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Systemic Inflammation-Associated Proteins and Retinopathy of Prematurity in Infants Born Before the 28th Week of Gestation.

ABSTRACT: To assess the association between systemic levels of inflammation-associated proteins and severe retinopathy of prematurity (ROP) in extremely preterm infants.We collected whole blood on filter paper on postnatal days 1, 7, 14, 21, and 28 from 1205 infants born before the 28th week of gestation, and measured the concentrations of 27 inflammation-associated, angiogenic, and neurotrophic proteins. We calculated odds ratios with 95% confidence intervals for the association between top quartile concentrations of each protein and prethreshold ROP.During the first three weeks after birth, high concentrations of VEGF-R1, myeloperoxidase (MPO), IL-8, intercellular adhesion molecule (ICAM)-1, matrix metalloproteinase 9, erythropoietin, TNF-?, and basic fibroblast growth factor were associated with an increased risk for prethreshold ROP. On day 28, high levels of serum amyloid A, MPO, IL-6, TNF-?, TNF-R1/-R2, IL-8, and ICAM-1 were associated with an increased risk. Top quartile concentrations of the proinflammatory cytokines TNF-? and IL-6 were associated with increased risks of ROP when levels of neuroprotective proteins and growth factors, including BDNF, insulin-like growth factor 1, IGFBP-1, VEGFR-1 and -2, ANG-1 and PlGF, were not in the top quartile. In contrast, high concentrations of NT-4 and BDNF appeared protective only in infants without elevated inflammatory mediators.Systemic inflammation during the first postnatal month was associated with an increased risk of prethreshold ROP. Elevated concentrations of growth factors, angiogenic proteins, and neurotrophins appeared to modulate this risk, and were capable of reducing the risk even in the absence of systemic inflammation.

SUBMITTER: Holm M

PROVIDER: S-EPMC5736326 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Systemic Inflammation-Associated Proteins and Retinopathy of Prematurity in Infants Born Before the 28th Week of Gestation.

Holm Mari M Morken Tora S TS Fichorova Raina N RN VanderVeen Deborah K DK Allred Elizabeth N EN Dammann Olaf O Leviton Alan A

Investigative ophthalmology & visual science 20171201 14

<h4>Purpose</h4>To assess the association between systemic levels of inflammation-associated proteins and severe retinopathy of prematurity (ROP) in extremely preterm infants.<h4>Methods</h4>We collected whole blood on filter paper on postnatal days 1, 7, 14, 21, and 28 from 1205 infants born before the 28th week of gestation, and measured the concentrations of 27 inflammation-associated, angiogenic, and neurotrophic proteins. We calculated odds ratios with 95% confidence intervals for the assoc ...[more]

PMID: 29260199

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Project description:ObjectiveThyroid disorders are commonly concomitant with premature birth; however, indications to start therapy remain unclear due to a lack of gestational age (GA)-specific reference ranges. We aimed to evaluate the age-specific thyroid-stimulating hormone (TSH), free thyroxine (FT4) levels and the correlation between TSH and FT4 serum levels and ultrasound thyroid volume in preterm infants.Materials and methodsThis was an observational, prospective, single-center study of 98 preterm infants born before 33 weeks GA. The infants were divided into the 24-28 weeks and 29-32 weeks GA groups. TSH and FT4 serum levels were measured at two time points: at postnatal age (PNA) 2 weeks and at postmenstrual age (PMA) 32 weeks; the results were compared between groups at two consecutive time points.ResultsThere was a statistically significant between-group difference in FT4 concentration. There was a positive correlation between FT4 and GA at both screening times. FT4 in the 24-28 weeks GA group was significantly lower than in the 29-32 weeks GA group. The mean (standard deviation [SD]) FT4 at PNA 2 weeks was 11.72 ± 2.16 pmol/l for the 24-28 weeks GA group vs. 13.33 ± 1.80 pmol/l for the 29-32 weeks GA group (p<0.001). The mean (SD) FT4 at PMA 32 weeks was 11.96 ± 1.98 pmo/l for the 24-28 weeks GA group vs. 13.33 ± 1.80 pmol/l for the 29-32 weeks GA group (p=0.001). Our results reflect a slow and gradual upward trend of FT4 in the 24-28 weeks GA. It is of interest that the correlation between thyroid volume and FT4 was statistically significant (rho=0.25, p=0.019) for all studied preterm infants. The correlation between thyroid volume and weight was statistically significant for the entire study group (rho=0.37, p<0.001). We did not find statistically significant differences in TSH and FT4 values between consecutive time points at 24-28 weeks GA. The thyroid volume was not significantly different between both groups. The total thyroid volume was 0.26 vs. 0.27 ml for the 24-28 and 29-32 weeks GA groups, respectively.ConclusionThe results of this study indicate that preterm infants require lower FT4 values depending on GA. Moreover, ultrasound thyroid imaging may facilitate the evaluation of questionable thyroid disorders.

Project description:BACKGROUNDHyperglycemia, insulin insensitivity, and low IGF1 levels in extremely preterm infants are associated with an increased risk of retinopathy of prematurity (ROP), but the interactions are incompletely understood.METHODSIn 117 extremely preterm infants, serum glucose levels and parenteral glucose intake were recoded daily in the first postnatal week. Serum IGF1 levels were measured weekly. Mice with oxygen-induced retinopathy alone versus oxygen-induced retinopathy plus streptozotocin-induced hyperglycemia/hypoinsulinemia were assessed for glucose, insulin, IGF1, IGFBP1, and IGFBP3 in blood and liver. Recombinant human IGF1 was injected to assess the effect on glucose and retinopathy.RESULTSThe highest mean plasma glucose tertile of infants positively correlated with parenteral glucose intake [r(39) = 0.67, P < 0.0001]. IGF1 plasma levels were lower in the high tertile compared with those in low and intermediate tertiles at day 28 (P = 0.038 and P = 0.03). In high versus lower glucose tertiles, ROP was more prevalent (34 of 39 versus 19 of 39) and more severe (ROP stage 3 or higher; 71% versus 32%). In oxygen-induced retinopathy, hyperglycemia/hypoinsulinemia decreased liver IGF1 expression (P < 0.0001); rh-IGF1 treatment improved normal vascular regrowth (P = 0.027) and reduced neovascularization (P < 0.0001).CONCLUSIONIn extremely preterm infants, high early postnatal plasma glucose levels and signs of insulin insensitivity were associated with lower IGF1 levels and increased ROP severity. In a hyperglycemia retinopathy mouse model, decreased insulin signaling suppressed liver IGF1 production, lowered serum IGF1 levels, and increased neovascularization. IGF1 supplementation improved retinal revascularization and decreased pathological neovascularization. The data support IGF1 as a potential treatment for prevention of ROP.TRIAL REGISTRATIONClinicalTrials.gov NCT02760472 (Donna Mega).FUNDINGThis study has been supported by the Swedish Medical Research Council (14940, 4732, 20144-01-3, and 21144-01-3), a Swedish government grant (ALFGB2770), Lund medical faculty grants (ALFL, 11615 and 11601), the Skåne Council Foundation for Research and Development, the Linnéa and Josef Carlsson Foundation, the Knut and Alice Wallenberg Foundation, the NIH/National Eye Institute (EY022275, EY017017, EY017017-13S1, and P01 HD18655), European Commission FP7 project 305485 PREVENT-ROP, Deutsche Forschungsgemeinschaft (CA-1940/1-1), and Stiftelsen De Blindas Vänner.

Dataset Information

Systemic Inflammation-Associated Proteins and Retinopathy of Prematurity in Infants Born Before the 28th Week of Gestation.

Publications

Systemic Inflammation-Associated Proteins and Retinopathy of Prematurity in Infants Born Before the 28th Week of Gestation.

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