Dataset Information

Preterm Brain Injury, Antenatal Triggers, and Therapeutics: Timing Is Key.

ABSTRACT: With a worldwide incidence of 15 million cases, preterm birth is a major contributor to neonatal mortality and morbidity, and concomitant social and economic burden Preterm infants are predisposed to life-long neurological disorders due to the immaturity of the brain. The risks are inversely proportional to maturity at birth. In the majority of extremely preterm infants (<28 weeks' gestation), perinatal brain injury is associated with exposure to multiple inflammatory perinatal triggers that include antenatal infection (i.e., chorioamnionitis), hypoxia-ischemia, and various postnatal injurious triggers (i.e., oxidative stress, sepsis, mechanical ventilation, hemodynamic instability). These perinatal insults cause a self-perpetuating cascade of peripheral and cerebral inflammation that plays a critical role in the etiology of diffuse white and grey matter injuries that underlies a spectrum of connectivity deficits in survivors from extremely preterm birth. This review focuses on chorioamnionitis and hypoxia-ischemia, which are two important antenatal risk factors for preterm brain injury, and highlights the latest insights on its pathophysiology, potential treatment, and future perspectives to narrow the translational gap between preclinical research and clinical applications.

SUBMITTER: Ophelders DRMG

PROVIDER: S-EPMC7464163 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Preterm Brain Injury, Antenatal Triggers, and Therapeutics: Timing Is Key.

Ophelders Daan R M G DRMG Gussenhoven Ruth R Klein Luise L Jellema Reint K RK Westerlaken Rob J J RJJ Hütten Matthias C MC Vermeulen Jeroen J Wassink Guido G Gunn Alistair J AJ Wolfs Tim G A M TGAM

Cells 20200810 8

With a worldwide incidence of 15 million cases, preterm birth is a major contributor to neonatal mortality and morbidity, and concomitant social and economic burden Preterm infants are predisposed to life-long neurological disorders due to the immaturity of the brain. The risks are inversely proportional to maturity at birth. In the majority of extremely preterm infants (<28 weeks' gestation), perinatal brain injury is associated with exposure to multiple inflammatory perinatal triggers that inc ...[more]

PMID: 32785181

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Project description:BACKGROUND AND PURPOSE:Early disturbances in systemic and cerebral hemodynamics are thought to mediate prematurity-related brain injury. However, the extent to which CBF is perturbed by preterm birth is unknown. Our aim was to compare global and regional CBF in preterm infants with and without brain injury on conventional MR imaging using arterial spin-labeling during the third trimester of ex utero life and to examine the relationship between clinical risk factors and CBF. MATERIALS AND METHODS:We prospectively enrolled preterm infants younger than 32 weeks' gestational age and <1500 g and performed arterial spin-labeling MR imaging studies. Global and regional CBF in the cerebral cortex, thalami, pons, and cerebellum was quantified. Preterm infants were stratified into those with and without structural brain injury. We further categorized preterm infants by brain injury severity: moderate-severe and mild. RESULTS:We studied 78 preterm infants: 31 without brain injury and 47 with brain injury (29 with mild and 18 with moderate-severe injury). Global CBF showed a borderline significant increase with increasing gestational age at birth (P = .05) and trended lower in preterm infants with brain injury (P = .07). Similarly, regional CBF was significantly lower in the right thalamus and midpons (P < .05) and trended lower in the midtemporal, left thalamus, and anterior vermis regions (P < .1) in preterm infants with brain injury. Regional CBF in preterm infants with moderate-severe brain injury trended lower in the midpons, right cerebellar hemisphere, and dentate nuclei compared with mild brain injury (P < .1). In addition, a significant, lower regional CBF was associated with ventilation, sepsis, and cesarean delivery (P < .05). CONCLUSIONS:We report early disturbances in global and regional CBF in preterm infants following brain injury. Regional cerebral perfusion alterations were evident in the thalamus and pons, suggesting regional vulnerability of the developing cerebro-cerebellar circuitry.

Project description:PurposeInjurious mechanical ventilation causes white matter (WM) injury in preterm infants through inflammatory and haemodynamic pathways. The relative contribution of each of these pathways is not known. We hypothesised that in vivo magnetic resonance imaging (MRI) can detect WM brain injury resulting from mechanical ventilation 24 h after preterm delivery. Further we hypothesised that the combination of inflammatory and haemodynamic pathways, induced by umbilical cord occlusion (UCO) increases brain injury at 24 h.MethodsFetuses at 124±2 days gestation were exposed, instrumented and either ventilated for 15 min using a high tidal-volume (VT) injurious strategy with the umbilical cord intact (INJ; inflammatory pathway only), or occluded (INJ+UCO; inflammatory and haemodynamic pathway). The ventilation groups were compared to lambs that underwent surgery but were not ventilated (Sham), and lambs that did not undergo surgery (unoperated control; Cont). Fetuses were placed back in utero after the 15 min intervention and ewes recovered. Twenty-four hours later, lambs were delivered, placed on a protective ventilation strategy, and underwent MRI of the brain using structural, diffusion tensor imaging (DTI) and magnetic resonance spectroscopy (MRS) techniques.ResultsAbsolute MRS concentrations of creatine and choline were significantly decreased in INJ+UCO compared to Cont lambs (P = 0.03, P = 0.009, respectively); no significant differences were detected between the INJ or Sham groups and the Cont group. Axial diffusivities in the internal capsule and frontal WM were lower in INJ and INJ+UCO compared to Cont lambs (P = 0.05, P = 0.04, respectively). Lambs in the INJ and INJ+UCO groups had lower mean diffusivities in the frontal WM compared to Cont group (P = 0.04). DTI colour mapping revealed lower diffusivity in specific WM regions in the Sham, INJ, and INJ+UCO groups compared to the Cont group, but the differences did not reach significance. INJ+UCO lambs more likely to exhibit lower WM diffusivity than INJ lambs.ConclusionsTwenty-four hours after injurious ventilation, DTI and MRS showed increased brain injury in the injuriously ventilated lambs compared to controls. DTI colour mapping threshold approach provides evidence that the haemodynamic and inflammatory pathways have additive effects on the progression of brain injury compared to the inflammatory pathway alone.

Dataset Information

Preterm Brain Injury, Antenatal Triggers, and Therapeutics: Timing Is Key.

Publications

Preterm Brain Injury, Antenatal Triggers, and Therapeutics: Timing Is Key.

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