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

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 1st 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.

Acalypha indica induced acute oxidative haemolysis and methaemoglobinaemia: two case reports.

BACKGROUND: Herbal products and traditional remedies are commonly used by individuals worldwide for the management of common ailments, even though most are not without risks. Acalypha indica is a popular medicinal plant consumed in some Asian countries. CASE PRESENTATION: This case report presents a 40-year-old previously unevaluated Sri Lankan female and her 8-year-old son who presented with severe glucose-6-phosphate dehydrogenase (G6PD) deficiency related acute intravascular oxidative haemolysis and methaemoglobinaemia precipitated by Acalypha indica consumption, successfully managed with supportive care and blood transfusion. CONCLUSIONS: This case highlights the potential hemolytic and methaemoglobinaemic effects of ingesting oxidant herbal products and the importance of considering such exposures in patients presenting with hemolysis and multiorgan involvement, particularly in communities where herbal product intake is popular. Healthcare providers should be aware of the risks associated with traditional remedies and maintain a high index of suspicion to ensure prompt recognition and appropriate management.

Prevalence and association of early onset severe hyperbilirubinemia in newborn in the East China region: Retrospective medical record analyses.

Research on the prevalence and association of hyperbilirubinemia is controversial because of different cultures, demographics, and clinical conditions. The etiology of hyperbilirubinemia is affected by the environment and other factors in the newborn. The World Health Organization recommended a 1-day hospital stay after uncomplicated delivery, jaundice assessment before discharge, and screening on 3rd and 7th days after birth for hyperbilirubinemia. However, the implementation of these recommendations is difficult in China. The objective of this study was to evaluate the prevalence and association of early onset severe hyperbilirubinemia in newborns in East China. Retrospective medical record analyses for 250 cesarean sections or vaginal deliveries, ≥2 kg body weight, and negative for Hepatitis B surface antigen by birth newborns were performed. A biochemical analyzer, quantitative assay, and quantitative polymerase chain reaction were used to evaluate total serum bilirubin, glucose-6-phosphate dehydrogenase (G6PD) deficiency, and gene variant phenotyping, respectively. A total in 33 (13%) newborns were reported with early onset severe hyperbilirubinemia (according to the American Academy of Pediatrics, total serum bilirubin ≥ 342 µmol/L within 6 hours of birth). All newborns with severe hyperbilirubinemia were hospitalized and underwent phototherapy. The mothers of all newborns had a gestational age ≥ 35 weeks. Hospitalization included artificial feeding, and breastfeeding was rare (P < .0001). ABO incompatibility ("O" blood type for mother and either "A" or "AB" or "B" blood type for newborn, P = .0411), G6PD deficiency (G6PD/6-phosphogluconate dehydrogenase ≤ 1.0 in quantitative assay, P = .0422), Rh incompatibility (the mother's blood type was Rh negative and newborn blood type was Rh positive, P = .0416), fewer genotype rs4149056 frequencies (P = .0452), higher genotype rs2306283 frequencies (P = .0461), and higher genotype rs1805173 frequencies (P = .0471) were independent parameter for early onset severe hyperbilirubinemia of newborns. The prevalence of early onset severe hyperbilirubinemia in Chinese newborns is 13% in the East China region. Blood incompatibility, G6PD deficiency, fewer genotype rs4149056 frequencies, higher genotype rs2306283 frequencies, and higher genotype rs1805173 frequencies were independent predictors of early onset severe hyperbilirubinemia among newborns in the East China region (Level of Evidence: IV; Technical Efficacy: Stage 5).

Risk Factors Predicting the Need for Phototherapy in Glucose 6 Phosphate Dehydrogenase-Deficient Infants in a Large Retrospective Cohort Study.

INTRODUCTION: Glucose 6-phosphate dehydrogenase (G6PD) deficiency increases the risk of severe neonatal hyperbilirubinemia. This study evaluates the risk factors predicting the need for phototherapy in G6PD-deficient neonates after 72 h of age and assesses the safety of early discharge. METHODS: A retrospective cohort study of 681 full-term G6PD-deficient infants with a birth weight ≥2,500 g over 4 years was conducted. We compared the baseline characteristics, bilirubin level on day 4 (after 72 h of life), day of peak bilirubin, G6PD levels, and concomitant ABO incompatibility between the group that required phototherapy (Group A) and those who did not (Group B). RESULTS: 396 infants (58%), predominantly males, required phototherapy in the first week of life. The infants who required phototherapy had a lower median gestational age (38.3 vs. 38.7 weeks, p < 0.01) and had lower G6PD levels (2.3 ± 2.5 vs. 3 ± 3.4 IU, p < 0.05) compared to the controls. The mean day-four total serum bilirubin (TSB) levels were higher (213 ± 32 vs. 151 ± 37 µmol/L, p < 0.01), with bilirubin level peaking earlier (3 vs. 4 days of life, p < 0.01) in group A. Regression analysis identified TSB levels on day 4, Chinese race, lower gestation, and concomitant ABO incompatibility as the significant predictors for the need for phototherapy in the study population. In particular, coexisting ABO blood group incompatibility increased the risk of jaundice requiring phototherapy (OR 4.27, 95% CI: 1.98-121, p < 0.01). Day four TSB values above 180 µmol/L predicted the need for phototherapy with 86% sensitivity and 80% specificity. The findings were similar across both male and female infants with G6PD deficiency. CONCLUSION: G6PD-deficient infants with day four TSB levels of >180 µmol/L (10.5 mg/dL) and associated ABO blood group incompatibility have a higher risk of requiring phototherapy in the first week of life and should be closely monitored.

Acalypha indica -induced transient glucose-6-phosphate dehydrogenase deficiency with acute haemolysis.

Acalypha indica is a tropical herb found in Asia. The entire plant, especially the leaves, is used in herbal medicine for several therapeutic purposes. Acute intravascular haemolysis and methaemoglobinaemia have been reported in patients who consume this herb. We present a case of a previously healthy middle-aged man who ingested boiled leaves of A. indica The patient developed clinical symptoms and signs of intravascular haemolysis 7 days after ingestion. Peripheral blood smear showed typical findings of glucose-6-phosphate dehydrogenase (G6PD) deficiency with acute haemolysis. The G6PD activity was low during active haemolysis. The G6PD level, however, returned to normal after 4 months of follow-up. The patient was further tested for common G6PD gene mutations in Southeast Asia and was negative. Ingestion of A. indica may induce transient G6PD deficiency, which in this patient led to acute haemolysis and methaemoglobinaemia.

Acute Hemolytic Anemia Caused by G6PD Deficiency in Children in Mayotte: A Frequent and Severe Complication.

Severe hemolytic anemia is a rare complication of glucose-6-phosphate dehydrogenase (G6PD) deficiency. It occurs with the Mediterranean (Med) variant corresponding to a class 2 deficiency according to the World Health Organization (WHO) classification, and it correlates with a severe deficiency in G6PD activity. In Mayotte, the majority of patients have the African (A-) variant as a WHO class 3 deficiency. Yet we have observed numerous cases of severe hemolytic anemia defined by a hemoglobin level of <6 g/dL. In this study, we aimed to describe the epidemiological, clinical, and biological features as well as the treatment modalities of children presenting with a severe hemolytic crisis secondary to G6PD deficiency in Mayotte. The secondary objective was to study the disease genotype when this information was available. Between April 2013 and September 2020, 73 children presented with severe anemia because of G6PD deficiency in Mayotte. The median hemoglobin level during the hemolytic crises was 3.9 g/dL. All of the patients underwent a transfusion and hospitalization. Twenty patients had a disease genotype: 11 had the African mutation and 9 had the Med mutation. Although they are among the most common triggers of G6PD acute hemolytic anemia, drugs were found to not be present and fava bean ingestion was found in only 1 child. One of the specific triggers was traditional medicine, including Acalypha indica . Severe hemolytic crisis in children because of G6PD deficiency is a frequent occurrence in Mayotte. The patients had severe disease symptoms, but the severity did not correlate with the genotype: the African (A-) variant and the Med variant resulted in the same level of disease severity.

Acute hemolysis and methemoglobinemia secondary to fava beans ingestion in a patient with G6PD deficiency: A case report of a rare co-occurrence.

RATIONALE: Favism is a well-known cause of acute hemolytic anemia. Rarely, methemoglobinemia can also happen because of fava bean ingestion in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Few cases with this co-occurrence have been reported in the literature. PATIENT CONCERNS: We report a case of a 47-year-old patient who presented with jaundice that started 2 days after eating fava beans. DIAGNOSES: Laboratory investigations revealed anemia with evidence of hemolysis (high reticulocytes count, high indirect bilirubin, bite cells in peripheral smear). Blood gases showed high methemoglobin level. Reduced level of G6PD enzyme confirmed the diagnosis of G6PD deficiency. INTERVENTION: The patient was kept on supplemental oxygen. He was counselled to avoid food and drugs that can cause acute hemolysis. OUTCOMES: Oxygen saturation improved gradually. The patient was discharged without any complications after 2 days. LESSONS: Patients with G6PD deficiency can develop both acute hemolytic anemia and methemoglobinemia secondary to fava beans ingestion. These patients should not receive methylene blue to avoid worsening hemolysis.

Evaluating the effect of ursodeoxycholic acid on total bilirubin of neonates with glucose-6-phosphate dehydrogenase deficiency complicated by indirect hyperbilirubinaemia.

AIM: This study aimed to investigate the effect of adding ursodeoxycholic acid (UDCA) to phototherapy in neonates with glucose-6-phosphate dehydrogenase (G6PD) deficiency and hyperbilirubinaemia. G6PD deficiency is a common cause of severe hyperbilirubinaemia in neonates. METHODS: This study was a triple blind, clinical trial study of 40 neonates with G6PD deficiency and hyperbilirubinaemia who admitted for phototherapy in hospitals affiliated to the University of Medical Sciences. The treatment group (n = 20) received UDCA 10 mg/kg (2 cc/kg) daily divided into 2 doses every 12 h. The control group (n = 20) received the same volume of placebo syrup. The drug and placebo treatments were continued until the bilirubin level dropped below 171 µmol/L. Both the control and treatment group received continuous phototherapy. Independent sample t-test, survival analysis and logrank test were used to statistically analyse the results. RESULTS: The mean total bilirubin level was 231.9 ± 18.8 µmol/L and 184.3 ± 18.6 µmol/L in the control and intervention group respectively, 24 h after drug administration and 209.7 ± 19.3 µmol/L and 157.4 ± 16.4 µmol/L, respectively, 48 h after intervention (P < 0.05). The median length of hospitalisation in the treatment group was approximately 1 day lower than the control group (logrank test P value: <0.001). CONCLUSION: The study showed that the addition of UDCA to phototherapy accelerates the reduction of total bilirubin level in neonates with G6PD deficiency and can reduce the duration of hospitalisation.

G6PD Deficiency Prevalence as a Cause of Neonatal Jaundice in a Neonatal Ward in Dohuk, Iraq.

OBJECTIVE: The current study initiated to address the effect of glucose-6-phosphate dehydrogenase (G6PD) deficiency on the pathogenesis and the severity of neonatal hyperbilirubinemia (NHB). STUDY DESIGN: A total of 100 newborns with moderate to severe indirect hyperbilirubinemia and 50 normal neonates without hyperbilirubinemia had been enrolled in the current case-control study. All enrolled neonates had been tested for ABO and Rh(D) blood grouping, Total serum bilirubin measurement, complete blood count, morphology, reticulocyte counts, direct Coombs' test, and G6PD enzyme assay. RESULTS: From all enrolled hyperbilirubinemic neonates, 16% were G6PD deficient and this displays a statistically significant difference in comparison to controls (only 6% were G6PD deficient). Also, significant difference was found in the level of serum indirect bilirubin among G6PD-deficient neonate in comparison to G6PD nondeficient neonates which had contributed significantly to the difference in the duration of phototherapy and hospitalization among deficient neonate. Despite this, no significant difference found in the onset of presentation, reticulocytes count, and age of neonates between the two groups (G6PD-deficient and G6PD nondeficient neonates). CONCLUSION: The current study augments the etiological role of G6PD in the causation and severity of NHB in the region; however, in the absence of significant difference in the reticulocytes and the hemoglobin level, the underlying mechanism cannot be backed to the excess hemolysis alone.

High dose vitamin C induced methemoglobinemia and hemolytic anemia in glucose-6-phosphate dehydrogenase deficiency.

Investigational use of intravenous vitamin C has been on the rise, but its side effects may be underreported. A 75-year-old woman presented with acute onset of jaundice, dark urine and shortness of breath after receiving 30 g of vitamin C infusion as an unconventional therapy for her hemifacial spasm. Diagnosis of methemoglobinemia and hemolytic anemia was made clinically and confirmed on laboratory tests. She recovered with supportive treatment and packed cell transfusion. Her previously unrecognised underlying condition of glucose-6-phosphate dehydrogenase (G6PD) deficiency was confirmed months after the initial presentation. This is the first reported case of methemoglobinemia and hemolytic anemia induced by high dose vitamin C in a female patient with G6PD deficiency. The dosage of vitamin C administered was also relatively low compared with previous adult reports. When administered at physiological dose, vitamin C can be used as an alternative to methylene blue in treatment of methemoglobinemia in patients with G6PD deficiency. However at supraphysiological dose vitamin C can paradoxically lead to hemolytic anemia in the same group of patients. Physicians should be alert of these potential complications of high dose vitamin C.

Sickle cell screening in Uganda: High burden, human immunodeficiency virus comorbidity, and genetic modifiers.

BACKGROUND: The Uganda Sickle Surveillance Study provided evidence for a large sickle burden among HIV-exposed infants in Uganda. To date, however, no large scale screening program has been developed for Central or East Africa. METHODS: A 3-year targeted sickle cell screening project in Uganda was designed by the Ministry of Health to (1) determine sickle cell trait and disease prevalence within high-burden districts, (2) document the prevalence among HIV-exposed and nonexposed children, (3) confirm previously suggested HIV comorbidity, and (4) estimate the co-inheritance of known genetic modifiers of sickle cell disease. RESULTS: A total of 163 334 dried blood spot samples collected between April 2015 and March 2018 were analyzed, including 112 352 samples within the HIV Early Infant Diagnosis program. A high burden with >1% sickle cell disease was found within targeted East Central and Mid-Northern districts, in both HIV-exposed and nonexposed children. Based on crude birth-rate data, 236 905 sickle cell trait births and 16 695 sickle cell disease births will occur annually in Uganda. Compared to sickle cell disease without HIV, the odds ratio of having sickle cell disease plus HIV was 0.50 (95% confidence interval = 0.40-0.64, P < .0001). Alpha-thalassemia trait and G6PD deficiency were common with sickle cell disease, but with different geospatial distribution. CONCLUSIONS: High sickle cell burden and potential HIV comorbidity are confirmed in Uganda. Genetic modifiers are common and likely influence laboratory and clinical phenotypes. These prospective data document that targeted sickle cell screening is feasible and effective in Uganda, and support development of district-level comprehensive care programs.

Hemolytic jaundice induced by pharmacological dose ascorbic acid in glucose-6-phosphate dehydrogenase deficiency: A case report.

RATIONALE: Hemolysis induced by high dose ascorbic acid (AA) in patients with G6PD deficiency has been reported, but is rare. To our knowledge, this is the first reported case of a male with G6PD deficiency, coexpressed with cholecystolithiasis and cholecystitis, who developed extreme hemolysis and hyperbilirubinemia after receiving pharmacological doses ascorbic acid infusion. PATIENT CONCERNS: A 27-year-old man history with glucose-6-phosphate dehydrogenase deficiency was admitted to our hospital because of cholecystolithiasis and cholecystitis. He appeared with scleral jaundice and very deep colored urine after receiving pharmacological doses ascorbic acid infusion. DIAGNOSES: Clinical findings when combined with his medical history and various laboratory results confirmed the diagnosis as hemolysis and hyperbilirubinemia induced by ascorbic acid. INTERVENTIONS: The patient was treated with steroids, hepatoprotective drugs, and folic acid in addition avoidance of agents with known hemolysis risk (such as vitamin C). OUTCOMES: As a result, the patient's symptoms from hemolytic jaundice improved, hemoglobin remained stable, and the patient was discharged 11 days later. LESSONS: Clinicians should bear in mind the possibility that vitamin C exposure may result in hemolysis in patients with G6PD deficiency, especially in those with known severe disease.

[How I do in front of an hemolytic anemia of unknown etiology?] / Que faire devant une anémie hémolytique sans étiologie retrouvée ?

The most frequent causes of hemolytic anemias are immune or infectious diseases, drug induced hemolysis, thrombotic microangiopathies, hereditary spherocytosis, glucose-6-phosphate dehydrogenase or pyruvate kinase deficiencies, thalassemia's and sickle cell disease. Sometimes no cause is found because a rarer etiology is involved. The goal of this review is to remember some unfrequent constitutional or acquired causes and to point out difficulties to avoid wrong interpretations of analysis results.

Indirect neonatal hyperbilirubinemia in hospitalized neonates on the Thai-Myanmar border: a review of neonatal medical records from 2009 to 2014.

BACKGROUND: Indirect neonatal hyperbilirubinemia (INH) is a common neonatal disorder worldwide which can remain benign if prompt management is available. However there is a higher morbidity and mortality risk in settings with limited access to diagnosis and care. The manuscript describes the characteristics of neonates with INH, the burden of severe INH and identifies factors associated with severity in a resource-constrained setting. METHODS: We conducted a retrospective evaluation of anonymized records of neonates hospitalized on the Thai-Myanmar border. INH was defined according to the National Institute for Health and Care Excellence guidelines as 'moderate' if at least one serum bilirubin (SBR) value exceeded the phototherapy threshold and as 'severe' if above the exchange transfusion threshold. RESULTS: Out of 2980 records reviewed, 1580 (53%) had INH within the first 14 days of life. INH was moderate in 87% (1368/1580) and severe in 13% (212/1580). From 2009 to 2011, the proportion of severe INH decreased from 37 to 15% and the mortality dropped from 10% (8/82) to 2% (7/449) coinciding with the implementation of standardized guidelines and light-emitting diode (LED) phototherapy. Severe INH was associated with: prematurity (< 32 weeks, Adjusted Odds Ratio (AOR) 3.3; 95% CI 1.6-6.6 and 32 to 37 weeks, AOR 2.2; 95% CI 1.6-3.1), Glucose-6-phosphate dehydrogenase deficiency (G6PD) (AOR 2.3; 95% CI 1.6-3.3), potential ABO incompatibility (AOR 1.5; 95% CI 1.0-2.2) and late presentation (AOR 1.8; 95% CI 1.3-2.6). The risk of developing severe INH and INH-related mortality significantly increased with each additional risk factor. CONCLUSION: INH is an important cause of neonatal hospitalization on the Thai-Myanmar border. Risk factors for severity were similar to previous reports from Asia. Implementing standardized guidelines and appropriate treatment was successful in reducing mortality and severity. Accessing to basic neonatal care including SBR testing, LED phototherapy and G6PD screening can contribute to improve neonatal outcomes.

A vegetable-induced hemolytic crisis in a G6PD deficient person: a case report.

BACKGROUND: Hemolysis can occur in people with G6PD deficiency under oxidative stress. Acalypha indica is a tropical plant used as a medicinal plant as well as a vegetable. There are a few reported cases of Acalypha indica ingestion induced hemolysis in G6PD deficient people. All except one of them are from Sri Lanka. The information available at present (2017) about G6PD deficiency prevalence and variants of the G6PD gene among Sri Lankans is very sparse. There are no past reports on hemolytic crisis in a G6PD deficient person presenting mimicking leptospirosis. CASE PRESENTATION: A middle-aged Sri Lankan man presented on the third day of illness complaining of fever, head ache, arthralgia, myalgia, abdominal pain, vomiting, passing dark urine and reduced of urine volume. He gave a history of possible exposure to leptospirosis. He was pale, icteric and his liver was palpable 1 cm below costal margin and there were no other remarkable findings upon physical examination. He had neutrophilic leucocytosis. Leptospirosis was diagnosed. During the second assessment we noticed he was very pale and his urine sample pointed towards hemoglobinuria. Further questioning revealed he had consumed leaves of Acalypha indica as a vegetable. Acute hemolysis in a G6PD deficient patient following Acalypha indica ingestion was diagnosed. Blood transfusions were given to correct his anemia. Later, Brewer's test and quantitative assay of G6PD levels confirmed the diagnosis of G6PD deficiency. CONCLUSIONS: A hemolytic crisis following oxidative stresses in G6PD deficient patients can present mimicking leptospirosis. Further investigations may reveal why the great majority of cases of acute hemolysis in G6PD deficient person following Acalypha indica ingestion are from Sri Lanka.