RSS 1.0Paediatrics
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Emerging integrase resistance in an international perinatal virtual clinicObjective: The aim of this study was to identify the prevalence of emergent integrase drug resistance mutations (INSTI-DRMs) in international referrals to a perinatal virtual clinic (PVC). Design: A retrospective cohort study. Setting: Monthly multidisciplinary PVC reviewing complex case management for children and adolescents with perinatally acquired HIV (CAWHIV). Participants: One hundred fourteen cases referred for virological failure between October 2018 and January 2024. Main outcome measures: Data collected included age, sex, weight, country of residence, antiretroviral therapy (ART) history, HIV viral load, CD4+ cell count, and comorbidities. Resistance mutations were interpreted using the Stanford HIV Drug Resistance database with emergent major INSTI-DRMs described. Results: Of 114 referrals, 103 (90%) had resistance sequences available. Prior INSTI exposure was documented in 61/103 (59%) with 19/61 (31%) having INSTI-DRMs. For these 19, median (IQR) age was 11 years (6-14), weight 25 kg (17-50), CD4+ cell count 485 cells/μl (153-805), and viral load 84 000 copies/ml (2380-137 000). Twelve of 19 (65%) were from low/middle-income countries (LMIC), 6/19 (32%) had current AIDS diagnoses with 14/19 (74%) referred from 2022 onwards. There were a median three prior regimens with 13/19 (68%) having at least 3 class resistance. Two developed INSTI-DRMs on first-line dolutegravir (DTG)-based ART, 17 on second+ line therapy. PVC recommendations were for tenofovir+ lamivudine/emtricitabine (six split adult tablets) with boosted darunavir [19; six twice daily (b.i.d.)], with b.i.d. DTG (6), plus fostemsavir (1) and ibalizumab (1). Conclusion: Although uncommon, INSTI resistance is emerging, mainly in highly treatment experienced CAWHIV from LMIC, highlighting the global need for access to boosted protease inhibitors and novel classes, including formulations for children less than 35 kg.
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The immune landscape of SARS-CoV-2-associated Multisystem Inflammatory Syndrome in Children (MIS-C) from acute disease to recoveryMultisystem inflammatory syndrome in children (MIS-C) is a life-threatening disease occurring several weeks after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Deep immune profiling showed acute MIS-C patients had highly activated neutrophils, classical monocytes and memory CD8+ T-cells, with increased frequencies of B-cell plasmablasts and double-negative B-cells. Post treatment samples from the same patients, taken during symptom resolution, identified recovery-associated immune features including increased monocyte CD163 levels, emergence of a new population of immature neutrophils and, in some patients, transiently increased plasma arginase. Plasma profiling identified multiple features shared by MIS-C, Kawasaki Disease and COVID-19 and that therapeutic inhibition of IL-6 may be preferable to IL-1 or TNF-α. We identified several potential mechanisms of action for IVIG, the most commonly used drug to treat MIS-C. Finally, we showed systemic complement activation with high plasma C5b-9 levels is common in MIS-C suggesting complement inhibitors could be used to treat the disease.
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TRAPPC11-related muscular dystrophy with hypoglycosylation of alpha-dystroglycan in skeletal muscle and brainAims: TRAPPC11, a subunit of the transport protein particle (TRAPP) complex, is important for complex integrity and anterograde membrane transport from the endoplasmic reticulum (ER) to the ER-Golgi intermediate compartment. Several individuals with TRAPPC11 mutations have been reported with muscle weakness and other features including brain, liver, skeletal and eye involvement. A detailed analysis of brain and muscle pathology will further our understanding of the presentation and aetiology of TRAPPC11 disease. Methods: We describe five cases of early-onset TRAPPC11-related muscular dystrophy with a systematic review of muscle pathology in all five individuals, post-mortem brain pathology findings in one and membrane trafficking assays in another. Results: All affected individuals presented in infancy with muscle weakness, motor delay and elevated serum creatine kinase (CK). Additional features included cataracts, liver disease, intellectual disability, cardiomyopathy, movement disorder and structural brain abnormalities. Muscle pathology in all five revealed dystrophic changes, universal hypoglycosylation of alpha-dystroglycan and variably reduced dystrophin-associated complex proteins. Membrane trafficking assays showed defective Golgi trafficking in one individual. Neuropathological examination of one individual revealed cerebellar atrophy, granule cell hypoplasia, Purkinje cell (PC) loss, degeneration and dendrite dystrophy, reduced alpha-dystroglycan (IIH6) expression in PC and dentate neurones and absence of neuronal migration defects. Conclusions: This report suggests that recessive mutations in TRAPPC11 are linked to muscular dystrophies with hypoglycosylation of alpha-dystroglycan. The structural cerebellar involvement that we document for the first time resembles the neuropathology reported in N-linked congenital disorders of glycosylation (CDG) such as PMM2-CDG, suggesting defects in multiple glycosylation pathways in this condition.
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HIV postnatal prophylaxis and infant feeding policies vary across Europe: results of a Penta surveyObjectives: This survey was conducted to describe current European postnatal prophylaxis (PNP) and infant feeding policies with the aim of informing future harmonized guidelines. Methods: A total of 32 senior clinicians with relevant expertise, working in 20 countries within the European Region, were invited to complete a REDCap questionnaire between July and September 2023. Results: Twenty-three of the 32 invited paediatricians responded, representing 16/20 countries. There were multiple respondents from the same country for Italy (n = 5), the UK (n = 2), Germany (n = 2) and France (n = 2). All countries use risk stratification to guide PNP regimen selection. Nine out of 16 countries reported three risk categories, six out of 16 reported two, and one country reported differences in categorization. Criteria used to stratify risk varied between and within countries. For the lowest risk category, the PNP regimen reported ranged from no PNP to up to four weeks of one drug; the drug of choice reported was zidovudine, apart from one country which reported nevirapine. For the highest risk category, the most common regimen was zidovudine/lamivudine/nevirapine (20/23 respondents); regimen duration varied from two to six weeks with variation in recommended dosing. Guidelines support breastfeeding for infants born to people living with HIV in eight out of 16 countries; in the other eight, guidelines do not support/specify. Conclusions: Guidelines and practice for PNP and infant feeding vary substantially across Europe and within some countries, reflecting the lack of robust evidence. Effort is needed to align policies and practice to reflect up-to-date knowledge to ensure the vertical transmission risk is minimized and unnecessary infant HIV testing and PNP avoided, while simultaneously supporting families to make informed decisions on infant feeding choice.
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Preventing tuberculosis in paediatric kidney transplant recipients: is there a role for BCG immunisation pre-transplantation in low tuberculosis incidence countries?The risk of tuberculosis (TB) disease is increased in children with chronic kidney disease (CKD), even higher in stage 5 CKD/kidney failure and especially high after kidney transplantation due to immunosuppression. TB disease may follow recent primary infection, or result from reactivation of latent infection. Reactivation is more common in adults, while progression following primary infection makes up a greater proportion of disease in children. Recommendations for preventing TB disease in some low TB incidence countries have previously included offering Bacillus Calmette-Guérin (BCG) vaccine to all children listed for kidney transplant if they had not received this as part of previous national immunisation programmes. Based on the available evidence, we recommend modifying this practice, focusing instead on awareness of risk factors for TB exposure, infection and disease and the use of appropriate testing strategies to identify and treat TB infection and disease.
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Prediagnosis pathway benchmarking audit in patients with Duchenne muscular dystrophyObjective: To describe age and time at key stages in the Duchenne muscular dystrophy (DMD) prediagnosis pathway at selected centres to identify opportunities for service improvement. Design: A multicentre retrospective national audit. Setting: Nine tertiary neuromuscular centres across the UK and Ireland. A prior single-centre UK audit of 20 patients with no DMD family history provided benchmark criteria. Patients: Patients with a definitive diagnosis of DMD documented within 3 years prior to December 2018 (n=122). Main outcome measures: Mean age (months) at four key stages in the DMD diagnostic pathway and mean time (months) of presentational and diagnostic delay, and time from first reported symptoms to definitive diagnosis. Type of symptoms was also recorded. Results: Overall, mean age at definitive diagnosis, age at first engagement with healthcare professional (HCP) and age at first reported symptoms were 53.9±29.7, 49.9±28.9 and 36.4±26.8 months, respectively. The presentational delay and time to diagnosis were 21.1 (±21.1) and 4.6 (±7.9) months, respectively. The mean time from first reported symptoms to definitive diagnosis was 24.2±20.9. The percentages of patients with motor and/or non-motor symptoms recorded were 88% (n=106/121) and 47% (n=57/121), respectively. Conclusions: Majority of data mirrored the benchmark audit. However, while the time to diagnosis was shorter, a presentational delay was observed. Failure to recognise early symptoms of DMD could be a contributing factor and represents an unmet need in the diagnosis pathway. Methods determining how to improve this need to be explored.
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The burden of critical illness in hospitalized children in low- and middle-income countries: protocol for a systematic review and meta-analysis.Background: The majority of childhood deaths occur in low- and middle-income countries (LMICs). Many of these deaths are avoidable with basic critical care interventions. Quantifying the burden of pediatric critical illness in LMICs is essential for targeting interventions to reduce childhood mortality. Objective: To determine the burden of hospitalization and mortality associated with acute pediatric critical illness in LMICs through a systematic review and meta-analysis of the literature. Data sources and search strategy: We will identify eligible studies by searching MEDLINE, EMBASE, CINAHL, and LILACS using MeSH terms and keywords. Results will be limited to infants or children (ages >28 days to 12 years) hospitalized in LMICs and publications in English, Spanish, or French. Publications with non-original data (e.g., comments, editorials, letters, notes, conference materials) will be excluded. Study selection: We will include observational studies published since January 1, 2005, that meet all eligibility criteria and for which a full text can be located. Data extraction: Data extraction will include information related to study characteristics, hospital characteristics, underlying population characteristics, patient population characteristics, and outcomes. Data synthesis: We will extract and report data on study, hospital, and patient characteristics; outcomes; and risk of bias. We will report the causes of admission and mortality by region, country income level, and age. We will report or calculate the case fatality rate (CFR) for each diagnosis when data allow. Conclusions: By understanding the burden of pediatric critical illness in LMICs, we can advocate for resources and inform resource allocation and investment decisions to improve the management and outcomes of children with acute pediatric critical illness in LMICs.
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Vitamin D status of children with paediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus 2 (PIMS-TS).Coronavirus disease 2019 (COVID-19) has caused mild illness in children, until the emergence of the novel hyperinflammatory condition paediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (PIMS-TS). PIMS-TS is thought to be a post-SARS-CoV-2 immune dysregulation with excessive inflammatory cytokine release. We studied 25 hydroxyvitamin D (25OHD) concentrations in children with PIMS-TS, admitted to a tertiary paediatric hospital in the UK, due to its postulated role in cytokine regulation and immune response. Eighteen children (median (range) age 8·9 (0·3-14·6) years, male = 10) met the case definition. The majority were of Black, Asian and Minority Ethnic (BAME) origin (89 %, 16/18). Positive SARS-CoV-2 IgG antibodies were present in 94 % (17/18) and RNA by PCR in 6 % (1/18). Seventy-eight percentage of the cohort were vitamin D deficient (< 30 nmol/l). The mean 25OHD concentration was significantly lower when compared with the population mean from the 2015/16 National Diet and Nutrition Survey (children aged 4-10 years) (24 v. 54 nmol/l (95 % CI -38·6, -19·7); P < 0·001). The paediatric intensive care unit (PICU) group had lower mean 25OHD concentrations compared with the non-PICU group, but this was not statistically significant (19·5 v. 31·9 nmol/l; P = 0·11). The higher susceptibility of BAME children to PIMS-TS and also vitamin D deficiency merits contemplation. Whilst any link between vitamin D deficiency and the severity of COVID-19 and related conditions including PIMS-TS requires further evidence, public health measures to improve vitamin D status of the UK BAME population have been long overdue.
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Paediatric mitral valve disease - from presentation to managementMitral valve diseases are relatively rare in the paediatric population; however, they can cause considerable mortality and morbidity worldwide. Acquired causes are a major contributor to cardiovascular disease burden in the paediatric population. Diseases can be detected before birth, at birth, or when the child is older and presents with symptoms of advanced heart failure. Definitive management consists of surgical intervention, with mitral valve replacement being the gold standard.Conclusion: Repair has been gaining popularity; however, its outcomes require further study. Percutaneous mitral balloon valvuloplasty is an emerging technique which holds promise as a bridge to surgical treatment. The effect of these interventions on quality of life must be emphasised and requires further study. What is Known: • The epidemiology of mitral valve disease in the paediatric population - predominant causes include rheumatic disease and congenital defects. • Mitral valve repair and replacement are the standard treatment methods for paediatric mitral valve disease. What is New: • Emergence of percutaneous mitral valve interventions and their potential as bridge-to-surgery or definitive treatment in high-risk surgical candidates. • Recent evidence comparing mitral valve repair and replacement in the paediatric population demonstrates increasing popularity of repair techniques.
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Obturator abscess in children: a delayed diagnosis.No abstract available
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Mortality and AIDS-defining events among young people following transition from paediatric to adult HIV care in the UK.Objectives: To investigate risk of AIDS and mortality after transition from paediatric to adult care in a UK cohort of young people with perinatally acquired HIV. Methods: Records of people aged ≥ 13 years on 31 December 2015 in the UK paediatric HIV cohort (Collaborative HIV Paediatric Study) were linked to those of adults in the UK Collaborative HIV Cohort (CHIC) cohort. We calculated time from transition to a new AIDS event/death, with follow-up censored at the last visit or 31 December 2015, whichever was the earliest. Cumulative incidence of and risk factors for AIDS/mortality were assessed using Kaplan-Meier and Cox regression. Results: At the final paediatric visit, the 474 participants [51% female, 80% black, 60% born outside the UK, median (interquartile range) age at antiretroviral therapy (ART) initiation = 9 (5-13) years] had a median age of 18 (17-19) years and CD4 count of 471 (280-663) cell/μL; 89% were prescribed ART and 60% overall had a viral load ≤ 400 copies/mL. Over median follow-up in adult care of 3 (2-6) years, 35 (8%) experienced a new AIDS event (n = 25) or death (n = 14) (incidence = 1.8/100 person-years). In multivariable analyses, lower CD4 count at the last paediatric visit [adjusted hazard ratio = 0.8 (95% confidence interval: 0.7-1.0)/100 cells/μL increment] and AIDS diagnosis in paediatric care [2.7 (1.4-5.5)] were associated with a new AIDS event/mortality in adult care. Conclusions: Young people with perinatally acquired HIV transitioning to adult care with markers of disease progression in paediatric care experienced poorer outcomes in adult care. Increased investment in multidisciplinary specialized services is required to support this population at high risk of morbidity and mortality.
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Paediatric major incident triage: UK military tool offers best performance in predicting the need for time-critical major surgical and resuscitative interventionBackground: Children are frequently injured during major incidents (MI), including terrorist attacks, conflict and natural disasters. Triage facilitates healthcare resource allocation in order to maximise overall survival. A critical function of MI triage tools is to identify patients needing time-critical major resuscitative and surgical intervention (Priority 1 (P1) status). This study compares the performance of 11 MI triage tools in predicting P1 status in children from the UK Trauma Audit and Research Network (TARN) registry. Methods: Patients aged <16 years within TARN (January 2008-December 2017) were included. 11 triage tools were applied to patients' first recorded pre-hospital physiology. Patients were retrospectively assigned triage categories (P1, P2, P3, Expectant or Dead) using predefined intervention-based criteria. Tools' performance in <16s were evaluated within four-yearly age subgroups, comparing tool-predicted and intervention-based priority status. Findings: Amongst 4962 patients, mortality was 1.1% (n = 53); median Injury Severity Score (ISS) was 9 (IQR 9-16). Blunt injuries predominated (94.4%). 1343 (27.1%) met intervention-based criteria for P1, exhibiting greater intensive care requirement (60.2% vs. 8.5%, p < 0.01) and ISS (median 17 vs 9, p < 0.01) compared with P2 patients. The Battlefield Casualty Drills (BCD) Triage Sieve had greatest sensitivity (75.7%) in predicting P1 status in children <16 years, demonstrating a 38.4-49.8% improvement across all subgroups of children <12 years compared with the UK's current Paediatric Triage Tape (PTT). JumpSTART demonstrated low sensitivity in predicting P1 status in 4 to 8 year olds (35.5%) and 0 to 4 year olds (28.5%), and was outperformed by its adult counterpart START (60.6% and 59.6%). Interpretation: The BCD Triage Sieve had greatest sensitivity in predicting P1 status in this paediatric trauma registry population: we recommend it replaces the PTT in UK practice. Users of JumpSTART may consider alternative tools. We recommend Lerner's triage category definitions when conducting MI evaluations.
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Cooking outdoors or with cleaner fuels does not increase malarial risk in children under 5 years: a cross-sectional study of 17 sub-Saharan African countries.Background: Smoke from solid biomass cooking is often stated to reduce household mosquito levels and, therefore, malarial transmission. However, household air pollution (HAP) from solid biomass cooking is estimated to be responsible for 1.67 times more deaths in children aged under 5 years compared to malaria globally. This cross-sectional study investigates the association between malaria and (i) cleaner fuel usage; (ii) wood compared to charcoal fuel; and, (iii) household cooking location, among children aged under 5 years in sub-Saharan Africa (SSA). Methods: Population-based data was obtained from Demographic and Health Surveys (DHS) for 85,263 children within 17 malaria-endemic sub-Saharan countries who were who were tested for malaria with a malarial rapid diagnostic test (RDT) or microscopy. To assess the independent association between malarial diagnosis (positive, negative), fuel type and cooking location (outdoor, indoor, attached to house), multivariable logistic regression was used, controlling for individual, household and contextual confounding factors. Results: Household use of solid biomass fuels and kerosene cooking fuels was associated with a 57% increase in the odds ratio of malarial infection after adjusting for confounding factors (RDT adjusted odds ratio (AOR):1.57 [1.30-1.91]; Microscopy AOR: 1.58 [1.23-2.04]) compared to cooking with cleaner fuels. A similar effect was observed when comparing wood to charcoal among solid biomass fuel users (RDT AOR: 1.77 [1.54-2.04]; Microscopy AOR: 1.21 [1.08-1.37]). Cooking in a separate building was associated with a 26% reduction in the odds of malarial infection (RDT AOR: 0.74 [0.66-0.83]; Microscopy AOR: 0.75 [0.67-0.84]) compared to indoor cooking; however no association was observed with outdoor cooking. Similar effects were observed within a sub-analysis of malarial mesoendemic areas only. Conclusion: Cleaner fuels and outdoor cooking practices associated with reduced smoke exposure were not observed to have an adverse effect upon malarial infection among children under 5 years in SSA. Further mixed-methods research will be required to further strengthen the evidence base concerning this risk paradigm and to support appropriate public health messaging in this context.
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Critical care course of pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 and response to immunomodulation.We describe the critical care course of children with a novel hyperinflammatory syndrome associated with coronavirus disease 2019 (COVID-19) pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with focus on trajectory before and after immunomodulation. Overall, 10 patients who met the U.K. Royal College of Pediatrics and Child Health case definition during a 2-month study period were analyzed. All tested positive for SARS-CoV-2 IgG antibody. Although only 20% were ventilated, 100% required inotropic or vasopressor support. All children had significantly raised inflammatory markers with a median C-reactive protein of 248 (175-263) mg/L, ferritin of 1,561 (726-2,255) µg/L, and troponin-I of 723 (351-2,235) ng/L. Six patients had moderately impaired myocardial function and two had severe impairment. None needed extracorporeal membrane oxygenation. Despite severe illness only a brief period of critical care support of 3 to 5 days was required. Eight received at least one dose of intravenous immunoglobulin. Six received high-dose steroids. Clinical improvement including cardiovascular stability and reduction in inflammatory markers may have occurred with and without immunomodulation.
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Etiology of hospital mortality in children living in low- and middle-income countries: a systematic review and meta-analysis.In 2019, 80% of the 7.4 million global child deaths occurred in low- and middle-income countries (LMICs). Global and regional estimates of cause of hospital death and admission in LMIC children are needed to guide global and local priority setting and resource allocation but are currently lacking. The study objective was to estimate global and regional prevalence for common causes of pediatric hospital mortality and admission in LMICs. We performed a systematic review and meta-analysis to identify LMIC observational studies published January 1, 2005-February 26, 2021. Eligible studies included: a general pediatric admission population, a cause of admission or death, and total admissions. We excluded studies with data before 2,000 or without a full text. Two authors independently screened and extracted data. We performed methodological assessment using domains adapted from the Quality in Prognosis Studies tool. Data were pooled using random-effects models where possible. We reported prevalence as a proportion of cause of death or admission per 1,000 admissions with 95% confidence intervals (95% CI). Our search identified 29,637 texts. After duplicate removal and screening, we analyzed 253 studies representing 21.8 million pediatric hospitalizations in 59 LMICs. All-cause pediatric hospital mortality was 4.1% [95% CI 3.4%-4.7%]. The most common causes of mortality (deaths/1,000 admissions) were infectious [12 (95% CI 9-14)]; respiratory [9 (95% CI 5-13)]; and gastrointestinal [9 (95% CI 6-11)]. Common causes of admission (cases/1,000 admissions) were respiratory [255 (95% CI 231-280)]; infectious [214 (95% CI 193-234)]; and gastrointestinal [166 (95% CI 143-190)]. We observed regional variation in estimates. Pediatric hospital mortality remains high in LMICs. Global child health efforts must include measures to reduce hospital mortality including basic emergency and critical care services tailored to the local disease burden. Resources are urgently needed to promote equity in child health research, support researchers, and collect high-quality data in LMICs to further guide priority setting and resource allocation. Keywords: acute illness; critical illness; global health; hospital admission; hospital death; low- and middle-income countries; resource-limited settings.
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Therapeutic Role of Nusinersen on Respiratory Progression in Pediatric Patients With Spinal Muscular Atrophy Type 2 and Nonambulant Type 3.Data were available for 69 treated patients, 53 were SMA type 2 and 16 type 3. The mean (SD) age at first injection was 8.5 (3.2) and 9.7 (3.7) years, respectively. The median (interquartile range) treatment duration was 1 (0.7; 1.9) and 1.2 (0.9; 1.9) years, respectively. At the time of the first nusinersen injection, 24 of 52 (46%) patients with SMA type 2 and 2 of 16 (13%) patients with SMA type 3 were on NIV. Forty-three of 53 (81%) and 4 of 16 (25%) patients used cough device. FVC% pred. in treated patients with SMA type 2 declined annually by 2.3% vs 3.9% in NH (p = 0.08) and in treated patients with type 3 by 2.6% vs 3.4% NH (p = 0.59). Patients treated reached FVC <60% later than untreated (12.1 vs 10 years, p = 0.05). A higher percentage of treated vs untreated patients maintained FVC% pred. equal/above their baseline after 12 (65% vs 36%) and 24 (50% vs 24%) months, respectively. NIV use among treated did not significantly change throughout 1-year follow-up.
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Chronic intestinal failure in children: an international multicenter cross-sectional survey.Background: The European Society for Clinical Nutrition and Metabolism database for chronic intestinal failure (CIF) was analyzed to investigate factors associated with nutritional status and the intravenous supplementation (IVS) dependency in children. Methods: Data collected: demographics, CIF mechanism, home parenteral nutrition program, z-scores of weight-for-age (WFA), length or height-for-age (LFA/HFA), and body mass index-for-age (BMI-FA). IVS dependency was calculated as the ratio of daily total IVS energy over estimated resting energy expenditure (%IVSE/REE). Results: Five hundred and fifty-eight patients were included, 57.2% of whom were male. CIF mechanisms at age 1−4 and 14−18 years, respectively: SBS 63.3%, 37.9%; dysmotility or mucosal disease: 36.7%, 62.1%. One-third had WFA and/or LFA/HFA z-scores < −2. One-third had %IVSE/REE > 125%. Multivariate analysis showed that mechanism of CIF was associated with WFA and/or LFA/HFA z-scores (negatively with mucosal disease) and %IVSE/REE (higher for dysmotility and lower in SBS with colon in continuity), while z-scores were negatively associated with %IVSE/REE. Conclusions: The main mechanism of CIF at young age was short bowel syndrome (SBS), whereas most patients facing adulthood had intestinal dysmotility or mucosal disease. One-third were underweight or stunted and had high IVS dependency. Considering that IVS dependency was associated with both CIF mechanisms and nutritional status, IVS dependency is suggested as a potential marker for CIF severity in children.