Increased postnatal concentrations of pro-inflammatory cytokines are associated with reduced IGF-I levels and retinopathy of prematurity

Hellgren, Gunnel; Löfqvist, Chatarina; Hansen‐Pupp, Ingrid; Gram, Magnus; Smith, Lois E.H.; Ley, David; Hellström, Ann

doi:10.1016/j.ghir.2017.11.006

Cited by 38 publications

(36 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Our finding that IGF-1 concentrations tend to be elevated in the presence of high concentrations of cytokines, chemokines, and adhesion molecules stands in sharp contrast to the literature documenting an inverse relationship between inflammation and IGF-1 concentrations. 26,[66][67][68][69][70] A possible explanation for this discrepancy is that our findings reflect developmental regulations of IGF-1, 71,72 or perhaps epigenetic phenomena. 73,74 IGF-1 has both proinflammatory effects 75,76 and antiinflammatory properties.…”

Section: Igf-1mentioning

confidence: 88%

“…Drops of blood were collected on filter paper on the first postnatal day (range: 1-3 days), the 7th postnatal day (range: 5-8 days), the 14th postnatal day (range: 12-15 days), the 21st postnatal day (range: 19-23 days), and the 28th postnatal day (range: [26][27][28][29]. All blood spots were from the remainder of specimens obtained for clinical indications.…”

Section: Collection Of Bloodmentioning

confidence: 99%

“…44,45 In addition, one set of measurements was made in 2009 to 2010 and the second in 2015, and, while the distributions of each were similar, they were not identical. Consequently, we divided our sample into 30 groups defined by gestational age category (23)(24)(25)(26), and 27 weeks), postnatal day of blood collection (1, 7, 14, 21, and 28), and two measurement sets (2009-2010 and 2015). As we were interested in the contribution of low and high concentrations, and the concentrations of most proteins did not follow a normal distribution, the distribution of each protein's concentration was divided into four quartiles among children in each of the 30 groups.…”

Section: Proteins Measuredmentioning

confidence: 99%

“…The heightened risk of organ damage among extremely preterm newborns is attributable, in part, to a propensity to inflammation. 24 Yet, the relationships among concentrations of inflammation-related proteins and growth factors, including IGF-I is complex, 25,26 and relatively unstudied. This prompted us to explore the interrelationships among ELGANs of IGF-1 and IGF-1-binding protein-1 (IGFBP-1) concentrations with the concentrations of a variety of inflammationrelated proteins.…”

mentioning

confidence: 99%

See 3 more Smart Citations

Early Postnatal IGF-1 and IGFBP-1 Blood Levels in Extremely Preterm Infants: Relationships with Indicators of Placental Insufficiency and with Systemic Inflammation

et al. 2019

View full text Add to dashboard Cite

Objective To evaluate to what extent indicators of placenta insufficiency are associated with low concentrations of insulin-like growth factor 1 (IGF-1) and IGF-1–binding protein-1 (IGFBP-1) in neonatal blood, and to what extent the concentrations of these growth factors are associated with concentrations of proteins with inflammatory, neurotrophic, or angiogenic properties. Study Design Using multiplex immunoassays, we measured the concentrations of IGF-1 and IGFBP-1, as well as 25 other proteins in blood spots collected weekly from ≥ 880 infants born before the 28th week of gestation, and sought correlates of concentrations in the top and bottom quartiles for gestational age and day the specimen was collected. Results Medically indicated delivery and severe fetal growth restriction (sFGR) were associated with low concentrations of IGF-1 on the first postnatal day and with high concentrations of IGFBP-1 on almost all days. Elevated concentrations of IGF-1 and IGFBP-1 were accompanied by elevated concentrations of many other proteins with inflammatory, neurotrophic, or angiogenic properties. Conclusion Disorders associated with impaired placenta implantation and sFGR appear to account for a relative paucity of IGF-1 on the first postnatal day. Elevated concentrations of IGF-1 and especially IGFBP-1 were associated with same-day elevated concentrations of inflammatory, neurotrophic, and angiogenic proteins.

show abstract

Section: Igf-1mentioning

confidence: 88%

Section: Collection Of Bloodmentioning

confidence: 99%

Section: Proteins Measuredmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Early Postnatal IGF-1 and IGFBP-1 Blood Levels in Extremely Preterm Infants: Relationships with Indicators of Placental Insufficiency and with Systemic Inflammation

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Increased risk of BPD was associated with elevated blood concentrations of a variety of proinflammatory cytokines 9 . Finally, neonatal exposure to inflammation appears to contribute to the increased ROP risk in very preterm infants 12,14 , especially within the first two postnatal weeks 13 .…”

Section: Discussionmentioning

confidence: 99%

In-line filtration in very preterm neonates: a randomized controlled trial

Virlouvet

Pansiot

Toumazi

et al. 2020

Sci Rep

View full text Add to dashboard Cite

In-line filtration is increasingly used in critically-ill infants but its benefits, by preventing micro-particle infusion in very preterm neonates, remain to be demonstrated. We conducted a randomized controlled trial among very preterm infants allocated to receive either in-line filtration of all the intra-venous lines or standard care without filters. The primary outcome was differences greater than 20% in the median changes in pro-inflammatory cytokine serum concentrations measured at day 3 and day 8 (+/−1) using a Luminex multianalytic profiling technique. Major neonatal complications were analyzed as secondary predefined outcomes. We randomized 146 infants, assigned to filter (n = 73) or control (n = 73) group. Difference over 20% in pro-inflammatory cytokine concentration between day 3 and day 8 was not found statistically different between the two groups, both in intent-to-treat (with imputation) and per protocol (without imputation) analyses. The incidences of most of neonatal complications were found to be similar. Hence, this trial did not evidence a beneficial effect of in-line filtration in very preterm infants on the inflammatory response syndrome and neonatal morbidities. These data should be interpreted according to local standards in infusion preparation and central line management.Despite improvements in perinatal care during the past three decades, prematurity is still associated with substantial mortality and morbidities for which inflammation plays a causal role 1,2 , including brain damage 3-6 , bronchopulmonary dysplasia (BPD) 7-9 and retinopathy of prematurity (ROP) 10-14 . Perinatal inflammation is not only a major risk factor for prematurity but also the best predictor of poor neurological outcome, leading to permanent sequelae in 9 million infants every year 2,4,15-17 . Therefore, reducing factors involved in systemic inflammation appears to be a relevant strategy to improve outcomes of infants delivered very preterm.Intra-venous (IV) drugs and parenteral nutrition infusion through central lines are among the most essential interventions in preterm neonates but they are associated with potential risks including bloodstream infections, thrombi and infusion of macro/micro particulates 18 . Particles in the infusion, containing metals, drug crystals 19 , glass fragments or cotton fibres 20 , can be generated by drug preparation process from packaging, incomplete reconstitution and chemical incompatibilities 21 . Parenteral infusion of micro-macro particles was reported to be associated with an increased risk of microvessels obstruction and inflammation, as reported in the lung and increased circulating cytokines release by the endothelium 22 . In-line filtration has therefore been proposed to limit the load of particles infused through central lines 23,24 , and to prevent bacterial and endotoxin infusion 25 . In-line filtration was found associated with a reduction of systemic inflammation and severe complications in critically-ill pediatric patients 26 . In neonates, a significant decrease...

show abstract

Neonatal Sepsis Episodes and Retinopathy of Prematurity in Very Preterm Infants

Glaser,

Härtel,

Klingenberg

et al. 2024

JAMA Netw Open

View full text Add to dashboard Cite

ImportanceRetinopathy of prematurity (ROP) is a major morbidity of preterm infants causing visual impairment, including blindness, for which timely treatment is vital and prevention is key. Increasing evidence suggests that exposure to neonatal sepsis contributes to ROP development.ObjectiveTo investigate the association between neonatal sepsis and ROP in 2 large-scale cohorts of preterm infants born at less than 29 weeks’ gestation.Design, Setting, and ParticipantsThis retrospective cohort study was conducted using data from the German Neonatal Network (GNN) and Norwegian Neonatal Network (NNN). The GNN involves 68 and the NNN includes 21 level III neonatal intensive care units. Participants were infants born at a gestation of 22 weeks and 0 days to 28 weeks and 6 days and enrolled in the GNN between January 1, 2009, and December 31, 2022, and NNN between January 1, 2009, and December 31, 2018. Data were analyzed from February through September 2023.ExposureSingle or multiple episodes of culture-proven sepsis.Main Outcomes and MeasuresAny ROP and treatment-warranted ROP.ResultsAmong 12 794 infants in the GNN (6043 female [47.2%] and 6751 male [52.8%]; mean [SD] gestational age, 26.4 [1.5] weeks) and 1844 infants in the NNN (866 female [47.0%] and 978 male [53.0%]; mean [SD] gestational age, 25.6 [1.5] weeks), the mean (SD) birth weight was 848 (229) g and 807 (215) g, respectively. Any ROP was present in 6370 infants (49.8%) in GNN and 620 infants (33.6%) in NNN, and treatment-warranted ROP was present in 840 infants (6.6%) in GNN and 140 infants (7.6%) in NNN. In both cohorts, there were increasing rates of treatment-warranted ROP with each sepsis episode (no sepsis: 572 of 10 658 infants [5.4%] in GNN and 85 of 1492 infants (5.7%) in NNN; 1 episode: 190 of 1738 infants in GNN [10.9%] and 29 of 293 infants [9.9%] in NNN; 2 episodes: 53 of 314 infants in GNN [16.9%] and 13 of 49 infants [26.5%] in NNN; 3 episodes: 25 of 84 infants [29.8%] in GNN and 3 of 10 infants [30.0%] in NNN). After adjusting for multiple confounders in the GNN dataset, the number of sepsis episodes was associated with ROP and treatment-warranted ROP compared with 0 episodes (1 episode: adjusted odds ratio [aOR], 1.44 [95% CI, 1.27-1.63]; P &lt; .001 and OR, 1.60 [95% CI, 1.31-1.96]; P &lt; .001, respectively; 2 episodes: OR, 1.81 [95% CI, 1.35-2.42]; P &lt; .001 and OR, 2.38 [95% CI, 1.68-3.37]; P &lt; .001, respectively; 3 episodes: OR, 4.39 [95% CI, 2.19-8.78]; P &lt; .001 and OR, 3.88 [95% CI, 2.29-6.55]; P &lt; .001, respectively). These associations were confirmed for any ROP by propensity score matching (for example, the aOR with propensity score matching was 1.76 [95% CI, 1.54-2.02]; P &lt; .001 for 1 episode vs 0 episodes and 1.58 [95% CI, 1.12-2.22]; P = .007 for 3 episodes vs 0 or 1 episode). In the NNN dataset, surgical NEC was associated with treatment-warranted ROP (multivariable analysis: aOR, 3.37 [95% CI, 1.78-6.37]; P &lt; .001).Conclusions and RelevanceThis study found that in the large-scale GNN cohort, recurrent culture-proven sepsis was associated with ROP and treatment-warranted ROP in infants born at less than 29 weeks.

show abstract

Increased postnatal concentrations of pro-inflammatory cytokines are associated with reduced IGF-I levels and retinopathy of prematurity

Cited by 38 publications

References 39 publications

Early Postnatal IGF-1 and IGFBP-1 Blood Levels in Extremely Preterm Infants: Relationships with Indicators of Placental Insufficiency and with Systemic Inflammation

Early Postnatal IGF-1 and IGFBP-1 Blood Levels in Extremely Preterm Infants: Relationships with Indicators of Placental Insufficiency and with Systemic Inflammation

In-line filtration in very preterm neonates: a randomized controlled trial

Neonatal Sepsis Episodes and Retinopathy of Prematurity in Very Preterm Infants

Contact Info

Product

Resources

About