Glucose-6-phosphate dehydrogenase deficiency and neonatal indirect hyperbilirubinemia: a retrospective cohort study among 40,305 consecutively born babies

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. The primary objective of this study was to estimate the incidence of neonatal jaundice among G6PD-deficient neonates and to explore its association with various risk factors. Neonatal jaundice defined as total serum bilirubin needing phototherapy according to American Academy of Pediatrics Subcommittee on Hyperbilirubinemia 2004 [17].

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. Normal G6PD results varied between 339 and 500 mU/10^9 as per our laboratory reference.

Follow up for G6PD deficient neonates

In Qatar, its routine to have G6PD screening test for all babies from cord blood sample. In few hours, the results usually available and if found deficient, close monitoring with transcutaneous bilirubin will be initiated. A dedicated G6PD screening team will follow up the results and educate the family regarding the results and follow up plans. American Academy of Pediatrics Subcommittee on Hyperbilirubinemia 2004 guidelines will be followed for the subsequent management and follow up of hyperbilirubinemia. When transcutaneous bilirubin is within the safe zone, babies will be discharged with follow up in a dedicated bilirubin clinic under the G6PD screening team who is maintaining a logbook of all G6PD deficient babies. Usually these babies are followed in bilirubin clinic for one week or till transcutaneous bilirubin falls within the safe zone.

Phototherapy criteria

All neonates with G6PD deficiency identified through cord blood screening were observed in the postnatal ward for a minimum of 24 h, during which their jaundice levels were monitored using a transcutaneous bilirubinometer. Phototherapy was administered in accordance with the standard guidelines of the American Academy of Pediatrics Subcommittee on Hyperbilirubinemia from 2004 [17]. Transcutaneous bilirubin levels close to the phototherapy threshold according to the phototherapy chart, will be confirmed by serum bilirubin.

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).”

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