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  1. Interaction of Hb South Florida (codon 1; GTG-->ATG) and HbE, with beta-thalassemia (IVS1-1; G-->A): expression of different clinical phenotypes
    Tan JA, Tan KL, Omar KZ, Chan LL, Wee YC, George E
    Eur J Pediatr, 2009 Sep;168(9):1049-54.
    PMID: 19034506 DOI: 10.1007/s00431-008-0877-9
    INTRODUCTION: Interactions of different hemoglobin variants with thalassemia alleles can result in various clinical phenotypes. HbE-beta-thalassemia generally manifests with severe anemia where individuals exhibit beta-thalassemia major with regular blood transfusions or beta-thalassemia intermedia with periodic blood transfusions. This study presents a unique Malay family with three beta-globin gene defects-HbE, Hb South Florida, and IVS1-1 (G-->A).

    MATERIALS AND METHODS: HbE activates a cryptic splice site that produces non-functional mRNAs. Hb South Florida is a rare beta-hemoglobin variant, and its interactions with other beta-thalassemia alleles have not been reported. IVS1-1 is a Mediterranean mutation that affects mRNA processing giving rise to beta(o)-thalassemia.

    RESULTS AND DISCUSSION: Fifteen mutations along the beta-globin gene complex were analyzed using the amplification refractory mutation system. Hb South Florida was identified by direct sequencing using genomic DNA.

    CONCLUSION: The affected child with HbE/IVS1-1 produced a beta-thalassemia major phenotype. Compound heterozygosity for Hb South Florida/IVS1-1 produced a beta-thalassemia carrier phenotype in the mother.

  2. Ten-year trend in prevalence and outcome of Down syndrome with congenital heart disease in a middle-income country
    Zahari N, Mat Bah MN, A Razak H, Thong MK
    Eur J Pediatr, 2019 Aug;178(8):1267-1274.
    PMID: 31222391 DOI: 10.1007/s00431-019-03403-x
    Limited data are available on the survival of patients with Down syndrome and congenital heart disease (CHD) from middle-income countries. This retrospective cohort study was performed to determine the trends in the prevalence and survival of such patients born from January 2006 to December 2015 in Malaysia. Among 754 patients with Down syndrome, 414 (55%) had CHD, and no significant trend was observed during the 10 years. Of these 414 patients, 30% had lesions that closed spontaneously, 35% underwent surgery/intervention, 9% died before surgery/intervention, and 10% were treated with comfort care. The overall mortality rate was 23%, the median age at death was 7.6 months, and no significant changes occurred over time. The early and late post-surgery/intervention mortality rates were 0.7% and 9.0%, respectively. Most deaths were of non-cardiac causes. The overall 1-, 5-, and 10-year survival rates were 85.5%, 74.6%, and 72.9%, respectively. Patients with severe lesions, persistent pulmonary hypertension of the newborn, atrioventricular septal defect, and pulmonary hypertension had low survival at 1 year of age.Conclusion: The prevalence of CHD in patients with Down syndrome is similar between Malaysia and high-income countries. The lower survival rate is attributed to limited expertise and resources which limit timely surgery. What is Known: • The survival of patients with Down syndrome with congenital heart disease (CHD) has improved in high-income countries. However, little is known about the survival of patients with Down syndrome with CHD from middle-income countries. • In the Caucasian population, atrioventricular septal defect is the most common type of CHD associated with Down syndrome. What is New: • In middle-income countries, the prevalence of CHD is the same as in high-income countries, but with a lower survival rate. • In the Asian population, ventricular septal defect is the most common type of CHD in patients with Down syndrome.
  3. Carbamoylphosphate synthetase 1 (CPS1) deficiency: clinical, biochemical, and molecular characterization in Malaysian patients
    Ali EZ, Khalid MK, Yunus ZM, Yakob Y, Chin CB, Abd Latif K, et al.
    Eur J Pediatr, 2016 Mar;175(3):339-46.
    PMID: 26440671 DOI: 10.1007/s00431-015-2644-z
    Carbamoyl phosphate synthetase 1 (CPS1) deficiency is a rare autosomal recessive disorder of ureagenesis presenting as life-threatening hyperammonemia. In this study, we present the main clinical features and biochemical and molecular data of six Malaysian patients with CPS1 deficiency. All the patients have neonatal-onset symptoms, initially diagnosed as infections before hyperammonemia was recognized. They have typical biochemical findings of hyperglutaminemia, hypocitrullinemia, and low to normal urinary excretion of orotate. One neonate succumbed to the first hyperammonemic decompensation. Five neonatal survivors received long-term treatment consisting of dietary protein restriction and ammonia-scavenging drugs. They have delayed neurocognitive development of varying severity. Genetic analysis revealed eight mutations in CPS1 gene, five of which were not previously reported. Five mutations were missense changes while another three were predicted to create premature stop codons. In silico analyses showed that these new mutations affected different CPS1 enzyme domains and were predicted to interrupt interactions at enzyme active sites, disturb local enzyme conformation, and destabilize assembly of intact enzyme complex.

    CONCLUSION: All mutations are private except one mutation; p.Ile1254Phe was found in three unrelated families. Identification of a recurrent p.Ile1254Phe mutation suggests the presence of a common and unique mutation in our population. Our study also expands the mutational spectrum of the CPS1 gene.

  4. Hyperexcretion of homocitrulline in a Malaysian patient with lysinuric protein intolerance
    Habib A, Md Yunus Z, Azize NA, Ch'ng GS, Ong WP, Chen BC, et al.
    Eur J Pediatr, 2013 Sep;172(9):1277-81.
    PMID: 23358709 DOI: 10.1007/s00431-013-1947-1
    Lysinuric protein intolerance (LPI; MIM 222700) is an inherited aminoaciduria with an autosomal recessive mode of inheritance. Biochemically, affected patients present with increased excretion of the cationic amino acids: lysine, arginine, and ornithine. We report the first case of LPI diagnosed in Malaysia presented with excessive excretion of homocitrulline. The patient was a 4-year-old male who presented with delayed milestones, recurrent diarrhea, and severe failure to thrive. He developed hyperammonemic coma following a forced protein-rich diet. Plasma amino acid analysis showed increased glutamine, alanine, and citrulline but decreased lysine, arginine and ornithine. Urine amino acids showed a marked excretion of lysine and ornithine together with a large peak of unknown metabolite which was subsequently identified as homocitrulline by tandem mass spectrometry. Molecular analysis confirmed a previously unreported homozygous mutation at exon 1 (235 G > A, p.Gly79Arg) in the SLC7A7 gene. This report demonstrates a novel mutation in the SLC7A7 gene in this rare inborn error of diamino acid metabolism. It also highlights the importance of early and efficient treatment of infections and dehydration in these patients.

    CONCLUSION: The diagnosis of LPI is usually not suspected by clinical findings alone, and specific laboratory investigations and molecular analysis are important to get a definitive diagnosis.

  5. Drug administration errors in paediatric wards: a direct observation approach
    Chua SS, Chua HM, Omar A
    Eur J Pediatr, 2010 May;169(5):603-11.
    PMID: 19823870 DOI: 10.1007/s00431-009-1084-z
    Paediatric patients are more vulnerable to drug administration errors due to a lack of appropriate drug dosages and strengths for use in this group of patients. Therefore, the aim of the present study was to determine the extent and types of drug administration errors in two paediatric wards and to identify measures to reduce such errors. A researcher was stationed in two paediatric wards of a teaching hospital to observe all drugs administered to paediatric inpatients in each of the ward, for 1 day in a week over ten consecutive weeks. All data were recorded in a data collection form and then compared with the actual drugs and dosages prescribed for the patients. Of the 857 drug administrations observed, 100 doses had errors, and this gave an error rate of 11.7% [95% confidence interval (CI) 9.5-13.9%]. If wrong time administration errors were excluded, the error rate reduced to 7.8% (95% CI 6.0-9.6%). The most common types of drug administration errors were incorrect time of administration (28.8%), followed by incorrect drug preparation (26%), omission errors (16.3%) and incorrect dose (11.5%). None of the errors observed were considered as potentially life threatening, although 40.4% could possibly cause patient harm. Drug administration errors are as common in paediatric wards in Malaysia as in other countries. Double-checking should be conducted, as this could reduce drug administration errors by about 20%, but collaborative efforts between all healthcare professionals are essential.
  6. Parental preferences in treatment of acute uncomplicated appendicitis comparing surgery to conservative management with antibiotics and their views on research participation
    Kyaw L, Pereira NK, Ang CX, Choo CSC, Nah SA
    Eur J Pediatr, 2020 May;179(5):735-742.
    PMID: 31897841 DOI: 10.1007/s00431-019-03555-w
    Studies show that conservative management in acute uncomplicated appendicitis (AUA) is an alternative to surgery. This study aims to determine factors affecting parental preference in management of AUA and their decision for research participation. We conducted surveys on parents whose children were admitted with suspicion of appendicitis but later confirmed not to have appendicitis. Information on appendicectomy versus conservative treatment with antibiotics was provided using a fixed script and standard information leaflet. Questionnaires covered factors influencing decisions, opinions regarding research, treatment preference and demographic data. We excluded parents not fluent in English. Of 113 respondents, 71(62.8%) chose antibiotics, 39(34.5%) chose appendicectomy, and 3(2.7%) had no preference. Reasons given for choosing antibiotics were fear of surgical risks and preferring less invasive treatment. Those choosing appendicectomy expressed preference for definitive treatment and fear of recurrence. Majority were against randomisation (n = 89, 78.8%) and blinding (n = 90, 79.7%). Over half found difficulty involving their child in research (n = 65, 57.5%). Most thought that research is important (66.4%) and beneficial to others (59.3%). Parents who perceived their child as healthy found research riskier (p = 0.039). Educated parents were more likely to find research beneficial to others (p = 0.012) but less accepting of randomisation (p = 0.001).Conclusion: More parents appear to prefer conservative treatment for acute uncomplicated appendicitis. Researchers must consider parental concerns regarding randomisation and blinding.What is Known:• Conservative management of acute uncomplicated appendicitis in paediatric patients is safe and effective, sparing the child the need for an operation; however, neither conservative nor surgical management is proven to be superior.• Randomised controlled trials provide the highest level of evidence, but it is challenging to recruit paediatric patients as participants in such clinical trials.What is New:• More parents prefer conservative management of uncomplicated appendicitis over surgical management for their children due to fear of surgical risks and complications• Randomisation in trial design is significantly associated with a parent's decision to reject their child's participation in a clinical trial.
  7. Prevalence and predictors of antibiotic use among children visiting the Emergency Department in a Tertiary Hospital in Malaysia
    Tham DWJ, Abubakar U, Tangiisuran B
    Eur J Pediatr, 2020 May;179(5):743-748.
    PMID: 31900590 DOI: 10.1007/s00431-019-03560-z
    Inappropriate use of antibiotics in human and animal is one of the causes of antimicrobial resistance. This study evaluates the prevalence and predictors of antibiotic use among pediatric patients visiting the Emergency Department (ED) in Malaysia. A retrospective cross-sectional study was conducted in the ED of a tertiary hospital. Data of children aged 2 to 11 years who visited the ED from January-May 2015 were extracted from the patient's assessment forms. A total of 549 children were included in the analysis (median age 5 years) of which 54.3% were boys. Upper respiratory tract infections (URTI) were the most common diagnosis. Antibiotic was prescribed in 43.5% of the children. Children who visited the ED during the weekend (OR, 1.65; 95% confidence interval (CI) 1.13-2.40, P = 0.009), those diagnosed with URTI (OR 3.81; 95% CI, 2.45-5.93, P 
  8. Correction to: Epidemiology, clinical characteristics, and immediate outcome of Kawasaki disease: a population-based study from a tropical country
    Mat Bah MN, Alias EY, Razak H, Sapian MH, Foo FH, Abdullah N
    Eur J Pediatr, 2021 Aug;180(8):2607.
    PMID: 34160651 DOI: 10.1007/s00431-021-04160-6
  9. Epidemiology, clinical characteristics, and immediate outcome of Kawasaki disease: a population-based study from a tropical country
    Mat Bah MN, Alias EY, Razak H, Sapian MH, Foo FH, Abdullah N
    Eur J Pediatr, 2021 Aug;180(8):2599-2606.
    PMID: 34086103 DOI: 10.1007/s00431-021-04135-7
    Data on Kawasaki disease from tropical countries are scarce. Hence, this population-based study aims to determine the epidemiology, clinical characteristics, and outcome of Kawasaki disease in children enrolled in the Kawasaki disease registry between 2006 and 2019 in Southern Malaysia. Diagnosis of Kawasaki disease was made using standard criteria. Primary outcome measure was a coronary artery aneurysm. Multivariable logistic regression was used to analyze the associated risk factors for coronary artery aneurysm. There were 661 Kawasaki disease, with 27% incomplete and 11% atypical presentations. Male-to-female ratio was 2:1, and median age of diagnosis was 1.4 years (interquartile range 9 to 32 months). Incidence in children of less than 5 years was 14.8 (95% confidence interval [CI]: 13.6 to 16.0) per 100,000 population, higher in males (19/100,000) and Chinese (22/100,000), with a gradual increase from 5.7/100,000 in 2006 to 19.6/100,000 in 2019, p < 0.001. Incidence in children between 5 and 9 years old was 1.3 (95% CI: 0.9 to 1.6) per 100,000 population and remained stable over time. There was a seasonal pattern with peak incidence during the rainy season. Out of 625 intravenous immunoglobulins (IVIG)-treated Kawasaki disease, 7.4% were resistant, and 9% had coronary artery aneurysms. Atypical presentation, male sex, late diagnosis, and IVIG resistance were independent risk factors for coronary artery aneurysms.Conclusions: Despite the tropical climate, Kawasaki disease epidemiology is similar to non-tropic regions with seasonal patterns and a rising incidence. Atypical presentation, male sex, late diagnosis, and IVIG resistance were significantly associated with coronary artery aneurysms. What is Known: • Kawasaki disease predominantly occurs in males, children less than 5 years old, and the Asian population. • Male sex, late diagnosis, incomplete Kawasaki disease, and IVIG resistance were associated with coronary artery aneurysms. What is New: • In multi-ethnic Asian countries such as Malaysia, ethnic Chinese have a higher prevalence of Kawasaki disease compared to other ethnicities. • Kawasaki disease with atypical presentation can occur in both complete and incomplete Kawasaki disease and is significantly associated with a coronary artery aneurysm.
  10. Bisphenol A and its effects on the systemic organs of children
    Zulkifli S, Rahman AA, Kadir SHSA, Nor NSM
    Eur J Pediatr, 2021 Oct;180(10):3111-3127.
    PMID: 33893858 DOI: 10.1007/s00431-021-04085-0
    For the past two decades, growing research has been pointing to multiple repercussions of bisphenol A (BPA) exposure to human health. BPA is a synthetic oestrogen which primarily targets the endocrine system; however, the compound also disturbs other systemic organ functions, in which the magnitude of impacts in those other systems is as comparable to those in the endocrine system. To date, the discoveries on the association between BPA and health outcomes mainly came from animal and in vitro studies, with limited human studies which emphasised on children's health. In this comprehensive review, we summarised studies on human, in vivo and in vitro models to understand the consequences of pre-, post- and perinatal BPA exposure on the perinatal, children and adult health, encompassing cardiovascular, neurodevelopmental, endocrine and reproductive effects.Conclusion: Evidence from in vitro and animal studies may provide further support and better understanding on the correlation between environmental BPA exposure and its detrimental effects in humans and child development, despite the difficulties to draw direct causal relations of BPA effects on the pathophysiology of the diseases/syndromes in children, due to differences in body system complexity between children and adults, as well as between animal and in vitro models and humans. What is known: • Very limited reviews are available on how BPA adversely affects children's health. • Previous papers mainly covered two systems in children. What is new: • Comprehensive review on the detrimental effects of BPA on children health outcomes, including expectations on adult health outcomes following perinatal BPA exposure, as well as covering a small part of BPA alternatives. • Essentially, BPA exposure during pregnancy has huge impacts on the foetus in which it may cause changes in foetal epigenetic programming, resulting in disease onsets during childhood as well as adulthood.
  11. The diuretic effect of adding aminophylline or theophylline to furosemide in pediatric populations: a systematic review
    Van Siang Lian Mang P, Hui JC, Tan RSJ, Hasan MS, Choo YM, Abosamak MF, et al.
    Eur J Pediatr, 2023 Jan;182(1):1-8.
    PMID: 36251063 DOI: 10.1007/s00431-022-04655-w
    The diuretic effect of the combined furosemide and aminophylline/theophylline among pediatric patients remains unclear. The primary aim of this systematic review was to examine the clinical diuretic effects (urine output and fluid balance) of co-administration of furosemide and aminophylline/theophylline as compared to furosemide alone in pediatric population. Ovid MEDLINE, CENTRAL, and EMBASE were searched from its inception until March 2022 for observational studies and randomized controlled trials (RCTs) comparing the administration of furosemide versus furosemide and aminophylline/theophylline in pediatric population. Case reports, case series, commentaries, letters to editors, systematic reviews, and meta-analyses were excluded. Five articles with a total sample population of 187 patients were included in this systematic review. As compared to the furosemide alone, our pooled data demonstrated that co-administration of furosemide and aminophylline/theophylline was associated with higher urine output (mean difference: 2.91 [90% CI 1.54 to 4.27], p 
  12. An international multicenter survey reveals health care providers' knowledge gap in childhood central nervous system tumors
    Rajagopal R, Moreira DC, Faughnan L, Wang H, Naqvi S, Krull L, et al.
    Eur J Pediatr, 2023 Feb;182(2):557-565.
    PMID: 36383283 DOI: 10.1007/s00431-022-04712-4
    Childhood central nervous system (CNS) tumors have longer delays in diagnosis than do other pediatric malignancies because health care providers (HCPs) lack awareness about clinical presentation of these tumors. To evaluate the knowledge gap among HCPs, we conducted a global cross-sectional survey. The survey consisted of a set of CNS tumor knowledge questions focused on symptoms, signs, and imaging indications. The survey was disseminated to HCPs via email (November 2018-March 2020). Participants had to complete a pre-test survey, attend an education seminar on CNS tumors, and complete a post-test survey. The knowledge gap was evaluated using pre-test and post-test scores. We received 889 pre-test and 392 post-test responses. Most respondents were from Asia (73.1% of pre-test responses; 87.5% of post-test responses). The median pre-test score was 40.0% (range: 13.1-92.9%). A high percentage of correct answers were given in post-test responses (median score: 77.1%, range: 14.9-98.2%). In the pre-test, 18.7% of participants accurately responded that Cushing's triad was a less common symptom, and 15.0% recognized that children aged > 10 years are at risk of late diagnosis. Surprisingly, 21.9% falsely reported that patients with malignancy experienced the longest pre-diagnostic symptom interval, and 54.5% of respondents wrongly selected medulloblastoma as the most common CNS tumor. Overall, pediatricians demonstrated a greater knowledge gap on both surveys than did other specialties.  Conclusion: Pre- and post-test surveys revealed significant knowledge gaps in childhood CNS tumors among HCPs. Thus, raising professional awareness on clinical presentations of CNS tumors through educational strategies is important to address this knowledge deficit. What is Known: • Diagnostic delay in childhood central nervous system (CNS) tumors continues to be a significant problem that negatively impacts the quality of life and treatment sequelae. • Lack of medical education on CNS tumors is a contributing factor to this problem. What is New: • Most health care providers do not realize that low-grade tumors are the most common neoplasm in children. • Health care providers fail to recognize that teenagers and adolescents are a vulnerable age group for diagnostic delays, with the longest pre-diagnostic symptom interval.
  13. Effects of twin-block appliance on upper airway parameters in OSA children with class II malocclusion and mandibular retrognathia: a CBCT study
    Zreaqat M, Hassan R, Samsudin AR, Alforaidi S
    Eur J Pediatr, 2023 Dec;182(12):5501-5510.
    PMID: 37777602 DOI: 10.1007/s00431-023-05226-3
    Twin-block appliance had been advocated as a potential treatment option in paediatric obstructive sleep apnoea (OSA) due to their favourable effect in enhancing upper airway parameters and improving OSA symptoms. The aim of this study was to evaluate the effect of twin-block appliance therapy on upper airway parameters/dimensions and the apnoea-hypopnea indexes (AHIs) in OSA children with class II mandibular retrognathic skeletal malocclusion using cone-beam computed tomography. This prospective longitudinal study comprised 34 polysomnography-proven OSA growing children with class II mandibular retrognathic skeletal malocclusion between the ages of 8 and 12 years who had completed myofunctional twin-block therapy and matched corresponding controls. The upper airway was segmented into the nasopharynx, oropharynx, and hypopharynx, and the effect of twin-bock treatment on upper airway parameters/dimensions was assessed pre- and posttreatment using CBCT analysis, while a second standard overnight PSG was performed to determine changes in the AHI. At the nasopharynx level, minimal (nonsignificant) increases in all variables were observed within the twin-block group and between the groups (P > 0.05). At the level of the oropharynx, all variables increased significantly in the treatment group and between groups (P 
  14. Survival and factors associated with mortality among infants with anorectal malformation: a population-based study from a middle-income country
    Mat Bah MN, Zahari N, Kasim AS, Mohamed Sharif NL
    Eur J Pediatr, 2024 Jan;183(1):271-279.
    PMID: 37870607 DOI: 10.1007/s00431-023-05292-7
    Limited data on the survival of anorectal malformation (ARM) patients from lower- and middle-income countries is available. This retrospective population-based study from the State of Johor, Malaysia, determines the incidence, mortality rate, and survival of ARM patients and factors associated with mortality. Kaplan-Meier survival analysis was used to estimate the survival of ARM patients at 1, 5, and 10 years. In addition, multivariate Cox regression analysis was used to analyze mortality-related factors. There were 175 ARM patients among 803,850 live births, giving an overall ARM incidence of 2.2 (95% confidence interval [CI], 1.9 to 2.5) per 10,000 live births. The male-to-female ratio was 1.5:1. There were 122 (69%) non-isolated ARM, of which 41 were Trisomy-21 and 34 had VACTERL association. Seventy-three (42%) had congenital heart disease (CHD), with 38 severe and 35 non-severe CHD. Overall, 33 (19%) patients died, with a median age of death of 5.7 months (interquartile range (IQR) 25 days to 11.2 months). The overall estimated 1-, 5-, and 10-year survival rate for ARM patients was 82% (95% CI, 76-89%), 77% (95% CI, 70-84%), and 77% (95% CI, 70-84%), respectively. Univariate analysis shows that non-isolated ARM, VACTERL association, and severe CHD were associated with mortality. However, only severe CHD is the independent factor associated with mortality, with a hazard ratio of 4.0 (95% CI, 1.9-8.4).  Conclusion: CHD is common among ARM patients, and one in five ARM patients had a severe cardiac defect, significantly affecting their survival. What is Known: • VACTERL association and congenital heart disease are common in patient with anorectal malformation. • Low birth weight and prematurity are associated with a lower rate of survival. What is New: • Congenital heart disease is common in ARM patients in a middle-income country. • Severe congenital heart disease plays a significant role in the survival of patients with an anorectal malformation in lower- and middle-income countries.
  15. Navigating through 65 years of insights: lessons learned on functional abdominal pain in children
    Rajindrajith S, Boey CC, Devanarayana NM, Niriella MA, Thapar N, Benninga MA
    Eur J Pediatr, 2024 Jul 08.
    PMID: 38972964 DOI: 10.1007/s00431-024-05667-4
    In 1958, Apley and Naish authored a groundbreaking paper in Archives of Disease in Childhood, elucidating the epidemiology and risk factors of recurrent abdominal pain in children-a subject that had confounded clinicians of their time. Surprisingly, even after 65 years, there are several unanswered questions regarding the etiology, pathophysiology, and management of pediatric abdominal pain. Contrary to the prevailing notion that children naturally outgrow functional abdominal pain, compelling evidence suggests it's possible these children develop a number of clinically significant psychological issues that could profoundly impact their quality of life and, consequently, future health and educational outcomes. In this light, we aimed to comprehensively review the current literature to update the knowledge of practicing clinicians on functional abdominal pain, summarizing the evidence from the last 65 years.Conclusion: The enduring unanswered questions surrounding childhood abdominal pain continue to challenge clinicians, resulting in unnecessary investigations, thereby contributing to substantial healthcare expenditures. It is also evident that children with long-standing symptoms would progress to adulthood with the potential to develop irritable bowel syndrome and many psychological disturbances. Several key interventions using pharmacological agents, such as amitriptyline, showed that some of these drugs are no more effective than the placebo in clinical trials. Several research during the recent past suggest that psychological interventions such as gut-directed hypnotherapy alleviate symptoms and ensure better prognosis in the long run. Therefore, clinicians and researchers must join hands to explore the pathophysiological mechanisms underpinning functional abdominal pain and novel therapeutic strategies to ensure the well-being of these children. What is Known: • Functional abdominal pain disorders are common among children, with a worldwide prevalence of 13.5% of children suffering from at least one of these disorders • These disorders contribute to a significant reduction in the quality of life of affected children and their families and lead to an array of psychological problems What is New: • The biological basis of functional abdominal pain is becoming more explicit, including complex interactions between altered microbiome, deranged motility, and psychological dysfunction with gut-brain interactions • Novel approaches giving minimal emphasis on pharmacological interventions and exploring psychological interventions are showing promising results.
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