Abstract
Background:
The study tested the hypothesis that hyperoxemia and hypoxemia differentially alter cerebral blood flow velocity (CBFV) in a gestational age–dependent manner.
Methods:
Cases comprised 98 neonates with mild respiratory distress, receiving oxygen for >24 h in first 48 h of life. Ninety-eight age- and-weight-matched healthy neonates served as controls. Infants with perinatal asphyxia, shock, sepsis, malformations, acidosis/alkalosis, and hypo/hypercarbia were excluded. Resistance index (RI), pulsatility index (PI), peak systolic flow velocity (PSV), and vascular diameter were measured in internal carotid, vertebral, and middle cerebral arteries by transcranial doppler ultrasonography between 24 and 48 h of life with immediate postdoppler arterial blood gas analysis. For subgroup analysis, neonates were divided by gestational age and PaO2.
Results:
An overall decrease in RI/PI and increase in PSV and vasodilation was observed in cases. Hyperoxemia (PaO2 >90 mm Hg) was more common in premature neonates. Neonates <32 wk showed an increase in CBFV (decreased RI/PI and increased PSV/diameter) in association with hyperoxemia. An opposite response was observed in neonates ≥32 wk, where CBFV increased in response to hypoxemia (PaO2 <50 mm Hg) and decreased in hyperoxemia. Increased CBFV showed high predictive accuracy for immediate mortality and intracranial hemorrhage.
Conclusion:
Depending on gestational maturity, hyperoxemia or hypoxemia produce differential effects in CBFV.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
de Vries LS, Eken P, Dubowitz LM . The spectrum of leukomalacia using cranial ultrasound. Behav Brain Res 1992;49:1–6.
De Vries LS, Van Haastert IL, Rademaker KJ, Koopman C, Groenendaal F . Ultrasound abnormalities preceding cerebral palsy in high-risk preterm infants. J Pediatr 2004;144:815–20.
Baburamani AA, Ek CJ, Walker DW, Castillo-Melendez M . Vulnerability of the developing brain to hypoxic-ischemic damage: contribution of the cerebral vasculature to injury and repair? Front Physiol 2012;3:424.
Trommer BL, Groothuis DR, Pasternak JF . Quantitative analysis of cerebral vessels in the newborn puppy: the structure of germinal matrix vessels may predispose to hemorrhage. Pediatr Res 1987;22:23–8.
Nishimura N, Iwasaki K, Ogawa Y, Shibata S . Oxygen administration, cerebral blood flow velocity, and dynamic cerebral autoregulation. Aviat Space Environ Med 2007;78:1121–7.
Macri MA, D’Alessandro N, Di Giulio C, et al. Region-specific effects on brain metabolites of hypoxia and hyperoxia overlaid on cerebral ischemia in young and old rats: a quantitative proton magnetic resonance spectroscopy study. J Biomed Sci 2010;17:14.
Iwasaki K, Ogawa Y, Shibata S, Aoki K . Acute exposure to normobaric mild hypoxia alters dynamic relationships between blood pressure and blood flow at very low frequency. J Cereb Blood Flow Metab 2007;27:776–84.
Riyas PK, Vijayakumar KM, Kulkarni ML . Neonatal mechanical ventilation. Indian J Pediatr 2003;70:537–40.
Kamei A, Houdou S, Mito T, Konomi H, Takashima S . Developmental change in type VI collagen in human cerebral vessels. Pediatr Neurol 1992;8:183–6.
Ballabh P . Intraventricular hemorrhage in premature infants: mechanism of disease. Pediatr Res 2010;67:1–8.
Linder N, Haskin O, Levit O, et al. Risk factors for intraventricular hemorrhage in very low birth weight premature infants: a retrospective case-control study. Pediatrics 2003;111(5 Pt 1):e590–5.
Pellicer A, Valverde E, Gayá F, Quero J, Cabañas F . Postnatal adaptation of brain circulation in preterm infants. Pediatr Neurol 2001;24:103–9.
Lee SJ, Hatran DP, Tomimatsu T, Peña JP, McAuley G, Longo LD . Fetal cerebral blood flow, electrocorticographic activity, and oxygenation: responses to acute hypoxia. J Physiol (Lond) 2009;587(Pt 9):2033–47.
Gerstner B, DeSilva TM, Genz K, et al. Hyperoxia causes maturation-dependent cell death in the developing white matter. J Neurosci 2008;28:1236–45.
Vottier G, Pham H, Pansiot J, et al. Deleterious effect of hyperoxia at birth on white matter damage in the newborn rat. Dev Neurosci 2011;33:261–9.
Bittigau P, Sifringer M, Genz K, et al. Antiepileptic drugs and apoptotic neurodegeneration in the developing brain. Proc Natl Acad Sci USA 2002;99:15089–94.
Pena JP, Tomimatsu T, Hatran DP, McGill LL, Longo LD . Cerebral blood flow and oxygenation in ovine fetus: responses to superimposed hypoxia at both low and high altitude. J Physiol (Lond) 2007;578(Pt 1):359–70.
Liem KD, Greisen G . Monitoring of cerebral haemodynamics in newborn infants. Early Hum Dev 2010;86:155–8.
Lassen NA . Cerebral blood flow and oxygen consumption in man. Physiol Rev 1959;39:183–238.
Caicedo A, De Smet D, Vanderhaegen J, et al. Impaired cerebral autoregulation using near-infrared spectroscopy and its relation to clinical outcomes in premature infants. Adv Exp Med Biol 2011;701:233–9.
Lou HC, Lassen NA, Friis-Hansen B . Impaired autoregulation of cerebral blood flow in the distressed newborn infant. J Pediatr 1979;94:118–21.
Tsuji M, Saul JP, du Plessis A, et al. Cerebral intravascular oxygenation correlates with mean arterial pressure in critically ill premature infants. Pediatrics 2000;106:625–32.
Nishimura N, Iwasaki K, Ogawa Y, Aoki K . Decreased steady-state cerebral blood flow velocity and altered dynamic cerebral autoregulation during 5-h sustained 15% O2 hypoxia. J Appl Physiol 2010;108:1154–61.
Niijima S, Shortland DB, Levene MI, Evans DH . Transient hyperoxia and cerebral blood flow velocity in infants born prematurely and at full term. Arch Dis Child 1988;63(10 Spec No):1126–30.
Leahy FA, Cates D, MacCallum M, Rigatto H . Effect of CO2 and 100% O2 on cerebral blood flow in preterm infants. J Appl Physiol Respir Environ Exerc Physiol 1980;48:468–72.
Meek JH, Tyszczuk L, Elwell CE, Wyatt JS . Low cerebral blood flow is a risk factor for severe intraventricular haemorrhage. Arch Dis Child Fetal Neonatal Ed 1999;81:F15–8.
Ment LR, Ehrenkranz RA, Lange RC, Rothstein PT, Duncan CC . Alterations in cerebral blood flow in preterm infants with intraventricular hemorrhage. Pediatrics 1981;68:763–9.
Ojala T, Kääpä P, Helenius H, et al. Low cerebral blood flow resistance in nonventilated preterm infants predicts poor neurologic outcome. Pediatr Crit Care Med 2004;5:264–8.
Baenziger O, Mueller AM, Morales CG, et al. Cerebral blood flow and neurological outcome in the preterm infant. Eur J Pediatr 1999;158:138–43.
Basu S, Dewangan S, Shukla RC, Anupurva S, Kumar A . Cerebral blood flow velocity in early-onset neonatal sepsis and its clinical significance. Eur J Pediatr 2012;171:901–9.
Payne SJ, Selb J, Boas DA . Effects of autoregulation and CO2 reactivity on cerebral oxygen transport. Ann Biomed Eng 2009;37:2288–98.
Tin W, Gupta S . Optimum oxygen therapy in preterm babies. Arch Dis Child Fetal Neonatal Ed 2007;92:F143–7.
Deuber C, Terhaar M . Hyperoxia in very preterm infants: a systematic review of the literature. J Perinat Neonatal Nurs 2011;25:268–74.
Saugstad OD, Aune D . In search of the optimal oxygen saturation for extremely low birth weight infants: a systematic review and meta-analysis. Neonatology 2011;100:1–8.
Deulofeut R, Critz A, Adams-Chapman I, Sola A . Avoiding hyperoxia in infants < or = 1250 g is associated with improved short- and long-term outcomes. J Perinatol 2006;26:700–5.
SUPPORT Study Group of the Eunice Kennedy Shriver NICHD Neonatal Research Network. Target ranges of oxygen saturation in extremely preterm infants. N Engl J Med 2010;362:1959–69.
Stenson B, Brocklehurst P, Tarnow-Mordi W ; U.K. BOOST II trial; Australian BOOST II trial; New Zealand BOOST II trial. Increased 36-week survival with high oxygen saturation target in extremely preterm infants. N Engl J Med 2011;364:1680–2.
Carter BG, Carlin JB, Tibballs J, Mead H, Hochmann M, Osborne A . Accuracy of two pulse oximeters at low arterial hemoglobin-oxygen saturation. Crit Care Med 1998;26:1128–33.
Bohnhorst B, Peter CS, Poets CF . Detection of hyperoxaemia in neonates: data from three new pulse oximeters. Arch Dis Child Fetal Neonatal Ed 2002;87:F217–9.
Cochran DP, Shaw NJ . The use of pulse oximetry in the prevention of hyperoxaemia in preterm infants. Eur J Pediatr 1995;154:222–4.
Downes JJ, Vidyasagar D, Boggs TR Jr, Morrow GM 3rd . Respiratory distress syndrome of newborn infants. I. New clinical scoring system (RDS score) with acid–base and blood-gas correlations. Clin Pediatr (Phila) 1970;9:325–31.
Ballard JL, Khoury JC, Wedig K, Wang L, Eilers-Walsman BL, Lipp R . New Ballard Score, expanded to include extremely premature infants. J Pediatr 1991;119:417–23.
Volpe JJ . Intracranial hemorrhage: Germinal matrix-intraventricular hemorrhage of the preterm infant. In: Volpe JJ, ed. Neurology of the Newborn, 5th edn. Philadelphia, PA: Saunders Elsevier, 2008:517–88.
Zwibel WJ, Pellerito JS . Basic concepts of Doppler frequency spectrum analysis and ultrasound blood flow imaging. In: Zwibel WJ, Pellerito JS, eds. Introduction to Vascular Ultrasonography, 5th edn. Philadelphia, PA: Saunders Elsevier, 2005:61–89.
Author information
Authors and Affiliations
Corresponding author
PowerPoint slides
Rights and permissions
About this article
Cite this article
Basu, S., Barman, S., Shukla, R. et al. Effect of oxygen inhalation on cerebral blood flow velocity in premature neonates. Pediatr Res 75, 328–335 (2014). https://doi.org/10.1038/pr.2013.219
Received:
Accepted:
Published:
Issue date:
DOI: https://doi.org/10.1038/pr.2013.219
This article is cited by
-
Urinary Allantoin Is Elevated in Severe Intraventricular Hemorrhage in the Preterm Newborn
Translational Stroke Research (2016)


