Project description:Necrotizing enterocolitis (NEC) is a critical intestinal emergency condition, which mainly occurs in preterm very low birth weight (PVLBW) infants. Despite remarkable advances in the care of PVLBW infants, with considerable improvement of the survival rate in recent decades, the incidence of NEC and NEC-related mortality have not declined accordingly. The fast progression from nonspecific signs to extensive necrosis also makes primary prevention the first priority. Recently, increasing evidence has indicated the important role of several nutrients in primary prevention of NEC. Therefore, the aim of this review is to summarize some potential immunomodulatory nutrients in the prevention of NEC, including bovine colostrum, probiotics, prebiotics (e.g., human milk oligosaccharides), long chain polyunsaturated fatty acids, and amino acids (glutamine, cysteine and N-acetylcysteine, l-arginine and l-citrulline). Based on current research evidence, probiotics are the most documented effective method to prevent NEC, while others still require further investigation in animal studies and clinical randomized controlled trials.
Project description:Difference in human milk oligosaccharides (HMO) composition in breast milk may be one explanation why some preterm infants develop necrotizing enterocolitis (NEC) despite being fed exclusively with breast milk. The aim of this study was to measure the concentration of 15 dominant HMOs in breast milk during the neonatal period and investigate how their levels correlated to NEC, sepsis, and growth in extremely low birth weight (ELBW; <1000 g) infants who were exclusively fed with breast milk. Milk was collected from 91 mothers to 106 infants at 14 and 28 days and at postmenstrual week 36. The HMOs were analysed with high-performance anion-exchange chromatography with pulsed amperometric detection. The HMOs diversity and the levels of Lacto-N-difucohexaose I were lower in samples from mothers to NEC cases, as compared to non-NEC cases at all sampling time points. Lacto-N-difucohexaose I is only produced by secretor and Lewis positive mothers. There were also significant but inconsistent associations between 3'-sialyllactose and 6'-sialyllactose and culture-proven sepsis and significant, but weak correlations between several HMOs and growth rate. Our results suggest that the variation in HMO composition in breast milk may be an important factor explaining why exclusively breast milk fed ELBW infants develop NEC.
Project description:Evidence on the clinical effectiveness of probiotics in the prevention of necrotising enterocolitis (NEC) in preterm infants is conflicting and cohort studies lacked adjustment for time trend and feeding type. This study investigated the association between the introduction of routine probiotics (Lactobacillus acidophilus and Bifidobacterium bifidum; Infloran(®)) on the primary outcome 'NEC or death'. Preterm infants (gestational age <32 weeks or birth weight <1500?gram) admitted before (Jan 2008-Sep 2012; n?=?1288) and after (Oct 2012-Dec 2014; n?=?673) introduction of probiotics were compared. Interrupted time series logistic regression models were adjusted for confounders, effect modification by feeding type, seasonality and underlying temporal trends. Unadjusted and adjusted analyses showed no difference in 'NEC or death' between the two periods. The overall incidence of NEC declined from 7.8% to 5.1% (OR 0.63, 95% CI 0.42-0.93, p?=?0.02), which was not statistically significant in the adjusted models. Introduction of probiotics was associated with a reduced adjusted odds for 'NEC or sepsis or death' in exclusively breastmilk-fed infants (OR 0.43, 95% CI 0.21-0.93, p?=?0.03) only. We conclude that introduction of probiotics was not associated with a reduction in 'NEC or death' and that type of feeding seems to modify the effects of probiotics.
Project description:OBJECTIVE:To evaluate the combined prognostic value of neurological examination, head circumference and cranial ultrasound for neurodevelopmental delay (NDD) in very low birth weight (VLBW, <1500 g) preterm infants. METHODS:Prospective follow-up study. Preterm infants with VLWB were assessed for NDD using the Mullen Scales of Early Learning test at 24 months of corrected age. Abnormal neurological examination (≥2 deviant items of Hammersmith neurological examination), microcephaly and major ultrasound abnormalities, each performed at term age, were evaluated as predictors of NDD in a multivariable Poisson model. RESULTS:35/132 infants (26.5%) had NDD. In the multivariable analysis, microcephaly (RR, 3.2; 95% CI, 1.6-6.7) and major ultrasound abnormalities (RR, 2.7; 95% CI, 1.3-5.7) were associated to NDD. The combination of the two tests showed the highest positive predictive value (100%; 95% CI, 51%-100%), while the combination of normal neurological examination, no major US findings and normal head size at term showed the highest negative predictive value (89%; 95% CI, 78%-95%). The maximum under receiver operating characteristic curve area was for microcephaly or major ultrasound abnormalities (AUC 0.74 (0.65-0.83)). CONCLUSION:The combination of head circumference, cranial ultrasound and neurological examination at term age is useful to predict NDD in VLBW preterm infants.
Project description:ObjectivesThe aim of the present study was to examine the changes in bacteria in hospitalized preterm infants during the first month of life.MethodsRectal swabs were collected daily from 12 preterm infants. DNA was extracted from swabs from day of birth and weekly thereafter. Bacterial taxa were identified with next generation sequencing using universal bacterial primers targeted at the 16S ribosomal DNA on a 454 Roche titanium platform. Sequences were clustered into operational taxonomic units, and taxonomy was assigned against the Greengenes databank using Quantitative Insights Into Microbial Ecology version 1.4. Quantitative polymerase chain reaction was used to determine the abundance of Bifidobacterium spp. Functional assessment of the microbiome was performed with Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt).ResultsAverage birth weight and gestational age were 1055 g and 28 weeks, respectively. There were 6 to 35 different bacterial families identified in the day-of-birth samples, unrelated to the mode of delivery. Richness decreased through hospitalization (week 1, 16.9 ± 7.7 vs weeks 3-5, 10.7 ± 3.4, P < 0.001). The Shannon diversity index demonstrated the lowest diversity at birth, an increase at week 2, followed by a rapid decline at weeks 3 to 5, suggesting the development of a more uniform microbiota composition after 2 weeks of stay at a neonatal intensive care unit. Enterobacteriaceae, Staphylococcaceae, and Enterococcaceae constituted the majority of the bacterial families. Bifidobacterium spp were infrequently detected at extremely low levels. PICRUSt analysis revealed the enhancement of peroxisome, PPAR, and adipocytokine signaling; plant-pathogen interaction; and aminobenzoate degradation pathways in week 1 samples.ConclusionsOur results suggest that although preterm infants have individualized microbiota that are detectable at birth, the differences decrease during the neonatal intensive care unit hospitalization with increasing prominence of pathogenic microbiota.
Project description:Necrotizing enterocolitis (NEC) and focal intestinal perforation (FIP) are two of the most common emergencies of the gastrointestinal tract in preterm infants with very low birth weight (VLBW, birth weight < 1500 g). Identification of risk factors among these children is crucial for earlier diagnosis and prompt intervention. In this study, we investigated a relationship between ABO blood groups and the risk for surgical NEC/FIP. We genotyped the ABO locus (rs8176746 and rs8176719) in VLBW infants enrolled in a prospective, population-based cohort study of the German Neonatal Network (GNN). Of the 10,257 VLBW infants, 441 (4.3%) had surgical NEC/FIP. In univariate analyses, the blood group AB was more prevalent in VLBW infants with surgical NEC/FIP compared to non-AB blood groups (OR 1.51, 95% CI 1.07-2.13, p = 0.017; absolute risk difference 2.01%, 95% CI 0.06-3.96%). The association between blood group AB and surgical NEC/FIP was observed in a multivariable logistic regression model (OR of 1.58, 95% CI 1.10-2.26, p = 0.013) as well. In summary, our study suggests that the risk of surgical NEC and FIP is higher in patients with blood group AB and lower in those having non-AB blood groups.
Project description:Previous reviews (2005 to 2009) on preterm infants given probiotics or prebiotics with breast milk or mixed feeds focused on prevention of Necrotizing Enterocolitis, sepsis and diarrhea. This review assessed if probiotics, prebiotics led to improved growth and clinical outcomes in formula fed preterm infants.Cochrane methodology was followed using randomized controlled trials (RCTs) which compared preterm formula containing probiotic(s) or prebiotic(s) to conventional preterm formula in preterm infants. The mean difference (MD) and corresponding 95% confidence intervals (CI) were reported for continuous outcomes, risk ratio (RR) and corresponding 95% CI for dichotomous outcomes. Heterogeneity was assessed by visual inspection of forest plots and a chi² test. An I² test assessed inconsistencies across studies. I²> 50% represented substantial heterogeneity.Four probiotics studies (N=212), 4 prebiotics studies (N=126) were included. Probiotics: There were no significant differences in weight gain (MD 1.96, 95% CI: -2.64 to 6.56, 2 studies, n=34) or in maximal enteral feed (MD 35.20, 95% CI: -7.61 to 78.02, 2 studies, n=34), number of stools per day increased significantly in probiotic group (MD 1.60, 95% CI: 1.20 to 2.00, 1 study, n=20). Prebiotics: Galacto-oligosaccharide/Fructo-oligosaccharide (GOS/FOS) yielded no significant difference in weight gain (MD 0.04, 95% CI: -2.65 to 2.73, 2 studies, n=50), GOS/FOS yielded no significant differences in length gain (MD 0.01, 95% CI: -0.03 to 0.04, 2 studies, n=50). There were no significant differences in head growth (MD -0.01, 95% CI: -0.02 to 0.00, 2 studies, n=76) or age at full enteral feed (MD -0.79, 95% CI: -2.20 to 0.61, 2 studies, n=86). Stool frequency increased significantly in prebiotic group (MD 0.80, 95% CI: 0.48 to 1.1, 2 studies, n=86). GOS/FOS and FOS yielded higher bifidobacteria counts in prebiotics group (MD 2.10, 95% CI: 0.96 to 3.24, n=27) and (MD 0.48, 95% CI: 0.28 to 0.68, n=56).There is not enough evidence to state that supplementation with probiotics or prebiotics results in improved growth and clinical outcomes in exclusively formula fed preterm infants.