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.

A New IVH Scoring System Based on Laterality Enhances Prediction of Neurodevelopmental Outcomes at 3 Years Age in Premature Infants.

Objective To compare the new intraventricular hemorrhage (IVH) Abdi score to the Papile grading system of IVH for prediction of composite outcome of death or neurodevelopmental impairment (NDI). Methods In a cohort study, all preterm infants with IVH who were born ≤1,250 g and/or ≤ 28 weeks of gestation at birth were prospectively followed up in our neonatal follow-up clinic. All cranial ultrasounds of the included infants were reviewed by neuroradiologists who were blinded to the clinical data and neurodevelopmental outcomes. Cranial ultrasounds were graded according to the Papile scoring system and by calculation of the Abdi score. Results A total of 183 preterm infants met inclusion and exclusion criteria. Of these, 80 (44%) had the composite primary outcome of death or NDI (51 died, 29 survived with NDI). The area under receiver operating characteristic curve for predicting death or NDI was 0.87 (95% confidence interval [CI]: 0.81-0.93) for Abdi score and 0.85 (95% CI: 0.79-0.91) for Papile grading (p = 0.04). Abdi scores had higher specificity than Papile grade II at Abdi score 5 (63.9 vs. 39.2%; p < 0.001) and Abdi score 6 (73.2 vs. 39.2%; p < 0.001). Conclusion Abdi scores seem to be more specific than Papile grading system in predicting death or NDI by 3 years' corrected age.

The Potential of Ambroxol as a Panacea for Neonatal Diseases: A Scoping Review.

Ambroxol, a commonly used mucolytic agent, has been extensively studied for its clinical effectiveness in managing respiratory conditions in pediatric and adult patients. The existing body of research on ambroxol demonstrates its safety and efficacy. However, its potential role in preventing and treating neonatal diseases still needs to be explored. This scoping review aims to shed light on the unexplored potential of ambroxol, particularly its applications in perinatal and neonatal care. We aim to offer valuable insights for healthcare professionals, researchers, and academics, thus presenting a positive perspective. Key scientific databases such as Google Scholar, PubMed, Cochrane Library, and Europe PMC were meticulously searched for relevant literature on ambroxol in perinatal and neonatal medicine. Gray literature was also surveyed, and the search encompassed all study designs and languages up to June 2024. Furthermore, citations and reference lists of relevant articles were scrutinized to identify additional pertinent literature. Ambroxol has demonstrated promising effects in preventing and managing respiratory distress syndrome (RDS). It can enter the placental circulation and rapidly build up in human lung tissue to a much greater extent than in plasma. It promotes fetal lung maturation, surfactant production, and alveolar expansion. Numerous studies have demonstrated the efficacy of antenatal and postnatal ambroxol in the prevention and treatment of RDS. Ambroxol has the potential to be administered intravenously or through nebulization, offering the hopeful possibility of reducing the high failure rate typically associated with non-invasive ventilation in extremely preterm infants, instilling a sense of hope and optimism about the potential of ambroxol. It also shows potential in treating bronchopulmonary dysplasia, meconium aspiration syndrome, and neonatal infections. Ambroxol has been observed to assist in the closure of patent ductus arteriosus in preterm infants by inhibiting vasodilator agents such as nitric oxide and exerting vasoconstrictive properties. However, these biological actions may raise concerns regarding the potential induction of pulmonary hypertension and an increased risk of necrotizing enterocolitis. The present scoping review also examines the clinical evidence and the potential of ambroxol in reducing the incidence of intraventricular hemorrhage in preterm infants. Ambroxol may have potential analgesic properties in managing neonatal pain, and as it can penetrate the blood-brain barrier, it suggests potential neuroprotective properties. These properties may encompass the modulation of microglial activation and the antagonistic impact on glutamate receptors. Ambroxol's attributes could contribute to a decreased susceptibility to neurological complications and have demonstrated anticonvulsant effects in preclinical studies. While low-to-moderate-quality evidence indicates potential applications of ambroxol in neonatal care, further research is needed to determine the drug's optimal dosing, timing, and safety profiles in this patient population. We need to investigate ambroxol's potential synergistic effects with antenatal steroids. Exploration is required to assess ambroxol's potential in reducing the high failure rate associated with non-invasive respiratory support for RDS. Lastly, comprehensive studies on the long-term neurodevelopmental outcomes of neonates exposed to ambroxol are essential.

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.

A Saudi Girl With Co-occurring CHD1 (Pilarowski-Bjornsson Syndrome) and ASH1L Gene Variants.

Pilarowski-Bjornsson Syndrome (PBS) is a recently identified and rare genetic disorder. PBS is caused by missense variants in the CHD1 gene, a chromatin remodeler and helicase DNA-binding protein. In this report, we present the first case of PBS in Saudi Arabia. The patient exhibits a phenotype and genotype that are consistent with previously reported cases of PBS. Notably, this case is unique due to the coexisting presence of an absent, small, and homeotic disks protein 1 homolog like a histone lysine methyltransferase (ASH1L) variant and developmental dissociation. The ASH1L variant may contribute to the developmental dissociation observed in the patient. Furthermore, since the patient is female, this case contributes to the female-skewed distribution of PBS, although the exact cause of this phenomenon requires further investigation. This report highlights the importance of identifying and characterizing rare genetic disorders such as PBS. Understanding the genetic basis of these disorders can lead to improved diagnosis, treatment, and management strategies. Continued research on the genetic and molecular mechanisms underlying PBS and related disorders is crucial for advancing our knowledge and developing effective therapies.

A Saudi Hospital's Experience in the Management of Well-Appearing Neonates at Increased Risk for Early-Onset Bacterial Sepsis.

BACKGROUND: Early-onset neonatal bacterial sepsis (EOS) is a serious medical condition where pathogenic bacterial species are isolated from the blood of newborns within the first 72 hours of life. Neonatal healthcare providers face challenges in managing well-appearing newborns born at 35 weeks gestational age or more who are at an increased risk of developing EOS. The American Academy of Pediatrics (AAP) has recommended three approaches for managing EOS. One of these approaches includes enhanced observation to observe the progression of the newborn's clinical condition within the first 48 hours after birth. The AAP recommends that birth centers should adopt institutional approaches that are tailored to their specific local resources and structures. It recommends that the chosen approach is evaluated to identify infrequent negative outcomes and to confirm its effectiveness. AIMS: To report our experience in managing EOS in newborns born at 35 weeks gestation or later with an increased risk for EOS. METHODS: This was a review of electronic medical records from the past five years. We included a sample of newborns born at or after 35 weeks gestational age who were at increased risk of EOS and appeared to be healthy. We implemented universal antenatal culture-based screening for Group B streptococcus (GBS). We followed the recommendations of the AAP in 2012 to manage these newborns. We performed a complete blood count (CBC) with differential and C-reactive protein (CRP) tests to predict EOS. We also considered the newborns symptomatic if they displayed any clinical signs of EOS. RESULTS: A total of 806 newborns were included in the study, out of which 27 (3.3%) of them had symptoms of EOS, while the remaining 782 newborns appeared healthy. Predictive blood tests were performed on 281 (34.9%) of the newborns, out of which 126 (44.8%) of them had a positive test result. However, blood cultures were obtained from 134 (16.6%) of the total cohort. Intravenous antibiotics were administered to 33 (4.1%) of the newborns. All symptomatic newborns had a positive predictive blood test result, and two of them had culture-proven EOS. Blood cultures obtained from the remaining 107 asymptomatic newborns were negative. In this context, 140 newborns needed to be pricked for positive predictive blood tests to predict one case of EOS. However, if the positive predictive blood tests were only performed on symptomatic newborns, then only 14 newborns would need to be pricked to predict one case of EOS. CONCLUSION: Based on the present study, it is advised to follow the current AAP recommendation against predicting EOS by solely relying on CBC with differential or CRP. The study suggests that the enhanced observation approach is a more sensible option for managing EOS, but this needs to be confirmed in a larger study.

Cord Platelet Count of Full-Term Neonates in Relation to ABO Incompatibility and Glucose-6-Phosphate Dehydrogenase Levels: A Retrospective Cohort Study.

Background The immunoglobulin G of mothers with O blood type may sensitize the platelets of their neonates with A (O-A incompatibility) or B (O-B incompatibility) blood type. As the expression and antigenicity of the B antigen on platelets is less than that of the A antigens, we have hypothesized that platelet count is higher in the O-B incompatibility group compared to the O-A incompatibility group. There is controversy about whether glucose-6-phosphate dehydrogenase (G6PD) deficiency, without evidence of hemolysis, is associated with a lower platelet count than G6PD-normal. Aim To assess whether platelet count is higher in the O-B than in the O-A incompatible neonates and whether it correlates with their G6PD levels. Methods This study was a retrospective cohort study on a sample of 835 healthy neonates born at ≥38 weeks gestation who were either A or B blood types with mothers that carried the blood type O Rh-positive. The platelet count (thousand per microliter) from umbilical cord venous blood (UCVB) was used. A G6PD level of 11.0 units/gram of hemoglobin (U/g Hb) was considered the lower reference limit. G6PD deficiency was defined as a G6PD level of <3.3 U/g Hb in both sexes. Intermediate G6PD deficiency in females was described as a G6PD level of 3.3-8.8 U/g Hb. Results The mean UCVB platelet count was higher in female neonates compared to male neonates (n=389, 283±65 versus n=446, 272±73, p=0.01). The mean UCVB platelet count was higher in the O-B incompatibility group in both male (n=114, 291±82 versus n=103, 266±63) and female neonates (n=83, 303±66 versus n=81, 278±58) with G6PD levels of >8.8 U/g Hb. There was a positive weak correlation between UCVB platelet counts and G6PD levels only in O-B incompatible female neonates (n=176, r=0.23, p=0.002). The partitioning and combined 95% reference intervals (RIs) of the UCVB platelet count were presented. Conclusion The platelet count was higher in the O-B incompatibility group compared to the O-A incompatibility group, but only when the G6PD level was >8.8 U/g Hb. A correlation between UCVB platelet count and G6PD levels was found only among O-B incompatible female neonates. These findings may have an important implication in estimating RIs of the UCVB platelet count, however, they need to be confirmed and explored in future research.

Congenital Pseudarthrosis of the Clavicle: A Case Report and a Hypothesis for the Right-Side Predominance.

Congenital pseudarthrosis of the clavicle (CPC) is rare. It predominantly affects the right side for an unknown reason. Most of the reported cases are diagnosed outside the neonatal period. Only two CPC cases have been reported in Saudi Arabia, where both were diagnosed during childhood. Here, we present the case of a Saudi male newborn with right-sided CPC. The diagnosis was made shortly after birth because of the uneventful cesarean delivery and painless clavicular lump. Fetuses prefer keeping their head in a right lateral position which may be a plausible explanation for the right-side predominancy in the CPC.

Saudi mothers' preferences about breaking bad news concerning newborns: a structured verbal questionnaire.

BACKGROUND: Breaking bad news (BBN) to parents whose newborn has a major disease is an ethical dilemma. In Saudi Arabia, BBN about newborns is performed according to the parental preferences that have been reported from non-Arabic/non-Islamic countries. Saudi mothers' preferences about BBN have not yet been studied. Therefore, we aimed to elicit the preferences of Saudi mothers about BBN concerning newborns. METHODS: We selected a convenience sample of 402 Saudi mothers, aged 18-50 years, who had no previous experience with BBN. We selected them via a simple number-randomization scheme from the premises of a level III Saudi hospital between October of 2009 and January of 2011. We used a hypothetical situation (BBN about trisomy 21) to elicit their preferences about BBN concerning newborns via a structured verbal questionnaire composed of 12 multiple-choice questions. We expressed their preferences as percentages (95% confidence interval), and we used the Kendall's W test (W) to assess the degree of agreement in preferences. RESULTS: The Saudi mothers preferred that BBN be conducted with both parents together (64% [60-69]), albeit with weak levels of agreement (W = 0.29). They showed moderate agreement in their preferences that BBN should be conducted early (79% [75-83], W = 0.48), in detail (81% [77-85], W = 0.52), in person (88% [85-91], W = 0.58), and in a quiet setting (86% [83-90], W = 0.53). With extremely weak agreement, they preferred to have a known person present for support during BBN (56% [51-61], W = 0.01), to have close bodily contact with their babies (66% [61-70], W = 0.10), and to have no another patients present (64% [59-68], W = 0.08). They showed moderate levels of agreement in their desires to detail, in advance, their preferences about process of BBN by giving a reversible, written informed consent that could be utilized for guidance, if needed (80% [76-84], W = 0.36). CONCLUSIONS: In our experience, Saudi mothers' preferences about BBN concerning newborns are varied, suggesting that a "one-size-fits-all" approach is inappropriate. A reversible, written informed consent detailing their preferences about BBN that would be kept in their medical records and utilized for guidance, if needed, may be the best solution, given this level of diversity. These findings merit further study.

The effect of low to moderate patient volume on very low-birth-weight outcomes in a level III-B neonatal intensive care unit.

We studied the effect of a low- to moderate-volume, level III-B neonatal intensive care unit (NICU) on very low-birth-weight (VLBW) outcomes. We performed a retrospective analysis of the King Abdulaziz Hospital (KAH) NICU electronic database. Short-term outcomes of all inborn VLBW infants (501 to 1500 g) in the well-equipped, well-staffed KAH NICU (2003 to 2008) were benchmarked with data (1997 to 2002) from the National Institute of Children Health and Human Development and Neonatal Research Network (NICHD-NRN). Survival without major neonatal morbidity was defined as survival without bronchopulmonary dysplasia (BPD), grade III to IV intraventricular hemorrhage (IVH), and Bell's stage II to III necrotizing enterocolitis (NEC). The survival rates of VLBW infants at the KAH NICU ( N = 250) and the NICHD-NRN ( N = 18,153) were similar (84 versus 85%). A significantly higher rate of survival without major neonatal morbidity (80 versus 70%, P = 0.002) and lower rate of BPD (14 versus 22%, P = 0.005) were observed in KAH. The rates of grade III to IV IVH, Bell's stage II to III NEC, and late-onset sepsis were comparable in both cohorts. Our low- to moderate-volume, well-equipped, well-staffed, level III-B NICU achieved outcomes similar to the NICHD-NRN. Further study is warranted to ascertain how a lower-volume NICU achieved similar outcomes, as this could then be applied to quality improvement efforts.

A systematic comparison between infant formula compositions using the Bray-Curtis Similarity Index.

BACKGROUND: Making an informed choice between the available infant formulas is challenging, as there is no unbiased tool allowing a systematic comparison between the very long lists of infant formula compositions. AIM: The aim is to present the Bray-Curtis Similarity Index (BCSI) as a tool for systematic comparison between standard stage-1 infant formula (SS-1-IF) compositions. METHODS: We obtained the nutrient levels from the packaging labels of 23 SS-1-IFs available in Al-Ahsa, Saudi Arabia, in April 2018. The international legislations that launched infant formula standards endorse targeting the minimum rather than the maximum proposed nutrients levels. Thus, we blindly compared between displayed nutrients levels on each of the 23-studied SS-1-IF and the minimum international proposed nutrient levels via using the BCSI. RESULTS: The range of the total displayed components was 38-57. Except for docosahexaenoic acid, all displayed components were within the standard recommended range. The BCSI summarized all displayed nutrients in a single number. The BCSI of the studied SS-1-IF ranged from 0.4141 to 0.79730. We ranked the 23 studied SS-1-IFs based on the higher BCSI is the closer to the minimum proposed nutrient levels. A dendrogram segregated the SS-1-IFs into four clusters based on their BSCI and total numbers of all displayed components. CONCLUSIONS: We think the BCSI is an appropriate tool for a systematic comparison between SS-1-IFs compositions and may help for choosing a SS-1-IF.

Hospital-Based Prevalence of Iron Deficiency Anemia among Pre-School Children in Dubai.

INTRODUCTION: Iron deficiency anemia (IDA) is an internationally recognized leading cause of disability and contributes to childhood morbidity and mortality. The prevalence of IDA is higher in developing countries, especially in Arab countries, compared to the west. METHODS: To assess the prevalence of IDA, we analyzed the data of children aged between one to five years seen at Dr. Sulaiman Al-Habib Medical Group's tertiary care hospital in Dubai, United Arab Emirates (UAE) from 2016 to 2018. RESULTS: We found a high occurrence of IDA in male children and non-Emirati children. CONCLUSION: Appropriate screening and iron supplementation are required to see a decline in the rate of IDA. Further nationwide studies are required to identify the highly prevalent and high-risk areas of IDA in the UAE.

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.

Culture-proven early-onset neonatal sepsis in Arab states in the Gulf region: two-year prospective study.

OBJECTIVE: To investigate the incidence and the pattern of causative organisms of culture-proven early-onset sepsis (EOS) in Arab states in the Gulf region. METHODS: Five neonatal care units participated in this 2-year prospective study in Kuwait, the United Arab Emirates, and Saudi Arabia. Data were collected prospectively using a standardized data collection form. EOS was defined as the growth of a single potentially pathogenic organism from blood or cerebrospinal fluid in infants within 72h of birth, with clinical and laboratory findings consistent with infection. RESULTS: Out of 67 474 live births, 102 cases of EOS occurred. The overall incidence of EOS was 1.5 (95% confidence interval 1.2-1.8) per 1000 live-births, ranging from 2.64 per 1000 live-births in Kuwait to 0.40 per 1000 live-births in King Abdulaziz Hospital in Saudi Arabia. The most common causative organism of EOS was group B Streptococcus (GBS; 60.0%), followed by Escherichia coli (13%). The incidence of invasive GBS disease was 0.90 per 1000 live-births overall and ranged from 1.4 per 1000 live-births in Kuwait to 0.6 per 1000 live-births in Dubai Hospital. CONCLUSIONS: The incidence of EOS and the patterns of the causative organisms in the Arab states in the Gulf region are similar to those in developed countries before the era of intrapartum antibiotic prophylaxis. Efforts should be made to improve intrapartum antibiotic prophylaxis in the Arab state setting, which could avert large numbers of GBS infections.

Late-onset neonatal sepsis in Arab states in the Gulf region: two-year prospective study.

OBJECTIVES: This study aimed to investigate the incidence of late-onset sepsis (LOS) in neonatal intensive care units (NICUs) in Arab states in the Gulf region and to describe the main causative organisms and their antibiotic resistance. METHODS: This observational prospective cohort study was conducted over a 2-year period in five NICUs in Kuwait, Saudi Arabia, and the United Arab Emirates. LOS was defined as the growth of a single potentially pathogenic organism from blood or cerebrospinal fluid in infants >3days of age with clinical and laboratory findings consistent with infection. RESULTS: Seven hundred and eighty-five cases of LOS occurred among 67 474 live births. The overall incidence of LOS was 11.63 (95% confidence interval (CI) 10.84-12.47) per 1000 live births, or 56.14 (95% CI 52.38-60.08) per 1000 admissions. Coagulase-negative staphylococci and Klebsiella spp were the most common organisms, causing 272 (34.65%) and 179 (22.80%) of LOS cases, respectively. No evidence of a seasonal variation in the incidence of Klebsiella spp or in the incidence of all Gram-negative organisms was found. More than half of the Klebsiella spp were resistant to third-generation cephalosporins. CONCLUSION: LOS poses a major burden in this area, which could be due to the increasing care of premature babies. Gram-negative organisms, particularly Klebsiella spp, are having an increasing role in LOS in this region, with high levels of resistance to third-generation cephalosporins. NICUs in the area should create a platform through which to share experience in reducing neonatal sepsis and contribute to a common antibiotic stewardship program.

Pulmonary interstitial emphysema and continuous positive airway pressure in a premature infant.

Pulmonary interstitial emphysema PIE is a recognized sequel of high pressure mechanical ventilation. Nevertheless, with the improvement in perinatal medical care, PIE started to be seen in spontaneously breathing infants. We present a 29-week-old girl who developed PIE on the first day of life, while she was on nasal continuous positive airway pressure, and was successfully managed with high frequency oscillatory ventilation. There is a paucity of these cases in the literature. We report on the occurrence of this entity, early reorganization, and the possible associated or causation factors.