Arianna Aceti

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

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.

Gastro-oesophageal reflux increases the number of apnoeas in very preterm infants.

Objective: To document the existence of a relationship between apnoea of prematurity (AOP) and gastro-oesophageal reflux (GER) in preterm infants. Setting: Neonatal intensive care unit. Patients: Twenty-six preterm infants (gestational age ⩽32 weeks) with recurrent apnoeas. Intervention: Simultaneous and synchronised recording of polysomnography and pH-impedance monitoring (pH-MII). Polysomnography detects and characterises apnoeas, by recording of breathing movement, nasal airflow, electrocardiogram and pulse oximeter saturation. pH-MII is the state-of-the-art methodology for GER detection in preterm newborns. Main outcome measures: Relationship between AOP and GER, which were considered temporally related if both started within 30 seconds of each other. Results: One hundred and fifty-four apnoeas out of 1136 were temporally related to GER. The frequency of apnoea during the 1-minute time around the onset of GER was significantly higher than the frequency detected in the GER-free period (p = 0.03). Furthermore, the frequency of apnoea in the 30 seconds after GER (GER-triggered apnoeas) was greater than that detected in the 30 seconds before (p = 0.01). A great inter-individual variability was documented in the proportion of GER-triggered apnoeas. A strong correlation between total number of apnoeas and the difference between apnoeas detected 30 seconds after and before GER was found (p = 0.034). Conclusions: Our data show that a variable rate of apnoeas can be triggered by GER in very preterm infants. Further studies are needed to recognise clinical features that identify those patients who are more susceptible to GER-triggered apnoeas.

Near-infrared reflectance analysis to evaluate the nitrogen and fat content of human milk in neonatal intensive care units

Objective: To validate near-infrared reflectance analysis (NIRA) as a fast, reliable and suitable method for routine evaluation of human milk’s nitrogen and fat content. Setting: One neonatal intensive care unit. Patients: 124 samples of expressed human milk (55 from preterm mothers and 69 from term mothers). Intervention: Measurement of nitrogen and fat content by NIRA and traditional methods (Gerber method for fat and Kjeldahl method for nitrogen). Main outcome measures: Agreement between NIRA and traditional methods. Variability in fat and nitrogen content of human milk. Results: A strong agreement was found between the results of traditional methods and NIRA for both fat and nitrogen content (expressed as g/100 g of milk) in term (mean fat content: NIRA = 2.76; Gerber = 2.76; mean nitrogen content: NIRA = 1.88; Kjeldahl  = 1.92) and preterm (mean fat content: NIRA = 3.56; Gerber = 3.52; mean nitrogen content: NIRA = 1.91; Kjeldahl  = 1.89) mothers’ milk. Nitrogen content of the milk samples, measured by NIRA, ranged from 1.18 g/100 g to 2.71 g/100 g of milk in preterm milk and from 1.48 g/100 g to 2.47 g/100 g in term milk; fat content ranged from 1.27 g/100 g to 6.23 g/100 g of milk in preterm milk and from 1.01 g/100 g to 6.01 g/100 g of milk in term milk. Conclusion: NIRA can be used as a quick and reliable tool for routine monitoring of macronutrient content of human milk and for devising individualised human milk fortification regimens in the feeding of very premature infants.

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

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

Background  To evaluate whether physical and/or chemical features of gastro‐esophageal reflux (GER) influence its relationship with apnea of prematurity (AOP).

The efficacy of sodium alginate (Gaviscon) for the treatment of gastro-oesophageal reflux in preterm infants.

Background  Gastro‐oesophageal reflux is common in preterm newborns; at present, no studies have evaluated the efficacy of sodium alginate in this population.

Effect of Posture on Brain Hemodynamics in Preterm Newborns Not Mechanically Ventilated

Background: Changes in head posture influence brain hemodynamics. Optimal positioning has been recommended as 1 of 10 potentially better practices to reduce the incidence of brain injury in preterm newborns. Objectives: The aim of this study was to evaluate by near-infrared spectroscopy (NIRS) the effect of different head and body positions and the influence of gestational age (GA) and nasal continuous positive airway pressure on brain hemodynamics in very preterm newborns. Methods: 24 stable preterm newborns were studied by NIRS in 6 different postures including head rotation and head inclination in both supine and prone positions. Changes in normalized tissue hemoglobin index (nTHI) and tissue oxygenation index (TOI) were measured after posture variations. Results: No statistically significant changes in nTHI and in TOI were found in the 6 postures. nTHI variations, expression of cerebral blood volume variations, were influenced by GA. A reduction in nTHI, with a stable TOI, in the less mature infants (with GA ≤26 weeks), occurred on head rotation; nTHI increased again when the head was derotated. Conclusions: Hemodynamic changes after posture variations depend on GA. Head rotation in newborns with GA ≤26 weeks produced a reduction in nTHI with stable TOI. Possible physiopathological mechanisms are discussed.

Influence of Intrapartum Antibiotic Prophylaxis for Group B Streptococcus on Gut Microbiota in the First Month of Life.

Objectives: The effect of intrapartum antibiotic prophylaxis (IAP) for group B Streptococcus (GBS) on bacterial colonization of the infants gut has not been investigated extensively. We aimed to evaluate the effect of IAP on gut microbiota in healthy term infants, also exploring the influence of type of feeding. Methods: Healthy term infants, whose mothers had been screened for GBS in late gestation, were divided into 2 groups: infants born to GBS-positive mothers who had received IAP versus controls. Neonatal fecal samples were collected at 7 and 30 days of life; DNA was extracted, and quantification of selected microbial groups (Lactobacillus spp, Bifidobacterium spp, and Bacteroides fragilis group) was performed by real-time PCR. Results: A total of 84 infant–mother pairs were recruited. Bifidobacteria count was significantly lower in the IAP group at 7 days of life (median [interquartile range] 6.01 Log colony-forming unit per gram [5.51–6.98] vs 7.80 [6.61–8.26], P = 0.000). No differences in Bifidobacteria count at 30 days or in Lactobacilli and B fragilis counts at any time point were documented. Furthermore, at 7 days of life, infants who had not received IAP and were exclusively human milk–fed had higher counts of Bifidobacteria. Regardless of IAP treatment, infants fed exclusively human milk had higher Lactobacillus spp counts both at 7 and 30 days of life. Conclusions: IAP alters gut microflora by reducing the count of Bifidobacteria, which is further affected in infants receiving formula feeding. Whether these alterations could have long-term consequences on health and disease requires further investigation.

Extensively hydrolyzed protein formula reduces acid gastro-esophageal reflux in symptomatic preterm infants☆

BACKGROUND Gastro-esophageal reflux (GER) is diagnosed frequently in preterm infants. Pharmacological treatment of GER has some potential side effects. Conservative treatment of GER should be the first-line approach and should include body positioning and diet modifications. Formula-fed preterm infants experience frequently symptoms of feeding intolerance. Hydrolyzed protein formula (HPF) is often used in these infants due to their effects on gastrointestinal motility. AIMS To investigate the role of an extensively HPF (eHPF) on GER indexes in formula-fed preterm infants with symptoms of both GER and feeding intolerance. STUDY DESIGN Randomized crossover trial. SUBJECTS Preterm infants (gestational age ≤33 weeks) with symptoms of feeding intolerance (large gastric residuals, abdominal distension and constipation) and GER (frequent regurgitations and/or postprandial desaturations). OUTCOME MEASURES GER indexes detected by 24-h combined multichannel intraluminal impedance and pH monitoring. GER indexes detected after 4 feeds of an eHPF were compared to those detected after 4 feeds of a standard preterm formula (SPF) by Wilcoxon signed ranks test. A p<0.05 was considered statistically significant. RESULTS eHPF significantly reduced the number of GERs detected by pH monitoring (p=0.036) and also the reflux index (p=0.044) compared to SPF. No differences in impedance bolus exposure indexes nor in GER height were detected. CONCLUSIONS The use of an eHPF should be evaluated for reducing esophageal acid exposure in preterm infants with feeding intolerance and symptoms of GER. Future research should focus on the evaluation of an eHPF adequate for preterm infants in improving clinical symptoms of GER.

A thickened formula does not reduce apneas related to gastroesophageal reflux in preterm infants.

Background: Apnea of prematurity (AOP) occurs frequently in preterm infants and a variable proportion of AOP can be induced by gastroesophageal reflux (GER). Conservative treatment, including dietary modifications, should be the first-line approach for both GER and GER-related apneas in this population. Objectives: To evaluate the efficacy of a starch-thickened preterm formula (PF) in reducing the frequency of apneas related to GER. Methods: Preterm infants with AOP were studied by combined impedance and pH monitoring and polysomnography. The 6-hour study period included two feeds, one of a commercially available PF and one of the same formula thickened with amylopectin (TPF). GER indexes, apneas and GER-related apneas detected after TPF and PF feeds were compared by Wilcoxon signed-rank test. Results: 24 infants were studied. During 140 h of registration, 289 apneas (147 after TPF and 142 after PF; p = 0.876), and 861 GER episodes (400 after TPF and 461 after PF; p = 0.465) were recorded. No difference in the number of AOP was found between TPF and PF. A significant reduction in acid exposure was found after TPF; there was no influence on non-acid GER indexes. The frequency of GER-related apneas did not differ between TPF and PF. Conclusions: A formula thickened with amylopectin did not reduce the number of AOP or GER-related apneas. It reduced acid GER features but had no effect on non-acid GER indexes. Future research should focus on exploring different conservative strategies to treat GER-related apneas in preterm infants.