Unauthentic Information About Celiac Disease on Social Networking Pages: Is It a Matter of Concern in Celiac Disease Management?

BACKGROUND: Facebook (FB) is the most popular online networking platform. Many celiac disease Facebook (CD-FB) pages spread awareness about celiac disease (CD). To get the latest information, patients with CD frequently follow such pages. However, little is known about whether such pages provide authentic and reliable information. AIMS: This study aims to investigate whether CD-FB pages spread misleading information to patients with CD. METHODS: On the Facebook social networking platform, CD-FB pages created in three celiac-prevalent countries (Italy, the USA, and India) were explored using different combinations of keywords. The type/category of the CD-FB page, country of origin, purpose, page web link, and number of followers/members were documented in a Microsoft spreadsheet. All posts distributed on selected CD-FB pages in the last 3 years were thoroughly screened. RESULTS: From August 2022 to March 2023, a total of 200 CD-FB pages from Italy, the USA, and India were explored. Out of these 200 pages, 155 CD-FB (Italy 70; the USA 46; India 39) were found eligible. Of them, 20 (13%) CD-FB pages (Italy 4; the USA 5; India 11) shared misleading information about CD. Surprisingly, 11 (8%) of these 20 pages (Italy 0; the USA 2; India 9) supported alternative treatment options for CD. CONCLUSIONS: CD-FB pages are useful for disseminating celiac-disease-related information. While most such pages provide useful information, 13% of CD-FB pages allow misleading information. Patients with CD should consult their treating unit before following any uncertain information posted on CD-FB pages.

The use of urine peptidomics to define dietary gluten peptides from patients with celiac disease and the clinical relevance.

INTRODUCTION: Determination of urinary gluten immunogenic peptides (GIP) has emerged as one of the most attractive test to monitor the adherence to the gluten-free diet (GFD) of patients with celiac disease (CD), being a simple, noninvasive and direct method to detect gluten contamination of the GFD. AREAS COVERED: We conducted a scoping review in Medline (PubMed) of articles published up to April 2023 that analyzed any aspect of the clinical relevance of the use of urinary GIP measurement in patients with CD. A total of 17 articles reporting the clinical use of urinary peptidomics for the follow-up of CD patients were finally included. EXPERT OPINION: Available data suggest that a negative urinary GIP result is a reliable noninvasive predictor of intestinal mucosa healing in CD patients treated with the GFD, especially if testing three urine samples on different days including the weekend. Due to conflicting results about the sensitivity and the specificity of the urinary GIP determination, additional in-depth information is needed, particularly related to (1) the relationship between the amount of ingested gluten and the quantity of urinary GIP excreted in treated CD patients, (2) the GIP kinetics and best timing for sample collection.

18-year follow-up of enzyme-replacement therapy in two siblings with attenuated mucopolysaccharidosis I.

Mucopolysaccharidosis type I (MPS I) is an autosomal recessive disorder caused by the deficiency of α-L-iduronidase and characterized by a progressive course with multisystem involvement. Clinically, MPS I is divided into two forms: (1) severe (Hurler syndrome), which presents in infancy and is characterized by rapid progressive neurological involvement; (2) attenuated (Hurler/Scheie and Scheie syndromes), which displays a slower progression and absent to mild nervous system involvement. The specific treatment for attenuated MPS I consists of enzyme-replacement therapy with laronidase (human recombinant α-L-iduronidase, Aldurazyme). We present updated data after 18 years of laronidase treatment in two siblings affected by the attenuated form of MPS I who started therapy at 5 months and 5 years of age, respectively. Clinical and laboratory data of the siblings show that long-term enzyme replacement therapy may improve/stabilize many symptoms already present at the time of the diagnosis and reduce the disease progression. This study confirms that early diagnosis and early initiation of enzyme-replacement therapy are essential to modify positively the natural history of the attenuated form of MPS I.

First experience of combined enzyme replacement therapy and hematopoietic stem cell transplantation in alpha-mannosidosis.

We describe the first case of bridge therapy in alpha-mannosidosis (AM) in an infant diagnosed at only 5 months of life who underwent enzyme replacement therapy (ERT) in the pre- and peri-transplant phases. Eight ERT infusions were administered before hematopoietic stem cell transplantation (HSCT) and continued for additional 90 days until complete engraftment. The clinical and laboratory data after 3 years post-HSCT show that the early combined intervention may reduce the disease progression and the urine and plasma content of mannosyl-oligosaccharides (OS) monitored by liquid chromatography tandem mass spectrometry (LC-MS/MS). This report highlights that early diagnosis and prompt initiation of such treatments in AM are the best chance to minimize the progression of symptoms.

Early postnatal weight loss does not affect the 2-year neurodevelopment in preterm infants of less than 32 weeks.

AIM: It is still unclear if the magnitude of early postnatal weight loss (PWL) could be associated with neurodevelopmental outcomes in preterm infants. We studied the association between PWL and neurodevelopment at 2-year corrected age in preterm infants. METHODS: We retrospectively reviewed data of preterm infants with a gestational age between 24 + 0 and 31 + 6 weeks/days, admitted at the G.Salesi Children's Hospital, Ancona, Italy, between 1 January 2006 and 31 December 2019. Infants with PWL greater than or equal to 10% (PWL ≥ 10%) were compared with those with PWL of less than 10% (PWL < 10%). A matched cohort analysis was also performed using gestational age and birth weight as matching variables. RESULTS: We analysed 812 infants: 471 (58%) PWL ≥ 10% and 341 (42%) PWL < 10%. A subgroup of 247 PWL ≥ 10% was closely match-paired with 247 PWL < 10% infants. There were no differences in amino acid and energy intakes from birth to day 14 of life and from birth to 36 weeks. Although at 36 weeks, body weight and total length were lower in PWL ≥ 10% than PWL < 10%, anthropometry and neurodevelopment at 2 years were similar between groups. CONCLUSION: Given similar amino acid and energy intakes on PWL ≥ 10% and PWL < 10% preterm infants of less than 32 + 0 weeks/days, PWL does not affect 2-year neurodevelopment.

ESPGHAN Position Paper on Management and Follow-up of Children and Adolescents With Celiac Disease.

OBJECTIVES: To gather the current evidence and to offer recommendations for follow-up and management. METHODS: The Special Interest Group on Celiac Diseases of the European Society of Paediatric Gastroenterology Hepatology and Nutrition formulated ten questions considered to be essential for follow-up care. A literature search (January 2010-March 2020) was performed in PubMed or Medline. Relevant publications were identified and potentially eligible studies were assessed. Statements and recommendations were developed and discussed by all coauthors. Recommendations were voted upon: joint agreement was set as at least 85%. RESULTS: Publications (n = 2775) were identified and 164 were included. Using evidence or expert opinion, 37 recommendations were formulated on: The need to perform follow-up, its frequency and what should be assessed, how to assess adherence to the gluten-free diet, when to expect catch-up growth, how to treat anemia, how to approach persistent high serum levels of antibodies against tissue-transglutaminase, the indication to perform biopsies, assessment of quality of life, management of children with unclear diagnosis for which a gluten-challenge is indicated, children with associated type 1 diabetes or IgA deficiency, cases of potential celiac disease, which professionals should perform follow-up, how to improve the communication to patients and their parents/caregivers and transition from pediatric to adult health care. CONCLUSIONS: We offer recommendations to improve follow-up of children and adolescents with celiac disease and highlight gaps that should be investigated to further improve management.

Is low cerebral near infrared spectroscopy oximetry associated with neurodevelopment of preterm infants without brain injury?

OBJECTIVES: To evaluate the association between low regional cerebral oxygen saturation (rScO2) and neurodevelopment in preterm infants classified as no brain injury (NBI). METHODS: We retrospectively reviewed data of rScO2 monitoring during the first 3 days of life of infants with a gestational age (GA)<28 weeks or birth weight (BW)<1,000 g, with and without brain injury (BI). BI was defined as intraventricular haemorrhage, cystic periventricular leukomalacia or cerebellar haemorrhage. Univariate and multivariate analyses were used to study the association of rScO2<55% for more than 10 h in the first 3 days of life (NIRS<55%>10H) and the 24 months neurodevelopment. RESULTS: Of the 185 patients who met the inclusion criteria, 31% were classified as BI infants and 69% NBI. BI compared to NBI infants had a significantly lower GA and a higher incidence of complications of prematurity. Mean rScO2 in the first 72 h of life was significantly lower in BI than NBI. NIRS<55%>10H in NBI patients was negatively associated with neurodevelopmental scores both at the univariate and multivariate analysis (p<0.05). NBI infants with NIRS<55%>10H were found to have lower systemic oxygenation than their counterparts with rScO2<55% for less than 10 h. CONCLUSIONS: NIRS<55%>10H in NBI small preterm infants was found to be an independent predictor of neurodevelopment at 24 months and it was associated with low systemic saturation values.

Hypertriglyceridemia and Intravenous Lipid Titration During Routine Parenteral Nutrition in Small Preterm Infants.

OBJECTIVES: In case of hypertriglyceridemia (HiTG) during parenteral nutrition (PN), the 2018 European Society of Paediatric Gastroenterology, Hepatology and Nutrition guidelines recommend an intravenous (IV) lipid titration, but its consequences in small preterm infants are largely unknown. We compared macronutrient and energy intakes, growth, diseases associated with prematurity, and neurodevelopment in small preterm infants on PN who developed (cases) or did not develop HiTG (controls, CNTR). METHODS: We retrospectively reviewed data of preterm infants with a birth weight (BW) <1250 g consecutively admitted to our neonatal intensive care unit (2004-2016) who received routine PN. HiTG infants were defined by at least 1 triglyceride (TG) measurement >250 mg/dL during the first 10 days of life. Patients with and without HiTG were match-paired for BW and gestational age. RESULTS: A total of 658 infants were analyzed and 196 (30%) had HiTG. One hundred thirty-six HiTG patients were matched with 136 CNTR. In the first 10 days of life, IV lipid, non-protein energy and total energy intakes, but not IV amino acids and carbohydrates, were significantly lower in HiTG infants. We found no differences between groups in diseases associated with prematurity. Anthropometry at 36 weeks (W), anthropometry at 2-year (Y) corrected age (CA), and neurodevelopment at 2Y CA were not different. CONCLUSIONS: Growth, diseases associated with prematurity, and neurodevelopment at 2Y CA in HiTG infants were similar to CNTR. This occurred despite a statistically significant albeit small reduction in IV lipid and non-protein energy intakes due to a strict TG monitoring and IV lipid titration at TG levels >250 mg/dL.

Composition and structure of glycosaminoglycans in DBS from 2-3-day-old newborns for the diagnosis of mucopolysaccharidosis.

Dried blood spot (DBS) technology is a cheap and easy method largely applied in newborn screening. Mucopolysaccharidoses (MPS) are characterized by the deficit of enzymes that degrade glycosaminoglycans (GAGs) characterized by progressive worsening of the conditions. For a possible early diagnosis of MPS, we developed a method of uronic acid (UA)-GAGs determination in DBS of 600 healthy newborns and from a small group of MPS subjects matched for age. Spotted blood UA-GAGs of the normal newborns are composed of 67.2% chondroitin sulfate (CS), 28.6% heparan sulfate (HS) and 4.4% hyaluronic acid with a CS/HS ratio of 2.35 and a total GAGs content of 0.43 µg/DBS. A chemical evaluation of CS and HS structure was performed by measuring their disaccharide composition, sulfation and the overall charge density. The DBS of four different MPS types presented an increase of total or single UA-GAGs content and/or modifications of the CS and HS disaccharide composition as well as chemical signature also related to the MPS enzymatic defect. The modifications of the UA-GAGs composition, parameters and structure of healthy newborns determined in DBS would be useful for a possible early diagnosis of various MPS types.

Performance assessment of a new G12/A1 antibody-based rapid ELISA using commercially available and gluten-spiked food samples.

OBJECTIVE: Food products with <20 mg/kg gluten can be labeled 'gluten-free' according to international regulations. Several antibodies-based ELISAs have been develop to track gluten traces in food products. Among them, R5 and G12 antibody-based ELISAs are the frequently used methods. However, these antibodies have certain limitations. We evaluated the accuracy of G12/A1 antibody-based 'Glutentox ELISA Rapid G12' and compared the results with the current reference method i.e., R5 antibody-based 'Ridascreen R5 ELISA'. METHODS: In the first step, the performance of Glutentox ELISA Rapid G12 kit was inspected by determination of the threshold value i.e., > or <20 mg/kg gluten in different food products. In the second step, quantification accuracy was assessed by quantification of gluten in gluten-free food products spiked with gliadin reference material. RESULTS: In total 47 food products (naturally and labeled gluten-free, and food with traces of gluten) were included. Of them, 29 products were quantified with <20 mg/kg, and 18 with a low level of gluten by both the kits. Six out of 29 gluten-free products were used for the recovery test at different spike levels. Gluten concentration and mean recovery rates of individual kits showed consistency. CONCLUSION: GlutenTox Rapid G12 ELISA could be an appropriate choice for detecting gluten in food products but needs more in-house validation and collaborative tests.

Mother's own milk and bronchopulmonary dysplasia in appropriate for gestational age preterm infants.

OBJECTIVE: To evaluate the association between mother's own milk (MOM) and bronchopulmonary dysplasia (BPD) in appropriate for gestational age (AGA) preterm infants <32 weeks. METHODS: Clinical data of AGA preterm infants (24+0/7-31+6/7 weeks) were reviewed. Infants with ≥66% of cumulative prescribed enteral volumes as MOM from birth to 36 weeks were allocated to the high provision of MOM group (H-MOM), whereas those with <66% were assigned to the low provision of MOM group (L-MOM). Multiple regressions were used to assess the association of H-MOM with BPD and oxygen saturation to fraction inspired oxygen ratio (SFR) at 36 weeks. RESULTS: A total of 1041 infants met the inclusion criteria, with a median provision of cumulative enteral nutrition volumes of 5721 (IQR 2616) mL/kg. Among them, 517 (49.7%) were H-MOM and 524 (50.3%) L-MOM infants. H-MOM showed a reduction in the incidence of BPD to 31.6% compared to L-MOM infants. H-MOM had a lower risk of BPD than L-MOM infants after the adjustment for gestational age, sex, cesarean section, mean SFR at the first hours of life, surfactant administration, patent ductus arteriosus, sepsis, prolonged ventilatory supports/oxygen exposure, and cumulative energy intakes from birth to 36 weeks [aOR: 0.613, p = 0.047]. H-MOM was also associated with a lower risk of SFR in the first quartile at 36 weeks [aOR: 0.616, p = 0.028] than L-MOM. CONCLUSION: A high provision (≥66%) of enteral volume as MOM from birth to 36 weeks is associated with a reduced risk of both BPD and low SFR at 36 weeks in AGA preterm infants <32 weeks.

Cross-Cultural Participation in Food-Related Activities and Quality of Life among Children with Celiac Disease.

Children with celiac disease may face challenges in managing a gluten-free diet during their daily interactions and activities. The objective of this study was to compare how children with celiac disease manage their gluten-free diet and participate in food-related activities in Italy and Israel and to assess their quality of life. The previously validated Children's Activities Report (CD-Chart) and the Disease-specific Health-Related Quality of Life Questionnaire for Children with Celiac Disease (CDDUX) were administered in Italy to children aged 8-16 diagnosed with CD (n = 39). The results were compared to data that had been previously gathered from Israeli children with CD (n = 106). The CD-Chart demonstrated satisfactory internal reliability within each cultural group (Italy: α = 0.82; Israel: α = 0.76). Mann-Whitney U-tests indicated significant differences between the two groups. The Italian children exhibited a significantly higher preference for participating in the activities compared to the Israelis (U = 3283.50, p < 0.001). Nonetheless, the Italian children displayed a notable decrease in their level of involvement in the preparation required before engaging in different activities (U = 760.50, p < 0.001). Moreover, they exhibited significantly lower self-determination in this preparatory process compared to the Israeli children (U = 726.00, p < 0.001). Significant group differences were found between the CDDUX children's self-reports and parents' proxy reports in the Israeli group but not in the Italian group. The CD-Chart revealed both shared and distinct participation characteristics in daily food-related activities across different cultural contexts. By incorporating the CD-Chart and the CDDUX, healthcare professionals can emphasize crucial aspects of day-to-day health management and guide them in establishing suitable intervention objectives to enhance effective health self-management.

Vitamin D status in healthy Italian school-age children: a single-center cross-sectional study.

BACKGROUND: Vitamin D is involved in calcium homeostasis and bone metabolism, although its extra-skeletal actions are also well-known. Low serum 25(OH)D levels are common both in adults and children worldwide. METHODS: The purpose of this cross-sectional study was to determine the distribution of 25(OH)D levels in a cohort of healthy Italian school-age children, aged 5-10 years, in relationship to determinants of vitamin D deficiency such as season, BMI, gender, age and ethnicity. RESULTS: The mean serum 25(OH) D level was 28.2 ng/mL; the prevalence of 25(OH)D sufficiency (> 30 ng/mL), insufficiency (20-30 ng/mL), deficiency (10-20 ng/mL) and severe deficiency (< 10 ng/mL) was 36%, 37%, 21% and 6% of the study-group population, respectively. The lower serum 25(OH)D values were observed during winter (21.6 ng/mL) and spring (22.9 ng/mL), as compared to summer (46.7 ng/mL) (p < 0.001). Higher BMI z-scores were associated with lower 25(OH)D level while no statistical difference was observed as related to gender and age groups. CONCLUSIONS: Healthy Italian schoolchildren show low 25(OH)D levels, particularly during winter and spring time. Seasonality, ethnicity and overweight/obesity were confirmed to influence the vitamin D status, thus indicating the need for effective initiatives to support adequate vitamin D status in this population group.

Reduced pulmonary oxygen diffusion at 36 weeks of postmenstrual age in small-for-gestational-age preterm infants of less than 32 weeks without bronchopulmonary dysplasia.

BACKGROUND: Small-for-gestational-age (SGA) preterm infants are at increased risk of developing bronchopulmonary dysplasia (BPD). There is limited information on pulmonary oxygen diffusion of SGA preterm infants, particularly in those without BPD. OBJECTIVE: To compare the pulmonary oxygen diffusion of SGA to that of appropriate-for-gestational-age (AGA) preterm infants without BPD. STUDY DESIGN: Preterm infants with a gestational age (GA) between 24.0 and 31.6 weeks were studied. The oxygen saturation (SpO2 ), fraction to inspired oxygen (FiO2 ), and the SpO2 to FiO2 ratio (SFR) were compared between SGA and AGA infants. The association between SGA and SFR at 36 weeks was assessed using a multiple regression analysis. In the subgroup without BPD, SGA were match-paired for GA and gender with AGA infants. RESULTS: We analyzed 1189 infants surviving at 36 weeks: 194 (16%) were SGA and 995 (84%) AGA. The incidence of BPD was significantly higher in SGA than AGA infants (32% vs. 13%; p = .000). Out of the 995 infants without BPD, 132 (13%) were SGA and 863 (87%) AGA. SGA was negatively associated with the SFR value at 36 weeks, independently from BPD. SGA infants without BPD had significantly higher (better) SFR at birth, but lower (worse) SpO2 and SFR and from 33 to 36 weeks than their matched AGA counterpart. At 36 weeks, median SpO2 and SFR values were 97.7 versus 98.4 (p = .006) and 465 versus 468 (p = .010) in match-paired SGA and AGA, respectively. CONCLUSION: Among preterm infants of less than 32 weeks and without BPD, SGA infants had a reduced pulmonary oxygen diffusion at 36 weeks in comparison with AGA infants.

Incidence and two-year neurodevelopmental outcomes of small-for-gestational-age preterm infants: how do they relate to using different neonatal anthropometric charts?

BACKGROUND: The effect of different neonatal anthropometric charts on the incidence and neurodevelopmental outcomes at two years (Y) corrected age of small-for-gestational-age (SGA) preterm infants has still not been fully explored. METHODS: All preterm infants with a gestational age (GA) between 24.0 and 31.6 weeks (W), born from Jan-2004 to Dec-2017 in the Marche region (Italy) were studied. Intergrowth-21st, Beeby, Fenton, and Bertino anthropometric charts were used to classify infants with a birth weight less than 10th centile as SGA. Disabilities and neurodevelopmental scores assessed by Bayley-III Test were recorded at the 2Y follow-up visit. RESULTS: One thousand one hundred forty-seven preterm infants were evaluated. The incidence of SGA was significantly different among the study charts (from 12.9 to 17.5%). Nine hundred and twenty-seven study infants were assessed for neurodevelopmental outcomes at 2Y corrected age. The incidence of SGA with moderate cognitive impairment (COG Score: 70-84) and mild neurodevelopmental disability (NDD) were significantly different between the Intergrowth-21st and Bertino charts (31.7% vs. 19.6%, P=0.042; 30.8 vs. 19.2%, P=0.036; respectively). A statistically significant difference in COG Score was found between SGA preterm infants overlapping in all study charts and those classified as SGA only by the Intergrowth-21st chart (89.1±15.7 vs. 99.2±19.8; P=0.038). CONCLUSIONS: In a large cohort of preterm infants with a GA between 24.0 and 31.6W, the incidence and neurodevelopmental outcomes at 2Y corrected age of SGAs were significantly different depending on the anthropometric charts. These differences, albeit small, should be considered both in clinical practice and trials on SGA preterm infants.

Effects of the supplementation with a multispecies probiotic on clinical and laboratory recovery of children with newly diagnosed celiac disease: A randomized, placebo-controlled trial.

OBJECTIVE: To evaluate the efficacy of a multispecies probiotic on clinical and laboratory recovery of children with celiac disease (CeD) at diagnosis. METHODS: Children with newly diagnosed CeD entered a randomized double-blind placebo-controlled trial. A gluten-free diet (GFD) plus a multispecies probiotic or placebo were administered for 12 weeks. Growth, laboratory, and clinical parameters were recorded at enrollment, after 3 and 6 months of follow-up. RESULTS: Overall, 96 children completed the study: 49 in group A (placebo) and 47 in group B (probiotic). A significant increase of BMI-Z score was found in both groups after 3 and 6 months of treatment (p < 0.001), however the increase of BMI-Z score was significantly higher and faster in Group B than in Group A. Other clinical and laboratory parameters improved in both groups after 3 and 6 months (p<0.001), but no difference was found between the groups and a comparable time trend was observed in both groups. CONCLUSIONS: Treatment with a multispecies probiotic induced a higher and faster increase of BMI in children with newly diagnosed CeD. The mechanism of this positive effect remains to be elucidated.

Distribution of celiac disease predisposing genes HLA-DQ2 and HLA-DQ8 in the native population of southern India.

BACKGROUND: Celiac disease (CD) is an intestinal inflammatory condition caused by the ingestion of gluten peptides in wheat and related grains in individuals carrying HLA-DQ2 and/or HLA-DQ8 genes. In comparison to HLA-DQ8, a higher HLA-DQ2 prevalence is reported in European population where wheat has been the staple food for thousands of years. In non-European population, this pattern of HLA-DQ CD-predisposing gene distribution has not always been found. The aim of this study was to evaluate the HLA-DQ2 and HLA-DQ8 distribution in the native low-gluten consuming southern Indian population. METHODS: Overall, 211 dried blood spots (DBS) were collected from native southern Indian individuals. HLA-DQ characterization and the determination of homozygous/heterozygous status were performed using commercially available HLA-DQ typing kits. RESULTS: Of 211 collected DBS, 88 (42%, 95% CI: 36-48) were positive for HLA-DQ2 and/or HLA-DQ8 heterodimers. Overall, 40 (19%, 95% CI: 14-24) samples typed positive for HLA-DQ2 and 48 (23%, 95% CI: 18-28) typed positive for HLA-DQ8 genotypes. Of 40 HLA-DQ2-positive individuals, only one subject tested homozygous for the DQB1*02 allele. CONCLUSIONS: In the southern Indian native general population, the prevalence of HLA-DQ8 is higher in comparison to HLA-DQ2 prevalence. This finding could be related to the delayed introduction of wheat in the diet of the southern Indian population.

Diagnostic Accuracy of IgA Anti-Transglutaminase and IgG Anti-Deamidated Gliadin for Diagnosis of Celiac Disease in Children under Two Years of Age: A Systematic Review and Meta-Analysis.

The need of adding the determination of anti-deamidated gliadin peptide (DGP) IgG to anti-transglutaminase (TTG) IgA antibodies for diagnosis of celiac disease (CD) in children <2 years of age is controversial. We performed a systematic review and meta-analysis to evaluate, by head-to-head comparison, the diagnostic accuracy of TTG IgA and DGP IgG antibodies. We searched PubMed, MEDLINE, and Embase databases up to January 2021. The diagnostic reference was intestinal biopsy. We calculated the sensitivity and specificity of these tests and the odds ratio (OR) between the tests. Fifteen articles were eligible for the systematic review and ten were eligible for the meta-analysis. Sensitivity and specificity were 0.96 (95% confidence interval (CI), 0.91-0.98) and 0.96 (95% CI, 0.85-0.99) for DGP IgG and 0.93 (95% CI, 0.88-0.97) and 0.98 (95% CI, 0.96-0.99) for TTG IgA, respectively. TTG IgA specificity was significantly higher (OR 9.3 (95% CI, 2.3-37.49); p < 0.001) while the sensitivity of DGP IgG was higher without reaching statistical significance (OR: 0.6 (95% CI, 0.24-1.51); p = 0.28). Both the meta-analysis and the systematic review showed that some children with early CD are missed without the DGP IgG test. In children <2 years of age, TTG IgA is the best CD screening test; however, the addition of DGP IgG may increase the diagnostic sensitivity.