M.E. Baldassarre

The coeliac iceberg in Italy. A multicentre antigliadin antibodies screening for coeliac disease in school-age subjects

Background: Recent studies suggest that coeliac disease (CD) is one of the commonest, life‐long disorders in Italy. The aims of this multicentre work were: (a) to establish the prevalence of CD on a nationwide basis; and (b) to characterize the CD clinical spectrum in Italy. Patients and methods: Fifteen centres screened 17201 students aged 6–15 years (68.6% of the eligible population) by the combined determination of serum IgG‐ and IgA‐antigliadin antibody (AGA) test; 1289 (7.5%) were IgG and/or IgA‐AGA positive and were recalled for the second‐level investigation; 111 of them met the criteria for the intestinal biopsy: IgA‐AGA positivity and/or AEA positivity or IgG‐AGA positivity plus serum IgA deficiency. Results: Intestinal biopsy was performed on 98 of the 111 subjects. CD was diagnosed in 82 subjects (75 biopsy proven, 7 not biopsied but with associated AGA and AEA positivity). Most of the screening‐detected coeliac patients showed low‐grade intensity illness often associated with decreased psychophysical well‐being. There were two AEA negative cases with associated CD and IgA deficiency. The prevalence of undiagnosed CD was 4.77 × 1000 (95% CI 3.79–5.91), 1 in 210 subjects. The overall prevalence of CD, including known CD cases, was 5.44 × 1000 (95% CI 4.57–6.44), 1 in 184 subjects. The ratio of known to undiagnosed CD cases was 1 in 7. Conclusions: These findings confirm that, in Italy, CD is one of the most common chronic disorders showing a wide and heterogeneous clinical spectrum. Most CD cases remain undiagnosed unless actively searched.

Autoimmune thyroid disease and celiac disease in children.

Background: Celiac disease (CD) may be associated with other immunologic disorders in adults and children. Previous studies linking CD and autoimmune thyroid disease in children have included very few patients with limited biochemical and immunologic screening tests. The aim of this multicenter study was to establish the prevalence of autoimmune thyroid involvement in a large series of pediatric patients with CD. Methods: Five hundred seventy‐three consecutive pediatric patients were enrolled from clinics in Torino, Bologna, Foggia, Rome (two clinics), Naples, and Bari. Three hundred forty‐three patients with CD were studied, 230 girls and 113 boys (median age, 8.5 years). Two hundred fifty‐six of the patients with CD (median age, 9 years) had been following a gluten‐free diet for 3 months to 16 years; 87 patients were untreated (median age, 6.2 years). The diagnosis of CD was made using the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) criteria. A control group of 230 subjects (median age, 8.3 years) was enrolled. Serum free triiodothyronine, free thyroxine, and thyroid‐stimulating hormone (TSH), antithyroperoxidase, antithyroglobulin, anti‐TSH receptor antibodies, and thyroid echographic pattern were considered. Results: Autoimmune thyroid disease was found in 90 of 343 (26.2%) patients with CD (62 on a gluten‐free diet) and in 20 (10%) of the control subjects (P = 0.001). Fifty‐four (15.7%) patients with CD and autoimmune markers had normal thyroid function (euthyroidism) as did 12 (6.0%) of the control subjects; hypothyroidism was observed in 28 (8.1%) patients with CD and in 7 (3.5%) of the control subjects. Hyperthyroidism was diagnosed in four patients with CD and in none of the control subjects with autoimmune markers. An abnormal echographic pattern was seen in 37 patients with CD (16.8%) and only in 1 (1.6%) of the control subjects (P = 0.002). Conclusions: The high frequency of autoimmune thyroid disease found among patients with CD, even those on a gluten‐free diet, may justify a thyroid status assessment at diagnosis and at follow‐up evaluation of children with CD. JPGN 37:63‐66, 2003.

Fecal calprotectin: cutoff values for identifying intestinal distress in preterm infants.

This study aimed to determine cutoff levels for fecal calprotectin as a marker of intestinal distress in preterm neonates. A total of 126 infants born at a median gestational age of 33 weeks (range 25.7–35 weeks) were enrolled. Samples (n = 312) were collected weekly from the end of the first week of life until the end of the first month and if any gastrointestinal event occurred. Receiver operating characteristic curves analysis gave cutoff values of 363 μg/g (sensitivity 0.65, specificity 0.82) and 636 μg/g (sensitivity 0.72, specificity 0.95) for the development of mild or severe enteropathy.

Calprotectin levels in meconium.

Aim: To evaluate the effect of gender, gestational age, birthweight, mode of delivery, 5′‐Apgar score and maternal conditions on calprotectin concentrations in meconium. Methods: Calprotectin was measured in 131 neonates, in the first passed meconium. Results: Calprotectin levels (mean ± SD) resulted in 145.2 ± 78.5 mg kg−1 meconium, significantly correlated with birthweight (r=–0.333; p < 0.001), gestational age (r =–0.206; p = 0.018) and 5′‐Apgar score (r= ‐0.243, p= 0.035). The estimated regression model was: calprotectin levels (mg kg−1) = 269.58–41.54 weight (kg); r = 0.383, p < 0.001. No differences were found in relation to gender, mode of delivery and maternal conditions.

Does Calprotectin Represent a Regulatory Factor in Host Defense or a Drug Target in Inflammatory Disease

Calprotectin, a protein composed by two subunits of 8 and 14 kD respectively, is released by neutrophils in the biological fluids under inflammatory states. For instance, detection of calprotectin in faeces represents a diagnostic tool in the case of inflammatory bowel disease. Quite interestingly, calprotectin is increased in the stool of healthy newborns from day three up to day thirty and, physiologically, this increase may be interpreted as a defense mechanism against yeast and fungi. Therapeutic attempts at inhibiting the deleterious effect of calprotectin have been experimentally made by using lycoricinidol. This natural compound is able to hamper the calprotectin-induced apoptosis on the one hand. On the other hand, the same compound plays a prophylactic role in the course of experimental arthritis in rats.

Celiac Disease: Pathogenesis and Novel Therapeutic Strategies

Celiac disease is a digestive disease, considered as an autoimmune disorder, that damages the small intestine and interferes with absorption of nutrients. Individuals affected by celiac disease cannot tolerate a protein called gluten, present in wheat, rye, and barley, but also in other common products such as stamp and envelope adhesive, medicines, and vitamins. Celiac disease is a genetic condition that is triggered--or becomes active for the first time--after surgery, pregnancy, childbirth, viral infection, or severe emotional stress. Symptoms may occur in the digestive system, or in other parts of the body. Diagnosis involves blood tests and a biopsy of the small intestine. Recent findings estimate that about 2 million people in the United States have celiac disease, or about 1 in 133 people, as in Europe. Recent studies have shown that it may be more common in Africa, South America, and Asia than previously believed. The only treatment for celiac disease is to follow a gluten-free diet. Various other approaches are being studied that would reduce the need of dieting. One of those promising new approaches involves treating celiac patients with AT-1001, a paracellular permeability inhibitor, and with R-spondin1, a recombinant, secreted protein that early animal studies have shown to act as a highly specific stimulator of the gastrointestinal (GI) epithelial cells.

Fecal Expression of Human β-Defensin-2 following Birth

Background: Newborns display high intestinal permeability and a naive adaptive immune system, but infections are rare, indicating strong innate defense mechanisms. Objective: To measure the kinetics of fecal β-defensin-2 (HBD2), an inducible endogenous antimicrobial peptide produced by intestinal epithelial cells, in full-term and preterm infants. Methods: As a first step of this bicentric study, we enrolled 30 healthy full-term infants and 20 healthy preterm infants, with fecal samples collected at days 3, 7 12 and 30 in full-term infants and at days 15, 30 and 60 in preterm infants. As a second step, we enrolled 10 preterm infants with intestinal distress, either necrotizing enterocolitis (NEC) Bell’s stage III (n = 3) or isolated rectal bleeding (n = 7) and 20 controls, cross-matched for gestational age and age at sampling. Results: HBD2 decreased significantly from day 3 to day 7 (227 ng/g; 14–440 vs. 117 ng/g; 30–470, p = 0.01) then moderately until day 30 (84 ng/g; 10–500) in healthy full-term infants. Healthy preterm infants showed similar high levels between days 15 and 60 (82 ng/g; 30–154 and 85 ng/g; 26–390, respectively). No significant variation of fecal HBD2 levels was observed between infants with clinical features of intestinal distress (77 ng/g, 2–1,271) and cross-matched controls (56 ng/g, 31–164). However, 2/3 infants with NEC and 1/7 infants with isolated rectal bleeding had HBD2 levels above the maximal level observed in controls. Conclusions: The kinetics of fecal HBD2 in the neonatal period indicate that this inducible defensin can be detected at high level in the feces of full-term and preterm infants, independently of gestational age or mode of feeding. The potential role of fecal HBD2 in detecting NEC is suggested.

Longitudinally evaluation of human-beta defensins and Tumor necrosis factor- alfa in stools of preterm and term newborns

1-5yr 5-10yr 10-15yr >15yr No. of patients T o the Editor: We read with interest the article ‘‘Influence of gestational age, cesarean section, and type of feeding on fecal human a-defensins 2 and tumor necrosis factor-a’’ by Richter et al (1). Following this publication, we would like to report our longitudinal evaluation of human b-defensins 2 (hbD) and tumor necrosis factor-a (TNF-a) in stools of healthy preterm and term newborns, in relation to the method of delivery (cesarean section [CS] vs vaginal delivery [VD]), gestational age (GA), and type of feeding (breast-fed [BF], formula-fed [FF], breastand formula-fed [BF and FF]). We enrolled 39 preterm newborns (G1) (mean GA 31.2; mean birth weight 1870 g; 38 CS; 1 VD; 4 BF; 13 BFþ FF; 22 FF) and 29 term newborns (G2) (mean GA 39.3; mean birth weight 3306 g; 12 CS; 17 VD; 23 BF; 2 BFþFF; 4 FF), and stool samples were collected on days 15, 30, and 60 in the G1 group and on days 3, 7, 15, and 30 in the G2 group. All of the samples were frozen at 208 until analysis. hbD and TNF-a were analyzed by commercially available enzyme-linked immunosorbent assay kit (Immunodiagnostic, Bensheim, Germany; values: nanograms per milligram faeces). For statistical analysis, data were analyzed with the SAS package (SAS Institute, Cary, NC). Repeated measures analysis of variance was performed to evaluate the effect of time collection on TNF-a and hbD values in the 2 studied groups. Twoway analysis of variance models were used to evaluate the effect of delivery and feeding. A regression model was built to evaluate TNF-a and hbD values according to GA. We found that mean TNF-a values did not vary during the period of stool collection both in preterm (P1⁄4 0.12) and in term newborns (P1⁄4 0.34), but TNF-a was higher in preterm a newborns (P< 0.001). TNF-a values also decrease with GA (P1⁄4 0.02). No differences were found related to both delivery (P1⁄4 0.11) and type of feeding (at 1 month) (P> 0.05). Mean hbD values significantly differ both in G1 (increase from days 15–30 and then decrease until day 60; P< 0.0001) and in G2 (decrease from days 3–15 followed by stabilization until d30; P< 0.0001, as previously reported (2)). No significant differences in hbD values were found related to the method of delivery (P1⁄4 0.11) or type of feeding (after 1 month) (P> 0.05). Mean hbD values increased with GA, as reported by Richter et al (1). We conclude that hbD and TNF-a are present in intestinal lumen in both preterm and term newborns. TNF-a was higher in preterm newborns and inversely related to GA. hbD increased from days 15 to 30 in preterm newborns and it is positively correlated to GA. We have found different results compared with Richter et al (1), probably related to our longitudinal collection (days 3, 7, 15, 30, and 60) of stool samples. It could be interesting to understand whether higher TNF-a values and hbD increasing values in preterm newborns are the effect of the inflammatory condition of the gut or that of natural defense mechanisms.

Is it Possible to Modulate Microbiota in the Perinatal Period

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PO-0583 Is There An Association Between Functional Gastrointestinal Disorders In The First Three Months Of Life And Maternal Psychological Problems?

Aim of the study To investigate whether functional gastrointestinal disorders (DFGIs), defined according to Rome III criteria, are associated with postpartum mood disorders. Methods 113 mother/child pairs were enrolled in this perspective, longitudinal study. Maternal depressive symptoms were evaluated at birth, one and three months after delivery using Maternity Blues, Edinburgh Postpartum Depression Score (EPDS) and Symptom Check List for Anxiety and Depression. The Adult Attachment Interview (AAI) was used to determine the attachment style of the mother. Any sign/symptom was recorded weekly for the first three months of life, together with type of feeding. Statistical analysis (SPSS software): χ2 test, student t-test, linear regression. Results 37 (32,7%) newborns were exclusively BF. 16 (14,2%) newborns had regurgitation, 10 (9,7%) colics, 4 (3,5%) dischezia and 10 (9,7%) constipation. 60 (53,1%) mothers had postpartum depression and/or anxiety. 53,6% of infants with regurgitations had a depressed mother vs 23% of infants without regurgitations (χ2 =10,63, p = 0.003); 45,2% of infants with colics had a depressed mother vs 15,9% of infants without colics (χ2 =10,63, p = 0.001). A mother’s insecure attachment style was found in 36% of infants with persistence of regurgitations until third months of life vs 1,8% of infants with mother’s secure attachment style (p < 0.001). Conclusion Postpartum maternal depressive symptoms and anxiety are associated with infantile colic and regurgitations. Screening and early intervention in cases of postpartum depression could be useful to avoid inappropriate nutritional and pharmacologic treatments, promoting the health of both mother and infant.