scholarly journals Is late prevention of cerebral palsy in extremely preterm infants plausible?

2021 ◽  
Author(s):  
Benjamin A. Lear ◽  
Christopher A. Lear ◽  
Simerdeep K. Dhillon ◽  
Joanne O. Davidson ◽  
Laura Bennet ◽  
...  
Keyword(s):  
Cerebral Palsy ◽  
Preterm Birth ◽  
White Matter ◽  
Preterm Infants ◽  
White Matter Injury ◽  
Cystic Lesions ◽  
Extremely Preterm ◽  
Extremely Preterm Infants ◽  
Therapeutic Opportunity ◽  
Slow Evolution

Preterm birth continues to be associated with neurodevelopmental problems including cerebral palsy. Cystic white matter injury is still the major neuropathology underlying cerebral palsy, affecting 1-3% of preterm infants. Although rates have gradually fallen over time, the pathogenesis and evolution of cystic white matter injury are still poorly understood. Hypoxia-ischemia (HI) remains an important contributor yet there is no established treatment to prevent injury. Clinically, serial ultrasound and magnetic resonance imaging studies typically show delayed development of cystic lesions 2 to 4 weeks after birth. This raises the important and unresolved question as to whether this represents slow evolution of injury occurring around the time of birth, or repeated injury over many weeks after birth. There is increasing evidence that tertiary injury after HI can contribute to impairment of white and grey matter maturation. In the present review, we discuss preclinical evidence that severe, cystic white matter injury can evolve for many weeks after acute HI and is associated with microglia activity. This suggests the intriguing hypothesis that the tertiary phase of injury is not as subtle as often thought and that there may be a window of therapeutic opportunity for one to two weeks after hypoxic-ischemic injury to prevent delayed cystic lesions and so further reduce the risk of cerebral palsy after preterm birth.

scholarly journals Isoprostanes as Biomarker for White Matter Injury in Extremely Preterm Infants

2021 ◽  
Vol 8 ◽  
Author(s):  
Caterina Coviello ◽  
Serafina Perrone ◽  
Giuseppe Buonocore ◽  
Simona Negro ◽  
Mariangela Longini ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
White Matter ◽  
Preterm Infants ◽  
Neurodevelopmental Outcome ◽  
Area Under The Curve ◽  
White Matter Injury ◽  
Roc Curve Analysis ◽  
Extremely Preterm ◽  
Extremely Preterm Infants ◽  
Early Biomarker

Background and Aim: Preterm white matter is vulnerable to lipid peroxidation-mediated injury. F2-isoprostanes (IPs), are a useful biomarker for lipid peroxidation. Aim was to assess the association between early peri-postnatal IPs, white matter injury (WMI) at term equivalent age (TEA), and neurodevelopmental outcome in preterm infants.Methods: Infants with a gestational age (GA) below 28 weeks who had an MRI at TEA were included. IPs were measured in cord blood (cb) at birth and on plasma (pl) between 24 and 48 h after birth. WMI was assessed using Woodward MRI scoring system. Multiple regression analyses were performed to assess the association between IPs with WMI and then with BSITD-III scores at 24 months corrected age (CA). Receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive value of pl-IPs for the development of WMI.Results: Forty-four patients were included. cb-IPs were not correlated with WMI score at TEA, whereas higher pl-IPs and lower GA predicted higher WMI score (p = 0.037 and 0.006, respectively) after controlling for GA, FiO2 at sampling and severity of IVH. The area under the curve was 0.72 (CI 95% = 0.51–0.92). The pl-IPs levels plotted curve indicated that 31.8 pg/ml had the best predictive threshold with a sensitivity of 86% and a specificity of 60%, to discriminate newborns with any WMI from newborns without WMI. IPs were not associated with outcome at 24 months.Conclusion: Early measurement of pl-IPs may help discriminate patients showing abnormal WMI score at TEA, thus representing an early biomarker to identify newborns at risk for brain injury.

scholarly journals Nutritional Intake, White Matter Integrity, and Neurodevelopment in Extremely Preterm Born Infants

Nutrients ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 3409
Author(s):  
Lisa M. Hortensius ◽  
Els Janson ◽  
Pauline E. van van Beek ◽  
Floris Groenendaal ◽  
Nathalie H. P. Claessens ◽  
...  
Keyword(s):  
White Matter ◽  
Preterm Infants ◽  
Motor Development ◽  
Protein Intake ◽  
Diffusion Tensor ◽  
Neurodevelopmental Outcome ◽  
White Matter Integrity ◽  
Extremely Preterm ◽  
Extremely Preterm Infants ◽  
Preterm Born

Background: Determining optimal nutritional regimens in extremely preterm infants remains challenging. This study aimed to evaluate the effect of a new nutritional regimen and individual macronutrient intake on white matter integrity and neurodevelopmental outcome. Methods: Two retrospective cohorts of extremely preterm infants (gestational age <28 weeks) were included. Cohort B (n = 79) received a new nutritional regimen, with more rapidly increased, higher protein intake compared to cohort A (n = 99). Individual protein, lipid, and caloric intakes were calculated for the first 28 postnatal days. Diffusion tensor imaging was performed at term-equivalent age, and cognitive and motor development were evaluated at 2 years corrected age (CA) (Bayley-III-NL) and 5.9 years chronological age (WPPSI-III-NL, MABC-2-NL). Results: Compared to cohort A, infants in cohort B had significantly higher protein intake (3.4 g/kg/day vs. 2.7 g/kg/day) and higher fractional anisotropy (FA) in several white matter tracts but lower motor scores at 2 years CA (mean (SD) 103 (12) vs. 109 (12)). Higher protein intake was associated with higher FA and lower motor scores at 2 years CA (B = −6.7, p = 0.001). However, motor scores at 2 years CA were still within the normal range and differences were not sustained at 5.9 years. There were no significant associations with lipid or caloric intake. Conclusion: In extremely preterm born infants, postnatal protein intake seems important for white matter development but does not necessarily improve long-term cognitive and motor development.

scholarly journals Preterm birth and sustained inflammation: consequences for the neonate

2020 ◽  
Vol 42 (4) ◽  
pp. 451-468 ◽  
Author(s):  
Alexander Humberg ◽  
◽  
Ingmar Fortmann ◽  
Bastian Siller ◽  
Matthias Volkmar Kopp ◽  
...  
Keyword(s):  
Preterm Birth ◽  
Preterm Infants ◽  
Defense Mechanisms ◽  
Preterm Births ◽  
Immune Defense ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Organ Systems ◽  
Extremely Preterm ◽  
Extremely Preterm Infants

Abstract Almost half of all preterm births are caused or triggered by an inflammatory process at the feto-maternal interface resulting in preterm labor or rupture of membranes with or without chorioamnionitis (“first inflammatory hit”). Preterm babies have highly vulnerable body surfaces and immature organ systems. They are postnatally confronted with a drastically altered antigen exposure including hospital-specific microbes, artificial devices, drugs, nutritional antigens, and hypoxia or hyperoxia (“second inflammatory hit”). This is of particular importance to extremely preterm infants born before 28 weeks, as they have not experienced important “third-trimester” adaptation processes to tolerate maternal and self-antigens. Instead of a balanced adaptation to extrauterine life, the delicate co-regulation between immune defense mechanisms and immunosuppression (tolerance) to allow microbiome establishment is therefore often disturbed. Hence, preterm infants are predisposed to sepsis but also to several injurious conditions that can contribute to the onset or perpetuation of sustained inflammation (SI). This is a continuing challenge to clinicians involved in the care of preterm infants, as SI is regarded as a crucial mediator for mortality and the development of morbidities in preterm infants. This review will outline the (i) role of inflammation for short-term consequences of preterm birth and (ii) the effect of SI on organ development and long-term outcome.

scholarly journals Cerebral Palsy in Extremely Preterm Infants

PEDIATRICS ◽  
2017 ◽  
Vol 141 (1) ◽  
pp. e20171433 ◽  
Author(s):  
Maria Hafström ◽  
Karin Källén ◽  
Fredrik Serenius ◽  
Karel Maršál ◽  
Eva Rehn ◽  
...  
Keyword(s):  
Cerebral Palsy ◽  
Preterm Infants ◽  
Extremely Preterm ◽  
Extremely Preterm Infants

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

PLoS ONE ◽  
2013 ◽  
Vol 8 (8) ◽  
pp. e72974 ◽  
Author(s):  
Ulana Pogribna ◽  
Xintian Yu ◽  
Katrina Burson ◽  
Yuxiang Zhou ◽  
Robert E. Lasky ◽  
...  
Keyword(s):  
Diffusion Tensor Imaging ◽  
White Matter ◽  
Preterm Infants ◽  
Diffusion Tensor ◽  
Extremely Preterm ◽  
Extremely Preterm Infants

scholarly journals Systemic Inflammation and Cerebral Palsy Risk in Extremely Preterm Infants

2014 ◽  
Vol 29 (12) ◽  
pp. 1692-1698 ◽  
Author(s):  
Karl C. K. Kuban ◽  
T. Michael O’Shea ◽  
Elizabeth N. Allred ◽  
Nigel Paneth ◽  
Deborah Hirtz ◽  
...  
Keyword(s):  
Cerebral Palsy ◽  
Preterm Infants ◽  
Systemic Inflammation ◽  
Extremely Preterm ◽  
Extremely Preterm Infants

Late-Onset Circulatory Collapse and Risk of Cerebral Palsy in Extremely Preterm Infants

2019 ◽  
Vol 212 ◽  
pp. 117-123.e4 ◽  
Author(s):  
Kazuaki Yasuoka ◽  
Hirosuke Inoue ◽  
Naoki Egami ◽  
Masayuki Ochiai ◽  
Koichi Tanaka ◽  
...  
Keyword(s):  
Cerebral Palsy ◽  
Preterm Infants ◽  
Late Onset ◽  
Circulatory Collapse ◽  
Extremely Preterm ◽  
Extremely Preterm Infants

How does the BAPM Framework for Practice on Perinatal Management of Extreme Preterm Birth Before 27 Weeks of Gestation impact delivery of Newborn Life Support? A Resuscitation Council UK response

2020 ◽  
Vol 105 (6) ◽  
pp. 672-674
Author(s):  
Joe Fawke ◽  
Robert J Tinnion ◽  
Victoria Monnelly ◽  
Sean B Ainsworth ◽  
Jonathan Cusack ◽  
...  
Keyword(s):  
Decision Making ◽  
Preterm Birth ◽  
Preterm Infants ◽  
Life Support ◽  
Perinatal Care ◽  
Perinatal Medicine ◽  
Extremely Preterm ◽  
Extremely Preterm Infants ◽  
Perinatal Management ◽  
The Uk

In October 2019, the British Association of Perinatal Medicine (BAPM) published a Framework1 and associated infographic2 for ‘Practice on Perinatal Management of Extreme Preterm Birth Before 27 Weeks of Gestation’. This outlined an approach, based on data from the UK and abroad, to assist clinicians in decision-making relating to perinatal care at ≤26+6 weeks gestation. Many frontline providers of delivery room care of extremely preterm infants will have completed a Resuscitation Council UK (RCUK) Newborn Life Support or Advanced Resuscitation of the Newborn Infant course. This RCUK response to the BAPM Framework highlights how this might impact on their approach.

scholarly journals Preventing Brain Injury in the Preterm Infant—Current Controversies and Potential Therapies

2021 ◽  
Vol 22 (4) ◽  
pp. 1671
Author(s):  
Nathanael Yates ◽  
Alistair J. Gunn ◽  
Laura Bennet ◽  
Simerdeep K. Dhillon ◽  
Joanne O. Davidson
Keyword(s):  
Cerebral Palsy ◽  
Brain Injury ◽  
Preterm Infant ◽  
Brain Damage ◽  
Preterm Infants ◽  
Preclinical Studies ◽  
Recombinant Erythropoietin ◽  
Neurological Outcomes ◽  
Extremely Preterm ◽  
Extremely Preterm Infants

Preterm birth is associated with a high risk of morbidity and mortality including brain damage and cerebral palsy. The development of brain injury in the preterm infant may be influenced by many factors including perinatal asphyxia, infection/inflammation, chronic hypoxia and exposure to treatments such as mechanical ventilation and corticosteroids. There are currently very limited treatment options available. In clinical trials, magnesium sulfate has been associated with a small, significant reduction in the risk of cerebral palsy and gross motor dysfunction in early childhood but no effect on the combined outcome of death or disability, and longer-term follow up to date has not shown improved neurological outcomes in school-age children. Recombinant erythropoietin has shown neuroprotective potential in preclinical studies but two large randomized trials, in extremely preterm infants, of treatment started within 24 or 48 h of birth showed no effect on the risk of severe neurodevelopmental impairment or death at 2 years of age. Preclinical studies have highlighted a number of promising neuroprotective treatments, such as therapeutic hypothermia, melatonin, human amnion epithelial cells, umbilical cord blood and vitamin D supplementation, which may be useful at reducing brain damage in preterm infants. Moreover, refinements of clinical care of preterm infants have the potential to influence later neurological outcomes, including the administration of antenatal and postnatal corticosteroids and more accurate identification and targeted treatment of seizures.

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