational age <35 weeks group,' the adjusted odds (confidence interval) were 4.03 (1.05 to 15.5), and in the 'gestational age 35 to 37+6 weeks group,' the adjusted odds (confidence interval) were 2.18 (1.19 to 3.99) in comparison to the 'gestational age 38 weeks or more group'.

The mean day of onset of jaundice that needed phototherapy was 2.14 days, with a standard deviation of 1.49. 13.7% of babies had rebound hyperbilirubinemia once, and 4% had it twice after receiving initial phototherapy. In the study published by Atay et al., the day of onset of jaundice was 6.1 ± 3.7 days [19]. In our study, the detection of jaundice needing phototherapy was earlier; this may be due to the routine early follow-up of all high-risk neonates in the dedicated jaundice clinic. The mean peak bilirubin was 261.3 ± 76.9 umol/L, and the mean day of the peak was 3.81 ± 2.84. Hemoglobin was 16.9 gm/dL ± 2.37, and the reticulocyte count was 4.5% ± 1.91 among babies that needed phototherapy. Other study results are comparable to the study from demographically similar Bahrain, in which hemoglobin was 16.4 gm/dL and reticulocyte count was 3.3% [11].

G6PD deficiency can cause severe neonatal indirect hyperbilirubinemia, which may lead to kernicterus or bilirubin encephalopathy [16,24]. In a study from Oman, 71% of kernicterus patients were reported to be due to G6PD deficiency [25]. In our study, only 3 babies (0.29%, 3/1013) needed exchange transfusion. The routine screening of G6PD and subsequent close follow-up of G6PD-deficient neonates helped implement early phototherapy, thus reducing the need for exchange transfusion and preventing bilirubin-induced neurologic complications in Qatar.

G6PD deficiency is a major risk factor for neonatal hyperbilirubinemia and bilirubin-induced neuronal damage. Early detection and intervention with phototherapy are simple, cost-effective strategies to identify infants at risk, monitor and treat hyperbilirubinemia effectively to prevent kernicterus. Our study demonstrates that this model of routine G6PD screening and routine follow-up could reduce the need for exchange transfusion and help prevent chronic sequelae of hyperbilirubinemia associated with G6PD deficiency.

Being a retrospective study, the findings of this study should be evaluated carefully. In this study, we calculated associations of various parameters with the need for phototherapy among G6PD-deficient babies. We found that gestational age, gestational age groups, birth weight, and birth weight groups had a statistically significant association with the need for phototherapy, but in regression analysis, only the gestational age group was found to be statistically significant. No statistically significant association with sex or G6PD level was seen.

NIA: Neonatal Indirect Hyperbilirubinemia

NICU: Neonatal intensive care unit

LSCS: Lower segment caesarian section

SVD: Spontaneous vaginal delivery

G6PD- glucose 6 phosphate dehydrogenases

HMC: Hamad Medical Corporation

AWH: Al-Wakra Hospital

Ethics approval and consent to participate: The current study was carried out in accordance with the principles of the Declaration of Helsinki, Good Clinical Practice, and following the laws and regulations of MOPH (Ministry of Public Health) in Qatar. The study was conducted after obtaining approval from the institutional review board and ethical committee of the Medical Research Center, HMC, Qatar. The protocol number was MRC-01-21-756. This was a retrospective data collection, and no subjects were recruited for the study; thus, informed consent was not needed, and this was waivered by the institutional review board and ethical committee.

Consent for publication: No need for this research as no identity disclosure has been done in this manuscript.

Availability of data and materials:

Deidentified data will be provided as per request from journal.

Competing interests:

There are no conflicts of interest in this work to declare. No conflict of interest among authors.

Funding:

No funding was taken for this study. Once accepted for publication then we can request publication money from Medical Research Center, Qatar.

Authors contributions:

R. R. -Design of study, formulating research questions, data collection, writing of manuscript

K. S. -review and proof reading of manuscripts, S. A. writing and editing drafts, data analysis, writing of manuscript, BV.- Data collection, manuscript writing and reviewing, AK-Data collection, L.H- review and proof reading of manuscripts .

The authors read and approved the final manuscript.

Acknowledgements: NIL

Authors information:

All authors are from department of neonatology, al wakra hospital, Hamad medical corporation, Qatar.

Definition of term:

Neonatal jaundice: Defined as bilirubin level needing phototherapy as per standard guideline of American Academy of Pediatrics Subcommittee on Hyperbilirubinemia 2004. Maisels MJ, Baltz RD, Bhutani VK, et al; American Academy of Pediatrics Subcommittee on Hyperbilirubinemia. Management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics. 2004;114(1): 297–316 PMID: 15231951 DOI: 10.1542/peds.114.1.297.

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Table 1: Various maternal and neonatal parameters of G6PD deficient babies.

Parameters: (Total 1013 G6PD deficient)	Number	Percentage	Mean ±SD	Range
Sex: Male Female	776/1013 237/1013	76.6 23.4
Mode of delivery: NVD LSCS	700/1013 313/1013	69.1 30.9
Nationality: Middle east Indian subcontinent African Southeast Asia Other	406/1013 335/1013 178/1013 88/1013 6/1013	40.1 33.1 17.6 8.7 0.6
Gestation age, weeks			38.6 ±1.56	29 - 42
Gestation age group: Less than 35 weeks 35-37+6 weeks >38 weeks	27/1013 138/1013 848/1013	2.7 13.6 83.7
Weight, gm			3201 ±500	1300 - 4700
Weight group: <2500gm 2500-4000gm >4000 gm	83/1013 881/1013 49 /1013	8.2 87 4.8
G6PD level, mU/10^9 RBC, done in 92.8% (940/1013) babies			51.2 ± 55.56	4 - 338
G6PD level group: Level <30 mU/10^9RBC Level >30 mU/10^9RBC	377/1013 562/1013	40.1 59.9
Place of Education: Postnatal NICU By phone	711/1013 195/1013 106/1013	70.2 19.2 10.5
Phototherapy received	249/1013	24.6

NVD= normal vaginal delivery , LSCS= lower segmental cesarean section

Table 2: Association of Sex with G6PD level and need for phototherapy.

Parameters: Total 1013 babies	Male= 776	Female= 237	Odds ratio (CI)/ mean difference (CI)	P value
G6PD Level mU/10^9RBC mean±SD	34.4 ±34.6	104.7 ±73.3	-70.2 (-77.3 to -63.2)	<0.001
G6PD Level group: number(%) <30 mU/10^9 RBC 377 >30 mU/10^9 RBC 562	331/776 (46.2%) 384/776. (53.7%)	46/237 (20.5%) 178/237 (79.5%)	3.33 (2.33 to 4.76)	<0.001
Phototherapy received Number, percentage	200/776 (25.7%)	49/237 (20.6%)	0.75 (0.52 to 1.06)	0.11

Table 3: Associations of various parameters with need for phototherapy.

Parameters:

Total 1013 babies

Phototherapy received= 249

No photo received= 764

Odds ratio (CI)/mean difference (CI)

P value

Sex: Male 776

Female 237

200 25.7%

49 20.6%

576 74.2%

188 79.3%

0.75 (0.52 – 10.6)

0.11

MOD: NVD 700

LSCS. 313

173 24.7%

76 24.3%

527 75.3%

237 75.7%

0.97 (0.71 – 1.33)

0.882

Gestation age, weeks

38.16 ±2.01

38.8 1.34

0.65 (0.43 – 0.87)

<0.001

Gestation age groups:

<35 week 27

35-37+6 week 138

>38 week 848

17 62.9%

54 39.1%

178 20.9%

10 37%

84 60.8%

670 79%

<0.001

Weight, gm

3129 ± 575

3225 ±473

96 (24.3 – 167.6)

0.008

Weight groups

<2500gm 83

2500-4000gm 881

>4000gm 49

30 36.1%

206 23.4%

13 26.5%

53 63.8

675 76.6%

36 73.4%

0.033

G6PD level,

46.03 ±51.8

52.9 ±56.6

6.9 (-1.3 - 15.14)

0.100

Level group.

<30 mU/10^9RBC 337

>30 mU/10^9RBC 562

100 29.6%

133 23.6%

277 73.4%

429 76.3%

0.858 (0.63-1.16)

0.319

Nationality groups:

Middle east 406

Indian subcontinent 335

African 178

south east Asia 88

others 6

93 22.9%

87 25.9%

37 20.7%

31 35.2%

1 16.7 %

313 77%

248 74%

141 79.2%

57 64.7%

5 83. 3%

0.094

NVD= normal vaginal delivery , LSCS= lower segmental cesarean section, CI= Confidence interval

Table 4: Regression analysis: association of various maternal and neonatal factors with jaundice that received phototherapy.

Parameters: Total 1013 babies	Adjusted odds	Confidence interval	P value
SEX male	1.34	0.85 to 2.11	0.201
G6PD Level	0.99	0.99 to 1.00	0.592
G6PD level group, <30	0.97	0.67 to 1.42	0.913
Nationality groups:			0.119
Middle east	1.21	0.14 to 10.7	0.858
Indian subcontinent	1.38	0.15 to 12.2	0.768
African	1.09	0.12 to 9.83	0.933
Southeast Asia	2.34	0.25 to 21.31	0.449
Gestation age weeks	0.91	0.76 to 1.09	0.315
Gestation age groups:			0.033
<35 weeks	4.03	1.05 to 15.5	0.042
35 to 37+6 weeks	2.18	1.19 to 3.99	0.011
Birth weight, gm	1.00	0.99 to 1.00	0.610
Birth weight groups:			0.708
Weight <2500gm	0.69	0.21 to 2.35	0.556
Weight 2500 to 4000 gm	0.71	0.32 to 1.60	0.413
Delivery mode NVD	1.27	0.90 to 1.79	0.167
Constant	4.42		0.689

Reference group: in sex “female”, in G6PD level group “level >30 mU/10^9 RBC”, in nationality group “other nationality group”, in gestation age group “gestation age 38 week or more”, in weight group “weight more than 4000gm”, in mode of delivery “LSCS” is reference group.

Table 5: Various parameters of neonates received phototherapy.

Parameters:

Total 249 babies

Mean ±SD

Range

Number (percentage)

Sex male

Female

200 80.7%

49 19.2%

G6PD level mU/10^9RBC

45.8 ±51.8

4 - 331

Level groups: <30

>30

101 43.3%

132 56.7%

Birth weight, grams

3128 ±572

1300 - 4610

Gestation age, weeks

38.1 ±2.01

29 - 41

Gestation age groups:

<35 weeks

35 – 27+6 weeks

>38 weeks

17 6.8%

56. 22.4%

176 70.7%

Age of NNJ , days

2.14 ±1.49

0 - 8

Photo age groups:

<24 hours

24-72 hours

>72 hours

11 4.4%

202 81.1%

36. 14.5%

Peak bilirubin, umol/L

261.3 ±76.9

98 - 616

Day of peak bilirubin

3.81 ±2.84

0 – 25

Rebound jaundice:

No rebound

Once

Twice

205 82.3%

34 13.7%

10. 4%

Hb gm/dL

16.9 ±2.37

9.8 – 22.1

Peak reticulocyte, done in 238

4.5 ±1.91

0.4 – 16

Place of education:

Post Natal

NICU

BY PHONE

152 61%

79. 31.7%

18. 7.2%

NNJ- neonatal jaundice. Hb= hemoglobin

Table 6: Association of sex with various parameters among babies who received phototherapy.

Parameters: Total 249 babies	Male (201)	Female (48)	Odds ratio (CI)/mean difference (CI)	P value
G6PD level mU/10^9 RBC	35.5 ±42.8	88.7 ±63.6	-53.16 (-68.7 to -37.6)	0.001
Level <30 101 >30 132	91 (48.4%) 97 (51.5%)	10 (22.2%) 35 (77.8%)	3.28 (1.53 to 7.01)	0.001
Gestation age, weeks	38.2 ±1.88	37.5 ±2.43	0.78 (0.15 to 1.41)	0.015
Birth weight, gram	3181 ±558	2909 ±584	271 (93.4 to 450)	0.003
Age of NNJ, days	2.09 ±1.4	2.39 ±1.8	-0.3 (-0.77 to 0.16)	0.203
Age of NNJ <24 hour 24-72 hour >72 hour	7 (3.5%) 167 (83.1%) 27 (13.4%)	4 (8.3%) 35 (72.9%) 9 (18.7%)		0.190
Day of peak	3.86 ±2.83	3.62 ±2.89	0.23(-0.66 to 1.37)	0.607
Rebound need phototherapy No rebound Once Twice	162 (80%) 30 (15%) 8 (5%)	43 (89.5%) 4 (8.3%) 1 (2.1%)		0.524
Hb gram/dL	16.9 ±2.45	17.16 ±2.04	-0.24(-1 to 0.51)	0.521
Reticulocyte count	4.4 ±1.71	5.01 ±2.61	-0.57 (-1.19 to 0.05)	0.072

NNJ- neonatal jaundice. Hb= hemoglobin, CI= Confidence interval

There is NO conflict of interest to disclose.

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published 13 Mar, 2024

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Glucose-6-Phosphate Dehydrogenase Deficiency and Neonatal Indirect Hyperbilirubinemia: A Retrospective Cohort Study Among 40 305 Consecutively Born Babies.

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