Transanal irrigation in children with functional constipation: A systematic review and meta-analysis.

OBJECTIVES: Refractory functional constipation is a challenging condition to manage in children. The use of transanal irrigation (TAI) is well reported in children with neurological disorders as well as anorectal malformations but less so in children with functional disorders of defecation. The objective of our study was to evaluate the effectiveness, safety and outcomes of TAI in children with functional constipation. METHODS: PubMed, Scopus and Google Scholar were searched for publications related to the use of TAI in functional constipation. Data regarding the study design, sample size, patient characteristics, investigator-reported response to TAI and adverse effects were extracted from studies that met the selection criteria. The inverse variance heterogeneity model was used for ascertaining the summary effect in this meta-analysis. RESULTS: The search strategy yielded 279 articles of which five studies were included in the final review. The studies were from the United Kingdom (n = 2), Netherlands (n = 2) and Denmark (n = 1). These studies included 192 children with a median age ranging from 7 to 12.2 years old. The TAI systems used in these studies were: Peristeen (n = 2), Peristeen or Qufora (n = 1), Alterna (n = 1) and Navina (n = 1). The follow-up duration ranged from 5.5 months to 3 years. Eleven (5.7%) children did not tolerate TAI and withdrew from treatment soon after initiation. The pooled investigator-reported success of TAI was 62% (95% CI: 52%-71%). The most common adverse event was pain which was experienced by 21.7% of children. A total of 27 (14%) were successfully weaned off TAI at the last follow-up. CONCLUSIONS: TAI is reported to be successful in 62% of children with refractory functional constipation. There is a need for well-designed prospective trials to evaluate this treatment option in children with refractory functional constipation.

Prevalence and significance of autoantibodies in children with metabolic dysfunction-associated steatotic liver disease: A systematic review and meta-analysis.

Significance of autoantibodies in pediatric metabolic dysfunction-associated steatotic liver disease (MASLD) is unknown. Our aim was to determine the prevalence and significance of autoantibodies in MASLD. PubMed and Scopus were searched and six articles (689 [487 males] MASLD patients) were identified. Antinuclear antibodies (ANA) was positive in 28% (95% confidence interval [CI]: 17%-39%, n = 6 studies), Antismooth muscle antibodies (ASMA) in 28% (95% CI: 8%-50%, n = 5 studies), Actin-positive in 15% (95% CI: 10%-20%, n = 2 studies) and elevated immunoglobulin G in 17% (95% CI: 1%-39%, n = 4 studies). Anti-liver-kidney-microsomal antibody was not present in any patient. There was no significant association of ANA positivity with degree of liver steatosis, liver fibrosis or nonalcoholic fatty liver disease activity score (NAS) but patients with ASMA positivity had advanced fibrosis (pooled risk ratio [RR] 1.77; 95% CI 1.16-2.71) and higher risk of NAS ≥5 (pooled RR 1.21; 95% CI: 1.01-1.44, n = 2 studies, 243 patients). To conclude, non-organ specific autoantibodies are present in over one-fourth of children with MASLD and the presence of ASMA maybe associated with increased disease severity.

Shear-wave elastography for monitoring Fontan-associated liver disease: A prospective cohort study.

The spectrum of Fontan-associated liver disease (FALD) varies from abnormal liver function tests to fibrosis and even cirrhosis. In this prospective study, we evaluated the role of shear-wave elastography (SWE) in predicting the presence of advanced FALD. Forty-eight patients (30 males, 13.9 [6-21] years) with a Fontan circulation were evaluated at 8.3 (2.1-18.7) years since the Fontan surgery. The median liver stiffness measurement (LSM) value was higher than values in normal children at 15.4 (9.5-38.7) kPa. The LSMs had a weak but significant correlation with age at the time of LSM (r = 0.25, p = 0.01) and duration post-Fontan surgery (r = 0.31, p = 0.02). It had a poor correlation with the concomitant aspartate transaminase-to-platelet ratio index (r = 0.1, p = 0.39). No difference in the elastography values between children with and without ultrasound evidence of advanced liver disease (17.7 [interquartile range, IQR: 4] vs. 16.1 [IQR: 6], p = 0.62] was observed. Further studies are required to determine the precise role of SWE as a noninvasive marker of liver fibrosis in FALD.

Oral Tacrolimus in Steroid Refractory and Dependent Pediatric Ulcerative Colitis-A Systematic Review and Meta-Analysis.

BACKGROUND: There are limited treatment options for children with steroid-refractory or dependent ulcerative colitis (UC). A few observational studies suggest efficacy of oral tacrolimus. We performed a systematic review and meta-analysis to assess the efficacy of tacrolimus in pediatric UC. METHODS: PubMed and Scopus were searched for publications related to the use of oral tacrolimus in pediatric UC. Data regarding the clinical response and colectomy-free survival were extracted from studies that met the selection criteria. RESULTS: The search strategy yielded 492 articles of which 7 studies were included in the final review. They included 166 children (111 steroid-refractory, 52 steroid-dependent, 3 no steroids). Majority of cases (150/166 [90%]) were naïve to biologics. An initial response to tacrolimus therapy was seen in 84% (95% CI: 73%-93%) (n = 7 studies). No difference was observed between children with high (>10 ng/mL) or low tacrolimus levels (127/150 [85%] vs 12/16 [75%], P = 0.3). No difference in initial response between the children who were steroid refractory or dependent (92/111 [83%] vs 46/52 [88%], P = 0.36). The response in the biologic-exposed group (n = 10) was 70%. At 1-year follow-up, 15.2% (95% CI: 7%-21%) (n = 2 studies, 85 patients) had a sustained response on only tacrolimus. The pooled frequency of 1-year colectomy-free survival in children treated with initial oral tacrolimus was 64% (95% CI: 53%-75%). Twelve (7.2%) patients required cessation of therapy because of side effects. CONCLUSION: Tacrolimus has a high initial response in biologic naïve UC children. It can be effectively used as a bridge to other therapies with a 1-year colectomy-free survival of 64%.

Characterization of Colonoscopies in Preschool Children.

OBJECTIVES: The indications, diagnostic yield, complications, and cecal and ileal intubation rates (CIR and IIR) for colonoscopies in children aged <6 years, denoted preschoolers, is unclear since there is limited information for this group. We aimed to describe the above parameters in our cohort of preschoolers undergoing a colonoscopy. METHODS: Retrospective review of all colonoscopies in a tertiary pediatric hospital between December 1, 2014 to December 31, 2020 was undertaken. Demographic factors, indication for colonoscopy, extent of colonoscopy, CIR, IIR, and histologic findings were noted. Preschoolers were further subdivided into those aged <2 years, and those aged 2 to <6 years. RESULTS: One thousand six hundred seventy-one total colonoscopies were performed, of which 13% (n = 219) were in preschoolers with median age 3.9 (range 0.3-5.9) years. Most common indications in preschoolers were rectal bleeding 35% (n = 78), inflammatory bowel disease 24% (n = 53), diarrhea 13% (n = 30), iron-deficiency anemia 11% (n = 25), and abdominal pain 7% (n = 16). IIR and CIR were lower in preschoolers compared to older children, 81% vs 92% ( P = 0.0001), and 93% vs 96.4% ( P = 0.02), respectively, and even lower in those aged <2 years, 48.1% IIR ( P = 0.0001) and 85.1% CIR. Juvenile polyps, 31% (n = 27), were the most common positive finding in preschool children. CONCLUSION: Rectal bleeding was the most common indication and juvenile polyps the most common finding at colonoscopy in preschoolers. A high IIR is achievable in young children but rates are increasingly lower the younger the child.

Association of serum zinc levels and symptom control of asthma in children and adolescents- a prospective observational study.

Dysregulation of zinc (Zn) homeostasis causes a shift in the Th1/Th2 balance towards a Th2 response, which may lead to a heightened inflammatory response. Asthma is associated with an exaggerated Th2 response to antigens. This study attempts to find the association of serum Zn with the status of symptom control of asthma in children and adolescents with bronchial asthma. A total of 67 asthmatic children, diagnosed as per Global Initiative for Asthma (GINA) 2019 guidelines, were included in the study. Symptom control of asthma was assessed by Asthma Control Test (ACT) and Childhood Asthma Control Test (C-ACT) scores. Spirometry was performed on those participants who were able to perform satisfactorily. Serum Zn was analyzed using the photometric method. Participants were divided into two groups: controlled and uncontrolled groups according to ACT/C-ACT score. Mean age of the participants was 10.78 ± 3.67 years. The mean S. Zn (µg/dL) was 136.97 ± 48.37. This study found a higher mean S. Zn value in the controlled asthma group as compared to the uncontrolled group (158.06 vs 129.23, p = 0.006). At a cutoff of S. Zn (µg/dL) ≥ 126.84, it predicted controlled asthma with a sensitivity of 89% and a specificity of 55%. No significant difference was found between the mean serum Zn levels in terms of age, sex, severity, and CRP levels. CONCLUSION: A significant difference was observed between the mean value of Zn and symptom control of asthma (p = 0.006) with a weak positive correlation between the two which was statistically significant (rho = 0.26, p = 0.031). However, low levels of zinc were not significantly associated with symptom control of asthma. Thus, we conclude that maintaining an adequate zinc level could help in achieving better control of asthma in pediatric populations. WHAT IS KNOWN: • Zinc has a role in immunological response in the pathophysiology of immunological disorders such as bronchial asthma. WHAT IS NEW: • This study adds a significant association of serum zinc levels with symptom control of asthma in pediatric populations. • This study also gives a cut-off value of serum zinc level which predicts adequate symptom control of asthma.

Incidence, predictors and outcome of sepsis-associated liver injury in children: a prospective observational study.

Sepsis-associated liver injury (SALI) occurs as a result of the systemic and microcirculatory changes that happen because of sepsis. Its prognostic significance in the paediatric population is unclear. We enrolled all children < 19 years, admitted between July, 2020 and July, 2021 to the paediatric unit (ward or intensive care unit) with a diagnosis of sepsis for this study. Clinical and biochemical parameters of children with sepsis who developed SALI were compared with those without SALI to determine the risk factors of SALI and its impact on in-hospital mortality. A total of 127 children, median age 72 (1-204) months, 74 males were included. SALI developed in 45 (31.3%) at a median 1 (1-13) days after the diagnosis of sepsis. The SALI pattern was cholestatic in 18 (40%), hepatocellular in 17 (37.7%) and hypoxic hepatitis in 10 (22.3%). Paediatric sequential organ failure assessment (pSOFA) was an independent predictor of SALI - OR 1.17 (95% CI 1.067-1.302), p = 0.001. A pSOFA score of > 9.5 predicted the development of SALI with 66.7% sensitivity and 77.1% specificity. SALI was an independent predictor of mortality in children with sepsis - OR 1.9 (95% CI 1.3-3.4), p = 0.01.   Conclusions: SALI develops in 45 (31.3%) with sepsis. A higher pSOFA score is associated with SALI. Children who develop SALI have a ~ twofold higher risk of mortality than those without SALI. What is Known: • During the process of sepsis, the liver plays a role by scavenging bacteria and producing inflammatory mediators. However, at times the liver itself becomes a target of the dysregulated inflammatory response. This is known as sepsis-associated liver injury (SALI). • The incidence of sepsis-associated liver injury and its prognostic significance in children is not known.. What is New: • SALI develops in one-third children with sepsis and is associated with a higher pSOFA score. • Children who develop SALI have a higher risk of mortality.

Impact of ulcerative colitis on liver-related outcomes of children with primary sclerosing cholangitis.

AIM: Primary sclerosing cholangitis (PSC) is a chronic progressive cholestatic disorder associated with ulcerative colitis (UC). Although the inflammatory bowel disease phenotype has been characterised in patients with PSC, the impact of UC on the course and progression of PSC-UC is less clear. We aimed to evaluate the effects of UC on liver-related outcomes in children with PSC. METHODS: Retrospective analysis of children aged ≤18 years diagnosed with PSC with/without UC at a single tertiary paediatric liver unit between January 1998 and May 2016. Patients were followed up until transition to an adult service. Outcomes studied included biliary complications, clinically significant portal hypertension, need for liver transplantation and post-transplantation recurrence. RESULTS: Fifty-one children (31 female) were diagnosed with PSC (median age - 11.3 years (interquartile range 7)), follow-up median duration 54 months (interquartile range 56). Thirty-seven (73%) patients had concurrent UC, of which 26 had their diagnosis confirmed prior to or within 6 months of PSC diagnosis (early-onset). PSC complications were more common in children with PSC-UC compared with PSC alone (24/37 (65%) vs. 2/14 (14%); P = 0.001). Furthermore, children with endoscopically mild or moderate UC at diagnosis showed a greater propensity for liver-related complications compared with children with severe UC (24/32 vs. 0/5; P = 0.003). Children with late-onset UC had higher rates of clinically significant portal hypertension (5/11 (45%) vs. 3/26 (12%); P = 0.007) and liver transplantation (5/11(45%) vs. 2/26 (8%); P = 0.02). Children with PSC-UC had significantly higher rates of pancolitis, rectal sparing and milder colitis than those with UC alone. CONCLUSION: The presence and a later-onset of UC are associated with more significant progression to end-stage liver disease. There is an inverse trend between UC severity and PSC severity in children with concurrent PSC-UC.

Systematic Review and Meta-Analysis of Thiopurine Metabolite Levels and Biochemical Remission in Autoimmune Hepatitis.

BACKGROUND: The utility of measuring thiopurine metabolites (TM) to individualize therapy in autoimmune hepatitis (AIH) has not been defined, and the evidence regarding its use in clinical practice is heterogeneous. This systematic review and meta-analysis aimed to compare the mean concentration of TM between patients in biochemical remission and those not in remission. METHODS: A systematic literature search was conducted using PubMed, Scopus, the Cochrane Library, and Google Scholar for keywords related to TM and AIH. Two reviewers independently searched and selected studies comparing the levels of 6-methyl mercaptopurine (6-MMP) and 6-thioguanine nucleotide (6-TGN) and their ratio in cases of AIH in remission and otherwise. Meta-analysis was performed by calculating the weighted mean difference using the inverse variance heterogeneity model. RESULTS: A total of 1066 records were identified through systematic search; of which, 7 (n = 3 pediatric, n = 4 adults) were considered for inclusion, and 442 TM measurements (n = 128 in children) were analyzed. Mean 6-TGN levels were significantly higher among patients in remission than in those who were not, with a pooled weighted mean difference (WMD) of 15.67 [95% confidence interval (CI), 6.68-24.66] pmol/8 × 108 red blood cells (RBC). The difference was higher in the pediatric age group (WMD, 56.11; 95% CI, 13.60-98.62) than in adults (WMD, 13.77; 95% CI, 4.58-22.97). There was no significant difference in the 6-MMP levels (WMD, -431.7; 95% CI, -1237.4 to 373.9 pmol/8 × 108 RBC; I2 = 82%; n = 3 studies) or 6-MMP/6-TGN ratio among the patients who were in biochemical remission and those who were not (WMD, -0.97; 95% CI, -5.77 to 3.84; I2 = 82%; n = 3 studies). CONCLUSIONS: This meta-analysis suggests a link between 6-TGN levels and biochemical remission in AIH. Further high-quality studies are required to determine the therapeutic cutoff of 6-TGN.

Leptospira Triggered Anti-N-Methyl-d-Aspartate Receptor Encephalitis.

Primary neuroleptospirosis although rare but has been reported in the literature in the form of case reports and case series. However, there are no reports of autoimmune encephalitis triggered by leptospirosis in the literature, although four cases of acute disseminated encephalomyelitis, which is also considered to have autoimmune etiology have been reported. We are reporting an adolescent girl, who developed anti-N-methyl-d-aspartate receptor encephalitis after the resolution of systemic symptoms of leptospirosis. Her symptoms including neuropsychiatric and extrapyramidal features and sleep disturbances resolved completely after immunotherapy. As recently autoimmune encephalitis triggered by various infections are getting reported more frequently around the world, the clinicians need to consider this clinical possibility, even in patients with leptospirosis, who develop neurological symptoms while systemic clinical features are subsiding. Early recognition and timely administration of immunotherapy have the potential to completely reverse the neurological symptoms.

Gastrointestinal Manifestations of Pediatric Coronavirus Disease and Their Relationship with a Severe Clinical Course: A Systematic Review and Meta-analysis.

BACKGROUND: Data on the gastrointestinal (GI) manifestations of Pediatric Corona Virus Disease (COVID-19) are conflicting and the relationship between GI involvement and the severity of COVID-19 disease has not been evaluated. The objectives of this systematic review were to determine the GI manifestations of pediatric COVID-19 and to evaluate their role as risk factors for a severe clinical course. METHODS: : A systematic literature search was carried out in PubMed and Scopus for studies published before 31 December 2020 with information about the GI manifestations of pediatric COVID-19. Patients with a severe and nonsevere clinical course were compared using the inverse variance heterogeneity model and odds ratio (OR) as the effect size. A sensitivity analysis was performed if the heterogeneity was high among studies. RESULTS: A total of 811 studies were identified through a systematic search of which 55 studies (4369 patients) were included in this systematic review. The commonest GI symptoms were diarrhea-19.08% [95% confidence interval (CI) 10.6-28.2], nausea/vomiting 19.7% (95% CI 7.8-33.2) and abdominal pain 20.3% (95% CI 3.7-40.4). The presence of diarrhea was significantly associated with a severe clinical course with a pooled OR of 3.97 (95% CI 1.80-8.73; p < 0.01). Abdominal pain and nausea/vomiting were not associated with disease severity. CONCLUSIONS: Diarrhea, nausea/vomiting or abdominal pain are present in nearly one-fifth of all children with COVID-19. The presence of diarrhea portends a severe clinical course.

Normal Gamma Glutamyl Transferase Levels at Presentation Predict Poor Outcome in Biliary Atresia.

OBJECTIVES: Gamma-glutamyl transferase levels (GGT) are typically elevated in biliary atresia (BA), but normal GGT levels have been observed. This cohort of "normal GGT" BA has neither been described nor has the prognostic value of GGT level on outcomes in BA. We aimed to describe outcomes of a single-centre Australian cohort of infants with BA and assess the impact of GGT level at presentation on outcomes in BA. METHODS: Infants diagnosed with BA between 1991 and 2017 were retrospectively analysed. Outcomes were defined as survival with native liver, liver transplantation (LT), and death. Patients were categorized into normal (<200I U/L) or high GGT groups based on a mean of 3 consecutive GGT values done before Kasai portoenterostomy (KPE). Baseline parameters, age at surgery, clearance of jaundice (COJ), and outcomes were compared between the 2 groups. RESULTS: One hundred thirteen infants underwent KPE at median 61 (30-149) days. At a median follow-up of 14.2 (0.9-26.3) years, 35% (39/113) patients were surviving with native liver, 55% (62/113) underwent LT and 11% (12/113) died pretransplant. 12.3% (14/113) patients had normal GGT. Age at KPE and time to COJ were similar between normal and high GGT groups. Normal GGT group had shorter time from KPE to LT (11 vs 18 months, P = 0.02), underwent LT at a younger age (14 vs 20 months, P = 0.04), and had poorer transplant-free survival (P = 0.04) than high GGT group. CONCLUSIONS: 12.3% of infants with BA had normal GGT levels at diagnosis. Low GGT levels at presentation in BA was associated with a poorer outcome.

Paediatric constipation for general paediatricians: Review using a case-based and evidence-based approach.

Constipation is a common problem in childhood. The most common type of constipation is functional, accounting for 90-95% of all cases. The aim of this review is to provide clinical scenarios with treatment using evidence-based information, and management strategies and a clinical algorithm to guide the management of constipation in children. Recent guidelines and online information sites are detailed. Clinical red flags and organic causes of constipation are included. Four clinical scenarios are presented: case (1) 4-month-old child with constipation since birth and likely Hirschsprung disease; case (2) 6-month-old infant with infant dyschezia; case (3) 4-year old with functional constipation; and; case (4) 9-year old with treatment resistant constipation. Children with functional constipation need a thorough history and physical exam to rule out the presence of any 'red flags' but do not require laboratory investigations. Management includes education and demystification, disimpaction followed by maintenance therapy with oral laxatives, dietary counselling and toilet training. Treatment options differ between infants and children. Disimpaction and maintenance regimens for common laxatives are presented. On treatment failure or on suspicion of organic disease the patient should be referred for further evaluation. The radionuclide intestinal transit study (scintigraphy) is a useful modality for evaluation and planning of management in treatment-resistant children. Treatment options for treatment-resistant patients are presented. High-level evidence (meta-analyses) for pharmalogical and non-pharmalogical treatment modalities are reviewed and an algorithm for assessment and treatment are presented.

Pulmonary Embolism in Children: A Case Series.

BACKGROUND: Pulmonary embolism (PE) is a life-threatening event with a mortality of ~10%. It is relatively uncommon in children and literature regarding the condition is sparse. In adults, the classical clinical presentation is with pleuritic chest pain, hemoptysis, and dyspnea, whereas in children, the presentation is often nonspecific. MATERIALS AND METHODS: Clinical features, risk factors, and outcome of children with PE presenting to our unit between December, 19 and March, 2020 were recorded. RESULTS: Four children [mean age: 10 (6-16) years, 3 females], all presenting with tachycardia and dyspnea were diagnosed with PE. Different risk factors such as deep vein thrombosis, nephrotic syndrome, softtissue infection, and infective endocarditis (IE) were identified in all patients. One child died while others responded to anticoagulation. CONCLUSION: We aim to highlight the importance of timely recognition of PE in children with known risk factors for the same. Early recognition and timely treatment of PE are critical to save lives. HOW TO CITE THIS ARTICLE: Agrawal S, Shrivastava Y, Bolia R, Panda PK, Sharawat IK, Bhat NK. Pulmonary Embolism in Children: A Case Series. Indian J Crit Care Med 2020;24(12):1272-1275.

Pediatric CLIF-SOFA score is the best predictor of 28-day mortality in children with decompensated chronic liver disease.

BACKGROUND & AIMS: Early identification of children with decompensated chronic liver disease (DCLD) at risk of short-term mortality helps improve outcome. We aimed to evaluate the predictors of outcome and role of Child-Pugh, pediatric end-stage liver disease (PELD) and pediatric chronic liver failure sequential organ failure assessment (pCLIF-SOFA) score for prognosticating 28-day mortality in children with DCLD. METHODS: DCLD children were prospectively evaluated with a clinico-laboratory proforma and followed for 28 days to determine outcome. Child-Pugh, PELD and pCLIF-SOFA were calculated at admission. Univariate and multivariate analysis was performed to identify the best predictors of outcome. RESULTS: A total of 110 children (74 boys, 96 [4-204] months) were enrolled and 37 (33.6%) died at 28 days. Significant risk factors for mortality were a higher international normalized ratio (hazard ratio [HR] 1.17; 95% CI 1.04-1.31; p <0.001) and bilirubin (HR 1.04; 95% CI 1.01-1.08; p <0.001), lower albumin (HR 0.46; 95% CI 0.27-0.77; p = 0.03) and sodium (HR 0.93; 95% CI 0.89-0.98; p = 0.01), absence of treatable etiology (HR 2.00; 95% CI 1.40-2.87; p = 0.001) and presence of organ failure (HR 3.22; 95% CI 1.98-10.58; p <0.001). Organ failure and serum sodium were independent predictors of poor outcome on multivariate analysis. pCLIF-SOFA (16 [9-22] vs. 9 [5-15]), Child-Pugh (11 [9-15] vs. 10 [8-14]) and PELD (22.2 [7.5-45.3] vs. 15.3 [4.5-23.9]) scores were significantly higher in non-survivors. The area under the curve was 0.977 for pCLIF-SOFA, 0.815 for Child-Pugh score, and 0.741 for PELD score. A pCLIF-SOFA score of ≥11 identified 28-day mortality with a sensitivity and specificity of 94.9% and 91.5%, respectively. CONCLUSION: Thirty-four percent of children with DCLD have a poor short-term outcome. Organ failure and low serum sodium are independent predictors of outcome. pCLIF-SOFA performs better than Child-Pugh and PELD in prognostication of 28-day mortality. Our study supports the use of scores based on organ failure in prognosticating children with DCLD. LAY SUMMARY: The ability to predict the course of a disease is an important part of the assessment, enabling timely interventions that improve outcomes. We evaluated the outcome (death vs. survival) and compared three different scoring systems for their ability to predict mortality within 28 days in children with decompensated chronic liver disease (DCLD). One-third of children with DCLD died within 28 days and the pediatric chronic liver failure sequential organ failure assessment score, which considers the main organ systems of the body (lungs, liver, brain, kidney, blood and cardiac) fared better for identification of children with a poor outcome than the Child-Pugh and pediatric end-stage liver disease score which comprise of only liver-related parameters. Our study supports the use of scores based on organ failure in prognosticating children with DCLD.

Children with untreated coeliac disease have sub-clinical cardiac dysfunction: a longitudinal observational analysis.

INTRODUCTION: We assessed cardiac function (CF) in celiac disease (CD) patients and the effect of gluten-free diet (GFD) on CF. METHODS: Prospective evaluation of CF using conventional and tissue doppler echocardiography in 50 CD patients (age 4.2 ± 1.1 years) at diagnosis and after a year of GFD (group 1), 100 CD children (group 2; 47 compliant and 53 non-compliant) in follow-up and 25 healthy controls. RESULTS: Untreated CD (n = 50) children had larger left ventricle end diastolic dimension (35.33 ± 0.87 vs. 32.90 ± 0.91 mm; p = .04), reduced (<55%) left ventricular ejection fraction (20% vs. 0%; p = .01) and a higher (>0.6) myocardial performance index (MPI, 66% vs. 0%; p ≤ .01) as compared to controls. Re-evaluation after one year with good dietary compliance showed changes in isovolumic relaxation time (72.5 ± 4.2 vs. 50.62 ± 2.69; p = .0001) and deceleration time (121.05 ± 10.1 vs. 99.87 ± 8.5; p = .02), reflecting improved cardiac diastolic function. GFD compliant patients had lower MPI than non-compliant (0.60 ± .03 vs. 0.66 ± .08; p = .04), reflecting improvement in load-independent echocardiographic parameters. CONCLUSIONS: Subclinical cardiac dysfunction is common in CD children at diagnosis. Improvement in echocardiographic parameters occurs with GFD and non-compliant children continue to have persistent cardiac dysfunction.