Paola Roggero

Therapy With Gastric Acidity Inhibitors Increases the Risk of Acute Gastroenteritis and Community-Acquired Pneumonia in Children

OBJECTIVE. Gastric acidity (GA) inhibitors, including histamine-2 receptor antagonists (H2 blockers) and proton pump inhibitors (PPIs), are the mainstay of gastroesophageal reflux disease (GERD) treatment. A prolonged GA inhibitor–induced hypochlorhydria has been suggested as a risk factor for severe gastrointestinal infections. In addition, a number of papers and a meta-analysis have shown an increased risk of pneumonia in H2-blocker–treated intensive care patients. More recently, an increased risk of community-acquired pneumonia associated with GA inhibitor treatment has been reported in a large cohort of adult patients. These findings are particularly relevant to pediatricians today because so many children receive some sort of GA-blocking agent to treat GERD. To test the hypothesis that GA suppression could be associated with an increased risk of acute gastroenteritis and pneumonia in children treated with GA inhibitors, we conducted a multicenter, prospective study. METHODS. The study was performed by expert pediatric gastroenterologists from 4 pediatric gastroenterology centers. Children (aged 4–36 months) consecutively referred for common GERD-related symptoms (for example, regurgitation and vomiting, feeding problems, effortless vomiting, choking), from December 2003 to March 2004, were considered eligible for the study. Exclusion criteria were a history of GA inhibitors therapy in the previous 4 months, Helicobacter pylori infection, diabetes, chronic lung or heart diseases, cystic fibrosis, immunodeficiency, food allergy, congenital motility gastrointestinal disorders, neuromuscular diseases, or malnutrition. Control subjects were recruited from healthy children visiting the centers for routine examinations. The diagnosis of GERD was confirmed in all patients by standard criteria. GA inhibitors (10 mg/kg ranitidine per day in 50 children or 1 mg/kg omeprazole per day in 50 children) were prescribed by the physicians for 2 months. All enrolled children were evaluated during a 4-month follow-up. The end point was the number of patients presenting with acute gastroenteritis or community-acquired pneumonia during a 4-month follow-up study period. RESULTS. We obtained data in 186 subjects: 95 healthy controls and 91 GA-inhibitor users (47 on ranitidine and 44 on omeprazole). The 2 groups were comparable for age, gender, weight, length, and incidence of acute gastroenteritis and pneumonia in the 4 months before enrollment. Rate of subjects presenting with acute gastroenteritis and community-acquired pneumonia was significantly increased in patients treated with GA inhibitors compared with healthy controls during the 4-month follow-up period. In the GA inhibitor-treated group, the rate of subjects presenting with acute gastroenteritis and community-acquired pneumonia was increased when comparing the 4 months before and after enrollment. No differences were observed between H2 blocker and PPI users in acute gastroenteritis and pneumonia incidence in the previous 4 months and during the follow-up period. On the contrary, in healthy controls, the incidence of acute gastroenteritis and pneumonia remained stable. CONCLUSIONS. This is the first prospective study performed in pediatric patients showing that the use of GA inhibitors was associated with an increased risk of acute gastroenteritis and community-acquired pneumonia in GERD-affected children. It could be interesting to underline that we observed an increased incidence of intestinal and respiratory infection in otherwise healthy children taking GA inhibitors for GERD treatment. On the contrary, the majority of the previous data showed that the patients most at risk for pneumonia were those with significant comorbid illnesses such as diabetes or immunodeficiency, and this points to the importance of GA suppression as a major risk factor for infections. In addition, this effect seems to be sustained even after the end of therapy. The results of our study are attributable to many factors, including direct inhibitory effect of GA inhibitors on leukocyte functions and qualitative and quantitative gastrointestinal microflora modification. Additional studies are necessary to investigate the mechanisms of the increased risk of infections in children treated with GA inhibitors, and prophylactic measures could be considered in preventing them.

Inflammatory bowel disease in children and adolescents in Italy: data from the pediatric national IBD register (1996-2003).

Background: The purpose was to assess in Italy the clinical features at diagnosis of inflammatory bowel disease (IBD) in children. Methods: In 1996 an IBD register of disease onset was established on a national scale. Results: Up to the end of 2003, 1576 cases of pediatric IBD were recorded: 810 (52%) ulcerative colitis (UC), 635 (40%) Crohns disease (CD), and 131 (8%) indeterminate colitis (IC). In the period 1996–2003 an increase of IBD incidence from 0.89 to 1.39/105 inhabitants aged <18 years was observed. IBD was more frequent among children aged between 6 and 12 years (57%) but 20% of patients had onset of the disease under 6 years of age; 28 patients were <1 year of age. Overall, 11% had 1 or more family members with IBD. The mean interval between onset of symptoms and diagnosis was higher in CD (10.1 months) and IC (9 months) versus UC (5.8 months). Extended colitis was the most frequent form in UC and ileocolic involvement the most frequent in CD. Upper intestinal tract involvement was present in 11% of CD patients. IC locations were similar to those of UC. Bloody diarrhea and abdominal pain were the most frequent symptoms in UC and IC, and abdominal pain and diarrhea in CD. Extraintestinal symptoms were more frequent in CD than in UC. Conclusions The IBD incidence in children and adolescents in Italy shows an increasing trend for all 3 pathologies. UC diagnoses exceeded CD.

Results from the pediatric European register for treatment of Helicobacter pylori (PERTH).

Background and Aim:  Data on the eradication treatment for childhood Helicobacter pylori are scanty. A register was established on the European Society for Pediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) website to collect data on treatment performed by European pediatricians to ascertain what is practiced in the field.

Evaluation of air-displacement plethysmography for body composition assessment in preterm infants

Background:Adiposity may contribute to the future risk of disease. The aim of this study was to evaluate the accuracy and reliability of an air-displacement plethysmography (ADP) system to estimate percentage fat mass (%FM) in preterm infants and to evaluate interdevice reliability in infants.Methods:A total of 70 preterm and 9 full-term infants were assessed. The accuracy of ADP measurements was assessed by determining reference %FM values using H218O dilution measurement.Results:Mean %FM by ADP was 5.67 ± 1.84 and mean %FM by H218O dilution was 5.99 ± 2.56. Regression analysis showed that %FM by ADP was associated with %FM by H218O dilution (R2 = 0.63, SE of estimate (SEE) = 1.65, P = 0.006). Bland–Altman analysis showed no bias (r = −0.48, P = 0.16) and 95% limits of agreement were −3.40 to 2.76 %FM. There was no difference in mean interdevice reliability %FM values (8.97 vs. 8.55 %FM) between ADP 1 and 2. Regression analysis indicated a low SEE (1.14% FM) and high R2 (0.91); 95% limits of agreement were −1.87 to 2.71 %FM. The regression line did not differ significantly from the line of identity.Conclusion:ADP is a noninvasive, reliable, and accurate technique to measure preterm infants’ body composition in both research and clinical settings.

Longitudinal body composition data in exclusively breast-fed infants: a multicenter study.

Reference %fat and total fat‐free mass data is necessary for evaluating growth in infants. We aimed to develop longitudinal %fat and total fat‐free mass data in infants from birth to 6 months of age. An observational, multicenter, prospective cohort study was conducted with assessments at birth, 1 week, 2 weeks, 1, 2, 3, 4, 5, and 6 months of age. Subjects were exclusively breast‐fed and were enrolled at three centers. Whole‐body composition (i.e., %fat and total fat‐free mass) were assessed using air‐displacement plethysmography (ADP) (PEA POD; Life Measurement, Concord, CA). Maternal prepregnancy BMI, gestational weight gain, and infant anthropometric data were collected. A total of 160 infants (boys = 84) were assessed from birth to 4 months of age. Mean birth weight was 3.46 ± 0.39 kg %fat and fat‐free mass significantly increased from birth to 4 months of age (P < 0.0001). Gender‐specific %fat and total fat‐free mass curves for infants from birth to 4 months of age were created. This study will be beneficial to health‐care professionals in evaluating normal growth and nutritional patterns in the first months of life.

Adiposity in small for gestational age preterm infants assessed at term equivalent age

Objective: Infants classified as small for gestational age are considered to have developed under adverse intrauterine conditions that lead to lack of fat mass accretion. The aim of this study was to test the null hypothesis that the fat mass in preterm small for gestational age infants assessed at term equivalent age was not different from that of full-term small for gestational age newborns. Design: Observational study. Setting: Northern Italy. Patients: 67 small for gestational age preterm infants and 132 small for gestational age full-term newborns. Main outcome measures: Growth and body composition, assessed by means of a paediatric air displacement plethysmography system, were measured at term equivalent age in the preterm infants and on the third day of life in the full-term newborns. Results: The mean (SD) gestational age of preterm infants was 30.6 (2.3) weeks and their mean (SD) birth weight was 1140 (237) g. At assessment weight was not different between the preterm and full-term infants, whereas the percentage of total body fat mass was higher in the preterm infants (14.3% (SD 4.7%) vs 5.8% (SD 3.5%), p<0.005). Conclusions: Preterm infants, born small for gestational age, appear to be at risk for increased adiposity, which is a risk factor for the development of the metabolic syndrome.

Rapid recovery of fat mass in small for gestational age preterm infants after term

Background Preterm small for gestational age (SGA) infants may be at risk for increased adiposity, especially when experiencing rapid postnatal weight gain. Data on the dynamic features of body weight and fat mass (FM) gain that occurs early in life is scarce. We investigated the postnatal weight and FM gain during the first five months after term in a cohort of preterm infants. Methodology/Principal Findings Changes in growth parameters and FM were prospectively monitored in 195 infants with birth weight ≤1500 g. The infants were categorized as born adequate for gestational age (AGA) without growth retardation at term (GR−), born AGA with growth retardation at term (GR+), born SGA. Weight and FM were assessed by an air displacement plethysmography system. At five months, weight z-score was comparable between the AGA (GR+) and the AGA (GR−), whereas the SGA showed a significantly lower weight.The mean weight (g) differences (95% CI) between SGA and AGA (GR−) and between SGA and AGA (GR+) infants at 5 months were −613 (−1215; −12) and −573 (−1227; −79), respectively. At term, the AGA (GR+) and the SGA groups showed a significantly lower FM than the AGA (GR−) group. In the first three months, change in FM was comparable between the AGA (GR+) and the SGA groups and significantly higher than that of the AGA (GR−) group.The mean difference (95% CI) in FM change between SGA and AGA (GR−) and between AGA (GR+) and AGA (GR−) from term to 3 months were 38.6 (12; 65); and 37.7 (10; 65). At three months, the FM was similar in all groups. Conclusions Our data suggests that fetal growth pattern influences the potential to rapidly correct anthropometry whereas the restoration of fat stores takes place irrespective of birth weight. The metabolic consequences of these findings need to be elucidated.

Implementation of Nutritional Strategies Decreases Postnatal Growth Restriction in Preterm Infants

Background Prevention of postnatal growth restriction of very preterm infants still represents a challenge for neonatologists. As standard feeding regimens have proven to be inadequate. Improved feeding strategies are needed to promote growth. Aim of the present study was to evaluate whether a set of nutritional strategies could limit the postnatal growth restriction of a cohort of preterm infants. Methodology/Principal Findings We performed a prospective non randomized interventional cohort study. Growth and body composition were assessed in 102 very low birth weight infants after the introduction of a set of nutritional practice changes. 69 very low birth weight infants who had received nutrition according to the standard nutritional feeding strategy served as a historical control group. Weight was assessed daily, length and head circumference weekly. Body composition at term corrected age was assessed using an air displacement plethysmography system. The cumulative parenteral energy and protein intakes during the first 7 days of life were higher in the intervention group than in the historical group (530±81 vs 300±93 kcal/kg, p<0.001 and 21±2.9 vs 15±3.2 g/kg, p<0.01). During weaning from parenteral nutrition, the intervention group received higher parental/enteral energy and protein intakes than the historical control group (1380±58 vs 1090±70 kcal/kg; 52.6±7 vs 42.3±10 g/kg, p<0.01). Enteral energy (kcal/kg/d) and protein (g/kg/d) intakes in the intervention group were higher than in the historical group (130±11 vs 100±13; 3.5±0.5 vs 2.2±0.6, p<0.01). The negative changes in z score from birth to discharge for weight and head circumference were significantly lower in the intervention group as compared to the historical group. No difference in fat mass percentage between the intervention and the historical groups was found. Conclusions The optimization and the individualization of nutritional intervention promote postnatal growth of preterm infants without any effect on percentage of fat mass.

Neonatal Period: Body Composition Changes in Breast-Fed Full-Term Newborns

Background: Weight loss during initial days of life in healthy infants is known to consist of loss of both body solids and total body water. However, the nature of these body composition changes needs further investigation. Objective: To investigate the nature of changes in body composition that accompany weight loss during the first days of life in healthy term newborns. Methods: Body composition of healthy full-term newborns was assessed using air-displacement plethysmography. Cross-sectional (n = 262) and longitudinal samples (n = 28) were assessed during the first 4 and 5 days after delivery, respectively. Results: In the cross-sectional sample, mean body weight decreased significantly through day 4 (p < 0.001), mean fat mass (FM) and %FM decreased significantly (p = 0.005 and p = 0.031, respectively) by day 3. There was a significant decrease in mean fat-free mass on days 3 and 4 (p = 0.01 and p < 0.001, respectively). In the longitudinal sample, there was a significant decrease in mean body weight, FM and %FM (p < 0.001, p = 0.001, p = 0.013, respectively) by day 4. On day 5 there was a significant increase in mean body weight, FM and %FM (p < 0.001, p = 0.024, p = 0.036, respectively) when compared to day 4. There was no significant difference in mean FM and %FM values between day 1 and day 5. Conclusions: These results indicate that body composition changes are constituted by a reduction in both fat and fat free mass. However, a greater %FM is lost and consequently regained by day 5 when compared to fat-free mass.

Influence of protein and energy intakes on body composition of formula-fed preterm infants after term.

The aim of the present study was to evaluate changes in body composition in 48 preterm infants in relation to protein and energy intakes from term up to 3 months of corrected age, using air displacement plethysmography. Protein intake (grams per kilogram per day) was negatively associated with percentage of fat mass at 1 month of corrected age. The high-protein-intake group showed greater gain in lean body mass gain than did the low-protein-intake group. This finding suggests that during the first month of corrected age, high protein intake results in a significantly different weight gain composition.