Antecedents and correlates of blood concentrations of neurotrophic growth factors in very preterm newborns

Leviton, Alan; Allred, Elizabeth N.; Yamamoto, Hidemi S.; Fichorova, Raina N.; Kuban, Karl; Dammann, Olaf

doi:10.1016/j.cyto.2017.03.012

Cited by 22 publications

(21 citation statements)

References 87 publications

(67 reference statements)

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“… 56 In the ELGAN study, infants who developed systemic inflammation were more likely to have higher neurotrophin concentrations than their peers with no systemic inflammation. 57 Also in this sample, elevated concentrations of VEGF, VEGFR-1, VEGFR-2, PlGF, ANG-1, and ANG-2 were associated with same-day elevated concentrations of inflammation-related proteins, each other, as well as with proteins that have neurotrophic properties. 58 One explanation for the co-occurrence of elevated concentrations of inflammation-related, angiogenic, and neurotrophic factors (potential protectors) is that a common antecedent upregulates all of them.…”

Section: Discussionmentioning

confidence: 59%

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

Holm

Morken

Fichorova

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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PurposeTo assess the association between systemic levels of inflammation-associated proteins and severe retinopathy of prematurity (ROP) in extremely preterm infants.MethodsWe 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.ResultsDuring 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-α, 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-α, TNF-R1/-R2, IL-8, and ICAM-1 were associated with an increased risk. Top quartile concentrations of the proinflammatory cytokines TNF-α 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.ConclusionsSystemic 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.

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Section: Discussionmentioning

confidence: 59%

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

Holm

Morken

Fichorova

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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“…(Xing and Lo, 2017) The cooccurrence of elevated concentrations of inflammation and neurotrophic proteins has been documented in ELGANS. (Leviton et al, 2017) Others have emphasized the cross-talk between neurotrophins and inflammation. (da Silva Meirelles et al, 2017)…”

Section: Co-occurrence Of Inflammation and Neurotrophic Proteinsmentioning

confidence: 99%

Executive Dysfunction Early Postnatal Biomarkers among Children Born Extremely Preterm

Leviton

Joseph

Fichorova

et al. 2018

J Neuroimmune Pharmacol

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We evaluated the relationship between blood levels of inflammatory and neurotrophic proteins during the first postnatal month in 692 children born before the 28th week of gestation and executive function limitations among those 10-year olds who had an IQ ≥ 70. The measures of dysfunction were Z-scores ≤ -1 on the Differential Ability Scales-II working memory (WM) assessment) (N = 164), the NEPSY-II (A Developmental NEuroPSYchological Assessment-II) Inhibition-Inhibition assessment) (N = 350), the NEPSY-II Inhibition-Switching assessment) (N = 345), as well as a Z-score ≤ -1 on all three assessments (identified as the executive dysfunction composite (N = 104). Increased risks of the executive dysfunction composite associated with high concentrations of inflammatory proteins (IL-8, TNF-α, and ICAM-1) were modulated by high concentrations of neurotrophic proteins. This pattern of modulation by neurotrophins of increased risk associated with inflammation was also seen for the working memory limitation, but only with high concentrations of IL-8 and TNF-α, and the switching limitation, but only with high concentrations of ICAM-1. We infer that among children born extremely preterm, risks of executive function limitations might be explained by perinatal systemic inflammation in the absence of adequate neurotrophic capability.

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“…The lower birth weight in NAS infants was consistent with the effect of opiates on the birth weight previously described in the literature ( 32 ), but whether this factor may contribute to the higher BDNF levels in this group remains to be further elucidated. The existing data regarding the effects of low birth weight/intrauterine growth restriction on the BDNF levels are still conflicting; at term, the BDNF levels of infants with IUGR were not different from those born appropriate for gestational age (AGA) ( 33 ) while the BDNF levels were lower in very preterm infants with severe growth restriction ( 34 ).…”

Section: Discussionmentioning

confidence: 99%

Plasma Brain-Derived Neurotrophic Factor Levels in Newborn Infants with Neonatal Abstinence Syndrome

et al. 2017

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BackgroundBrain-derived neurotrophic factor (BDNF) is a type of growth factor that promotes growth and survival of neurons. Fetal exposure to opiates can lead to postnatal withdrawal syndrome, which is referred as neonatal abstinence syndrome (NAS). Preclinical and clinical studies have shown an association between opiates exposure and alteration in BDNF expression in the brain and serum levels in adult. However, to date, there are no data available on the effects of opiate exposure on BDNF levels in infant who are exposed to opiates in utero and whether BDNF level may correlate with the severity of NAS.ObjectiveTo compare plasma BDNF levels among NAS and non-NAS infants and to determine the correlation of BDNF levels and the severity of NAS.MethodsThis is a prospective cohort study with no intervention involved. Infants ≥35 weeks of gestation were enrolled. BDNF level was measured using enzyme-linked immunosorbent assay technique from blood samples drawn within 48 h of life. The severity of NAS was determined by the length of hospital stay, number of medications required to treat NAS.Results67 infants were enrolled, 34 NAS and 33 non-NAS. Mean gestational age did not differ between the two groups. Mean birth weight of NAS infants was significantly lower than the non-NAS infants (3,070 ± 523 vs. 3,340 ± 459 g, p = 0.028). Mean BDNF level in NAS group was 252.2 ± 91.6 ng/ml, significantly higher than 211.3 ± 66.3 ng/ml in the non-NAS group (p = 0.04). There were no differences in BDNF levels between NAS infants that required one medication vs. more than one medication (254 ± 91 vs. 218 ± 106 ng/ml, p = 0.47). There was no correlation between the BDNF levels and length of hospital stay (p = 0.68) among NAS infants. Overall, there were no significant correlations between BDNF levels and NAS scores except at around 15 h after admission (correlation 0.35, p = 0.045).ConclusionPlasma BDNF level was significantly increased in NAS infants during the first 48 h when compared to non-NAS infants. The correlations between plasma BDNF levels and the severity of NAS warrant further study. These results suggest that BDNF may play a neuromodulatory role during withdrawal after in utero opiate exposure.

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Antecedents and correlates of blood concentrations of neurotrophic growth factors in very preterm newborns

Cited by 22 publications

References 87 publications

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

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

Executive Dysfunction Early Postnatal Biomarkers among Children Born Extremely Preterm

Plasma Brain-Derived Neurotrophic Factor Levels in Newborn Infants with Neonatal Abstinence Syndrome

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