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Neuropediatrics 2019; 50(01): 015-021
DOI: 10.1055/s-0038-1669425
Original Article
Georg Thieme Verlag KG Stuttgart · New York

Early Retinal Findings Following Cooling in Neonatal Encephalopathy

Mustafa Ali Akin
1   Division of Neonatology, Department of Pediatrics, University of Medical Sciences Kayseri Training and Research Hospital, Kocasinan, Kayseri, Turkey
,
Ozlem Sahin
1   Division of Neonatology, Department of Pediatrics, University of Medical Sciences Kayseri Training and Research Hospital, Kocasinan, Kayseri, Turkey
,
Murat Cansever
2   Department of Pediatrics, University of Medical Sciences Kayseri Training and Research Hospital, Kocasinan, Kayseri, Turkey
,
Ender Sirakaya
3   Department of Ophthalmology, University of Medical Sciences Kayseri Training and Research Hospital, Kocasinan, Kayseri, Turkey
,
Nicola Jayne Robertson
4   Department of Neonatology, UCL EGA Institute for Women's Health (IfWH), University College London, London, United Kingdom
› Author Affiliations
Further Information

Publication History

21 February 2018

22 July 2018

Publication Date:
20 September 2018 (online)

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Abstract

Background and Aim Perinatal HI (hypoxia–ischemia)-related visual defects including blindness are known to be associated with ischemic lesions in intracerebral visual pathways and ischemic retinal damage (IRD). Intraocular hemorrhages (IOH) such as retinal hemorrhage (RH), which may result from perinatal HI, can cause IRD by various mechanisms. We aimed to evaluate the early retinal findings in neonates with moderate-to-severe neonatal encephalopathy (NE) who underwent TH and its relationship between coagulation status, amplitude-integrated electroencephalography (aEEG) patterns, and magnetic resonance imaging–magnetic resonance spectroscopy (MRI–MRS) findings.

Method and Patients A total of 31 newborn infants who underwent moderate-to-severe NE and TH included in the study. Coagulation parameters were taken immediately before starting TH, and daily during TH period. aEEG records were obtained during TH and rewarming period.

Binocular indirect ophthalmoscopic examination (BIOE) and MRI–MRS scanning were performed when TH protocol completed.

Results Total 13 (41.9%) patients had abnormal BIOE findings. Ten of them were (77%) IOH, other findings are as follows: RH (n = 7), optic disc hemorrhage (n = 2), and vitreous hemorrhage (n = 1). Initial coagulation status was not related to IOH. Worsened aEEG and MRI–MRS results were not related to BIOE findings.

Conclusion Frequency of IOH is high in newborns with NE who underwent TH being independent from severity of MRS–MRI findings, aEEG pattern, and disturbed coagulation status.

Keywords

hypothermia - perinatal hypoxia–ischemia - newborn - retinal hemorrhage
 

  • References

  • 1 Nelson KB, Leviton A. How much of neonatal encephalopathy is due to birth asphyxia?. Am J Dis Child 1991; 145 (11) 1325-1331
    PubMedGoogle Scholar
  • 2 Younkin DP. Hypoxic-ischemic brain injury of the newborn--statement of the problem and overview. Brain Pathol 1992; 2 (03) 209-210
    CrossrefPubMedGoogle Scholar
  • 3 Osborne NN, Casson RJ, Wood JP, Chidlow G, Graham M, Melena J. Retinal ischemia: mechanisms of damage and potential therapeutic strategies. Prog Retin Eye Res 2004; 23 (01) 91-147
    CrossrefPubMedGoogle Scholar
  • 4 Sickel W. Electrical and metabolic manifestations of receptor and higher-order neuron activity in vertebrate retina. Adv Exp Med Biol 1972; 24 (00) 101-118
    PubMedGoogle Scholar
  • 5 Hoyt CS. Brain injury and the eye. Eye (Lond) 2007; 21 (10) 1285-1289
    CrossrefPubMedGoogle Scholar
  • 6 Chong CF, McGhee CN, Dai S. A cross-sectional study of prevalence and etiology of childhood visual impairment in Auckland, New Zealand. Asia Pac J Ophthalmol (Phila) 2014; 3 (06) 337-342
    CrossrefPubMedGoogle Scholar
  • 7 Huo R, Burden SK, Hoyt CS, Good WV. Chronic cortical visual impairment in children: aetiology, prognosis, and associated neurological deficits. Br J Ophthalmol 1999; 83 (06) 670-675
    CrossrefPubMedGoogle Scholar
  • 8 Chong C, Dai S. Cross-sectional study on childhood cerebral visual impairment in New Zealand. J AAPOS 2014; 18 (01) 71-74
    CrossrefPubMedGoogle Scholar
  • 9 Huang HM, Huang CC, Hung PL, Chang YC. Hypoxic-ischemic retinal injury in rat pups. Pediatr Res 2012; 72 (03) 224-231
    CrossrefPubMedGoogle Scholar
  • 10 Eken P, de Vries LS, van der Graaf Y, Meiners LC, van Nieuwenhuizen O. Haemorrhagic-ischaemic lesions of the neonatal brain: correlation between cerebral visual impairment, neurodevelopmental outcome and MRI in infancy. Dev Med Child Neurol 1995; 37 (01) 41-55
    PubMedGoogle Scholar
  • 11 Hoyt CS. Visual function in the brain-damaged child. Eye (Lond) 2003; 17 (03) 369-384
    CrossrefPubMedGoogle Scholar
  • 12 Brodsky MC, Fray KJ, Glasier CM. Perinatal cortical and subcortical visual loss: mechanisms of injury and associated ophthalmologic signs. Ophthalmology 2002; 109 (01) 85-94
    CrossrefPubMedGoogle Scholar
  • 13 Salati R, Borgatti R, Giammari G, Jacobson L. Oculomotor dysfunction in cerebral visual impairment following perinatal hypoxia. Dev Med Child Neurol 2002; 44 (08) 542-550
    PubMedGoogle Scholar
  • 14 Van Hof-van Duin J, Mohn G. Visual defects in children after cerebral hypoxia. Behav Brain Res 1984; 14 (02) 147-155
    CrossrefPubMedGoogle Scholar
  • 15 Jung S, Polosa A, Lachapelle P, Wintermark P. Visual Impairments following term neonatal encephalopathy: do retinal impairments also play a role?. Invest Ophthalmol Vis Sci 2015; 56 (09) 5182-5193
    CrossrefPubMedGoogle Scholar
  • 16 Choi YJ, Jung MS, Kim SY. Retinal hemorrhage associated with perinatal distress in newborns. Korean J Ophthalmol 2011; 25 (05) 311-316
    CrossrefPubMedGoogle Scholar
  • 17 Shaikh S, Fishman ML, Gaynon M, Alcorn D. Diffuse unilateral hemorrhagic retinopathy associated with accidental perinatal strangulation. A clinicopathologic report. Retina 2001; 21 (03) 252-255
    CrossrefPubMedGoogle Scholar
  • 18 Rahman SU, Canpolat FE, Oncel MY. , et al. Multicenter randomized controlled trial of therapeutic hypothermia plus magnesium sulfate versus therapeutic hypothermia plus placebo in the management of term and near-term infants with hypoxic ischemic encephalopathy (The Mag Cool study): a pilot study. J Clin Neonatol 2015; 4: 158-163
    CrossrefPubMedGoogle Scholar
  • 19 Hellström-Westas L, Rosén I, Svenningsen NW. Predictive value of early continuous amplitude integrated EEG recordings on outcome after severe birth asphyxia in full term infants. Arch Dis Child Fetal Neonatal Ed 1995; 72 (01) F34-F38
    CrossrefPubMedGoogle Scholar
  • 20 Forman KR, Diab Y, Wong EC, Baumgart S, Luban NL, Massaro AN. Coagulopathy in newborns with hypoxic ischemic encephalopathy (HIE) treated with therapeutic hypothermia: a retrospective case-control study. BMC Pediatr 2014; 14: 277
    CrossrefPubMedGoogle Scholar
  • 21 Perk Y, Atasay B, Cetinkaya M. Türk Neonatoloji Derneği Kan Ürünleri Transfüzyon Rehberi-2016. Internet, http://neonatology.org.tr/wp-ontent/uploads/2016/12/kan_urunleri_transfuzyonu.pdf
    PubMedGoogle Scholar
  • 22 Li SY, Fu ZJ, Lo AC. Hypoxia-induced oxidative stress in ischemic retinopathy. Oxid Med Cell Longev 2012; 2012: 426769
    PubMedGoogle Scholar
  • 23 Shanmugalingam S, Thornton JS, Iwata O. , et al. Comparative prognostic utilities of early quantitative magnetic resonance imaging spin-spin relaxometry and proton magnetic resonance spectroscopy in neonatal encephalopathy. Pediatrics 2006; 118 (04) 1467-1477
    CrossrefPubMedGoogle Scholar
  • 24 Flammer J, Konieczka K, Bruno RM, Virdis A, Flammer AJ, Taddei S. The eye and the heart. Eur Heart J 2013; 34 (17) 1270-1278
    CrossrefPubMedGoogle Scholar
  • 25 Robertson CM, Perlman M. Follow-up of the term infant after hypoxic-ischemic encephalopathy. Paediatr Child Health 2006; 11 (05) 278-282
    PubMedGoogle Scholar
  • 26 Azzopardi D. Clinical management of the baby with hypoxic ischaemic encephalopathy. Early Hum Dev 2010; 86 (06) 345-350
    CrossrefPubMedGoogle Scholar
  • 27 Ladjimi A, Zaouali S, Messaoud R. , et al. Valsalva retinopathy induced by labour. Eur J Ophthalmol 2002; 12 (04) 336-338
    CrossrefPubMedGoogle Scholar
  • 28 Smith DC, Kearns TP, Sayre GP. Preretinal and optic nerve-sheath hemorrhage: pathologic and experimental aspects in subarachnoid hemorrhage. Trans Am Acad Ophthalmol Otolaryngol 1957; 61 (02) 201-211
    PubMedGoogle Scholar
  • 29 Michelson AD, Barnard MR, Khuri SF, Rohrer MJ, MacGregor H, Valeri CR. The effects of aspirin and hypothermia on platelet function in vivo. Br J Haematol 1999; 104 (01) 64-68
    CrossrefPubMedGoogle Scholar
  • 30 Wolberg AS, Meng ZH, Monroe III DM, Hoffman M. A systematic evaluation of the effect of temperature on coagulation enzyme activity and platelet function. J Trauma 2004; 56 (06) 1221-1228
    CrossrefPubMedGoogle Scholar
  • 31 Rey-Funes M, Dorfman VB, Ibarra ME. , et al. Hypothermia prevents gliosis and angiogenesis development in an experimental model of ischemic proliferative retinopathy. Invest Ophthalmol Vis Sci 2013; 54 (04) 2836-2846
    CrossrefPubMedGoogle Scholar
  • 32 Rey-Funes M, Ibarra ME, Dorfman VB. , et al. Hypothermia prevents the development of ischemic proliferative retinopathy induced by severe perinatal asphyxia. Exp Eye Res 2010; 90 (01) 113-120
    CrossrefPubMedGoogle Scholar
  • 33 Hofman P, van Blijswijk BC, Gaillard PJ, Vrensen GF, Schlingemann RO. Endothelial cell hypertrophy induced by vascular endothelial growth factor in the retina: new insights into the pathogenesis of capillary nonperfusion. Arch Ophthalmol 2001; 119 (06) 861-866
    CrossrefPubMedGoogle Scholar
  • 34 Rey-Funes M, Ibarra ME, Dorfman VB. , et al. Hypothermia prevents nitric oxide system changes in retina induced by severe perinatal asphyxia. J Neurosci Res 2011; 89 (05) 729-743
    CrossrefPubMedGoogle Scholar
  • 35 Eldred WD, Blute TA. Imaging of nitric oxide in the retina. Vision Res 2005; 45 (28) 3469-3486
    CrossrefPubMedGoogle Scholar
  • 36 Dorfman VB, Rey-Funes M, Bayona JC, López EM, Coirini H, Loidl CF. Nitric oxide system alteration at spinal cord as a result of perinatal asphyxia is involved in behavioral disabilities: hypothermia as preventive treatment. J Neurosci Res 2009; 87 (05) 1260-1269
    CrossrefPubMedGoogle Scholar
  • 37 Fernández AP, Alonso D, Lisazoaín I. , et al. Postnatal changes in the nitric oxide system of the rat cerebral cortex after hypoxia during delivery. Brain Res Dev Brain Res 2003; 142 (02) 177-192
    CrossrefPubMedGoogle Scholar
  • 38 Ekimova IV. Changes in the metabolic activity of neurons in the anterior hypothalamic nuclei in rats during hyperthermia, fever, and hypothermia. Neurosci Behav Physiol 2003; 33 (05) 455-460
    CrossrefPubMedGoogle Scholar