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CC BY-NC-ND 4.0 · Geburtshilfe Frauenheilkd
DOI: 10.1055/a-2593-0275
DOI: 10.1055/a-2593-0275
GebFra Science
Review
Perinatal Neuroprotection in Preterm Birth
Article in several languages: English | deutsch
Abstract
Preterm birth is one of the main causes of perinatal morbidity and mortality. The rate of grade III and IV cerebral hemorrhages in infants with a birth weight of less than 1500 g in Germany in 2022 was 2.97% and the periventricular leukomalacia rate was 1.07%. In addition to these severe forms of brain damage which are visible on sonography, recent MRI studies carried out at the calculated due date of affected children also showed diffuse white and grey matter injuries, especially of the basal ganglia and the cerebellum, indicating impaired brain development and function. To offer these children the best possible start in life it is essential that they are cared for in a level I perinatal center right from the start. In addition, a number of perinatal measures are available which may significantly improve the neuronal development in preterm infants. They include the use of antenatal corticosteroids and magnesium as well as deferred cutting of the umbilical cord. Recent studies have shown that in contrast to term-born infants, hypothermia treatment is unsuitable for neuroprotection in premature babies. As secondary and tertiary cell damage may occur days or even weeks after the primary insult due to persistent inflammation and the lack of trophic stimulation, in addition to providing premature infants with the best possible initial care, it is also necessary to optimize subsequent care in the intensive care unit in terms of providing a neuronal-positive stimulating environment. Breastfeeding and supply of breast milk are particularly important in this context.
Keywords
preterm birth - periventricular-intraventricular hemorrhage - neuroprotection - periventricular leukomalaciaPublication History
Received: 23 January 2025
Accepted after revision: 12 March 2025
Article published online:
30 June 2025
© 2025. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).
Georg Thieme Verlag KG
Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany
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References/Literatur
- 1 Murray CJ, Vos T, Lozano R. et al. Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 2012; 380: 2197-2223
- 2 IQTIG. Bundesauswertung 2023. Accessed September 23, 2024 at: https://iqtig.org/veroeffentlichungen/bundesqualitaetsbericht/
- 3 Yates N, Gunn AJ, Bennet L. et al. Preventing Brain Injury in the Preterm Infant-Current Controversies and Potential Therapies. Int J Mol Sci 2021; 22: 1671
- 4 Ophelders D, Gussenhoven R, Klein L. et al. Preterm Brain Injury, Antenatal Triggers, and Therapeutics: Timing Is Key. Cells 2020; 9: 1871
- 5 Hagberg H, Mallard C, Ferriero DM. et al. The role of inflammation in perinatal brain injury. Nat Rev Neurol 2015; 11: 192-208
- 6 Galinsky R, Lear CA, Dean JM. et al. Complex interactions between hypoxia-ischemia and inflammation in preterm brain injury. Dev Med Child Neurol 2018; 60: 126-133
- 7 Dean JM, Bennet L, Back SA. et al. What brakes the preterm brain? An arresting story. Pediatr Res 2014; 75: 227-233
- 8 Molloy EJ, El-Dib M, Soul J. et al. Neuroprotective therapies in the NICU in preterm infants: present and future (Neonatal Neurocritical Care Series). Pediatr Res 2024; 95: 1224-1236
- 9 Kidokoro H, Anderson PJ, Doyle LW. et al. Brain injury and altered brain growth in preterm infants: predictors and prognosis. Pediatrics 2014; 134: 444
- 10 Back SA. White matter injury in the preterm infant: pathology and mechanisms. Acta Neuropathol 2017; 134: 331-349
- 11 Verney C, Pogledic I, Biran V. et al. Microglial reaction in axonal crossroads is a hallmark of noncystic periventricular white matter injury in very preterm infants. J Neuropathol Exp Neurol 2012; 71: 251-264
- 12 Fleiss B, Gressens P. Tertiary mechanisms of brain damage: a new hope for treatment of cerebral palsy?. Lancet Neurol 2012; 11: 556-566
- 13 Chakkarapani AA, Aly H, Benders M. et al. Therapies for neonatal encephalopathy: Targeting the latent, secondary and tertiary phases of evolving brain injury. Semin Fetal Neonatal Med 2021; 26: 101256
- 14 Fleiss B, Murray DM, Bjorkman ST. et al. Editorial: Pathomechanisms and Treatments to Protect the Preterm, Fetal Growth Restricted and Neonatal Encephalopathic Brain. Front Neurol 2021; 12: 755617
- 15 Hüning B, Storbeck T, Bruns N. et al. Relationship between brain function (aEEG) and brain structure (MRI) and their predictive value for neurodevelopmental outcome of preterm infants. Eur J Pediatr 2018; 177: 1181-1189
- 16 Pascal A, Govaert P, Oostra A. et al. Neurodevelopmental outcome in very preterm and very-low-birthweight infants born over the past decade: a meta-analytic review. Dev Med Child Neurol 2018; 60: 342-355
- 17 Costeloe KL, Hennessy EM, Haider S. et al. Short term outcomes after extreme preterm birth in England: comparison of two birth cohorts in 1995 and 2006 (the EPICure studies). BMJ 2012; 345: e7976
- 18 Sellier E, Platt MJ, Andersen GL. et al. Decreasing prevalence in cerebral palsy: a multi-site European population-based study, 1980 to 2003. Dev Med Child Neurol 2016; 58: 85-92
- 19 Berger R, Söder S. Neuroprotection in preterm infants. Biomed Res Int 2015; 2015: 257139
- 20 Volpe J. Neurology of the Newborn. Philadelphia: Saunders; 1995
- 21 Ballabh P. Pathogenesis and prevention of intraventricular hemorrhage. Clin Perinatol 2014; 41: 47-67
- 22 Sá-Pereira I, Brites D, Brito MA. Neurovascular unit: a focus on pericytes. Mol Neurobiol 2012; 45: 327-347
- 23 Balabanov R, Dore-Duffy P. Role of the CNS microvascular pericyte in the blood-brain barrier. J Neurosci Res 1998; 53: 637-644
- 24 Jain RK. Molecular regulation of vessel maturation. Nat Med 2003; 9: 685-693
- 25 Armulik A, Genové G, Mäe M. et al. Pericytes regulate the blood-brain barrier. Nature 2010; 468: 557-561
- 26 Hirschi KK, D’Amore PA. Control of angiogenesis by the pericyte: molecular mechanisms and significance. EXS 1997; 79: 419-428
- 27 Gaengel K, Genové G, Armulik A. et al. Endothelial-mural cell signaling in vascular development and angiogenesis. Arterioscler Thromb Vasc Biol 2009; 29: 630-638
- 28 Lindahl P, Johansson BR, Levéen P. et al. Pericyte loss and microaneurysm formation in PDGF-B-deficient mice. Science 1997; 277: 242-245
- 29 Braun A, Xu H, Hu F. et al. Paucity of pericytes in germinal matrix vasculature of premature infants. J Neurosci 2007; 27: 12012-12024
- 30 Persidsky Y, Ramirez SH, Haorah J. et al. Blood-brain barrier: structural components and function under physiologic and pathologic conditions. J Neuroimmune Pharmacol 2006; 1: 223-236
- 31 Tilling T, Engelbertz C, Decker S. et al. Expression and adhesive properties of basement membrane proteins in cerebral capillary endothelial cell cultures. Cell Tissue Res 2002; 310: 19-29
- 32 Hallmann R, Horn N, Selg M. et al. Expression and function of laminins in the embryonic and mature vasculature. Physiol Rev 2005; 85: 979-1000
- 33 Xu H, Hu F, Sado Y. et al. Maturational changes in laminin, fibronectin, collagen IV, and perlecan in germinal matrix, cortex, and white matter and effect of betamethasone. J Neurosci Res 2008; 86: 1482-1500
- 34 Hawkins BT, Davis TP. The blood-brain barrier/neurovascular unit in health and disease. Pharmacol Rev 2005; 57: 173-185
- 35 El-Khoury N, Braun A, Hu F. et al. Astrocyte end-feet in germinal matrix, cerebral cortex, and white matter in developing infants. Pediatr Res 2006; 59: 673-679
- 36 Liedtke W, Edelmann W, Bieri PL. et al. GFAP is necessary for the integrity of CNS white matter architecture and long-term maintenance of myelination. Neuron 1996; 17: 607-615
- 37 Trimmer PA, Reier PJ, Oh TH. et al. An ultrastructural and immunocytochemical study of astrocytic differentiation in vitro: changes in the composition and distribution of the cellular cytoskeleton. J Neuroimmunol 1982; 2: 235-260
- 38 Ribotta MG, Menet V, Privat A. Glial scar and axonal regeneration in the CNS: lessons from GFAP and vimentin transgenic mice. Acta Neurochir Suppl 2004; 89: 87-92
- 39 McGoldrick E, Stewart F, Parker R. et al. Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database Syst Rev 2020; (12) CD004454
- 40 Milligan DW. Failure of autoregulation and intraventricular haemorrhage in preterm infants. Lancet 1980; 1: 896-898
- 41 Alderliesten T, Lemmers PM, Smarius JJ. et al. Cerebral oxygenation, extraction, and autoregulation in very preterm infants who develop peri-intraventricular hemorrhage. J Pediatr 2013; 162: 698-704.e2
- 42 Vinukonda G, Dummula K, Malik S. et al. Effect of prenatal glucocorticoids on cerebral vasculature of the developing brain. Stroke 2010; 41: 1766-1773
- 43 Clyman RI, Rosenstein MG, Liebowitz MC. et al. Betamethasone treatment-to-delivery interval, retreatment, and severe intraventricular hemorrhage in infants < 28 weeks’ gestation. Am J Obstet Gynecol 2025; 232: 400.e1-400.e10
- 44 Travers CP, Clark RH, Spitzer AR. et al. Exposure to any antenatal corticosteroids and outcomes in preterm infants by gestational age: prospective cohort study. BMJ 2017; 356: j1039
- 45 Räikkönen K, Gissler M, Kajantie E. Associations Between Maternal Antenatal Corticosteroid Treatment and Mental and Behavioral Disorders in Children. JAMA 2020; 323: 1924-1933
- 46 Räikkönen K, Gissler M, Tapiainen T. et al. Associations Between Maternal Antenatal Corticosteroid Treatment and Psychological Developmental and Neurosensory Disorders in Children. JAMA Netw Open 2022; 5: e2228518
- 47 Grether JK, Nelson KB, Emery 3rd ES. et al. Prenatal and perinatal factors and cerebral palsy in very low birth weight infants. J Pediatr 1996; 128: 407-414
- 48 Shepherd ES, Goldsmith S, Doyle LW. et al. Magnesium Sulfate Before Preterm Birth for Neuroprotection: An Updated Cochrane Systematic Review. Obstet Gynecol 2024; 144: 161-170
- 49 Berger R, Garnier Y. Pathophysiology of perinatal brain damage. Brain Res Rev 1999; 30: 107-134
- 50 Nowak L, Bregestovski P, Ascher P. et al. Magnesium gates glutamate-activated channels in mouse central neurones. Nature 1984; 307: 462-465
- 51 Hallak M, Hotra JW, Kupsky WJ. Magnesium sulfate protection of fetal rat brain from severe maternal hypoxia. Obstet Gynecol 2000; 96: 124-128
- 52 Euser AG, Cipolla MJ. Magnesium sulfate for the treatment of eclampsia: a brief review. Stroke 2009; 40: 1169-1175
- 53 Faragó M, Szabó C, Dóra E. et al. Contractile and endothelium-dependent dilatory responses of cerebral arteries at various extracellular magnesium concentrations. J Cereb Blood Flow Metab 1991; 11: 161-164
- 54 Garnier Y, Middelanis J, Jensen A. et al. Neuroprotective effects of magnesium on metabolic disturbances in fetal hippocampal slices after oxygen-glucose deprivation: mediation by nitric oxide system. J Soc Gynecol Investig 2002; 9: 86-92
- 55 Koning G, Leverin AL, Nair S. et al. Magnesium induces preconditioning of the neonatal brain via profound mitochondrial protection. J Cereb Blood Flow Metab 2019; 39: 1038-1055
- 56 Katheria A, Reister F, Essers J. et al. Association of Umbilical Cord Milking vs Delayed Umbilical Cord Clamping With Death or Severe Intraventricular Hemorrhage Among Preterm Infants. JAMA 2019; 322: 1877-1886
- 57 Seidler AL, Aberoumand M, Hunter KE. iCOMP Collaborators. et al. Deferred cord clamping, cord milking, and immediate cord clamping at preterm birth: a systematic review and individual participant data meta-analysis. Lancet 2023; 402: 2209-2222
- 58 Seidler AL, Libesman S, Hunter KE. iCOMP Collaborators. et al. Short, medium, and long deferral of umbilical cord clamping compared with umbilical cord milking and immediate clamping at preterm birth: a systematic review and network meta-analysis with individual participant data. Lancet 2023; 402: 2223-2234
- 59 Ott F, Kribs A, Stelzl P. et al. Resuscitation of Term Compromised and Asphyctic Newborns: Better with Intact Umbilical Cord?. Geburtshilfe Frauenheilkd 2022; 82: 706-718
- 60 Jacobs SE, Berg M, Hunt R. et al. Cooling for newborns with hypoxic ischaemic encephalopathy. Cochrane Database Syst Rev 2013; (01) CD003311
- 61 Laptook AR, Shankaran S, Faix RG. Hypothermia for Hypoxic-ischemic Encephalopathy: Second-generation Trials to Address Gaps in Knowledge. Clin Perinatol 2024; 51: 587-603
- 62 Lear CA, Koome ME, Davidson JO. et al. The effects of dexamethasone on post-asphyxial cerebral oxygenation in the preterm fetal sheep. J Physiol 2014; 592: 5493-5505
- 63 Lear BA, Lear CA, Davidson JO. et al. Tertiary cystic white matter injury as a potential phenomenon after hypoxia-ischaemia in preterm f sheep. Brain Commun 2021; 3: fcab024
- 64 Fabres J, Carlo WA, Phillips V. et al. Both extremes of arterial carbon dioxide pressure and the magnitude of fluctuations in arterial carbon dioxide pressure are associated with severe intraventricular hemorrhage in preterm infants. Pediatrics 2007; 119: 299-305
- 65 Miller SS, Lee HC, Gould JB. Hypothermia in very low birth weight infants: distribution, risk factors and outcomes. J Perinatol 2011; 31 (Suppl. 1) S49-S56
- 66 Vesoulis ZA, Flower AA, Zanelli S. et al. Blood pressure extremes and severe IVH in preterm infants. Pediatr Res 2020; 87: 69-73
- 67 Kuitunen I, Räsänen K. Less Invasive Surfactant Administration Compared to Intubation, Surfactant, Rapid Extubation Method in Preterm Neonates: An Umbrella Review. Neonatology 2024; 121: 485-493
- 68 Goswami IR, Abou Mehrem A, Scott J. et al. Metabolic acidosis rather than hypo/hypercapnia in the first 72 hours of life associated with intraventricular hemorrhage in preterm neonates. J Matern Fetal Neonatal Med 2021; 34: 3874-3882
- 69 Malusky S, Donze A. Neutral head positioning in premature infants for intraventricular hemorrhage prevention: an evidence-based review. Neonatal Netw 2011; 30: 381-396
- 70 Anand KJ. Clinical importance of pain and stress in preterm neonates. Biol Neonate 1998; 73: 1-9
- 71 Lee HJ, Lee BS, Do HJ. et al. Early sodium and fluid intake and severe intraventricular hemorrhage in extremely low birth weight infants. J Korean Med Sci 2015; 30: 283-289
- 72 Murthy P, Zein H, Thomas S. et al. Neuroprotection Care Bundle Implementation to Decrease Acute Brain Injury in Preterm Infants. Pediatr Neurol 2020; 110: 42-48
- 73 de Bijl-Marcus K, Brouwer AJ, De Vries LS. et al. Neonatal care bundles are associated with a reduction in the incidence of intraventricular haemorrhage in preterm infants: a multicentre cohort study. Arch Dis Child Fetal Neonatal Ed 2020; 105: 419-424
- 74 McLendon D, Check J, Carteaux P. et al. Implementation of potentially better practices for the prevention of brain hemorrhage and ischemic brain injury in very low birth weight infants. Pediatrics 2003; 111: e497-e503
- 75 Benlamri A, Murthy P, Zein H. et al. Neuroprotection care bundle implementation is associated with improved long-term neurodevelopmental outcomes in extremely premature infants. J Perinatol 2022; 42: 1380-1384
- 76 Mohammad K, Momin S, Murthy P. et al. Impact of quality improvement outreach education on the incidence of acute brain injury in transported neonates born premature. J Perinatol 2022; 42: 1368-1373
- 77 Cho ES, Kim SJ, Kwon MS. et al. The Effects of Kangaroo Care in the Neonatal Intensive Care Unit on the Physiological Functions of Preterm Infants, Maternal-Infant Attachment, and Maternal Stress. J Pediatr Nurs 2016; 31: 430-438
- 78 Gonya J, Ray WC, Rumpf RW. et al. Investigating skin-to-skin care patterns with extremely preterm infants in the NICU and their effect on early cognitive and communication performance: a retrospective cohort study. BMJ Open 2017; 7: e012985
- 79 Smith SW, Ortmann AJ, Clark WW. Noise in the neonatal intensive care unit: a new approach to examining acoustic events. Noise Health 2018; 20: 121-130
- 80 Braid S, Bernstein J. Improved Cognitive Development in Preterm Infants with Shared Book Reading. Neonatal Netw 2015; 34: 10-17
- 81 Shellhaas RA, Burns JW, Hassan F. et al. Neonatal Sleep-Wake Analyses Predict 18-month Neurodevelopmental Outcomes. Sleep 2017; 40: zsx144
- 82 O’Brien K, Robson K, Bracht M. FICare Study Group and FICare Parent Advisory Board. et al. Effectiveness of Family Integrated Care in neonatal intensive care units on infant and parent outcomes: a multicentre, multinational, cluster-randomised controlled trial. Lancet Child Adolesc Health 2018; 2: 245-254
- 83 Chorna O, Filippa M, De Almeida JS. et al. Neuroprocessing Mechanisms of Music during Fetal and Neonatal Development: A Role in Neuroplasticity and Neurodevelopment. Neural Plast 2019; 2019: 3972918
- 84 Forcada-Guex M, Pierrehumbert B, Borghini A. et al. Early dyadic patterns of mother-infant interactions and outcomes of prematurity at 18 months. Pediatrics 2006; 118: e107-e114
- 85 Belfort MB, Anderson PJ, Nowak VA. et al. Breast Milk Feeding, Brain Development, and Neurocognitive Outcomes: A 7-Year Longitudinal Study in Infants Born at Less Than 30 Weeks’ Gestation. J Pediatr 2016; 177: 133-139.e1
- 86 Vohr BR, Poindexter BB, Dusick AM. et al. Beneficial effects of breast milk in the neonatal intensive care unit on the developmental outcome of extremely low birth weight infants at 18 months of age. Pediatrics 2006; 118: e115-e123
- 87 Sullivan G, Vaher K, Blesa M. et al. Breast Milk Exposure is Associated With Cortical Maturation in Preterm Infants. Ann Neurol 2023; 93: 591-603
- 88 Anderson JW, Johnstone BM, Remley DT. Breast-feeding and cognitive development: a meta-analysis. Am J Clin Nutr 1999; 70: 525-535
- 89 Rozé JC, Darmaun D, Boquien CY. et al. The apparent breastfeeding paradox in very preterm infants: relationship between breast feeding, early weight gain and neurodevelopment based on results from two cohorts, EPIPAGE and LIFT. BMJ Open 2012; 2: e000834
- 90 Ballard O, Morrow AL. Human milk composition: nutrients and bioactive factors. Pediatr Clin North Am 2013; 60: 49-74
- 91 Zhou Q, Li M, Wang X. et al. Immune-related microRNAs are abundant in breast milk exosomes. Int J Biol Sci 2012; 8: 118-123
- 92 Picáns-Leis R, Vázquez-Mosquera ME, Pereira-Hernández M. et al. Characterization of the functional component in human milk and identification of the molecular mechanisms undergoing prematurity. Clin Nutr 2025; 44: 178-192
- 93 Piras M, Coni P, Piludu M. et al. Human breast milk cells are positive for the pioneer transcription factor ISL1. Eur Rev Med Pharmacol Sci 2023; 27: 8842-8849
- 94 Blesa M, Sullivan G, Anblagan D. et al. Early breast milk exposure modifies brain connectivity in preterm infants. Neuroimage 2019; 184: 431-439
- 95 Ottolini KM, Andescavage N, Kapse K. et al. Improved brain growth and microstructural development in breast milk-fed very low birth weight premature infants. Acta Paediatr 2020; 109: 1580-1587
- 96 Atayde AMP, Kapoor NR, Cherkerzian S. et al. Lactoferrin intake from maternal milk during the neonatal hospitalization and early brain development among preterm infants. Pediatr Res 2024; 96: 159-164
- 97 Colaizy TT, Poindexter BB, McDonald SA. et al. Neurodevelopmental Outcomes of Extremely Preterm Infants Fed Donor Milk or Preterm Infant Formula: A Randomized Clinical Trial. JAMA 2024; 331: 582-591
- 98 Singh P, Al Mohannadi N, Murugesan S. et al. Unveiling the dynamics of the breast milk microbiome: impact of lactation stage and gestational age. J Transl Med 2023; 21: 784
- 99 Conboy-Stephenson R, Ross RP, Kelly AL. et al. Donor human milk: the influence of processing technologies on its nutritional and microbial composition. Front Nutr 2024; 11: 1468886
- 100 Fu ZY, Huang C, Lei L. et al. The effect of oropharyngeal colostrum administration on the clinical outcomes of premature infants: A meta-analysis. Int J Nurs Stud 2023; 144: 104527
- 101 Keller T, Körber F, Oberthuer A. et al. Intranasal breast milk for premature infants with severe intraventricular hemorrhage-an observation. Eur J Pediatr 2019; 178: 199-206
- 102 Malhotra A. Neurotherapeutic potential of intranasal administration of human breast milk. Pediatr Res 2023; 94: 1872-1873
- 103 Gallipoli A, Unger S, El Shahed A. et al. Outcomes after intranasal human milk therapy in preterm infants with intraventricular hemorrhage. J Perinatol 2025; 45: 202-207
- 104 Hoban R, Gallipoli A, Signorile M. et al. Feasibility of intranasal human milk as stem cell therapy in preterm infants with intraventricular hemorrhage. J Perinatol 2024; 44: 1652-1657
- 105 Lear CA, Lear BA, Davidson JO. et al. Tumour necrosis factor blockade after asphyxia in foetal sheep ameliorates cystic white matter injury. Brain 2023; 146: 1453-1466
- 106 Ohls RK, Ehrenkranz RA, Das A. et al. Neurodevelopmental outcome and growth at 18 to 22 months’ corrected age in extremely low birth weight infants treated with early erythropoietin and iron. Pediatrics 2004; 114: 1287-1291
- 107 Ohls RK, Kamath-Rayne BD, Christensen RD. et al. Cognitive outcomes of preterm infants randomized to darbepoetin, erythropoietin, or placebo. Pediatrics 2014; 133: 1023-1030
- 108 Natalucci G, Latal B, Koller B. et al. Effect of Early Prophylactic High-Dose Recombinant Human Erythropoietin in Very Preterm Infants on Neurodevelopmental Outcome at 2 Years: A Randomized Clinical Trial. JAMA 2016; 315: 2079-2085
- 109 Song J, Sun H, Xu F. et al. Recombinant human erythropoietin improves neurological outcomes in very preterm infants. Ann Neurol 2016; 80: 24-34
- 110 Juul SE, Comstock BA, Wadhawan R. et al. A Randomized Trial of Erythropoietin for Neuroprotection in Preterm Infants. N Engl J Med 2020; 382: 233-243
- 111 Robertson NJ, Tan S, Groenendaal F. et al. Which neuroprotective agents are ready for bench to bedside translation in the newborn infant?. J Pediatr 2012; 160: 544-552.e4
- 112 Drury PP, Davidson JO, Bennet L. et al. Partial neural protection with prophylactic low-dose melatonin after asphyxia in preterm fetal sheep. J Cereb Blood Flow Metab 2014; 34: 126-135
- 113 Marseglia L, Gitto E, Laschi E. et al. Antioxidant Effect of Melatonin in Preterm Newborns. Oxid Med Cell Longev 2021; 2021: 6308255
- 114 Häusler S, Robertson NJ, Golhen K. et al. Melatonin as a Therapy for Preterm Brain Injury: What Is the Evidence?. Antioxidants (Basel) 2023; 12: 1630
- 115 Schmidt B, Roberts RS, Davis P. et al. Caffeine therapy for apnea of prematurity. N Engl J Med 2006; 354: 2112-2121
- 116 Back SA, Craig A, Luo NL. et al. Protective effects of caffeine on chronic hypoxia-induced perinatal white matter injury. Ann Neurol 2006; 60: 696-705
- 117 McLeod RM, Rosenkrantz TS, Fitch RH. et al. Sex Differences in Microglia Activation in a Rodent Model of Preterm Hypoxic Ischemic Injury with Caffeine Treatment. Biomedicines 2023; 11: 185
- 118 Alexander M, Smith AL, Rosenkrantz TS. et al. Therapeutic effect of caffeine treatment immediately following neonatal hypoxic-ischemic injury on spatial memory in male rats. Brain Sci 2013; 3: 177-190
- 119 Kilicdag H, Daglioglu YK, Erdogan S. et al. Effects of caffeine on neuronal apoptosis in neonatal hypoxic-ischemic brain injury. J Matern Fetal Neonatal Med 2014; 27: 1470-1475
- 120 Schmidt B, Roberts RS, Davis P. et al. Long-term effects of caffeine therapy for apnea of prematurity. N Engl J Med 2007; 357: 1893-1902
- 121 Smith MJ, Paton MCB, Fahey MC. et al. Neural stem cell treatment for perinatal brain injury: A systematic review and meta-analysis of preclinical studies. Stem Cells Transl Med 2021; 10: 1621-1636
- 122 Passera S, Boccazzi M, Bokobza C. et al. Therapeutic potential of stem cells for preterm infant brain damage: Can we move from the heterogeneity of preclinical and clinical studies to established therapeutics?. Biochem Pharmacol 2021; 186: 114461
- 123 Malhotra A, Novak I, Miller SL. et al. Autologous transplantation of umbilical cord blood-derived cells in extreme preterm infants: protocol for a safety and feasibility study. BMJ Open 2020; 10: e036065