Early Elevation in Interleukin-6 is Associated with Reduced Growth in Extremely Low Birth Weight Infants.
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ABSTRACT:
SUBMITTER: Denson LA
PROVIDER: S-EPMC5296404 | biostudies-literature | 2017 Feb
REPOSITORIES: biostudies-literature
Publications
Early Elevation in Interleukin-6 is Associated with Reduced Growth in Extremely Low Birth Weight Infants.
Denson Lee A LA McDonald Scott A SA Das Abhik A Schendel Diana E DE Skogstrand Kristin K Hougaard David M DM Shankaran Seetha S Higgins Rosemary D RD Carlo Waldemar A WA Ehrenkranz Richard A RA
American journal of perinatology 20160725 3
<b>Objective</b> To determine whether reduced growth velocity (GV) in extremely low birth weight infants is preceded by elevated inflammatory cytokines. <b>Study Design</b> GV was determined at 36 weeks' postmenstrual age (PMA) in 768 infants 401 to 1,000 g birth weight (BW). Association between blood cytokines measured through day of life 21 and GV was explored using linear regression models that adjusted for late-onset sepsis (LOS), BW, small for gestational age (SGA), gender, race, energy int ...[more]
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Project description:ObjectiveTo determine if selected pro-inflammatory and anti-inflammatory cytokines and/or mediators of inflammation reported to be related to the development of cerebral palsy (CP) predict neurodevelopmental outcome in extremely low birth weight infants.Study designInfants with birth weights ?1000 g (n = 1067) had blood samples collected at birth and on days 3 ± 1, 7 ± 1, 14 ± 3, and 21 ± 3 to examine the association between cytokines and neurodevelopmental outcomes. The analyses were focused on 5 cytokines (interleukin [IL] 1?; IL-8; tumor necrosis factor-?; regulated upon activation, normal T-cell expressed, and secreted (RANTES); and IL-2) reported to be most predictive of CP in term and late preterm infants.ResultsIL-8 was higher on days 0-4 and subsequently in infants who developed CP compared with infants who did not develop CP in both unadjusted and adjusted analyses. Other cytokines (IL-12, IL-17, tumor necrosis factor-?, soluble IL r?, macrophage inflammatory protein 1?) were found to be altered on days 0-4 in infants who developed CP.ConclusionsCP in former preterm infants may, in part, have a late perinatal and/or early neonatal inflammatory origin.
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Project description:BackgroundIt is unclear whether aggressive phototherapy to prevent neurotoxic effects of bilirubin benefits or harms infants with extremely low birth weight (1000 g or less).MethodsWe randomly assigned 1974 infants with extremely low birth weight at 12 to 36 hours of age to undergo either aggressive or conservative phototherapy. The primary outcome was a composite of death or neurodevelopmental impairment determined for 91% of the infants by investigators who were unaware of the treatment assignments.ResultsAggressive phototherapy, as compared with conservative phototherapy, significantly reduced the mean peak serum bilirubin level (7.0 vs. 9.8 mg per deciliter [120 vs. 168 micromol per liter], P<0.01) but not the rate of the primary outcome (52% vs. 55%; relative risk, 0.94; 95% confidence interval [CI], 0.87 to 1.02; P=0.15). Aggressive phototherapy did reduce rates of neurodevelopmental impairment (26%, vs. 30% for conservative phototherapy; relative risk, 0.86; 95% CI, 0.74 to 0.99). Rates of death in the aggressive-phototherapy and conservative-phototherapy groups were 24% and 23%, respectively (relative risk, 1.05; 95% CI, 0.90 to 1.22). In preplanned subgroup analyses, the rates of death were 13% with aggressive phototherapy and 14% with conservative phototherapy for infants with a birth weight of 751 to 1000 g and 39% and 34%, respectively (relative risk, 1.13; 95% CI, 0.96 to 1.34), for infants with a birth weight of 501 to 750 g.ConclusionsAggressive phototherapy did not significantly reduce the rate of death or neurodevelopmental impairment. The rate of neurodevelopmental impairment alone was significantly reduced with aggressive phototherapy. This reduction may be offset by an increase in mortality among infants weighing 501 to 750 g at birth. (ClinicalTrials.gov number, NCT00114543.)
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Project description:BackgroundParenteral nutrition associated cholestasis (PNAC) is a frequently observed pathology in extremely low birth weight (ELBW) infants. Its pathogenesis is determined by the composition and duration of parenteral nutrition (PN) as well as the tolerance of enteral feeds (EF). "Aggressive" nutrition is increasingly used in ELBW infants to improve postnatal growth. Little is known about the effect of "aggressive" nutrition on the incidence of PNAC. We analyzed the influence of implementing an "aggressive" nutritional regimen on the incidence of PNAC and growth in a cohort of ELBW infants.MethodsELBW infants were nourished using a "conservative" (2005-6; n = 77) or "aggressive" (2007-9; n = 85) nutritional regimen that differed in the composition of PN after birth as well as the composition and timing of advancement of EFs. We analyzed the incidence of PNAC (conjugated bilirubin > 1.5 mg/dl (25 µmol/l)) corrected for confounders of cholestasis (i.e., NEC and/or gastrointestinal surgery, sepsis, birth weight, Z-score of birth weight, time on PN and male sex), growth until discharge (as the most important secondary outcome) and neonatal morbidities.ResultsThe incidence of PNAC was significantly lower during the period of "aggressive" vs. "conservative "nutrition (27% vs. 46%, P < 0.05; adjusted OR 0.275 [0.116-0.651], P < 0.01). Body weight (+411g), head circumference (+1 cm) and length (+1 cm) at discharge were significantly higher. Extra-uterine growth failure (defined as a Z-score difference from birth to discharge lower than -1) was significantly reduced for body weight (85% vs. 35%), head circumference (77% vs. 45%) and length (85% vs. 65%) (P < 0.05). The body mass index (BMI) at discharge was significantly higher (11.1 vs. 12.4) using "aggressive" nutrition and growth became more proportionate with significantly less infants being discharged below the 10th BMI percentile (44% vs. 9%), while the percentage of infants discharged over the 90th BMI percentile (3% vs. 5%) did not significantly increase.Discussion"Aggressive" nutrition of ELBW infants was associated with a significant decrease of PNAC and marked improvement of postnatal growth.
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Project description:OBJECTIVE:The goal was to develop multivariate logistic regression models for the outcome of bronchopulmonary dysplasia and/or death at postmenstrual age of 36 weeks by using clinical and cytokine data from the first 28 days. METHODS:For 1067 extremely low birth weight infants in the Neonatal Research Network of the National Institute of Child Health and Human Development, levels of 25 cytokines were measured in blood collected within 4 hours after birth and on days 3, 7, 14, and 21. Stepwise regression analyses using peak levels of the 25 cytokines and 15 clinical variables identified variables associated with bronchopulmonary dysplasia/death. Multivariate logistic regression analysis was performed for bronchopulmonary dysplasia/death by using variables selected through stepwise regression. Similar analyses were performed by using average cytokine values from days 0 to 21, days 0 to 3, and days 14 to 21. RESULTS:Of 1062 infants with available data, 606 infants developed bronchopulmonary dysplasia or died. On the basis of results from all models combined, bronchopulmonary dysplasia/death was associated with higher concentrations of interleukin 1beta, 6, 8, and 10 and interferon gamma and lower concentrations of interleukin 17, regulated on activation, normal T cell expressed and secreted, and tumor necrosis factor beta. Compared with models with only clinical variables, the addition of cytokine data improved predictive ability by a statistically significant but clinically modest magnitude. CONCLUSIONS:The overall cytokine pattern suggests that bronchopulmonary dysplasia/death may be associated with impairment in the transition from the innate immune response mediated by neutrophils to the adaptive immune response mediated by T lymphocytes.
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Project description:Infants born prematurely, particularly extremely low birth weight infants (ELBW) have altered gut microbial communities. Factors such as maternal health, gut immaturity, delivery mode, and antibiotic treatments are associated with microbiota disturbances, and are linked to an increased risk of certain diseases such as necrotising enterocolitis. Therefore, there is a requirement to optimally characterise microbial profiles in this at-risk cohort, via standardisation of methods, particularly for studying the influence of microbiota therapies (e.g. probiotic supplementation) on community profiles and health outcomes. Profiling of faecal samples using the 16S rRNA gene is a cost-efficient method for large-scale clinical studies to gain insights into the gut microbiota and additionally allows characterisation of cohorts were sample quantities are compromised (e.g. ELBW infants). However, DNA extraction method, and the 16S rRNA region targeted can significantly change bacterial community profiles obtained, and so confound comparisons between studies. Thus, we sought to optimise a 16S rRNA profiling protocol to allow standardisation for studying ELBW infant faecal samples, with or without probiotic supplementation.Using ELBW faecal samples, we compared three different DNA extraction methods, and subsequently PCR amplified and sequenced three hypervariable regions of the 16S rRNA gene (V1 + V2 + V3), (V4 + V5) and (V6 + V7 + V8), and compared two bioinformatics approaches to analyse results (OTU and paired end). Paired shotgun metagenomics was used as a 'gold-standard'.Results indicated a longer bead-beating step was required for optimal bacterial DNA extraction and that sequencing regions (V1 + V2 + V3) and (V6 + V7 + V8) provided the most representative taxonomic profiles, which was confirmed via shotgun analysis. Samples sequenced using the (V4 + V5) region were found to be underrepresented in specific taxa including Bifidobacterium, and had altered diversity profiles. Both bioinformatics 16S rRNA pipelines used in this study (OTU and paired end) presented similar taxonomic profiles at genus level.We determined that DNA extraction from ELBW faecal samples, particularly those infants receiving probiotic supplementation, should include a prolonged beat-beating step. Furthermore, use of the 16S rRNA (V1 + V2 + V3) and (V6 + V7 + V8) regions provides reliable representation of ELBW microbiota profiles, while inclusion of the (V4 + V5) region may not be appropriate for studies where Bifidobacterium constitutes a resident microbiota member.
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