Antecedents of inflammation biomarkers in preterm newborns on days 21 and 28.
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ABSTRACT:
SUBMITTER: Leviton A
PROVIDER: S-EPMC4747803 | biostudies-literature | 2016 Mar
REPOSITORIES: biostudies-literature
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Antecedents of inflammation biomarkers in preterm newborns on days 21 and 28.
Leviton Alan A Allred Elizabeth N EN Fichorova Raina N RN Kuban Karl C K KC O'Shea T Michael TM Dammann Olaf O
Acta paediatrica (Oslo, Norway : 1992) 20151223 3
<h4>Aim</h4>Most studies of systemic inflammation in very preterm newborns focus on assessments made during the first two weeks. The purpose of this study was to identify some of the antecedents of systemic inflammation evident during postnatal weeks three and four.<h4>Methods</h4>We measured the protein concentrations in blood spots collected on postnatal days 21 (N = 176) and 28 (N = 157) from infants born before the 28th week of gestation and sought correlates of measurements in the top quart ...[more]
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Project description:BackgroundSepsis is one of the most important causes of morbidity and mortality in the neonatal period, especially in preterms. Diagnosis is difficult because of specific signs and symptoms. The diagnostic gold standard is blood culture, but its sensibility is low. Much effort has been made to identify early, sensitive, and specific diagnostic markers; among these markers particular attention was paid to procalcitonin. However, reference ranges of serum procalcitonin (PCT) shortly after birth have not been sufficiently studied in healthy preterms, and literature is still contradictory.ObjectivesThe aim of the study is to define PCT age-specific reference ranges in the first 72 h of life in uninfected VLBW preterms.MethodsSerum levels of PCT were assessed for each newborn at birth and every 24 h until the 3rd day of life. The eligible patients were classified into two groups according to their sepsis status.ResultsApproximately 343 patients were enrolled; 28 were septic and 315 non-septic. In non-septic infants, 1,015 determinations of PCT values were performed. Our data showed a trend in average value of PCT to increase after birth up to a peak between 24 and 48 h of life and, subsequently, to fall. The average peak value was 15.12 ng/ml achieved at nearly 36 h of life.ConclusionOur study shows a PCT nomogram of healthy preterms, which is different from the one of term newborns. Data agree with what is reported in literature on the reference ranges and trends of PCT in non-septic preterms shortly after birth.
| S-EPMC9464813 | biostudies-literature
Project description:Study questionWhich inflammation biomarkers detected in the vaginal fluid are most informative for identifying preterm delivery (PTD) risk?Summary answerElevated interleukin (IL)-6 at mid-trimester was associated with increased odds of spontaneous PTD at <35 weeks and with PTD plus histologic chorioamnionitis (HCA), and had the greatest sensitivity for detecting these two PTD subtypes.What is known alreadyMaternal and/or fetal inflammation play a role in some preterm deliveries, therefore inflammation biomarkers might help to identify women at greater risk.Study design, size, durationWe examined 1115 women from the Pregnancy Outcomes and Community Health Study, a cohort study conducted from September 1998 through June 2004, for whom data were available on mid-pregnancy inflammatory biomarkers.Participants/materials, setting, methodsAt enrollment at 16-27 weeks gestation, vaginal fluid samples were collected from a swab and 15 eluted biomarkers were measured using the Meso Scale Discovery multiplex electrochemiluminescence platform. Associations of biomarkers with PTD were examined, according to clinical circumstance, week at delivery and presence/absence of HCA. Weighted logistic regression was used to determine odds ratios (OR) and 95% confidence intervals (CI) adjusted for race. Sensitivity and specificity were compared between individual and multiple biomarkers, identified by a bootstrapping method.Main results and the role of chanceElevated IL-6 (>75th percentile) displayed the strongest association with spontaneous PTD <35 weeks (OR 2.3; CI 1.3-4.0) and PTD with HCA (OR 2.8; CI 1.4-6.0). The sensitivity of IL-6 to detect spontaneous PTD <35 weeks or PTD with HCA was 0.43 and 0.51, respectively, while specificity was 0.74 and 0.75, respectively. IL-6 plus IL1β, IL-6r, tumor necrosis factor-alpha or granulocyte-macrophage colony-stimulating factor increased specificity (range 0.84-0.88), but decreased sensitivity (range 0.28-0.34) to detect both PTD subtypes. Results were similar when a combination of IL-6 and bacterial vaginosis (BV) was explored. Thus, the use of multiple biomarkers did not detect PTD subtypes with a greater sensitivity than IL-6 alone, and IL-6 is a specific but non-sensitive marker for the detection of spontaneous PTD.Limitations, reasons for cautionOur ability to find small effect size associations between PTD and inflammation biomarkers (OR <2.0) might have been limited by the modest number of less common PTD subtypes in our population (e.g. spontaneous delivery <35 weeks, PTD accompanied by HCA) and by relatively higher variability for some cytokines, for example tumor necrosis factor-α, IL-12p70, IL-10 and granulocyte-macrophage colony-stimulating factor, that are less stable and commonly undetectable or detectable at low levels in human vaginal secretions.Wider implications of the findingsLarger studies are needed to further explore a role of inflammation biomarkers in combination with other risk factors, including specific BV-associated organisms, for the prediction of PTD subtypes.Study funding/competing interest(s)This work was supported by the National Institute of Child Health and Human Development, National Institute of Nursing, March of Dimes Foundation, Thrasher Research Foundation and Centers for Disease Control and Prevention. The authors have no conflicts of interest.
| S-EPMC3600841 | biostudies-literature
Project description:Multi-marker tests hold promise for identifying symptomatic women at risk of imminent preterm delivery (PTD, <37 week's gestation). This study sought to determine the relationship of inflammatory mediators and metabolites in cervicovaginal fluid (CVF) with spontaneous PTD (sPTD) and delivery within 14 days of presentation with symptoms of preterm labour (PTL). CVF samples from 94 (preterm = 19, term = 75) singleton women with symptoms of PTL studied between 19+0-36+6 weeks' gestation were analysed for cytokines/chemokines by multiplexed bead-based immunoassay, while metabolites were quantified by enzyme-based spectrophotometry in a subset of 61 women (preterm = 16, term = 45). Prevalence of targeted vaginal bacterial species was determined for 70 women (preterm = 14, term = 66) by PCR. Overall, 10 women delivered within 14 days of sampling. Predictive capacities of individual biomarkers and cytokine-metabolite combinations for sPTD and delivery within 14 days of sampling were analysed by logistic regression models and area under the receiver operating characteristic curve. Fusobacterium sp., Mubiluncus mulieris and Mycoplasma hominis were detected in more preterm-delivered than term women (P<0.0001), while, M. curtisii was found in more term-delivered than preterm women (P<0.0001). RANTES (0.91, 0.65-1.0), IL-6 (0.79, 0.67-0.88), and Acetate/Glutamate ratio (0.74, 0.61-0.85) were associated with delivery within 14 days of sampling (AUC, 95% CI). There were significant correlations between cytokines and metabolites, and several cytokine-metabolite combinations were associated with sPTD or delivery within 14 days of sampling (e.g. L/D-lactate ratio+Acetate/Glutamate ratio+IL-6: 0.84, 0.67-0.94). Symptomatic women destined to deliver preterm and within 14 days of sampling express significantly higher pro-inflammatory mediators at mid to late gestation. In this cohort, IL-6, Acetate/Glutamate ratio and RANTES were associated with delivery within 14 days of sampling, consistent with their roles in modulating infection-inflammation-associated preterm labour in women presenting with symptoms of preterm birth. Replication of these observations in larger cohorts of women could show potential clinical utility.
| S-EPMC6742395 | biostudies-literature
Project description:Restrictions of preterm newborns' movements could have consequences ranging from stress enhancement to impairment of their motor development. Therefore, ability to freely express motor activities appears crucial for their behavioural and physiological development. Our aim was to evaluate behavioural issues of two types of clothing used in NICU. We observed 18 healthy 34-37 post-conception week-old preterm newborns, during resting periods, when they were undisturbed by any interventions. Newborns wore either light clothing (bodysuit and a light wrapping) or heavy clothing (pyjamas, cardigan and sleep-sack). The percentages of time each subject spent in different postures were compared between clothing situations. Arm and hand postures differed in relation to clothing: babies bent their arms more and held their hands nearer their heads when in bodysuits than when in sleepwear. Consequently, babies in bodysuits spent more time touching their body or their environment whereas the others generally were touching nothing. Self-touch is an important way to comfort one's self. Heavy clothing may impair self-soothing behaviours of preterm newborn babies that already lack other forms of contact. Results suggest that more attention should be paid to apparently routine and marginal decisions such as choice of clothes.
| S-EPMC4361844 | biostudies-other
Project description:The main objective of this study was to evaluate the relationship between mother's socioeconomic disadvantage and blood concentrations of inflammation-related proteins among extremely preterm newborns (<28 weeks gestation), a group at heightened risk of cognitive impairment when exposed to systemic inflammation. We measured the concentrations of 27 inflammatory and neurotrophic proteins in blood specimens collected a week apart during the first postnatal month from 857 extremely preterm newborns in the United States. We classified children according to 3 indicators/correlates of socioeconomic disadvantage, mother's eligibility for government-provided medical care insurance (Medicaid), mother's formal education level, and mother's IQ approximated with the Kaufman Brief Intelligence Test- 2. The risks of a top-quartile concentration of each protein on each of 5 days a week apart, on two occasions during the first two postnatal weeks, and during the next two weeks were modeled as functions of each indicator of socioeconomic disadvantage. The risks of top quartile concentrations of multiple (2-5) inflammation-related proteins on multiple days during the first two weeks were increased for each of the 3 indicators of socioeconomic disadvantage, while the risks of top quartile concentrations of selected neurotrophic proteins were reduced. Adjustment for socioeconomic disadvantage did not alter the relationships between protein concentrations and both low IQ and low working memory 10 years later. Among extremely preterm newborns, indicators of socioeconomic disadvantage are associated with modestly increased risk of systemic inflammation in postnatal blood during the first postnatal month and with a slightly reduced risk of a neurotrophic signal, but do not confound relationships between protein concentrations and outcomes.
| S-EPMC6435168 | biostudies-literature
Project description:BackgroundPreterm newborns exposed to intrauterine inflammation are at an increased risk of neurodevelopmental disorders. We hypothesized that adverse outcomes are more strongly associated with a combination of antenatal and postnatal inflammation than with either of them alone.MethodsWe defined antenatal inflammation as histologic inflammation in the placenta. We measured the concentrations of seven inflammation-related proteins in blood obtained on postnatal days 1, 7, and 14 from 763 infants born before 28 weeks of gestation. We defined postnatal inflammation as a protein concentration in the highest quartile on at least 2 days. We used logistic regression models to evaluate the contribution of antenatal and postnatal inflammation to the risk of neurodevelopmental disorders.ResultsThe risk of white matter damage was increased when placental inflammation was followed by sustained elevation of C-reactive protein or ICAM-1. We found the same for spastic cerebral palsy when placental inflammation was followed by elevation of TNF-α or IL-8. The presence of both placental inflammation and elevated levels of IL-6, TNF-α, or ICAM-1 was associated with an increased risk for microcephaly.ConclusionCompared with a single hit, two inflammatory hits are associated with stronger risk for abnormal cranial ultrasound, spastic cerebral palsy, and microcephaly at 2 years.
| S-EPMC5599336 | biostudies-literature
Project description:IntroductionPreterm infants are at risk of free radical-mediated diseases from oxidative stress (OS) injury. Increased free radical generation has been demonstrated in preterm infants during the first seven days of life. Melatonin (MEL) is a powerful antioxidant and scavenger of free radicals. In preterm neonates, melatonin deficiency has been reported. Exogenous melatonin administration appears a promising strategy in the treatment of neonatal morbidities in which OS has a leading role.ObjectiveThe aim was to evaluate plasma MEL concentrations and OS biomarkers in preterm newborns after early administration of melatonin.MethodsA prospective, randomized double-blind placebo-controlled pilot study was conducted from January 2019 to September 2020. Thirty-six preterm newborns were enrolled. Starting from the first day of life, 21 received a single dose of oral melatonin 0.5 mg/kg once a day, in the morning (MEL group); 15 newborns received an equivalent dose of placebo (placebo group). Samples of 0.2 mL of plasma were collected at 24 and 48 hours after MEL administration. Plasma concentrations of melatonin, non-protein-bound iron (NPBI), advanced oxidation protein products (AOPP), and F2-isoprostanes (F2-Isopr) were measured. Babies were clinically followed until discharge.ResultsAt 24 and 48 hours after MEL administration, the MEL concentrations were significantly higher in the MEL group than in the placebo group (52759.30 ± 63529.09 vs. 28.57 ± 46.24 pg/mL and 279397.6 ± 516344.2 vs. 38.50 ± 44.01 pg/mL, respectively). NPBI and AOPP did not show any statistically significant differences between the groups both at 24 and 48 hours. At 48 hours, the mean blood concentrations of F2-Isopr were significantly lower in the MEL group than in the placebo group (36.48 ± 33.85 pg/mL vs.89.97 ± 52.01 pg/mL).ConclusionsEarly melatonin administration in preterm newborns reduces lipid peroxidation in the first days of life showing a potential role to protect high-risk newborns. Trial Registration. This trial is registered with NCT04785183, Early Supplementation of Melatonin in Preterm Newborns: the Effects on Oxidative Stress.
| S-EPMC8626170 | biostudies-literature
Project description:To find out why children born extremely preterm are at heightened risk of executive dysfunctions, the authors assessed 716 children who were 10 years old born extremely preterm whose IQ was ? 70. A working memory dysfunction (n = 169), an inhibition dysfunction (n = 360), a switching dysfunction (355), and all 3 (executive dysfunction; n = 107) were defined on the basis of Z-scores ? -1 on the Differential Ability Scales-II Working Memory composite, and/or on the NEPSY-II Inhibition-Inhibition and Inhibition-Switching subtests. All risk profiles include an indicator of socioeconomic disadvantage. The risk profile of each of the 3 individual dysfunctions includes an indicator of the newborn's immaturity, and the risk profiles of the inhibition dysfunction and switching dysfunction also include an indicator of inflammation. Only the switching dysfunction was associated with fetal growth restriction. The risk factors for executive dysfunction can be subsumed under the 4 themes of socioeconomic disadvantage, immaturity/vulnerability, inflammation, and fetal growth restriction.
| S-EPMC5807158 | biostudies-literature
Project description:BACKGROUND: Renal failure in neonates is associated with an increased risk of mortality and morbidity. But critical values are not known. OBJECTIVE: To define critical values for serum creatinine levels by gestational age in preterm infants, as a predictive factor for mortality and morbidity. STUDY DESIGN: This was a retrospective study of all preterm infants born before 33 weeks of gestational age, hospitalized in Nantes University Hospital NICU between 2003 and 2009, with serum creatinine levels measured between postnatal days 3 to 30. Children were retrospectively randomized into either training or validation set. Critical creatinine values were defined within the training set as the 90(th) percentile values of highest serum creatinine (HSCr) in infants with optimal neurodevelopmental at two years of age. The relationship between these critical creatinine values and neonatal mortality, and non-optimal neural development at two years, was then assessed in the validation set. RESULTS AND CONCLUSION: The analysis involved a total of 1,461 infants (gestational ages of 24-27 weeks (n=322), 28-29 weeks (n=336), and 30-32 weeks (803)), and 14,721 creatinine assessments. The critical values determined in the training set (n=485) were 1.6, 1.1 and 1.0 mg/dL for each gestational age group, respectively. In the validation set (n=976), a serum creatinine level above the critical value was significantly associated with neonatal mortality (Odds ratio: 8.55 (95% confidence interval: 4.23-17.28); p<0.01) after adjusting for known renal failure risk factors, and with non-optimal neurodevelopmental outcome at two years (odds ratio: 2.06 (95% confidence interval: 1.26-3.36); p=0.004) before adjustment. Creatinine values greater than 1.6, 1.1 and 1.0 mg/dL respectively at 24-27, 28-29, 30-32 weeks of gestation were associated with mortality before and after adjustment for risk factors, and with non-optimal neurodevelopmental outcome, before adjustment.
| S-EPMC3875547 | biostudies-literature
Project description:Premature infants are exposed to increased generation of reactive oxygen species, and on the other hand, they have a deficient antioxidant defense system. Oxidative insult is a salient part of lung injury that begins as acute inflammatory injury in respiratory distress disease and then evolves into chronic and structural scarring leading to bronchopulmonary dysplasia. Oxidative stress is also involved in the pathogenesis of pulmonary hypertension in newborns through the modulation of the vascular tone and the response to pulmonary vasodilators, with consequent decrease in the density of the pulmonary vessels and thickening of the pulmonary arteriolar walls. Oxidative stress has been recognized as both a trigger and an endpoint for several events, including inflammation, hypoxia, hyperoxia, drugs, transfusions, and mechanical ventilation, with impairment of pulmonary function and prolonged lung damage. Redoxomics is the most fascinating new measure to address lung damage due to oxidative stress. The new challenge is to use omics data to discover a set of biomarkers useful in diagnosis, prognosis, and formulating optimal and individualized neonatal care. The aim of this review was to examine the most recent evidence on the relationship between oxidative stress and lung diseases in preterm newborns. What is currently known regarding oxidative stress-related lung injury pathogenesis and the available preventive and therapeutic strategies are also discussed.
| S-EPMC8625766 | biostudies-literature