Prolonged indirect hyperbilirubinemia in a moderately preterm boy with Mediterranean glucose-6-phosphate dehydrogenase and glutathione S-transferase Mu 1 null mutations.

A 33-week gestation boy with Mediterranean glucose-6-phosphate dehydrogenase (G6PD) and a glutathione S-transferase Mu 1 null mutations (GSTM1*0/*0) developed prolonged indirect hyperbilirubinemia (PIH). He had no laboratory evidence of haemolysis or infection, and no exposure to oxidising agents. He has two full-term older brothers who have no history of neonatal hyperbilirubinemia. One brother, who was exclusively breast fed, has only Mediterranean G6PD and the other has only GSTM1*0/*0. The three boys have no mutation in the uridine diphosphate glucuronosyltransferase 1A1 gene. This suggests that a combination of all or any two of prematurity, G6PD deficiency and GSTM1*0/*0 is a possible risk factor for PIH. However, this remains to be confirmed.

Decreased Glutathione S-transferase Level and Neonatal Hyperbilirubinemia Associated with Glucose-6-phosphate Dehydrogenase Deficiency: A Perspective Review.

Classically, genetically decreased bilirubin conjugation and/or hemolysis account for the mechanisms contributing to neonatal hyperbilirubinemia associated with glucose-6-phosphate dehydrogenase (G6PD) deficiency. However, these mechanisms are not involved in most cases of this hyperbilirubinemia. Additional plausible mechanisms for G6PD deficiency-associated hyperbilirubinemia need to be considered. Glutathione S-transferases (GST) activity depends on a steady quantity of reduced form of glutathione (GSH). If GSH is oxidized, it is reduced back by glutathione reductase, which requires the reduced form of nicotinamide adenine dinucleotide phosphate (NADPH). The main source of NADPH is the pentose phosphate pathway, in which G6PD is the first enzyme. Rat kidney GSH, rat liver GST, and human red blood cell GST levels have been found to positively correlate with G6PD levels in their respective tissues. As G6PD is expressed in hepatocytes, it is expected that GST levels would be significantly decreased in hepatocytes of G6PD-deficient neonates. As hepatic GST binds bilirubin and prevents their reflux into circulation, hypothesis that decreased GST levels in hepatocytes is an additional mechanism contributing to G6PD deficiency-associated hyperbilirubinemia seems plausible. Evidence for and against this hypothesis are discussed in this article hoping to stimulate further research on the role of GST in G6PD deficiency-associated hyperbilirubinemia.

Prevalence and Characteristics of Infant's Unexplained Breast Preference for Nursing One Breast: A Self-Administered Survey.

BACKGROUND: Breastfeeding is recommended by international bodies as the only source of infant nutrition during the first 6 months of life. Sometimes infants prefer to nurse on one breast for no obvious reason (hereafter called infant's unexplained breast preference [IUBP]). IUBP might reduce the rate of exclusive breastfeeding. The prevalence of IUBP is unknown because most of the literature on IUBP so far has been anecdotal. This study's objective was to investigate the prevalence and characteristics of IUBP among healthy infants in Al-Ahsa, Saudi Arabia. MATERIALS AND METHODS: We conducted a population-based, cross-sectional study between March and August 2013 in the Al-Ahsa area, Eastern Province, Saudi Arabia. Healthy infants who had been born at full term (≥37 weeks of gestation) and were 2-24 months of age were included. We distributed 600 self-administered surveys to mothers who attended vaccination clinics in nine primary healthcare centers. RESULTS: Of 478 mothers who responded to the survey, 121 (25.3%) reported unilateral breastfeeding. IUBP was the most common reason for unilateral breastfeeding, with a prevalence of 13.6% (65/478). IUBP developed at a median age of 1 month (range, 1 day-9 months) and was familial in 42.9% of cases. It was the only reason for formula feeding during the first 6 months of life in 18.5% of cases. CONCLUSIONS: IUBP is common, develops very early in life, and can be familial and a reason for formula feeding. However, these findings need to be confirmed in other studies of other populations.

A Systematic Review and Meta-analysis of the Timing of Early Intraventricular Hemorrhage in Preterm Neonates: Clinical and Research Implications.

A considerable number of intraventricular hemorrhages (IVH) occur within the first hours of life (HOL). Temporality between IVH and its antecedents as well as a consistent definition of "early IVH" is lacking in a large and growing body of literature. We performed a systematic review of prospective studies that reported onset of IVH in preterm neonates within the first HOL and afterwards. The English literature was searched using three databases up to March 2013. Four timing periods of IVH can be compared in 16 identified studies: 0-6; 7-12; 13-24; after 24 HOL. The 0-6 and after 24 HOL were the major modes of IVH timing. Pooled IVH proportions were estimated through a meta-analysis of studies that were conducted after antenatal steroid and surfactant era. In neonates weighing ≤1500 g at birth: 48% of IVH (95% CI: 42-58%, 5 studies, 279 IVH cases) occurred during 0-6 HOL and 38% (95% CI: 19-57%, 4 studies, 241 IVH cases) after 24 HOL. The 0-6 HOL is the shortest, most vulnerable period for IVH, thus, an early IVH is an IVH occurs in it. Such early IVH had prognostic, etiological/preventive and medicolegal implications. Accordingly, preterm neonates at risk of IVH should have their first routine screening head ultrasound at about 6 HOL. Future research exploring the antecedents of IVH should guaranty the temporality between these antecedents and IVH. Additional research will be required to determine whether the long term neurological outcomes of early and late IVH are the same.

Lower reference limits of quantitative cord glucose-6-phosphate dehydrogenase estimated from healthy term neonates according to the Clinical and Laboratory Standards Institute guidelines: a cross sectional retrospective study.

BACKGROUND: Previous studies have reported the lower reference limit (LRL) of quantitative cord glucose-6-phosphate dehydrogenase (G6PD), but they have not used approved international statistical methodology. Using common standards is expecting to yield more true findings. Therefore, we aimed to estimate LRL of quantitative G6PD detection in healthy term neonates by using statistical analyses endorsed by the International Federation of Clinical Chemistry (IFCC) and the Clinical and Laboratory Standards Institute (CLSI) for reference interval estimation. METHODS: This cross sectional retrospective study was performed at King Abdulaziz Hospital, Saudi Arabia, between March 2010 and June 2012. The study monitored consecutive neonates born to mothers from one Arab Muslim tribe that was assumed to have a low prevalence of G6PD-deficiency. Neonates that satisfied the following criteria were included: full-term birth (37 weeks); no admission to the special care nursery; no phototherapy treatment; negative direct antiglobulin test; and fathers of female neonates were from the same mothers' tribe. The G6PD activity (Units/gram Hemoglobin) was measured spectrophotometrically by an automated kit. This study used statistical analyses endorsed by IFCC and CLSI for reference interval estimation. The 2.5th percentiles and the corresponding 95% confidence intervals (CI) were estimated as LRLs, both in presence and absence of outliers. RESULTS: 207 males and 188 females term neonates who had cord blood quantitative G6PD testing met the inclusion criteria. Method of Horn detected 20 G6PD values as outliers (8 males and 12 females). Distributions of quantitative cord G6PD values exhibited a normal distribution in absence of the outliers only. The Harris-Boyd method and proportion criteria revealed that combined gender LRLs were reliable. The combined bootstrap LRL in presence of the outliers was 10.0 (95% CI: 7.5-10.7) and the combined parametric LRL in absence of the outliers was 11.0 (95% CI: 10.5-11.3). CONCLUSION: These results contribute to the LRL of quantitative cord G6PD detection in full-term neonates. They are transferable to another laboratory when pre-analytical factors and testing methods are comparable and the IFCC-CLSI requirements of transference are satisfied. We are suggesting using estimated LRL in absence of the outliers as mislabeling G6PD-deficient neonates as normal is intolerable whereas mislabeling G6PD-normal neonates as deficient is tolerable.