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.

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.

BACKGROUND:ABO incompatibility is a major risk factor for neonatal indirect hyperbilirubinemia (NIH), requiring treatment. It has been shown that there are racial differences in direct antiglobulin test (DAT) positivity and phototherapy need in the O--B versus (vs) O--A incompatibility. The comparison between the O--B and O--A incompatibility is not well studied in Saudi Arabia.AIMS:We aimed to compare DAT positivity and phototherapy need in O-B vs O-A incompatibility in Saudi Arabia.METHODS:This retrospective cohort study was conducted in one Saudi hospital. We included a convenience sample of neonates born between 01 January 2013 and 31 December 2021. We included healthy neonates admitted to the nursery care unit only, born at≥38 weeks gestation, and had normal G6PD levels. Neonates that had no G6PD level measurement or lost follow-up post-discharge were excluded. The data span was the first 14 days of life.RESULTS:A total of 611 neonates met our inclusion criteria. Positive DAT was more prevalent in the O-B than the O-A incompatibility [43.5% vs 29.2%, p < 0.001). A greater odd of phototherapy need was observed in the O--B vs O-A incompatibility across various strata. Readmission for NIH, use of 360° exposure phototherapy, or intravenous immunoglobulin administration was more prevalent in the O-B than the O-A incompatibility (13.2% vs 5.0%, p < 0.001). A logistic regression analysis revealed that the O-B incompatibility modified the association between DAT positivity and phototherapy need.CONCLUSIONS:The O-B incompatibility had a mediator effect on the relationship between DAT positivity and the need for phototherapy in the study population, which emphasizes that the O-B and O-A are not the same from the NIH point of view.

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.

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.

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 (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.

Sir, I read with deep sorrow the article \"Preeclampsia was a risk factor for pulmonary interstitial emphysema in preterm infants born ≤ 32 weeks of gestational age\" by Behnke et al. (1). In October 2005, we have published a case report \"Pulmonary interstitial emphysema and continuous positive airway pressure in a premature infant\" (2). We have stated in the introduction of this case report \".

Fluorescent spot test for glucose-6-phosphate dehydrogenase (G6PD) deficiency was performed in 5 boys and 14 girls who had confirmed COVID-19. Out of those, 4 (80%) boys and 5 (36%) girls were found to be G6PD deficient.

Sir, I read with deep sorrow the article "Preeclampsia was a risk factor for pulmonary interstitial emphysema in preterm infants born ≤ 32 weeks of gestational age" by Behnke et al. (1). In October 2005, we have published a case report "Pulmonary interstitial emphysema and continuous positive airway pressure in a premature infant" (2). We have stated in the introduction of this case report ".

Necrotizing pneumonia due to Methicillin-Resistant Staphylococcus Aureus (MRSA) is devastating and difficult to treat in preterm infants. We report a case of severe MRSA necrotizing pneumonia in a preterm infant. As an add-on rescue therapy to vancomycin, linezolid rapidly cured this case after the failure of vancomycin plus rifampicin. This rapid cure suggests that adjunctive rather than rescue linezolid may be considered in such cases.

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.

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.

Reports on pediatric multisystem inflammatory syndrome (PMIS) temporally related to coronavirus disease 2019 (COVID-19) are increasing. African and Afro-Caribbean children constituted about 47% of the cases in these reports. Despite the fact that glucose-6-phosphatase dehydrogenase (G6PD) deficiency is common among this population, the G6PD status of these cases has not been reported in these reports. We reported the first case of PMIS related to COVID-19 from Saudi Arabia. This case was a Saudi G6PD deficient girl who died with PMIS related to COVID-19. G6PD deficiency induces redox imbalance and exaggerates the inflammatory response; thus, it might contribute to the development or the grave outcome of our case. We urgently need to assess the association between G6PD deficiency and COVID-19 in a large study as the G6PD deficiency may be a useful predictor for the progression of the COVID-19.

BACKGROUND:Contradictory evidence exists whether a prophylactic coagulation factor transfusion in the first hours of life (HOL) prevents intraventricular hemorrhage (IVH) in extreme preterm infants (EPI, <28 weeks gestation). We aimed to determine whether selective prophylactic solvent-detergent plasma and cryoprecipitate transfusion within 12 hours of life (SP-SDP/Cryoprecipitate-T) could prevent IVH in EPI.METHOD:This is a retrospective analysis, case-historical control, of prospectively collected data from a pre-existing electronic neonatal database at a Saudi tertiary neonatal intensive care unit. We compared the IVH rate in EPI born in the first 4 years (Jan 2010-Dec 2013) of the SP-SDP/Cryoprecipitate-T period with that of EPI born during the last 4 years (Jan 2006-Dec 2009) of the rescue SDP/Cryoprecipitate-T period.RESULTS:The IVH rate was lower in the SP compared to the rescue- SDP/Cryoprecipitate-T period (30.8% versus 51.2%, odds ratio 0.42, 95% confidence interval 0.21, 0.88, p = 0.02). This difference remained significant after controlling for six other IVH risk factors.CONCLUSIONS:Early SP-SDP/Cryoprecipitate-T may reduce the IVH rate in EPI. A large multicenter clinical trial is required for confirm the short and long-term benefit and risk of this intervention. Until then, early SP-SDP/Cryoprecipitate-T may be considered by an institution with a persistently high IVH rate.

Mechanical ventilation is one of the most common therapies in the neonatal intensive care unit (NICU), it is an area where technical complexity overlap individual preferences due to lack of extensive scientific evidence. Our aim is to provide clinical practice guidelines for conventional mechanical ventilation of newborn infants, utilizing the best available scientific evidence and to address the controversies. These guidelines are meant to help the clinician in managing ventilated newborn infants; it should not replace clinical judgment.

ObjectivesThis 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.MethodsThis 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 >3 days of age with clinical and laboratory findings consistent with infection.ResultsSeven 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.ConclusionLOS 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.

BACKGROUND Hyperbilirubinemia is one of the most common causes of neonatal readmission to hospital. AIMS To assess risk factors for hyperbilirubinemia among neonates readmitted for this condition and the ratio of the mean corpuscular hemoglobin concentration (MCHC) to the mean corpuscular volume (MCV). METHODS We retrospectively studied the clinical and laboratory findings, management and possible risk factors for hyperbilirubinemia in 301 neonates born at ≥35 weeks gestation and readmitted to hospital owing to hyperbilirubinemia over five years. RESULTS No risk factors for hyperbilirubinemia were identified in 64 (21.3%) neonates, and one or more risk factors were found in 237 neonates (78.7%). The most prevalent risk factor (41.9%) was G6PD deficiency, which occurred in 11 of the 15 neonates with a serum bilirubin level ≥427 μmol/l. A double-volume exchange blood transfusion was performed in two neonate boys in whom G6PD deficiency was the single risk factor for hyperbilirubinemia. One of them developed kernicterus later. The MCHC/MCV ratio of neonates with idiopathic hyperbilirubinemia, unexplained hemolysis, or other risk factors overlapped. CONCLUSIONS This study confirmed that in an area where G6PD deficiency is prevalent, it is the most common and most severe risk factor for hyperbilirubinemia. This finding supports routine neonatal screening for G6PD deficiency in such areas. The usefulness of determining the MCHC/MCV ratio in the management of hyperbilirubinemia is uncertain.

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.