Luigi Corvaglia

Prophylactic Use of a Probiotic in the Prevention of Colic, Regurgitation, and Functional Constipation: A Randomized Clinical Trial

IMPORTANCE Infantile colic, gastroesophageal reflux, and constipation are the most common functional gastrointestinal disorders that lead to referral to a pediatrician during the first 6 months of life and are often responsible for hospitalization, feeding changes, use of drugs, parental anxiety, and loss of parental working days with relevant social consequences. OBJECTIVE To investigate whether oral supplementation with Lactobacillus reuteri DSM 17938 during the first 3 months of life can reduce the onset of colic, gastroesophageal reflux, and constipation in term newborns and thereby reduce the socioeconomic impact of these conditions. DESIGN A prospective, multicenter, double-masked, placebo-controlled randomized clinical trial was performed on term newborns (age <1 week) born at 9 different neonatal units in Italy between September 1, 2010, and October 30, 2012. SETTING Parents were asked to record in a structured diary the number of episodes of regurgitation, duration of inconsolable crying (minutes per day), number of evacuations per day, number of visits to pediatricians, feeding changes, hospitalizations, visits to a pediatric emergency department for a perceived health emergency, pharmacologic interventions, and loss of parental working days. PARTICIPANTS In total, 589 infants were randomly allocated to receive L reuteri DSM 17938 or placebo daily for 90 days. INTERVENTIONS Prophylactic use of probiotic. MAIN OUTCOMES AND MEASURES Reduction of daily crying time, regurgitation, and constipation during the first 3 months of life. Cost-benefit analysis of the probiotic supplementation. RESULTS At 3 months of age, the mean duration of crying time (38 vs 71 minutes; P < .01), the mean number of regurgitations per day (2.9 vs 4.6; P < .01), and the mean number of evacuations per day (4.2 vs 3.6; P < .01) for the L reuteri DSM 17938 and placebo groups, respectively, were significantly different. The use of L reuteri DSM 17938 resulted in an estimated mean savings per patient of €88 (US

Probiotics for prevention of atopic diseases in infants: systematic review and meta‐analysis

118.71) for the family and an additional €104 (US

Detection of Helicobacter pylori infection in children with a standardized and simplified 13C-urea breath test.

140.30) for the community. CONCLUSIONS AND RELEVANCE Prophylactic use of L reuteri DSM 17938 during the first 3 months of life reduced the onset of functional gastrointestinal disorders and reduced private and public costs for the management of this condition. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01235884.

Accuracy of serology and 13C-urea breath test for detection of Helicobacter pylori in children.

Growing evidence underlines the pivotal role of infant gut colonization in the development of the immune system. The possibility to modify gut colonization through probiotic supplementation in childhood might prevent atopic diseases. The aim of the present systematic review and meta‐analysis was to evaluate the effect of probiotic supplementation during pregnancy and early infancy in preventing atopic diseases. PubMed, Embase and Cochrane Library were searched for randomized controlled trials evaluating the use of probiotics during pregnancy or early infancy for prevention of allergic diseases. Fixed‐effect models were used, and random‐effects models where significant heterogeneity was present. Results were expressed as risk ratio (RR) with 95% confidence interval (CI). Seventeen studies, reporting data from 4755 children (2381 in the probiotic group and 2374 in the control group), were included in the meta‐analysis. Infants treated with probiotics had a significantly lower RR for eczema compared to controls (RR 0.78 [95% CI: 0.69–0.89], P = 0.0003), especially those supplemented with a mixture of probiotics (RR 0.54 [95% CI: 0.43–0.68], P < 0.00001). No significant difference in terms of prevention of asthma (RR 0.99 [95% CI: 0.77–1.27], P = 0.95), wheezing (RR 1.02 [95% CI: 0.89–1.17], P = 0.76) or rhinoconjunctivitis (RR 0.91 [95% CI: 0.67–1.23], P = 0.53) was documented. The results of the present meta‐analysis show that probiotic supplementation prevents infantile eczema, thus suggesting a new potential indication for probiotic use in pregnancy and infancy.

Twelve year observation of primary and secondary antibiotic-resistant Helicobacter pylori strains in children

BACKGROUND The 13C-urea breath test, a reliable noninvasive method of detection of Helicobacter pylori in adults, needs validation in children. METHODS In order to evaluate the diagnostic accuracy of 13C-urea breath test in children, the results of this test performed in 144 children were correlated with the histology and culture of contemporaneous gastric (antral and fundic) biopsy specimens. The test was performed with 2 mg/kg body weight 13C-Urea (maximum, 100 mg) ingested after a fat-rich test meal. Samples of expired breath taken at 0, 5, 10, 20, and 30 minutes were assayed with mass spectrometry. Results were considered positive when the curve of excretion of labeled carbon dioxide in the expired breath increased by 5%O or more above the baseline. RESULTS Discrepancies in H. pylori status were observed in 14 children. To improve and simplify the test, the results were reanalyzed using different cutoff values for each sampling time. The best results, with sensitivity of 95.7% and specificity of 95.2%, were obtained with a cutoff of 3.5%O at 20 minutes. CONCLUSIONS The 13C-urea breath test is a reliable method for the noninvasive detection of H. pylori infection in children. The test can be simplified and its accuracy improved using only the 0- and 20-minute breath samples and a cutoff of 3.5%O instead of the classical 5%O used in adults. The need for modification of the cutoff value may reflect the higher production of endogenous CO2 in children.

Influence of intrapartum antibiotic prophylaxis against group B Streptococcus on the early newborn gut composition and evaluation of the anti-Streptococcus activity of Bifidobacterium strains

BACKGROUND Indirect noninvasive methods, such as the 13C-urea breath test and serology, can be useful for the detection of Helicobacter pylori infection in children. We analyzed retrospectively the diagnostic accuracy of these two methods. PATIENTS AND METHODS Between September, 1989, and October, 1996, H. pylori status was determined in 139 children by means of culture and histologic study of gastric biopsies. We performed 146 13C-urea breath tests and serologic assays (Cobas core; Roche). RESULTS H. pylori infection was detected in 91 of 139 (65%) children. The 13C-urea breath test was discordant with H. pylori status in 4 of 146 tests; serology was discordant in 24 and indeterminate in 7 of 146. The 13C-urea breath test was more sensitive than serology (98% vs. 79%, P < 0.01) but comparable in specificity (96% vs. 92%). The serology yielded false negative results more often in children younger than 5 years of age (P < 0.05). CONCLUSIONS The 13C-urea breath test is more reliable than serology for the detection of active H. pylori infection in children. Below 10 years of age serology is insufficiently sensitive for clinical purposes, whereas the 13C-urea breath test remains a reliable test.

Combined oesophageal impedance‐pH monitoring in preterm newborn: comparison of two options for layout analysis

BACKGROUND The effectiveness of Helicobacter pylori eradication regimens is influenced by antibiotic susceptibility of infecting strains. Data concerning antibiotic resistance in children are limited. We report the evolution of primary and secondary resistance in a series of Belgian children during the last 12 years. PATIENTS AND METHODS From 1989 through 2000, H. pylori gastritis was diagnosed in 569 children, and antibiotic susceptibility tests were performed in 555. Eradication, using different schemes, failed in 128 of 457 treated children. After eradication failure antibiotic susceptibility determination was performed in 87 of 128. Comparison of antibiotic susceptibility of strains isolated from the gastric body and from the antrum was performed in 238 samples. RESULTS Resistance to amoxicillin was not observed. The rate of primary resistance to nitroimidazole derivatives was 18.0% (101 of 555) and remained constant throughout this period, whereas primary resistance to macrolides increased from an average of 6.0% (range, 0 to 10%) before 1995 to 16.6% (range, 10 to 25%, P < 0.001) thereafter. Antibiotic consumption in Belgium, especially macrolides, did not show important fluctuations during the study period. Secondary resistance developed in 39 of 87 patients (46%). Strains isolated from different gastric locations show identical susceptibility testing in all but 5 of 238. CONCLUSIONS Resistance of H. pylori to macrolides increased in our pediatric population which did not appear to correlate with macrolides prescription habits in our country. After eradication failure acquired secondary resistance was observed in one-half of the patients.

Laboratory diagnosis of late-onset sepsis in newborns by multiplex real-time PCR.

Several factors are known to influence the early colonization of the gut in newborns. Among them, the use of antibiotics on the mother during labor, referred to as intrapartum antibiotic prophylaxis (IAP), has scarcely been investigated, although this practice is routinely used in group B Streptococcus (GBS)-positive women. This work is therefore aimed at verifying whether IAP can influence the main microbial groups of the newborn gut microbiota at an early stage of microbial establishment. Fifty-two newborns were recruited: 26 born by mothers negative to GBS (control group) and 26 by mothers positive to GBS and subjected to IAP with ampicillin (IAP group). Selected microbial groups (Lactobacillus spp., Bidobacterium spp., Bacteroides fragilis, Clostridium difficile, and Escherichia coli) were quantified with real-time PCR on DNA extracted from newborn feces. Further analysis was performed within the Bidobacterium genus by using DGGE after amplification with genus-specific primers. Results obtained showed a significant decrease of the bifidobacteria counts after antibiotic treatment of the mother. Bifidobacteria were found to be affected by IAP not only quantitatively but also qualitatively. In fact, IAP determined a decrement in the frequency of Bidobacterium breve, Bidobacterium bifidum, and Bidobacterium dentium with respect to the control group. Moreover, this study has preliminarily evaluated that some bifidobacterial strains, previously selected for use in infants, have antibacterial properties against GBS and are therefore potential candidates for being applied as probiotics for the prevention of GBS infections.

Positive Effect of Human Milk Feeding during NICU Hospitalization on 24 Month Neurodevelopment of Very Low Birth Weight Infants: An Italian Cohort Study

Abstract  Gastro‐oesophageal reflux (GOR) is common in preterm infants. Combined multichannel intraluminal impedance and pH monitoring (pH‐MII) is emerging as an useful tool to study both acid and non‐acid GOR in this population. We aimed to highlight main advantages and limits of pH‐MII in preterm infants and to test whether the inclusion of GOR episodes detected only by pH monitoring details better the features of GOR. Fifty‐two symptomatic preterm infants underwent a 24‐hour, continuous and simultaneous measurement of pH‐MII. Each layout was analyzed using two different options: option 1 included GOR episodes detected by MII and then classified as acid or non‐acid according to the associated pH change; option 2 included GOR episodes detected by MII and also GOR episodes detected only by pH sensor. By adopting option 1, a total number of 2834 GOR episodes was detected by MII: 2162 of them were characterized as non‐acid and 672 were characterized as acid. The median (range) number of acid MII‐GOR episodes was 10 (1–52); the median (range) number of non‐acid MII‐GOR episodes was 36.5 (2–119). Median (range) acid MII‐GOR‐bolus exposure index was 0.28% (0.02–2.73%); median (range) non‐acid MII‐GOR‐bolus exposure index was 1.03% (0.06–38.15%). By adopting option 2, an average of 53.2 acid GOR episodes and an average of 11% oesophageal exposure to acid GOR more than by option 1 was detected. An accurate and detailed description of GOR in preterm infants can be obtained only by including in the analysis all acid GOR episodes detected by pH sensor.

The frequency of apneas in very preterm infants is increased after non‐acid gastro‐esophageal reflux

Bloodstream infections (BSIs) are an important cause of neonatal morbidity and mortality, and often result in prolonged hospitalization of infants who are admitted to neonatal intensive care units (VerboonMaciolek et al., 2006). Late-onset neonatal sepsis (occurring in newborns aged older than 3 days) occurs in approximately 0.1 % of all newborns and in up to ~25 % of very low birth weight infants (birth weight ,1500 g) (Kaufman & Fairchild, 2004). Early diagnosis of sepsis and prompt treatment are critical in preventing severe and life-threatening complications in these patients (Harbarth et al., 2003; Kollef, 2003; Lodise et al., 2003). The clinical recognition of sepsis in neonates is difficult, however, because the signs and symptoms are often non-specific (Gerdes, 1991; Verboon-Maciolek et al., 2006) and blood cultures (BCs) are rarely positive.