Caffeine and brain development in very preterm infants

Doyle, Lex W.; Cheong, Jeanie L.Y.; Hunt, Rod W.; Lee, Katherine J.; Thompson, Deanne K.; Davis, Peter G; Rees, Sandra; Anderson, Peter J.; Inder, Terrie E.

doi:10.1002/ana.22098

Cited by 84 publications

(58 citation statements)

References 37 publications

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“…What has been shown, that only a prolonged apnea and bradycardia were associated with a long-term neurodevelopmental delay in prematurely born infants (Pillekamp et al, 2007). Caffeine administration, known pharmacological strategy against apnea of prematurity, preserved WM development and myelination and improved neurologic outcome in premature human infants and neonatal rats exposed to a chronic hypoxia Doyle et al, 2010). This clinical scenario, however, differs from that targeted in our study, as no bradycardia, or prolonged hypoxemia was replicated in our model.…”

Section: Discussioncontrasting

confidence: 83%

Mild intermittent hypoxemia in neonatal mice causes permanent neurofunctional deficit and white matter hypomyelination

Juliano

Sosunov

Niatsetskaya

et al. 2015

Experimental Neurology

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Section: Discussioncontrasting

confidence: 83%

Mild intermittent hypoxemia in neonatal mice causes permanent neurofunctional deficit and white matter hypomyelination

Juliano

Sosunov

Niatsetskaya

et al. 2015

Experimental Neurology

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“…Additional studies are required to comprehensively evaluate the microstructural mechanisms through which maternal milk may enhance cognitive development. A limited amount of information is available about the mechanism of neuroprotection following caffeine in very preterm infants [34], [35]. Our data and those of Doyle et al [35] indicate that this benefit may be mediated through preserving white matter microstructural integrity.…”

Section: Discussionsupporting

confidence: 54%

Perinatal Clinical Antecedents of White Matter Microstructural Abnormalities on Diffusion Tensor Imaging in Extremely Preterm Infants

Pogribna

Burson

et al. 2013

PLoS ONE

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ObjectiveTo identify perinatal clinical antecedents of white matter microstructural abnormalities in extremely preterm infants.MethodsA prospective cohort of extremely preterm infants (N = 86) and healthy term controls (N = 16) underwent diffusion tensor imaging (DTI) at term equivalent age. Region of interest-based measures of white matter microstructure - fractional anisotropy and mean diffusivity - were quantified in seven vulnerable cerebral regions and group differences assessed. In the preterm cohort, multivariable linear regression analyses were conducted to identify independent clinical factors associated with microstructural abnormalities.ResultsPreterm infants had a mean (standard deviation) gestational age of 26.1 (1.7) weeks and birth weight of 824 (182) grams. Compared to term controls, the preterm cohort exhibited widespread microstructural abnormalities in 9 of 14 regional measures. Chorioamnionitis, necrotizing enterocolitis, white matter injury on cranial ultrasound, and increasing duration of mechanical ventilation were adversely correlated with regional microstructure. Conversely, antenatal steroids, female sex, longer duration of caffeine therapy, and greater duration of human milk use were independent favorable factors. White matter injury on cranial ultrasound was associated with a five weeks or greater delayed maturation of the corpus callosum; every additional 10 days of human milk use were associated with a three weeks or greater advanced maturation of the corpus callosum.ConclusionsDiffusion tensor imaging is sensitive in detecting the widespread cerebral delayed maturation and/or damage increasingly observed in extremely preterm infants. In our cohort, it also aided identification of several previously known or suspected perinatal clinical antecedents of brain injury, aberrant development, and neurodevelopmental impairments.

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“…Although this method permits assessment of overt axonal damage (axonal disruption and axonal spheroids) and densitometry of SMI-312-IR within the WM, it is not an accurate measure of axonal density; for that, electron microscopy would be required. Magnetic resonance imaging of preterm infants at term equivalent age, treated with standard doses of caffeine revealed a reduction in axial diffusivity in treated infants (31), which may be explained by axonal preservation and/or a greater axonal density. However, it should be noted that this was following doses of caffeine lower than that used in the present study, and MRI scans were performed at a more advanced stage of brain development than in the present study.…”

Section: Caffeine and Developing White Mattermentioning

confidence: 92%

Impact of daily high-dose caffeine exposure on developing white matter of the immature ovine brain

et al. 2014

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Background: Caffeine is widely used to treat apnea of prematurity, but the standard dosing regimen is not always sufficient to prevent apnea. Before higher doses of caffeine can be used, their effects on the immature brain need to be carefully evaluated. Our aim was to determine the impact of daily highdose caffeine administration on the developing white matter of the immature ovine brain. Methods: High-dose caffeine (25 mg/kg caffeine base loading dose; 20 mg/kg daily maintenance dose; n = 9) or saline (n = 8) were administered to pregnant sheep from 0.7 to 0.8 of term, equivalent to approximately 27-34 wk in humans. At 0.8 of term, the white and gray matter were assessed histologically and immunohistochemically. results: Daily caffeine administration led to peak caffeine concentration of 32 mg/l in fetal plasma at 1 h, followed by a gradual decline, with no effects on mean arterial pressure and heart rate. Initial caffeine exposure led to transient, mild alkalosis in the fetus but did not alter oxygenation. At necropsy, there was no effect of daily high-dose caffeine on brain weight, oligodendrocyte density, myelination, axonal integrity, microgliosis, astrogliosis, apoptosis, or neuronal density. conclusion: Daily high-dose caffeine administration does not appear to adversely affect the developing white matter at the microstructural level.

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Caffeine and brain development in very preterm infants

Abstract: These diffusion changes are consistent with improved white matter microstructural development in preterm infants who received caffeine.

Cited by 84 publications

References 37 publications

Mild intermittent hypoxemia in neonatal mice causes permanent neurofunctional deficit and white matter hypomyelination

Mild intermittent hypoxemia in neonatal mice causes permanent neurofunctional deficit and white matter hypomyelination

Perinatal Clinical Antecedents of White Matter Microstructural Abnormalities on Diffusion Tensor Imaging in Extremely Preterm Infants

Impact of daily high-dose caffeine exposure on developing white matter of the immature ovine brain

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